Introduction to Pharmacology - Study Note

PHARMACOLOGY Introduction to Pharmacology What is a generic name? - Chemical name of a drug Refers to the chemical make-up rather than the advertised brand A term referring to any drug marketed under its chemical name without advertising What is drug classification?      Similar chemical structures Same mechanism of action Drugs that have similar chemical structures Same mechanism of action A related mode of action Used to treat the same disease SAMPLES OF CLASSIFICATIONS OF DRUGS 5-Alpha-reductase inhibitor Angiotensin II receptor antagonist ACE inhibitor Alpha-adrenergic agonist Beta blocker Dopamine agonist Dopamine antagonist Incretin mimetic Nonsteroidal anti-inflammatory drug – cyclooxygenase drug Proton-pump inhibitor Renin inhibitor Pharmacokinetics - Process of absorption, distribution, metabolism and elimination of drugs. 1. Absorption- movement of drug particles from GI tract to the body fluids. 2. Distribution- is the process by which drugs become available to the body fluids and tissues. 3. Protein Binding- portion of the drug that is bound inactive. 4. Metabolism- process by which body inactivates or biotransforms drug.  Hepatic firstpass- drugs pass first in the liver before going to the blood. 5. Excretion/Elimination- main route is through kidneys. 6. Half Life- the time it takes for the one half of drug to be concentrated to be eliminated. Pharmacodynamics - Study how drug affects the body. 1. Onset of Action- time it takes to reach the minimum effective concentration after the drug is administered. 2. Peak of Action- occurs when the drug reaches its highest blood or plasma concentration. 3. Duration of Action- Length of time the drug has a pharmacologic effect. 4. Agonist- produce a response 5. Antagonist- Blocks a response 6. Side Effects- Physiologic effect not related to the desired effect 7. Adverse Effect- more severe than side effect. It is dangerous and detrimental. 8. Toxic effects or toxicity- occurs when there is unintentional over dosage of a drug. 9. Tolerance- a decreased responsiveness over the course of the therapy 10. Placebo effect- is a psychological benefit from a compound that may not have the chemical structure of a drug effect. RA 9165-Comprehensive Dangerous Drug Act 2002 - Creation of PDEA Nurses must administer controlled drugs with a witness 1|Pharmacology - Sharing of controlled drugs is prohibited Dosage Calculation Conversion - 1 grain= 60 mg 1 teaspoon 1tablespoon 1 oz 1oz 1 lbs 1 kg 1 cup 1 pint 1 quart = = = = = = = = = 5 ml 15 ml 30 ml 2 tbsp 0.45 kg 2.2 lbs 180 ml 500 ml 1000ml Calculating Oral Dosages Formula: D/S X Q= Amount to give Example: 1. Give 150 mg of ibuprofen syrup every 6 hours for 7 days. The available stock dose is 150 mg/ml. How many ml of syrup should be given to the patient? Answer: 28 ml per week Computation: 1. 150mg/150mg x 1 ml= 1ml 2. 1ml x 4 (6 hours in a day is x4)= 4ml/day 3. 4ml x 7 (7 days)= 28 ml per week Take note: Dosage above 5000mg causes toxicity Calculation of Flow Rates 1. Milliliters per hours Formula: number of ml/number of hours= ml/hr 2|Pharmacology Example: Infuse 1000ml lactated ringer’s solution over 10 hours. Answer: 100 ml/hr Computation: 1000ml/10 hours= 100 ml/hr IV SETS Microdrip- 60 gtts/min Macrodrip- 15 gtts/ min Formula: Ml/hr x gtts/min all over 60= gtts/min Pediatric Calculation 1. Fried’s Rule (under 2 y.o) Formula: age in mos/ 150 lbs x adult dose= infant dose 2. Young’s Rule ( 2-12 y.o) Formula: age in yrs./ age in yrs. + 12 3. Clark’s Rule Formula: Child’s weight in lbs./ 150 lbs x adult dose ANTIBACTERIALS Bacteriostatic drugs – inhibit the growth of bacteria (inhibit growth to prevent multiplication) Bactericidal drugs – kill bacteria Culture and Sensitivity test (C&S)-can detect the infective microorganism present in a sample and what drug can kill it. Additive – equal to the sum of the effects of the two antibiotics Potentiative – occurs when one antibiotic potentiates the effects of the second antibiotic, increasing the effectiveness Anatagonistic – is a combination of a drug that is bactericidal and a drug that is bacteriostatic. When these two drugs are used together, the desired effect may be greatly reduced. Narrow-spectrum – primarily effective against one type of organism Broad-spectrum – can be effective against both gram-positive and gram-negative organisms. Mechanisms of Antibacterial Action 1. Inhibition of bacterial cell-wall synthesis( prevent bacterial cell wall to build up) 2. Alteration of membrane permeability (when taking antibiotics, the cell wall will allow fluids to enter and it will swell, it will rupture and the cell will die) 3. inhibition of protein synthesis (when taking some antibiotics it will prevent the cell of the bacteria to produce protein and if no protein, the cell will die) Ribosomes = protein (Rough ER) 4. inhibition of the synthesis of bacterial ribonucleic acid (RNA) and deoxyribonucleic acid (DNA) (A cell cannot live without DNA, it will not multiply. No DNA = dead cell) ANTIBIOTIC RESISTANCE 1. Self-Medicating (DO NOT SELF MEDICATE!!) 2. Don’t stop taking medications even to symptoms subsided 3|Pharmacology 3. 4. 5. 6. 7. 8. Repeated exposures Do not argue with the doctor’s order (do not demand a drug you don’t need) Follow orders, take prescribed drugs religiously Do not take antibiotics if it is a viral infection (Antibiotics are ineffective against viruses) Do not give left over/expired antibiotics Give it round the clock General Adverse Reactions to Antibacterials 1. 2. Allergic (hypersensitivity) reactions, most common side effect = skin test!! Superinfection (kills normal flora or the body) – *E. coli – large colon, helps produces Vitamin K – *Bile – large intestine that produces colon bacili that produces brown color in stool – *Lactobacillus – vagina, helps keep acidic environment – *Improve normal flora: Drink yakult to increase colon bacili, yogurt, probiotics, kimchi 3. Organ toxicity PENICILLINS Penicillin - Penicillin’s beta lactam structure (beta lactam ring)interferes with bacterial-cell wall synthesis by inhibitingthe bacterial enzyme that is necessary for cell divisionand cellular synthesis. Can be both bacteriostatic and bactericidal Mainly referred to as beta-lactam antibiotics Beta lactamase - enzyme produced by microorganisms, the penicillin cannot penetrate/activate, so that penicillin cannot kill the bacteria Pharmacokinetics – Penicillin After oral administration, penicillin are absorbed mainly in the duodenum and upper jejunum of the small intestine. Pharmacodynamics – Penicillin - Bactericidal in action Penicillin: Mechanism of Action - Penicillins enter the bacteria via the cell wall. Inside the cell, they bind to penicillin-binding protein. Once bound, normal cell wall synthesis is disrupted. Result: bacteria cells die from cell lysis. Penicillins do not kill other cells in the body. Natural penicillins - penicillin G (Pentids, Pfizerpen, Celinex) penicillin V (V-Cillin, Betapen-VK) Aminopenicillins - Amoxicillin (Amoxin) Ampicillin Penicillinase-resistant penicillins - Cloxacillin (Ciclox) Dicloxacillin (Dynapen) Nafcillin (Nafcil) Extended-spectrum penicillins - piperacillin, ticarcillin, carbenicillin, mezlocillin Penicillin-beta-lactamase inhibitor combination drugs: – ampicillin + sulbactam = Unasyn 4|Pharmacology – amoxicillin + clavulanic acid = Augmentin – ticarcillin + clavulanic acid = Timentin – piperacillin + tazobactam = Zosyn Beta-Lactamase Inhibitors - inhibits the bacterial beta-lactamases, making the antibiotic effective and extending its antimicrobial effect Oral use: Clavulanic acid (Augmentin, TImentin) Parenteral use: Sulbactam (Unasyn) and Tazobactam (Zosyn) Side effects and Adverse Reactions - Nausea, vomiting and diarrhea are common GI disturbances Severe allergic reaction leads toanaphylactic shock. Clinical manifestations of a severe allergic reaction include laryngeal edema, severe bronchoconstriction with stridor, and hypotension. CEPHALOSPHORINS - administered when patient is sensitive to penicillin have a beta lactam structure and act byi nhibiting the bacterial enzyme necessary for cell wall synthesis Pharmacokinetics - Adminitered orally Food decreases absorption Administered parenterally. Not Absorbed in the GI tract. Pharmacodynamics - Inhibit cell wall synthesis Indications: - Pharyngitis Tonsillitis Lower resp tract infections Septicemia Meningitis Perioperative prophylaxis CEPHALOSPHORIN GENERATIONS 1. First Generation of Cephalosporins – effective against gram postivie bacteria and most gram negative bacteria) 2. Second Generation of Cephalosporins – same effectiveness as first generation. Possess a broader spectrum against other gram negative bacteria *First and second generation of Cephalosporins are usually localized 3. Third Generation of Cephalosporins – same effectiveness of second and first generations. Also effective against gram negative bacteria, less effective against gram positive bacteria 4. Fourth Generation of Cephalosporins – is similar to third generation. It is resistant to most beta-lactamase bacteria. Has broader gram positive coverage than third generation. * Third and fourth generation of Cephalosporins can cross the blood-brain barrier 5|Pharmacology Cephalosporins: First Generation - Cefadroxil Cephalexin (Keflex, Cefalin, Ceporex) Cephradine Cefazolin Na (Ancef and Kefzol) Good gram-positive coverage Poor gram-negative coverage used for surgical prophylaxis, URIs, otitis media Cephalosporins: Second Generation - Cefaclor (Ceclor) Cefoxitine (Mefoxin) Cefuroxime (Kefurox and Ceftin) Good gram-positive coverage Better gram-negative coverage than first generation Used prophylactically for abdominal or colorectal surgeries Cephalosporins: Third Generation - Ceftizoxime (Tergecin, Ceftizox) Ceftazidime (Fortaz, Fortum) Cefotaxime (Claforan) Cefixime (Suprax) Ceftriaxone (Rocephin) Most potent group against gram-negative Less active against gram-positive Used for difficult-to-treat organisms such as Pseudomonas Cephalosporin: Fourth Generation - cefepime (Maxipime) Newest cephalosporin agents. Broader spectrum of antibacterial activity than third generation, especially against gram-positive bacteria. MACROLIDES - Azithromycin (Zithromax) – long half-life, up to 3 days Clarithromycin (Biaxin) – Klaricid Erythromycin (E-Mycin) administered orally or intravenously (IV) Pharmacodynamics: 1. Macrolides suppress bacterial protein synthesis (no protein synthesis – attack ribosomes of the cell to prevent protein synthesis) 2. Azithromycin (Zithromax) has up to a 40- to 68- hour half-life and is prescribed to be taken only once a day for 3-5 days. SIDE EFFECTS AND ADVERSE REACTIONS - GI disturbances such as nausea, vomiting, diarrhea and abdominal cramping NURSING PROCESS FOR MACROLIDES 1. Monitor patient for liver damage resulting from prolonged use and high dosage of macrolides such as azithromycin. Signs of liver dysfunction include elevated liver enzyme levels (Alt and Ast) and jaundice. 2. Administer oral azithromycin 1 hour before or 2 hours after meals. Give with a full glass of water, not fruit juice. Give the drug with food if GI upset occurs. 6|Pharmacology 3. Administer antacids either 2 hours before or 2 hours after azithromycin (decrease absorption of drug) NEVER GIVE ANTACID WITH OTHER DRUGS!! Lacrosamides – very strong and expensive Clindamycin (Cleocin) and Lincomycin (Lincocin) - active against most gram positive organisms Glycopeptides 1. Vancomycin (Vancocin) – when penicillin is resistant (because of self medication = superinfection), will take a patient a longer time to heal. Pharmacokinetics: Vancomycin is given IV for severe infection. Pharmacodynamics: - Vancomycin inhibits bacterial cell wall synthesis (for it not to enter the cell wall) Side Effects and Adverse Reactions - Vancomycin may cause nephrotoxicity and ototoxicity. *Ototoxicity results in damage of cranial nerve VIII, can result in a permanent hearing loss (auditory branch) or temporary or permanent loss of balance (vestibular branch) TETRACYCLINE - - inhibiting bacterial protein synthesis have bacteriostatic effect Tetracycline in combination with metronidazole and bismuth subsalicylate is useful in treating Helicobacter pylori, a bacterium in the stomach that causes peptic ulcer. Tetracycline should not be taken with magnesium and aluminum antacidpreparations, milk products containing calciumor iron containing drugs, because thesesubstances bind with tetracycline and prevent absorption of the drug. Should be taken with an empty stomach 1 hour or 2 hours after mealtime. Side effects and Adverse Reaction - Gi disturbances such as nausea, vomiting, and diarrhea Photosensitivity (sunburn reaction) NURSING PROCESS FOR TETRACYCLINE 1. Advise patient to use sunblock and protective clothing (sunglasses, umbrella) during sun exposure. Photosensitivity is associated with tetracycline. 2. Educate patient to avoid milk products, iron and antacids. Tetracycline should be taken 1 hour before or 2 hours after meals with a full glass of water. If GI upset occurs, the drug can be taken with nondairy foods. AMINOGLYCOSIDES - inhibiting bacterial protein synthesis are for serious infections Pharmacodynamics: - usually administered IV Streptomycin - first aminoglycoside available used to treat tuberculosis Because of ototoxicity and the bacterial resistance that can develop, it is infrequently used today. Despite its toxicity, streptomycin is the drug of choice to treat tularemia and bubonic pneumonic forms of plague. 7|Pharmacology • Parenteral anti-tb Neomycin sulfate - for liver diseases decreases bacteria in bowel preoperative bowel antiseptic abdominal surgery (for killing of colon basili to prevent E. coli from spreading) Side effects and Adverse Reactions - ototoxicity and nephrotoxicity the nurse must assess changes in patient’s hearing, balance, and urinary output. FLUOROQUINOLONES (QUINOLONES) - used to interfere with the enzyme DNA gyrase Norfloxacin is indicated for urinary tract infections. Ciprofloxacin is approved for use for urinary tract infections Levofloxacin (Levaquin) is used primarily to treat respiratory problems NURSING PROCESS FOR FLUOROQUINOLONES 1. Administer levoflaxin 2 hours before or after antacids and iron products for absorption. Give with a full glass of water. If GI distress occurs, drug may be taken with food. 2. Inform patient that photosensitivity is a side effect of most fluoroquinolones. Patient should use sunglasses, sun block, and protective clothing when in the sun. ANTITUBERCULARS - Antitubercular Drugs –take religiously, if not repeat! Isoniazid (INH) - When a person is diagnosed with TB, family members are usually given prophylactic doses of isoniazid for 6 months to 1 year. - Single drug therapy with isoniazid proved ineffective in treating TB, because resistance to the drug developed in a short time. When a combination of antitubercular drugs was used, bacterial resistance did not occur, and the duration of treatment was reduced from 2 years to 6 to 9 months. Side effects and Adverse Reactions - peripheral neuropathy (destroys nerves, tingling sensation/numbness) can be prevented by taking pyridoxine (VitaminB6) Hepatotoxicity is an adverse reaction to isoniazid, streptomycin, pyrazinamide and rifampicin. Side effects and Adverse Reactions 1. 2. 3. 4. 5. Isoniazid = hyperglycemia, hyperkalemia,hypophosphatemia, and hypocalcemia Rifampin = body fluids orange, soft contact lenses permanently discolored Pyrazinamide = gout, sensitivity to light, liver toxicity Ethambutol = dizziness, confusion, hallucinations and join pain Streptomycin = ototoxicity, optic nerve toxicity, encephalopathy, angioedema, CNS and respiratory depression, nephrotoxicity, and hepatoxicity NURSING PROCESS ANTITUBERCULAR DRUGS 1. Isoniazid (INH) 1 hour before or 2 hours after meals. Food decreases absorption rate. 2. give pyridoxine (B6) as prescribed with isoniazid to prevent peripheral neuropathy 3. encourage eye examinations (every 3 months) for patients taking isoniazid and ethambutol, because these antitubercular drugs may cause visual disturbances. 4. teach patient not to take antacid while taking antitubercular drugs, because they decrease drug absorption. patient should also avoid alcohol, because it may increase risk of hepatotoxicity 5. inform patient taking rifampicin that urine, feces, saliva, sputum, sweat, and tears may turn a harmlessr edorange color. soft contact lenses may be permanently stained Metronidazole (Flagyl) - intestinal antibiotic 8|Pharmacology - used to treat intestinal amebiasis classified as an antibacterial/antiprotozoal commonly used with other agents to treat Helicobacter pylori, which is associated with frequent recurrent peptic ulcers Side effects and adverse reaction - dark or reddish brown urine metallic taste nausea head aches Allergies seizures PHARMACOLOGY REVIEWER FOR MIDTERMS Pain Medications Inflammation      Part of the first line defense Response to tissue and injury infection A vascular reaction takes place in which fluids, elements of blood, leukocytes(WBCs), and chemical mediators accumulate Supposed to be normal and counteract infection Protective mechanism in which the body attempts to neutralize and destroy harmful agents at the site of injury and to establish conditions for tissue repair Infection  Caused by microorganisms and results in inflammation Chemical Mediators    Histamine o First mediator in inflammatory process o Cause dilation of arterioles o Increase capillary permeability Kinins(Bradykinin) o Increase capillary permeability o Increase pain Prostaglandin o Increase capillary permeability o Increase vasodilation o Increase fever and pain Pathophysiology  Cardinal signs o Redness o Swelling o Heat o Pain o Loss of function Important Terms    We don’t reverse histamine and bradykinin Prostaglandins (chemical mediator) Effects: vasodilation, relaxation of smooth muscle, increased capillary permeability, and sensitization of nerve cells to pain cause of inflammation and pain Cyclooxygenase (COX)- Enzyme responsible for converting arachidonic acid to prostaglandins    COX 1- traditional; converts arachidonic acids to prostaglandins o The stomach has prostaglandin coating= protection and regulate blood platelets o COX 1 converted to COX 2= prostaglandins COX 2- triggers inflammation and pain Stopping the pathway= decreases inflammation 9|Pharmacology Earliest type of NSAIDs   Aspirin (salicylates)- Inhibit biosynthesis of prostaglandins (prostaglandin inhibitor) o Prostaglandin inhibitor- Affect the inflammatory process (anti-inflammatory agents) o Anti-inflammatory agents- relieve pain (analgesic), reduce elevated body temperature (antipyretic) also an anticoagulant (platelet aggregation) to prevent stroke and MI; it is over the counter; not safe for children; not any more used for inflammation and pain due to many side effects and adverse Most NSAIDs are used to decrease inflammation and pain for patients who have some type of arthritic condition o For chronic pain or arthritis- NSAIDS is used Anti-Inflammatory Drugs   Anti-inflammatory drug groups o Non-steroidal and anti-inflammatory drugs o Corticosteroids o Disease modifying antirheumatic drugs o Anti-gout drugs Either steroidal or non-steroidal Non-Steroidal Anti-Inflammatory Drugs       More appropriate for reducing swelling, pain, and stiffness of joints Common but has a lot of side and adverse reactions Common for arthritic pain, menstrual cramps, migraine, and toothache COX 2- more potent in inflammation 1st- blocks cox 1; 2nd- blocks cox 2 Prostaglandin- potent inflammatory agent First generation of NSAIDs   Blocks COX 1 and COX 2, but blocks COX 1 first which prevents the conversion to COX 2 Ketorolac- given as IV; post-op patients 2nd gen  Cox 2 inhibitors- safer compared to the first generation Aspirin     Not used as an antipyretic but anti-coagulant Gastric distress- prostaglandins lines the stomach w/o cox 1= Upper GI bleeding Pharmacokinetics- if taken as anticoagulant should be given with meals; after lunch or 12 afternoon; PC (post meals) Hypersensitivity to aspirin o Effects: tinnitus (ringing of the ears), vertigo (dizziness), anaphylaxis, and bronchospasm (contraction of the bronchial muscles=difficulty in breathing) Nursing process   Observe patients for signs of bleeding o Melena- black tarry stools- sign of upper GI bleeding o Bleeding gums, petechiae, ecchymosis, and purpura when taking high dosages of aspirin 300 mg for pain; 81 mg for anticoagulant Pharmacokinetics  Aspirin is well absorbed in the GI tract which can cause GI upset o Should be taken with food, milk, or water o Should not be taken on the last trimester of pregnancy= causes premature closure of the ductus arteriosus Nursing Interventions      Eliminate risk for injuries Advise patient to not take aspirin with alcohol (increases gastric juices) Educate patient to inform dentist if aspirin is taken Instruct to discontinue aspirin 5 to 7 days before surgery to reduce bleeding W/ dengue= cannot prescribe aspirin will cause platelet drop due to anticoagulant effect 10 | P h a r m a c o l o g y    Keep aspirin out of reach of children Reye’s syndrome- problem for aspillet or aspirin o Viral problem then given aspirin; <7 yrs old= causes liver damage= brain encephalopathy. New formula for aspillet- neo-aspillet Phenylacetic acid dervatives Ketorolac (Toradol)      First injectable NSAID Recommended for short term management of pain o IV formula; usually given to post-op patients Possible of GI bleeding and irritation Because it is not safe it is used as creams Skin test first Propionic acid derivatives Ibuprofen    Reduce fever Treat pain or inflammation caused by many conditions such as headache, toothache, back pain, arthritis, menstrual cramps, or minor injuries Nephrotoxicity and GI distress= GI ulcers= most common Side and adverse effects of NSAIDs          Ototoxic- tinnitus GI distress Dizziness, confusion, and edema Blood dyscrasia and dysrhythmias Nephrotoxic- worst adverse reaction= acute kidney injury Upper GI bleeding CVD- in long term use Allergy Constipation Selective COX-2 Inhibitors (Second generation NSAIDs)      Coxibs- end names Celecoxibs (Celebrex) and Nabumetone (Relafen) COX 2 inhibitors- decrease risk of peptic ulcers o Clinical trials revealed effects= cardiovascular diseases and stroke Designed for arthritis NSAIDs are not really safe; prescriptions and advices are needed. Anti-gout Medications Anti—inflammatory gout medication  For elderly- gouts can cause bone and joint deformity Colchicine- first drug to be given for gouts    Stops migration of WBCs to the injured site o Reduce swelling= reduce pain Gastric inflammation- a common problem o Should be taken with food o With high doses- nausea, vomiting, diarrhea, or abdominal pain occurs in approximately 75% of patients taking the drug Has drug interaction with antibiotics Uric acid inhibitor      Prophylaxis/To prevent gouty arthritis- allopurinol; for maintenance only Allopurinol (Zyloprim)- never given for acute pain Inhibits final steps or uric acid biosynthesis o Lowers serum uric acid levels, preventing the precipitation of an attack Diet modification+allopurinol Taken during chemotheraphy 11 | P h a r m a c o l o g y Pharmacodynamics: xanthine oxidase inhibitor     Inhibits the production of uric acid by inhibiting the enzyme xanthine oxidase o Hypoxanthine=xanthine=uric acid o Needed in the synthesis of uric acid If not converted to uric acid it would stay as a nonpotent serum Interferes with conversion of ATP/ADP Side effects and adverse reactions- GI distress and dysrhythmias Uricosurics     Increase excretion uric acid through urine Probenecid-Affects the nephrons- In the distal tubule; prevent recycling of uric acid Colchicine (prevent migration of WBC)+probenecid(excretion)= prevent acute attack Use of aspirin should be avoided, because it causes uric acid retention Corticosteroids- from the adrenal cortex           Prednisone, prednisolone, and dexamethasone Control inflammation by suppressing or preventing the many components of the inflammatory process Not the drug of choice for arthritis o Due to numerous side effects Frequently used to control arthritic flare ups Last option for inflammation Exact mechanism is unknown thought to decrease lysosomal activities Decreases immune system Can cause cushing’s syndrome as effect o Buffalo hump o Moon face o Central obesity Can also cause GI ulcers Taper off when discontinuing- if patient is using a steroid tablet; it should not be immediately stopped because it will cause hypertension. o Gradually decrease dosages Non opioid and opioid analgesic  NSAIDs- can be classified in non-opioid analgesic Non opioid  Known as non-narcotic analgesic Acetaminophen aka paracetamol- inhibit prostaglandin synthesis   Antipyretic and analgesic Non-opioid but is not an NSAID Pharmacokinetics    Short half-life can be administered every 4 hours as needed o Max dose- 4g/day o Frequent takes should limit the dose to 2 g/day to avoid possibility of hepatic or renal dysfunction o Large doses or overdoses can be toxic to hepatic cells o Adult- 10 days max o Children- 5 days max Or 1,000 mg Q6/day- abroad to prevent seizures Antidote for paracetamol overdose- acetylcysteine- mucolytic (respiratory drug; lyses mucus secretions) and also a liver protectant Pharmacodynamics   Eliminates mild to moderate pain Side effects and adverse reactions o Overdoses- extremely toxic to the liver cells= hepatotoxicity= s/sx (NAVDA) Opiod: Narcotic Analgesic  Known as narcotic analgesic 12 | P h a r m a c o l o g y       Addiction- psychological and physical dependence upon a substance beyond normal volume control, usually after prolonged use of a substance Effects: analgesia, respiratory depression, euphoria, sedation, orthostatic hypotension (decrease in blood pressure when rising from a sitting-lying position) Pain=peripheral nerves=chemical mediators (histamine, bradykinin, and prostaglandins) =spinothalamic tract= thalamus (pain is already determined) =parietal lobe(processing; pain)= frontal lobe(reaction) Non opioid- blocks only the chemical mediators o Mild to moderate pain Narcotic (opioids)- moderate to severe pain o Acts on the brain; decreases function of brain so it cannot interpret pain; depresses CNS function Patients can die due to apnea; respiratory arrest Tramadol        Opioid medication used to treat moderate to severe pain Often combined with paracetamol to relieve pain 1/10 the potency of morphine Equally potent compared to pethidine and codeine Can be in IV and tablet form Vomiting and hypotension- side effect Side effects and adverse reactions: it is a downer- not recommended for suicidal patients o Constipation, itchiness, nausea, and seizures Morphine       For chronic pain Check PR, if below 101 bpm do not give morphine Only used for patients with MI; last option Patients with cancer and post-op patients Antidote for morphine- Naloxone or Narcan o When there is respiratory depression Opioids does not only suppress pain impulses but also respiration and coughing by acting on the respiratory and cough centers in the medulla of the brainstem Nursing process for Morphine  Morphine overdose: pinpoint pupils and slower reaction to light; decreased RR; decrease gag reflex Codeine      Analgesic but not as strong as morphine o But also relieves pain and cough 1/15 to 1/20 potency but can also relieve mild to moderate pain Most opioids (except meperidine; Demerol) has an antitussive effect= cough suppression= cause sore throat and chest pain A derivative of morphine Used as an antitussive- cough suppression Meperedine (Demerol)      Common for OB px; pacreatitis Large doses= neurotoxicity; nervousness, tremors, agitation, irritability, and worst case: seizures Not for long-term usage Dose is limited to 600 mg/24-hour period no longer than 48 to 72 hours Patient controlled analgesia(PCA)-Syringe pump a patient can control and it will deliver the drug; everytime there is pain the patient can press it the Demerol will enter. Fentanyl      Can be mixed with anesthesia Available in injections and dermal patches Side effect: hypotension, decrease in HR 75 times stronger than morphine Most widely used synthetic opioid Hydromorphone (dilaudid)  A semisynthetic opioid similar to morphine 13 | P h a r m a c o l o g y     Analgesic effect is approximately 6 times stronger/more potent then morphine with fewer hypnotic effects and GI distress Patients with stage 4 cancer Side effects and adverse reactions: respiratory depression, orthostatic hypotension, tachycardia, drowsiness, and mental clouding Withdrawal syndrome- irritability, diaphoresis, restlessness, muscle twitching, increased PR and BP, agitation, and anxiousness Side effects and Adverse Reactions of opioid analgesics In general  Anxiety, depression, flu-like symptoms, headache, GI upset, hallucinations, hypoventilation and apnea Naloxone (Narcan)    Opiod antagonist Administered IM or IV Monitor for bleeding and hypotension Anxiety   Anxiety is more on GABA- drugs decreases this SSRI- used for depression; selective serotonin receptor inhibitor Sleep and Insomnia    Following stage 4 of NREM sleep, will have 5-20 minutes of REM sleep with dreaming and increased physiologic activity REM sleep is felt to be mentally and emotionally restorative REM deprivation can lead to psychological problems and psychosis Insomnia  Can result from pain, anxiety, illness, changes in environment, and from certain medications Benzodiazepines          Used for anxiety and insomnia Prototype: diazepam Can result in psychologic dependency, thus, abuse Withdrawal symptoms can result if abruptly stopped; should be gradually tapered and discontinued Can cause excessive sedation, impairment of physical and mental activities, and respiratory depression Not for long-term use Do not suppress REM sleep Vary in plasma half-lives, metabolites, and uses Bind with benzodiazepine receptors in nerve cells of the brain, the receptor also has binding sites for GABA o When benzo/GABA binding occurs, then chloride ions in the cells causing decreased response to the excitatory neurotransmitters such as norepinephrine Na K Pro Mg Pho Ca Cl HCO3   Competes with the GABA sites Action potential- positive causes it o Na goes in= electrical impulse o Blocking GABA= chloride (-) goes inside= less excitation= more relaxation 14 | P h a r m a c o l o g y  Classifications: muscle relaxants, hypnotics, and for anxiety Pharmacokinetics             Well-absorbed orally o Given oral or IV Widely distributed in body tissues Highly bound to plasma proteins Lipid soluble; can easily enter the CNS Metabolized by the liver by cytochrome p450 enzymes and by CYP3A4 enzymes in intestines Most benzodiazepines are metabolized into active metabolites that require further metabolism before clearance Depending on half-life, can result in accumulation and subsequent adverse drug effects High doses= decrease brain function (CNS depression), decreases vital signs Do not give together with downer drugs Shorter-acting benzos o Versed(midazolam)- 30-60 minutes o Halcion(triazolam)- 4-6 hours o Dalmane(flurazepam)- 6-8 hours o Xanax(alprazolam)-4-6 hours  given to px with cardiac conditions; MI patients  Given at 9 pm  One of the safe types of benzodiazepines o Serax(oxazepam)- 2-4 hours Longer-acting benzos indicated for seizure px o Klonopin(clonazepam)- action may last for weeks o Librium(chlordiazepoxide)- several days o Tranxene(chloraxepate)- lasts for days Drugs and its common uses         Xanax(alprazolam)- anxiety and panic disorder Librium(chlordiazepoxide)- anxiety and alcohol withdrawal Klonopin(clonazepam)- seizure disorders and panic disorders Valium(diazepam)- anxiety, seizure disorders, alcohol withdrawal, muscle spasms, and for preoperation medication o For active seizure give valium IV (for babies) o If no IV, IM or anal Dalmane(flurazepam)- insomnia Ativan(lorazepam)- anxiety and preop medication Versed(midazolam)- preop sedation and anesthetic induction Restoril(temazepam)- insomnia Contraindication to use     Respiratory disorders Severe liver or kidney disease History of alcohol or drug abuse o If there is alcohol abuse= higher doses are needed Hypersensitivity reactions o Skin tests are not needed= because allergic reactions are not common Valium (Diazepam)    Valium is prescribed 30 minutes before operation o Only lasts for 1 hour; short acting o Decrease stress and anxiety o Antidote- flumazenil Used as hypnotics Anti-anxiety meds may also be given to px with cardiac diseases Miscellaneous antianxiety and sedative-hypnotic agents  Noctec (chloral hydrate)- chloroform o Oldest sleeping medication o Does not affect REM sleep o Tolerance increases after two weeks 15 | P h a r m a c o l o g y  Natural hypnotics o Melatonin-hormone- produced by the pineal gland o Endogenous melatonin is derived from tryptophan= converted to serotonin= melatonin o Melatonin affects sleep-wake cycles; released during sleep and levels are low during waking hours o Used for jet lag due to disruption of circadian rhythms o Caution with patients with liver or renal problems Benzodiazepine withdrawal    Mild s/sx- sweating, irritation o Occurs to half of clients after taking doses for 6-12 weeks or longer o Severe s/sx if taking large doses for 4 months or longer with abrupt discontinuation o Effects are related to decrease in GABA neurotransmission resulting to CNS stimulation Signs and symptoms include: anxiety, psychomotor agitation, insomnia, irritability, headache, tremors, and palpitations o Others- confusion, depersonalization, psychosis, and seizures Severe s/sx most pronounced in short-acting drugs such as Xanax, Ativan, and Halcion. Reduce dose by 10-25% every 1-2 weeks over 4-16 weeks Benzodiazepine toxicity     Effects include: excessive sedation, respiratory depression, and coma Has shorter duration than many benzos, so, repeated dosing may be necessary o For overdose, give 0.2 mg/30 seconds, wait 30 seconds, then 0.3 mg/30 seconds, then 0.5 mg/60 seconds up to max of 3 mg Toxicity is common in geriatric patients and children Antidote: Romazicon (flumazenil) Naloxone is for opioids, flumazenil is for benzodiazepines Drug therapy for anxiety   Not recommended for everyday stress For chronic pain, have not proven to be effective Antipsychotics    Psychosis- severe mental disorder characterized by disordered thought processes, inappropriate emotional responses, bizarre behavior, agitation, aggressiveness, hostility, social withdrawal, deterioration in occupational and social functioning, hallucinations, and paranoid delusions Nursing diagnosis: Altered thought processes To be classified as psychotic: should be observed with paranoid delusions and hallucinations Psychosis      Hallucinations- false interpretations of sensory perceptions o Objects or people are absent o Unable to distinguish between false perception and reality o Schizophrenia or bipolar disorder- auditory o Delirium- visual or tactile o Dementia- visual Common in alcoholics- delirium and visual or tactile Illusions- objects are present but different interpretation Delusions- false beliefs that persist in absence of reason or evidence o Delusion of grandeur- perceives self with high standing o May believe others control their thoughts, feelings, or seek to harm them Psychosis may be acute or chronic o Acute- confusion or delirium; can be precipitated by illness, drug effects, or superimposed on chronic dementias Schizophrenia     Consist of variety of related disorders Does have a genetic predisposition Positive symptoms- high brain activity o CNS stimulation, agitation, behavioral disturbances, delusions, hallucinations, insomnia, and paranoia Negative symptoms- low brain activity 16 | P h a r m a c o l o g y o Anhedonia, lack of motivation, blunted effect, poor hygiene, poor social skills, and social withdrawal Etiology of schizophrenia      Evidence indicates abnormal neurotransmission systems in the dopaminergic, serotonergic, and glutamatergic system Interplay between the systems; one system may affect the other Real reason is still unknown Theoretical o More on dopamine= increased levels which leads to psychosis o Imbalance in amount of neurotransmitters, most notably dopamine o Overacitivity accounts for the positive symptoms of schizophrenia and underactivity in another part of the brain may account for the negative Glutamatergic dysfunction may be genetically linked as well as causative in the cognitive impairments and negative s/sx of this disorder Antipsychotic drugs     Categorized as “typical”, “first generation”, or “conventional”= phenothiazine “Atypical” or “second generation”= newer nonphenothiazine Discovered in the 1950s- first generations Second generations- modern drugs Mechanism of action     Most bind to D2 dopamine receptors and block the action of dopamine but positive effects only occur overtime Theory: blockage of dopamine receptors leads to changes in receptors with effects on cell metabolism and function With chronic drug administration, it is postulated that drugs re-regulate the abnormal neurotransmission systems First generations are only effective to positive symptoms Indications of Phenothiazine   Schizophrenia o Psychotic symptoms associated with brain impairment (injuries) o Useful in manic phase of bipolar affective disorder until Lithium (drug of choice) becomes effective Antipsychotics may also be given to intractable hiccups Uses   Schizophrenia o Nausea and vomiting- affect chemoreceptor trigger zone in medulla o Intractable hiccups- mechanism of action is unclear Use with caution in: o BPH o Seizure disorders o Glaucoma Contraindications of Phenothiazine        Liver damage CAD Cerebrovascular disease Parkinsonism Bone marrow depression Severe hypotension and hypertension Before administering check the vital signs Pharmacokinetics      PO or IM Prototype: Thorazine(chlorpromazine) Metabolized by the cytochrome p450 system No psychological dependency but physical dependency can occur Withdrawal s/sx may occur 17 | P h a r m a c o l o g y   Side effects include: o CNS depression o Anticholinergic effects o Antiemetic effects o Lowering of body temperature o Hypersensitivity reactions o EPS o Weight gain o Orthostatic hypotension Examples of phenothiazines o Thorazine(chlorpromazine) o Prolixin(fluphenazine) o Compazine(prochlorperazine) o Stelazine(trifluoperazine) o Mellaril(thioridazine)- used less commonly due to cardiac side effects Thorazine (chlorpromazine)    1st generation phenothiazine- has higher risk of having the side effects For psychosis or post-op patients with hiccups EPS- extrapyramidal symptoms= parkinsonism o Robot-like o Extrapyramidal Symptoms (EPS) Extrapyramidal Symptoms (EPS)      Affects EPS and basal ganglia o System includes descending fibers that reach the medulla other than by the corticospinal tracts o Important in maintenance of equilibrium and muscle tone o Symptoms: dystonia, akathisia, tardive dyskinesia, and parkinsonism Dystonia- prolonged muscle contractions causing twisting and repetitive movements or abnormal posture. May have rhythmic jerks Akathisia- restless, unable to sit still o Most common symptom Chloreiform movements- involuntary muscular twitching Tardive dyskinesia- hyperkinetic movements of the face o Sucking and smacking lips, facial grimaces, and tongue protrusion Non-phenothiazines 1st generation antipsychotics        Haldol(haloperidol)- potent, long-acting Causes high incidence of EPS Useful in mental retardation with hyperkinesia, Tourette’s and Huntington’s disease Comes in oral form and even once in a month injection form Loxitane(loxapine) Moban(molindone) Orap(pimozide)- for Tourette’s when Haldol is not effective o Can cause tardive dyskinesia, motor seizures, and even sudden death 2nd generation of antipsychotics     Drugs of choice Effective in treating the positive s/sx of psychosis and have greater effectiveness in relieving the negative s/sx Less likely to cause EPS Effective for both positive and negative symptoms Clozaril (clozapine)    Prototype of atypicals Effective but considered a second line drug because of association with agranulocytosis Check weekly WBCs  Neutrophils will go down to <50 Haldol (Haloperidol) 18 | P h a r m a c o l o g y   A mild sedative IM injection Zyprexa(olanzapine)   Can cause EPS but not agranulocytosis Cause less sedation, less orthostasis, and anticholinergic effects Seroquel(quetiapine)    Blocks dopamine and serotonin Relieves positive and negative symptoms Many drug interactions o Metabolized by the cytochrome p450 system Risperdal(risperidone)        Blocks dopamine and serotonin Affects both positive and negative symptoms Safest and is the first choice of treatment Also metabolized by the cytochrome p450 system Can cause parkinsonism 2nd generations have better results and less probability to EPS Duration of drug intake is for years or forever, once stopped psychosis will go back Drug selection    Duration of therapy- generally for many years as relapses can occur Drug withdrawal- can occur if medications are stopped abruptly o Can result in cholinergic effects such as diarrhea, drooling, and insomnia. o Should be tapered over several weeks Atypicals are drugs of choice as they: o May be more effective o Produce milder adverse effects o Patients display greater compliance in taking them o Drawback include: glucose intolerance, weight gains, and also are costs Treatment of EPS     Treat with anticholinergic antiparkinson medication such as: o Benadryl(diphenhydramine) o Symmetrel(amantadine) o Eldepryl(selegiline) More likely to occur with older antipsychotic drugs Treatment is usually for three months then gradual discontinuation S/sx generally do not recur Neuroleptic malignant syndrome (NMS)    Rare but potentially fatal reaction o May occur hours to months after initial psychotic drug use Present with high grade fever, muscle rigidity, agitation, confusion, delirium, tachycardia, respiratory failure, and acute renal failure Tx- stop drug, supportive care o Dantrolene and amandatine- anti Parkinson drugs; also used to counteract NMS No prophylactic for psychosis Haloperidol- has highest EPS probability; 2nd is thorazine Benadryl- anti-histamine to counter act side effects: EPS Antidepressants and mood stabilizers Mood disorders  Include: depression, dysthymia o bipolar disorder (manic/panic= span of 2 weeks) o cyclothimia- sad then happy but does not reach manic-panic situation 19 | P h a r m a c o l o g y  o Seasonal affective disorders- moods varies on the season If there was one depressive episode, higher risk for having another Monoamine neurotransmitter dysfunction    Complex ethiology affecting neurotransmitter and receptors Felt to be partially a result of deficiency in norepinephrine and serotonin Interplay bet neurotransmitters: norepinephrine, serotonin, dopamine, and acetylcholine Neuroendocrine factors  Increased secretion of corticotrophin-releasing hormone by hypothalamus, adrenocorticotrophic hormone by pituitary, and cortisol by the adrenal gland o Cortisol- steroid; acts on the fight or flight o Increased cortisol may decrease numbers of sensitivity of cortisol receptors and lead to depression Other factors     Interplay with thyroid and growth hormones Immunity May be linked in genetics Environmental factors resulting in structural changes in brain such as child abuse Types of mood disorders      Depression- imbalance of a neurotransmitter o Lack of self-interest, anhedonia Dysthmia- chronically depressed mood o For at least 2 years Bipolar- depression alternating with mania Cyclothymia- mild type of bipolarity Must be present for 2 years to be considered a form of depression General characteristics of antidepressants      Vary in adverse effects Must achieve serum level before improvement seen (2-4 weeks) Taken orally, undergo significant first pass metabolism Multiple drug interactions as are metabolized by cytochrome 450 enzymes Medications will not work immediately Mechanism of action    Normalize neurotransmission systems by altering the transmitters and receptors Also modify interactions between neurotransmission system and endocrine functions o ACTH (adrenocorticotrophic hormone) and cortisol levels Neurotransmitters that are not bound are inactivated by reuptake or are metabolized by monoamine oxidase o Monoamine oxidase- enzyme that destroys norepinephrine and epinephrine- which is high during stress Contraindications      Used cautiously in schizophrenia, mixed mania, and depression o Schizophrenia- can be used in positive symptoms Suicidal tendencies In severe renal, hepatic, or cardiovascular disease Narrow-angle glaucoma- fluid buildup in the iris; increase intraocular pressure Seizure disorders Antidepressants  Tricyclics- oldest type of antidepressant o More serious adverse effects especially anticholinergic and cardiac effects, weight gain, and sedation o Can cause photosensitivity o Elavil (Amitriptyline)- most common antidepressant o Tofranil (imipramine) o Sinequan (doxepin) 20 | P h a r m a c o l o g y    o Norpramin (desipramine) Selective serotonin reuptake inhibitors (SSRI) o Adverse effects include: nausea, sexual dysfunction, headache, increased risk of gastrointestinal bleeding o Safest antidepressant; most prescribed o Never coadminister with monoamine oxidase inhibitor (MAOI) o Prozac (fluoxetine)- long duration o Zoloft (sertraline) o Celexa (citalopram) o Paxil (paroxetine)- long duration Monoamine oxidase inhibitor (MAOI) o Considered dangerous due to a lot of interactions with food and drugs o Preserve norepinephrine o Should not be combined with any other antidepressant o Foods that contain tyramine, a monoamine precursor of norepinephrine, when taken with MAOIs can lead to severe hypertension, stroke, or heart attack o Diets should be checked  Tyramine can lead to severe hypertension (severe adverse effect of MAOI)  Avoid high in MSG  Avoid aged cheese, meats, concentrated yeast extracts, sauerkraut, and fava beans o Marplan (isocarboxazid) o Nardil (phenelzine) o Parnate (tranylcypromine) Lithium o Mood stabilizing agent o For bipolarity- mania phase o Must be closely monitored o Excreted by kidneys, so must have adequate renal functioning o If hyponatremic= lithium toxicity o This is toxic and can damage the kidneys o Before administering check creatinine levels and clearance o Diet should be on the normal salt level  2L water/2g salt o Lithium toxicity  Therapeutic levels- should be checked weekly  0.6-1.2 MEQ(milliequivalent)/L  Severe toxicity- <2  Liver cannot detoxify because it is a mineral o Mild toxicity- diarrhea, vomiting, fatigue o Severe toxicity- If not excreted by the body adverse effects will occur  Seizure, coma, hypotension, hyperthermia, kidney failure, and death Drugs acting on the CNS and PNS    Barbiturates o Antisizure o Sedative o Muscle relaxant o Anti-anxiety o Secobarbital (seconal)- treatment for insomnia o Pentobarbital (Nembutal)- used in intracranial pressure  most common barbital o Thiopental sodium (pentonal)- treatment for insomnia o These are antiseizure medicines  Seizure- abnormal firing of the neurons; most common in pediatric patients o Not used on ongoing seizures; due to long onset of action Action of barbiturates o Activates GABA receptors o Delayed closing of chloride receptors o Hyperpolarization of cells- becomes more negative polarity  Depression of CNS Benzodiazepines o Also considered as antiseizures o Should only be used for 10 days o Valium should be ready on bed side for active seizures (5mg; syringe); due to fast onset of drug 21 | P h a r m a c o l o g y          o Valium (diazepam); used to alleviate anxiety, and Klonopin (clonazepam) o Valium administered IV during active seizures o Dalmane (Flurazepam) o Xanax (alprazolam) o Restoril (temazepam) o Ativan (lorazepam)- alleviate anxiety Action of benzodiazepines o Binds to GABA receptors o Increases number of opening in the chloride channel o Hyperpolarization of cells  CNS depression o Epilepsy- To confirm epilepsy EEG is done; maintenance drug is phenytoin  Chronic, usually lifelong disorder Classification of seizures o Grand-mal(tonic-clonic); more on motor neurons o Petit mal(absence)- has memory loss after Action of anticonvulsants o Antiseizures o Suppresses sodium influx through the drug binding to the sodium channel= prevention of neuron firing o Suppress calcium influx  Valproic acid and ethosuximide are examples of drugs that suppress calcium influx o Increase action of GABA= inhibit neurotransmitter throughout the brain Identification of seizures o Gran mal (tonic-clonic) and petit mal (absence) o With the use of anticonvulsants 70% of seizures are controlled o Take throughout the person’s lifetime o In some cases, it is discontinued if no seizures have occurred in the past 3 to 5 years Hydantoins (classification); Phenytoin o Prophylactic for seizures o Not given with active seizures; just maintenance to avoid seizures o Should not be given to pregnant patients; fetus may be aborted is taken in the 1 st trimester  Teratogenic=congenital defects o Maintenance: capsule form; wards: IV form and is only compatible with NS  If D5 water is used it will lead to precipitation=crystallization of the drug=embolus if given IV  Flush line with NS before and after administering to reduce venous irritation  Cannot be given as IM injection; irritates tissues and may cause damage  It is acidic, therefore, it may irritate patient if IV is out o Effective for gran mal and psychomotor seizures; not effective for petit mal seizures o Side effects and adverse reactions  Always check for gingival hyperplasia, because it is common for phenytoin  Overgrowth of gum tissues or reddened gums that bleeds easily  Thrombocytopenia-low platelet count  Leukopenia- low white blood cell count  Elevated blood sugar (hyperglycemia) results from the drug which inhibits the release of insulin Baribiturates (Phenobarbital) o Long-acting; effective for grand mal, partial seizures, and acute episodes of status epilepticus  Status epilepticus- rapid succession of epileptic seizures o Can depress vital signs Succinimides o Zarontin (ethosuximide)- drug of choice for the absence or petit mal seizures o Succinimide of choice o Calcium influx inhibitor Valproate (valproic acid) o Hepatotoxicity is one if the possible adverse reactions o Given as a maintenance drug; can be given every day for patients with epilepsy  Not be given to very young children and to patients with liver disorder  Can cause reye’s syndrome to children Nursing considerations/process o Phenytoin o Teach patient to shake suspension form thoroughly before use to adequately mix medication and assure accurate dosage 22 | P h a r m a c o l o g y o o o o o Do not drive or perform hazardous activities when initiating anticonvulsant therapy  Drowsiness may occur If pregnant, consult with healthcare provider, phenytoin and valproic acid may have teratogenic effects Avoid alcohol and other CNS depressants= cause added depressive effects on the body Do not stop abruptly, if medications are stopped abruptly effects will be reversed (seizure rebound) Pinkish or reddish brown urine= normal and harmless Neuromuscular blocking agents     o Paralytic agents o Given IV o Atracurium o Cisatracurium o Rocuronium o Succinylcholine Drug function of neuromuscular agents o By blocking acetylcholine in the neuromuscular junctions (NMJ) o Stop binding in the acetylcholine sites Indications of neuromuscular blocking agents o Skeletal muscle relaxant o Used in endotracheal intubation o Aid in muscle spasm in tetanus o Reduce use of anesthesia o Mechanical ventilation o There should be an ambubag at bedside before administering paralytic agents Nursing process o Usually given by an anesthetist o Assess for renal, hepatic, or pulmonary disease o Assess for neurologic disorders such as  myasthenia gravis  Spinal cord injury  Multiple sclerosis- decrease in the sensations; problem in the myelin sheaths; slow transmission of sensations Anticonvulsants leads to CNS depression Drugs affecting the autonomic nervous system      Autonomic nervous system o Self-governing and automatic o Composed of the sympathetic and parasympathetic o In pharmacology  Adrenergic agents- sympathomimetic  Cholinergic agents- parasympathomimetic Considered as inotropes- increases blood pressure; produces sympathetic response Sympathetic- thoracic Parasympathetic-vagus nerve Drug class: Adrenergic agents o Dopamine, dobutamine, norepinephrine, and epinephrine o Used for shock; if <90/60 it is considered to be in hypovolemic shock o If in 6 hours and not corrected it will lead to renal damage; if not corrected can cause multiple organ damage o Types of receptors  Alpha- vasoconstriction  Beta- heart rate  Dopaminergic- motivation, pleasure, cognition, memory, learning, and fine motor control, as well as modulation of neuroendocrine signaling. o Most common adrenergic drugs  Alpha 1- for vasoconstriction  Norepinephrine and dopamine  Beta 1- for heart rate (because of epinephrine)  Dopamine, dobutamine, norepinephrine, and epinephrine o Indications 23 | P h a r m a c o l o g y     Epi only has an effect for 5 minutes; does not have an overdose; used for cardiac arrest others are for blood pressure  Cardiac arrest  Anaphylaxis  Superficial bleeding Norepinephrine  used for hypotension  Treatment of cardiovascular problems  shock Dopamine  Shock  Hypotension  Bradycardia Dobutamine  Cardiogenic shock  Heart failure Antihypertensive, diuretics, anticoagulants, and dyslipidemics     Hypertension o Common in the US, up to 60 million afflicted o Leads to MI, heart failure, stroke, and renal disease  MI- cessation of blood supply to the heart, necrosis  Heart failure- complication of MI; contractility of the heart o Strong correlation with metabolic syndrome  Related to stress, lack of sleep  More on weight gain Types of hypertension o Essential or primary  Etiology/ cause: unknown  Contributors: include- salt sensitivity, insulin resistance, genetics (most common factor), sleep apnea, environmental factors, etc. o Secondary- renal, adrenal, coarctation of the aorta (dilation of the aorta), steroids, and pregnancy  Etiology: related to another disease condition/ underlying disease condition BP review o Any condition that affects the heart rate, stroke volume, or peripheral vascular resistance affects arterial blood pressure o Compensatory mechanisms to maintain balance between hypotension and hypertension Normally, when the arterial blood pressure is elevated: o Kidneys will excrete more fluid  Alpha I- BP  Alpha II  Receptors related to sympathetic= SA node and peripheral vascular resistance  -70 millivolts resting phase of SA node  Sodium goes to cell= increase conductivity to 70 MV o Fluid loss will result in decreases extracellular fluid volume and blood volume  Blood volume- the more the blood volume, the higher the BP o Decreased blood flow to the heart will reduce cardiac output  Renin-angiotensin-aldosterone system o Decreased CO reduces arterial blood pressure  Repolarization of cells  Potassium will go out; calcium takes place here- has effect contractility- prolongs; affects also muscles (contractions; smooth muscles= vasoconstricition)- prevented by blocking calcium o Beta receptors  Beta I- heart  Beta II- heart and lungs o Vascular endothelium produces vasodilating substances (nitric oxide and prostatacyclin) which reduces blood pressure Nonpharmacologic management of hypertension 24 | P h a r m a c o l o g y o o o o o o Weight reduction Exercise Salt restriction in diet Stress reduction Moderation in alcohol intake If systolic BP cannot be maintained <140 systolic, time to take treatment Antihypertensive drugs  Classes: o Angiotensin converting enzyme (ACEI) o Angiotensin II receptor blockers o Antiadrenergic o Calcium channel blockers o Diuretics o Direct vasodilators o Renin inhibitors Angiotensin converting enzyme I inhibitor                Blocks the enzyme that converts angiotensin I to angiotensin II (potent vasoconstrictor) o Cannot totally block but only decrease Have action of vasodilation and decrease in aldosterone production Inhibit breakdown of bradykinins (vasodilator) prolonging effect Reversed remodeling of heart muscle and blood vessels Reno-protective o Affects renin; also has a protection in the kidneys Excellent for heart failure and hypertension Improves post-myocardial infarction survival Used alone or in combination Useful in heart failure as decrease peripheral vascular resistance, cardiac workload and ventricular remodeling Captopril—prototype; most common Low incidence of side effects Can cause cough or hypotension when first started- normal and most common Can cause hyperkalemia Should never be used during pregnancy May not be effective in African—americans- may add diuretic in this population to increase efficacy  Lotensin (benazepril)  Capoten (captopril)  Vasotec (enalapril)  Zestril (Lisinopril)  Altace (Ramipril)  Aceon (perindopril)  Classes of hypertension Classes of hypertension Class I (140-149) Class II (150-159) Class III (160-169) Class IV (>170) Medications ACE I inhibitor and diuretics Vasodilators and diuretics Clonidine, beta blockers, and calcium channel blockers Clonidine, beta blockers, and calcium channel blockers Angiotensin II receptor blockers (ARBs)    More potent than ACE I Blocks effects of angiotensin II, compete with angiotensin II for tissue binding sites Blocks the receptors in brain, kidneys, heart, vessels, and adrenal tissue 25 | P h a r m a c o l o g y             Has less side effects Most common side effect: orthostatic hypotension o Teach to slowly change position SARTAN- end name of ACE II blockers Similar end results as seen with ACE I Less likely to cause hyperkalemia Persistence of cough is rare Prototype is Cozaar (losartan) Atacand (candesartan) Cozaar (losartan) Diovan (valsartan) o Recalled because it may cause cancer o Because of rocket fuel contents- preservatives Micardia (telmisartan) Benicar (olmesartan) Antiadrenergic       inhibit the activity of the sympathetic nervous system blocking alpha receptors- epinephrine and norepinephrine effective in decreasing heart rate, force of myocardial contraction, cardiac output, and blood pressure short acting has a lot of side effects Alpha 1 adrenergics receptor blocking agents dilate vessels and decrease peripheral vascular resistance Can experience first dose phenomenon with orthostatic hypotension, dizziness, syncope (can cause head trauma, temporary loss of consciousness caused by a fall in blood pressure), possible sodium and fluid retention Antiadrenergics – Alpha 1      ZOSIN- end name of alpha-1 Blocks alpha I and causes vasodilation Cardura- (doxazosin) Minipress (prazosin) Hytrin (terazosin) Alpha 2 antagonists         Centrally acting sympatholytics stimulate presynaptic alpha 2 receptors in the brain Less norepinephrine is released and sympathetic outflow is reduced Results in decrease cardiac output, heart rate, peripheral vascular resistance, and blood pressure Vasoconstriction and has little effect on the heart rate Centrally acting agents also can result in fluid and sodium retention Catapres (clonidine)- orally or by patch o Decrease BP; used in the community as emergency medication for sudden findings of hypertension o Short acting o > 180- hypertensive emergency Tenex (guanfacine) Aldomet (methyldopa) Beta adrenergic blockers  Decrease heart rate, force of myocardial contraction, cardiac ouput and renin release from the kidneys 26 | P h a r m a c o l o g y  Drug of choice for patients with tachycardia, angina, MI, left ventricular hypertrophy, and high renin hypertension  Technically, it blocks beta 1  Beta 1- heart rate o Can lead to exhaustion and myocardial death  Beta 2- heart and lungs  Angina- heavy crashing pain; sign of early possibility of MI  Pregnancy- teratogenic C and D (most is the phenytoin A) Beta blockers I   o         End name OLOL Inderal (propranolol)- hyperthyroid Increase HR due to T3 and T4 Inderal (propranolol) Corgard (nadolol) Lopressor (metoprotol) Tenormin (atenolol) Kerlone (betaxolol)- for glaucoma (ophthalmic) o Hypertension- orally IV-short acting Oral- maintenance If not selective- bronchoconstriction or asthma may occur o If so, take ACE II to prevent side effects Calcium channel blocking agents              Calcium effects is more on electrolyes= has effects on the heart rate itself CALCIUM CHANNEL BLOCKER PICTURE End name: Dipine- vasodilation Verap and diltiazem (SVT supraventricular tachy- >150) o For emergency cases Norvasc (amlodipine)- most common Cardizem (diltiazem) Plendil (felodipine) Procardia (nifedepine) Calan (verapamil)- may cause gingival hyperplasia These are also pregnancy category C teratogenic Useful in hypertension as it dilates peripheral arteries and decrease peripheral vascular resistance by relaxing vascular smooth muscle Monotherapy or in combination Tolerated well even with renal failure 27 | P h a r m a c o l o g y Vasodilators  Limited effect when used alone  Cannot be used alone or as monotherapy o If vasodilator only, there is rebound effect  Vasodilating action that lowers BP also stimulates SNS. This in turn, triggers reflexive compensatory mechanisms that raise BP  Corlopam (felodapam)- IV infusion, in hypertensive emergencies avoid in patients with allergies to sulfites  Apresoline (hydralazine)- IV, IM, or PO o Can cause orthostatic hypotension o Most common vasodilator  In 2 minutes decrease in BP; 30 minutes effects will subside  Rogaine (minoxidil)- PO or topical Hypertensive emergencies     > 180 systolic  > 120 diastolic  Is defined as having end organ damage or diastolic BP of 120 Hg or higher  With oral medications, use captopril 25-50 mg PO every 1-2 hours or clonidine 0.2 initially then 0.1 mg every hour until diastolic blood pressure falls below 100 Hg or if 0.7 mg has been given Can cause stroke, MI, kidney damage Nitroglycerine- antianginal medication o Taken as a vasodilator o Chest pains o Sublingual- will alleviate pain o In some consequences may decrease BP o Emergency medication for angina o Only lasts for 30 days- expiration MAP- main arteria pressure o Systolic (diastolic x 2) / 3 o Perfusion- < 60 low perfusion  Multiorgan damage o > 120- hypertensive emergency Herbals that affect the BP     Ephedra (ma huang)- medicinal preparation from the plant Ephedra sinica Ginseng- root of plants in the genus Panax Yohimbe (for erectile dysfunction)- dietary supplement made from the bark of an African evergreen tree Caffeine- most common Other information    Viagra- vasodilation of pulmonary arteries o Do not take beta blockers= lead to hypotension Check VS before giving o < 60 bpm do not give beta blockers Cut off of BP- 100 systolic; antihypertensives should not be given Diuretics     Indicated for the treatment of edematous and non edematous conditions o pulmonary edema Only medication that decreases blood volume May be useful in preventing renal failure by sustaining urine flow A minimum of daily urine output approximately 400 ml is required to remove normal amount of metabolic end products o Polyuria- > 4L o Oliguria- < 400-500 mL o Anuria- < 100 mL; end stage renal disease 28 | P h a r m a c o l o g y     Acts on the kidneys to decrease absorption of sodium, chloride, water, and other substances such as calcium o Actions is in the nephrons Major subclasses- thiazides, osmotic diuretic, loop, and potassium-sparing diuretics Each act at different sites of the nephron o Thiazides- affect is in distal tubule o Loop- affects the ascending loop of Henle o Potassium- sparing; quick diuretic (collecting; already urine form and distal tubule) Used to manage o Edema and ascites o Management of heart failure- decrease fluids and water o hypertension Thiazide diuretics           End name- Thiazide Chemically related to sulfonamides so caution to patients with sulfa allergies Used in long term management of heart failure and hypertension Affect distal convoluted tubule Effectiveness decreases as the GFR decreases o GFR output should be 30 mL/ hour o If less than 30 mL/hour it becomes ineffective o As rising creatinine is noted, alternatives should be used such as loop diuretic Contraicdicated to px with renal damage or failure Can cause hypokalemia= leads to heart attack o Potassium most sensitive electrolyte for the heart Diuril (cholorothiazide) Hygroton (chlorthalidone) Hydrodiuril (hydrochlorthiazide) Loop diuretics            Inhibit sodium and chloride reabsorption in the ascending limb of the loop of Henle Potent diuretic Most common diuretic Need to restrict dietary sodium when taking these medications Lasix (Furosemide)- prototype and most common; if not hypokalemic o But if hypokalemic- potassium-sparing diuretic o Given with px with pulmonary edema o Potent diuretic o Only work with px without kidney problems o Excessive fluids in the lungs (crackles etc.) Bumex (bumetamide)- more potent than Lasix Oral- more on maintenance; treatment for hypertension; IV form- diuresis Ototoxic Max dose 120 mg/day Given slow, because If rapid= deafness Must monitor potassium levels, intake and output, and also weight o 80% of potassium is excreted in the urine= lead to hypokalemia Potassium-sparing diuretics     Act at distal tubule to decrease reabsorption of sodium and potassium excretion Spironolactone- prototype, blocks sodium retaining effects of aldosterone o Conserve potassium; excrete sodium o Where sodium goes water follows Weak diuretic when used alone, often used in combination Contraindicated in renal failure Osmotic diuretics      Produce rapid diuresis by increasing the solute load of the glomerular filtrate Water is pulled into the intravascular space and excreted via kidneys Useful in managing oliguria and anuria Can prevent acute renal failure during prolonged surgery, trauma, or during chemotherapy Helps reduce increased ICP, reduction of intraocular pressure before certain ophthalmic surgery and for urinary excretion of toxic substances 29 | P h a r m a c o l o g y      o Stroke= increased intracranial pressure Effect pull fluids IV space Crystal form Not used for oliguria and anuria Osmitrol (mannitol)- most common osmotic diuretic o For increased ICP o Also for blood transfusion reactions o Should be given fast drip- because it is a solute load; 50, 75, 100 mL Q4 large gauges of IV cannula; because it precipitates o Put inwarm water to dissolve Ismotic (isosorbide), and osmoglyn (glycerin) PHARMACOLOGY REVIEWER FOR FINALS Anticoagulants Drugs that affect coagulation    Thrombosis may occur in both arteries and veins Arterial thrombi cause disease by obstructing blood flow which can result in tissue ischemia or death o Coronary, cerebral, carotid, and the aorta o Smoking can cause peripheral arterial disease Venous thrombosis is associated with venous stasis. A venous thrombus is less cohesive than an arterial embolus so no venous emboli is more prevalent o Common to people with sedentary lifestyle, no exercise, people with varicose veins, and common with long flights Hemostasis  Hemostasis is the prevention or stoppage of blood loss from an injured blood vessel. Process Involves vasoconstriction, formation of a platelet plug (platelet aggregation), activation of clotting factors and growth of fibrous tissue into the blood clot (fibrin) making it more stable o Localized vasoconstriction is usually in the capillaries o When blood is exposed to air it will start to clot Clot lysis   When clot is being formed, plasminogen is bound to fibrin and becomes a component of a clot After tear in blood vessel is repaired, plasminogen is activated by plasminogen activator to produce plasmin. Plasmin (enzyme) breaks down the fibrin mesh and dissolves the clot o Fibrin mesh is in the capillary o Fibrin is broken down then is reabsorbed in the body Blood coagulation factors                I- fibrinogen II- prothrombin III- thromboplastin IV- calcium V- labile factor VIVII- proconvertin or stable factor VIII- antihemophilic factor IX- Christmas factor X- stuart factor XI- plasma thromboplastin antecedent XII- Hageman factor XIII- fibrin-stabilizing factor Clotting factors can be found in the plasma For patients with bleeding- give fresh frozen plasma Anticoagulants      Given to prevent formation of new clots and extension of clots already present; does not dissolve clots that are already present Prototype: Heparin Heparin may be used during pregnancy Used during hemodialysis Heparin is used with IU 30 | P h a r m a c o l o g y  Weight is based dosing per international nomogram Differences Route Indications Heparin IV or SQ Acute/ immediate cases Antidote Protamine sulfate aPTT Monitoring Warfarin Oral Long-term cases (2 weeks ); maintenance Vitamin K PT Heparin         Usually given a loading dose then calculated dosage per 24h; e.g. 15-25 units/kg/hr for IV dosing Can be given IV, SQ, or continuous infusion; cannot be given oral or IM Contraindication of heparin: if patient has presentation of bleeding e.g. GI bleeding To know therapeutic effect of heparin- monitor activated partial thromboplastin time (aPTT) o Should be 1.5-2.5 control value—normal value is 35 seconds HIT- Heparin induced thrombocytopenia o Can cause low platelet count o If patient has low platelet count check if it can be given o Normal platelet count: 150,000-400,000 o < 100,000 is considered as low platelet count Antidote: Protamine sulfate Combines with antithrombin III which will inactivate clotting factors IX, X, XI, and XII, inhibits conversion of prothrombin to thrombin and prevents thrombus formation. Further affects coagulation by preventing conversion of fibrinogen to fibrin, inhibiting factors V, VIII, XIII, and platelet aggregation INR checked Q6 Low molecular weight heparins     Given subcutaneously in abdomen and do not require close blood monitoring of blood coagulation tests Still should follow platelet counts Fragmin (dalteparin) Lovenox (enoxaparin); clexane- name used in the Philippines o Lesser chance of heparin-induced thrombocytopenia Coumadin (Warfarin)           Most commonly used as oral anticoagulant Drug acts in the liver to prevent synthesis of vitamin K- dependent clotting factors (II, VI, IX, X). Acts as competitive antagonist to hepatic use of vitamin K Anticoagulant choice for long-term maintenance therapy Can be combined with heparin International normalized ratio (INR) is based on prothrombin time o Normal baseline or control of PT is 12 seconds; therapeutic value is 1.5 times the control or 18 seconds Therapeutic effect will occur in two weeks o Check using prothrombin time (PT) INR should be checked weekly o INR- normal value: 1 o INR has eliminated disparities in different labs Dosage reduction in patients with biliary tract disorders, liver disease, malabsorption syndrome, and hyperthyroidism. o Conditions increase anticoagulant drug effects by reducing absorption of vitamin K or decreasing hepatic synthesis of clotting factors Has multiple drug interactions Counteract with vitamin K When to combine heparin and warfarin  Give heparin until stable or up until patient is still admitted in the hospital; then at discharge give maintenance of warfarin= once it already has effect discontinue heparin 31 | P h a r m a c o l o g y Other anticoagulants      Orgaran (danaparoid)- low molecular weight, heparin-like drug. Given subcutaneously. o Used in management of hip surgery, ischemic stroke or in those who cannot take heparin. o Does not contain heparin Refludan (lepirudin)- used as heparin substitutes Arixtra (fondaparinux)- binds to clot bound factor Xa, inhibits thrombin productions o given subcutaneously Argatroban Angiomax (bivalirudin) Antiplatelet aggregate drugs         Arterial thrombi are composed of primary platelets Antiplatelet drugs act by inhibiting platelet activation, adhesion, aggregation, or procoagulant activity Include drugs that block platelet receptors for thromboxane, adenosine diphosphate, glycoprotein IIIa/IIb, and phosphodiesterase inhibitors Prevents clumping of platelets Blood thinners Weaker compared to warfarin and heparin Used as maintenance Mostly oral tablets Thromboxane A2 inhibitors    Work by inhibiting synthesis of prostaglandins. TA inhibitors work by acetylating cyclooxygenase, the enzyme in platelets that synthesizes thromboxane A2 (which causes platelet aggregation) ASA- acetyl salicylic acid; aspirin, is an example. It affects the platelets during its life o Total life of a platelet- 9-10 days NSAIDs are not so useful as action wears off as drug wears off Adenosine diphosphate receptor antagonist        Ticid (ticlodipine) Inhibit platelet aggregation by preventing ADP-induced binding between platelets and fibrinogens. This reaction inhibits platelet aggregation irreversibly and persist for the lifespan of the platelet Indicated for TIA- transient ischemic attack o Blockage in the carotid artery o A sign of stroke for the next 5 years Adverse effects: neutropenia, diarrhea, and skin rashes o Neutropenia- 65-80% low neutrophils Even used for post angioplasty Taken for 1 year only- due to price Plavix (clopidogrel) o Has fewer side effects than ASA or ticlid o Indicated for patients with atherosclerosis for reduction of myocardial infarction, stroke, and vascular death o Does not need reduction in those with renal problems Glycoprotein IIb/IIIa receptor antagonist     Reopro (abciximab)- is a monoclonal antibody that prevents binding of fibrinogen, von willerbrand factor, and other molecules to GP IIb/IIIa receptors on activated platelets. This action inhibits platelet aggregation o Given during angioplasty Used with percutaneous transluminal coronary angioplasty (PTCA) or removal of atherosclerotic plaque to prevent rethrombosis Used with aspirin and heparin and is contraindicated in clients who have recently received oral anticoagulants or IV dextran Other contraindications include active bleeding, thrombocytopenia, history of stroke, surgery or trauma within the past 6 weeks, uncontrolled hypertension, or hypersensitivity Other glycoprotein IIb/IIIa receptor antagonist    Integrilin (Eptifibatide)- only given for 24 hours after angioplasty o Potent antiplatelet aggregate Aggrasat (tirofiban) Similar mechanism to the action of reopro 32 | P h a r m a c o l o g y   Indicated for acute coronary syndrome who are managed medically or by angioplasty or atherectomy Contraindications include o Recent bleeding o History of thrombocytopenia o History of stroke within 30 days o Major surgery or severe trauma within the past month o Severe hypertension o History of intracranial hemorrhage o Neoplasm o AV malformation o Aneurysm o Platelet count < 100,000 o Creatinine greater than 2 mg/dl Phosphodiesterase inhibitor      Pletal (cilostazol)- increases cAMP which then inhibits platelet aggregation and produces vasodilation. Drug reversibly inhibits platelet aggregation Indicated for intermittent claudication Indicated for peripheral vascular disease o Buerger’s disease o Reynaud’s syndrome Contraindicated for patients with heart failure Most common side effect is diarrhea and headache Miscellanous   Persantine (dipyridamole)- inhibits platelets aggregation but mechanism is unclear Used for prevention of thromboembolism after cardiac valve replacement and is given with Coumadin Thrombolytics                Given to dissolve thrombi Stimulate conversion of plasminogen to plasmin, an enzyme that breaks down fibrin (the framework of a thrombus) Used in severe thromboembolic diseases such as myocardial infarction, PE and ileofemoral thrombosis Goal is to re-establish blood flow and prevent tissue damage Also used to dissolve clots in arterial or venous cannulas or catheters Must obtain baseline INR, aPTT, platelet count, and fibrinogen Will monitor tabs 2-3 hours after thrombolytic therapy is instituted to determine efficacy Activase (alteplase), Retavase (reteplase), and TNKase (tenecteplase) are tissue plasminogen activators o Mainly used in acute MI to dissolve clots Eminase (anistreplase), Streptase (streptokinase), and Abbokinase (urokinase) are enzymes that break down fibrin o Used to lyse coronary clots in acute MI o Streptokinase- problem allergy; byproduct of streptococcus o Can cause anarrhytmia Xigris (drotrecogin alfa) is a recombinant version of human activate protein C o Approved for use in sepsis o Sepsis causes inappropriate blood clot formation and may lead to DIC o DIC- last part of sepsis o Blood clots due to consumption of platelets o experimental medication Strongest type of anticoagulants Used to dissolve clots Last option Heart attack- 6 hours timeframe for thrombolytics Stroke- 4 hours Drugs used to control bleeding   Amicar (aminocaproic acid) and Cyklokapron (tranaxemic acid) are used to stop bleeding caused by thrombolytic agents o Tranexamic acid- used for trauma Trasylol (aprotinin) indicated in patients undergoing CABG o Inhibits breakdown of blood clotting factors 33 | P h a r m a c o l o g y Drugs affecting the cardiovascular system ANTILIPIDS Important Reminders  Risk factors for Thromboembolism 1. Obesity 2. Myocardial infarction 3. Atrial Fibrillation 4. Prosthetic heart valves 5. Arteriosclerotic heart disease 6. OCP or HRT 7. History of deep vein thrombosis or pulmonary embolism 8. Cigarette smoking 9. Immobility Overview of Cholesterol Panel Total Cholesterol Desirable – Less than 200 Borderline high – 200 - 239 High – 240 or greater Low-density lipoprotein Desired – <100 Above optimal – 100 – 139 Borderline high – 130 – 159 High – 160 – 189 Very high – 190 High-density lipoprotein High - >60 Low - <40 Triglycerides Normal – Less than 150 – 199 High – 200 to 499 Very high – 500 or above DYSLIPIDEMIA       Associated with atherosclerosis and numerous pathophysiologic effects Elevated total cholesterol, high HDL and low HDL are all risk factors for CAD Triglycerides indicated excessive caloric intake, excessive proteins and carbohydrates are converted to TG and obesity Atherosclerosis is narrowing of arteries due to plaques CAD most risky at 40 due to CHO / plaque starts from infancy – Accumulation, checked through angiogram Hypothyroidism – decrease in T3 and T4. Slow speak and slow thinking, edema Contributors to Dyslipidemia      Hypothyroidism Diabetes mellitus Alcoholism Obesity, beta blockers, oral estrogen, glucocorticoids, sertraline, thiazide, diuretics, protease inhibitors High dietary intake also increases the conversion of VLDL to LDL cholesterol, and high dietary intake of TG and saturated fat decreases the activity of LDL receptors and increases synthesis of cholesterol. Types of Lipoproteins 34 | P h a r m a c o l o g y    LDL – Unfavorable type. Transports 75% of serum cholesterol to peripheral tissues and the liver. High levels are atherogenic VLDL – Contains 75% TG and 25% cholesterol. Transports endogenous TG to fat and muscle cells HDL – Favorable type. This LP transports cholesterol back to the liver to catabolism and excretion Initial Management         Treat conditions that contribute to elevated lipids (DM, Hypothyroidism) Start low fat diet Increase intake of fiber – lowers LDL Cholestetol lowering margarines Weight Reduction Exercise – Increase HDL Smoking cessation HRT (Hormonal Replacement Therapy) Drug Therapy     Based on the type of dyslipidemia and its severity Classes of agents include: HMB-CoA reductase inhibitors or “Statins”, fibrates, bile acid sequestrants and niacin in different forms Lovaza Zetia HMG-CoA reductase inhibitors or “Statins”              Inhibits an enzyme (Hydroxymethylglutaryl-coenzyme A reductase) required for hepatic synthesis of cholesterol Decrease serum cholesterol, LDL, VLDL and TG Reach maximal effects within about 6 weeks Drugs also reduce C reactive protein associated with inflammation and development of coronary artery disease Undergo extensive first pass metabolism Metabolism occurs in liver Adverse effects include: HA, diarrhea, rashes, headaches, constipation, hepatotoxicity and myopathy o Reason to stop statins is because of myopathy= rhabdomyolysis (serious syndrome due to a direct or indirect muscle injury. It results from the death of muscle fibers and release of their contents into the bloodstream.)= due to secretion of creatinine kinase to the bloodstream= stocked in kidneys= renal failure Should obtain baseline LFTs and then at 6 and 12 weeks after starting then every 6 months If serum aminotransferases increase to more than 3x normal, should be reduced or DCed Do not take with grapefruit juice Pregnancy category X Examples: Lipitor (Atorvastatin), Pravachol (pravastatin), Zocor (Simvastatin), Lescol (Fluvastatin) Rosuvastatin- Another common statin Bile Acid Sequestrants       Bind bile acids in the intestinal lumen. This causes the bile acids to be excreted in the feces and prevents their being recirculates to the liver. Thus, the liver will use cholesterol to produce bile acids thus decreasing serum levels Especially lower LDL Examples: Questran (Cholestyramine) and Welchol (Colesevelam) Often used with patients already on a statin Long term use can affect absorption of folate and vitamins A, D, E, K If feces turns white= pancreatitis or liver problem FIBRATES       Tricor (Fenofibrate) Lopid (Gemfibrozil) These drugs increase oxidation of fatty acids in liver and muscle tissue thus decreasing hepatic production of TG, VLDL, and increase HDL Most effective drugs for reducing TG can cause hepatotoxicity Main side effects include: diarrhea, GI discomfort, cause gallstones, interact with Coumadin NIACIN (Nicotinic Acid)  Decreases both cholesterol and triglycerides 35 | P h a r m a c o l o g y      Bottom line – decreases hepatic synthesis of TG and secretion of VLDL (which leads to decreased production of LDL) Need high doses for efficacy Side effects: Flushing, pruritus, gastric irritation. May cause hyperglycemia, hyperuricemia, elevated hepatic aminotransferase enzymes and hepatitis Can reduce flushing by starting with low doses, taking dose with meals, and taking ASA 325mg thirty minutes before taking dose More effective in preventing heart diseases when used in combination with another dyslipidemic such as a bile acid sequestrant or fibrate. Drugs affecting the respiratory system Key terms       Ventilation Perfusion Diffusion Pulmonary circulation Surfactant Pneumocytes drugs for asthma and other bronchoconstrictive disorders    Asthma- inflammation, hyperreactivity, and bronchoconstriction Gastroesphageal reflux disease (GERD) may cause microaspiration/resultant nighttime cough ___- medications can also exacerbate GERD Asthma        May be triggered by __, __, and allergies Can develop at any age Seen more often in children who are exposed to allergens during infancy Bronchoconstriction Inflammation Mucosal edema Excessive mucous Pathophysiology of asthma    Mast cells Chemical mediators such as histamine, prostaglandins, acetylcholine, cGMP, interleukins, and leukotrienes are released when triggered. Mobilization of eosinophils. All cause movement of fluid and proteins into tissues. Bronchoconstrictive substances antagonized by cAMP Chronic obstructive pulmonary disease (COPD)     Combination of chronic bronchitis and emphysema Bronchoconstriction and inflammation are more contant, less reversibility Anatomic and physiologic changes occur over the years Leads to increasing dyspnea and activity intolerance Drug therapy   Bronchodilators Anti-inflammatories Bronchodilators    Adrenergics- stimulate beta II receptors in smooth muscles of bronchi and bronchioles Receptors stimulates cAMP= bronchodilation Cardiac stimulation is an adverse effect of these medications Bronchodilators- adrenergics    Cautious use in hypertension and cardiac disease Selective beta II agonists by inhalation are drugs of choice Epinephrine subcutaneous in acute bronchoconstriction Short acting bronchodilators  Treatment of first choice to relive acute asthma 36 | P h a r m a c o l o g y      Aerosol or nebulization May be given by MDI Overuse will diminish their bronchodilating effects= tolerance Proventil (albuterol) Xopenex (levalbuterol) Other bronchodilators       Foradil (formoterol) and serevent (salmeterol) are long acting beta II adrenergic agonists used only for prophylaxis Serevent (salemeterol)- used in deteriorating asthma can be life-threatening Alupent (metaprotenerol)- intermediate acting. Useful in exercise induced asthma, treatment for acute bronchospasm Brethine (terbutaline)- selective beta II adrenergic agonist that is a long-acting bronchodilator When give subcutaneous, loses selectivity Also used to decrease premature uterine contractions during pregnancy Xanthines         Theophylline Mechanism of action is unclear Bronchodilate, inhibit pulmonary edema, increase action of cilia, strengthen diaphragmatic contractions, over-all anti-inflammatory action Increases CO, causes peripheral vasodilation, mild diuresis, and stimulates SNS Contraindicated in acute gastritis and PUD Second line Narrow therapeutic window- therapeutic range is 5-15 mcg/mLh Multiple drug interactions Anticholinergics     Block the action of acetylcholine in bronchial smooth muscles when given by inhalation Action reduces intracellular guanosine monophosphate (GMP) which is a bronchoconstrictive substance Atrovent (ipratropium)- caution in BPH, narrow-angle glaucoma Spiriva (tiotropium) Anti-inflammatory agents   Suppress inflammation by inhibiting movement of fluid and protein into tissues; migration and function of neutrophils and eosinophils, synthesis of histamine in mast cells, and production if proinflammatory substances Benefits: decrease mucous secretions, decreases edema, and reduced reactivity STEROIDS Corticosteroids  Second action is to increase the number and sensitivity of beta 2 adrenergic receptors  Can be given PO or IV  Pulmonary function usually improves within 6-8 hours  Continue drugs for 7-10 days Steroids  Fewer long term side effects if inhaled  End –stage COPD may become steroid dependent  In asthma, systemic steroids generally are used only temporarily  Taper high dose oral steroids to avoid hypothalamic-pituitary axis suppression For inhalation: o Beclovent (beclomethasone) o Pulmicor (budesonide) o Aerobid (flunisolide) o Flovent (fluticasone) o Azmacort (triamcinolone)  Most inhaled steroids are being reformulated with HFA  HFA – hydrofluoroalkane  Systemic use: prednisone, methylprednisolone, and hydrocortisone  In acute, severe asthma – a systemic corticosteroid may be indicated when inhaled beta 2 agonists are ineffective 37 | P h a r m a c o l o g y MODIFIERS Leukotriene Modifiers  Leukotrienes are strong chemical mediators of bronchoconstriction and inflammation  Increase mucous secretion and mucosal edema  Formed by the lipooxygenase pathway of arachidonic acid metabolism in response to cellular injury  Are released more slowly than histamine Leukotriene Modifier Drugs  Developed to counteract the effects of leukotriene  Indicated for long term treatment of asthma in adults and children  Prevent attack induced by some allergens, exercise, cold air, hyperventilation, irritants and ASA/NSAIDs  Not useful in acute attacks Leukotrience Modifiers  Injured cell  Arachidonic acid  XXXXXXXXX  Lipooxygenase  Leukotrienes  XXXXXXX  Bronchi, WBCs  Bronchoconstriction Leukotriene Modifier Drugs  Singulair (montelukast) and Accolate (zafirlukast) are leukotriene receptor antagonists  Can be used in combination with bronchodilators and corticosteroids  Less effective than low doses of inhaled steroids  Should not be used during lactation  Can cause HA, nausea, diarrhea Mast Cell Stabilizers Intal (cromolyn) Tilade (nedocromil)  Prevent release of bronchoconstrictive and inflammatory substances when mast cells are confronted with allergens and other stimuli  Prophylaxis only  Inhalation, nebulizer or MDI, nasal spray as well  MDI – Metered-dose inhaler ANTI-HISTAMINE AND ALLERGIES Antihistamines and Allergic Disorders  Histamine is the first chemical mediator released in immune and inflammatory responses  Concentrated in skin, mucosal, surfaces of eyes, nose, lungs, CNS and GI tract  Located in mast cells and basophils  Interacts with histamine receptors on target organs called H1 and H2 Antihistamines  H1 receptors are located mainly on smooth muscle cells in blood vessels and the respiratory and GI tracts  H1 binding causes: pruritus, flushing, increased mucous production, increased permeability of veins – edema, contraction of smooth muscle in bronchi>>bronchoconstriction and cough  With H2 receptor stimulation, main effects are increased secretion of gastric acid and pepsin, decreased immunologic and proinflammatory reactions, increased rate and force of myocardial contraction Allergic reactions  These are the exaggerated response by the immune system that produce tissue injury and possible serious disease  Allergic reactions may result from specific antibodies, sensitized T lymphocytes, or both, formed during exposure to an antigen TYPES OF RESPONSES TO CELL-MEDIATED INVASION Type 1: Immediate hypersensitivity (IgE induced) response triggered by the interaction of antigen with antigenspecific IgE bound on mast cells  Anaphylaxis is an example 38 | P h a r m a c o l o g y  Does not occur on first exposure to an antigen  Can develop profound vasodilation resulting in hypotension, laryngeal edema, bronchoconstriction Type II: (IgM or IgM) immunoglobulin mediated which generate direct damage to cell surfaces.  Example: BT reactions, hemolytic disease of newborns, hypersensitivity reactions to drugs such as heparin or penicillin. Type III: IgM or IgM medicated reaction characterized by formation of antigen-antibody complexes that induce inflammatory reaction in tissues.  Prototype: Serum sickness  Immune response can occur following antitoxin administration or sulfa drugs Type IV hypersensitivity  Delayed hypersensitivity  Cell mediated response where sensitized T lymphocytes react with an antigen to cause an inflammation, release of lymphokines, direct cytotoxicity or both  Classic examples: tuberculin test, contact dermatitis and some graft rejections Allergic Rhinitis  IgE mediated  Inflammation of nasal mucosa caused by a hypersensitivity reaction to inhaled allergies  Presents with itching of throat, eyes and ears  Seasonal and perennial  Can lead to chronic fatigue, difficulty sleeping, sinus infections, postnasal drip, cough and headache Intranasal Drugs for Allergic Rhinitis  Atrovent nasal spray  Beconase (beclomethasone)  Rhinocort (budesonide)  Flonase (fluticasone)  Nasonex (mometasone)  Nasalcrom (a mast cell stabilizer) SKIN ALLERGIES Allergic Contact Dermatitis  Type IV (hypersensitivty reaction)  Usually occurs >24 hour after reexposure o Example: Poison Ivy Other reactions  Allergic food reaction: result from ingestion of a protein  Most common food allergy is shellfish, others include milk, eggs, peanuts  Allergic drug reaction: unpredictable, may occur 7-10 days after initial exposure  Pseudoallergic drug reactions: resemble immune response but do not produce antibodies, i.e. anaphylactoid ANTIHISTAMINES  Inhibit smooth muscle constriction in blood vessels and respiratory tract and GI tract  decrease capillary permeability  decrease salivation and tear formation  act by binding with the histamine receptor Indications for use:  allergic rhinitis  anaphylaxis  allergic conjunctivitis  drug allergies  transfusion of blood products  dermatologic conditions  nonallergic such as motion sickness, nausea, vomiting, and sleep Precautions 39 | P h a r m a c o l o g y     Caution in pregnancy Benign Prostatic H bladder neck obstruction narrow angle glaucoma 1ST GEN. H1 RECEPTORS ANTAGONISTS  Bind to central and peripheral receptors  Can cause CNS depression or stimulation  Have substantial cholinergic effects EXAMPLES:  Chlor-Trimeton (chlorpheniramine)  Benadryl (dipenhydramine)  vistaril (hydroxyzine)  phenergan (promethazine) 2ND GEN. H1 RECEPTORS ANTAGONISTS  Selective or nonsedating  Does not cross BBB EXAMPLES:  astelin (azelastine)  allegra (fexofenadine)  claritin (loratadine)  clarinex (desloratadine)  zyrtec  Xyzal NASAL DECONGESTANTS  Relieve nasal obstruction and discharge  Adrenergic  Rebound nasal swelling called "rhinitis medicamentosa" EXAMPLES: Afrin Sudafed (pseudoephedrine) contraindicated in severe hypertension, CAD, narrow angle glaucoma, TCAs, MAOIs ANTITUSSIVES  Suppress cough by depressing cough center in medulla or by increasing flow of saliva  For dry, hacking, nonproductive cough  not recommended for children and adolescents EXAMPLES: codeine hydrocodone dextromethorphan EXPECTORANTS  Liquefy respiratory secretions Guiafenesin MUCOLYTICS  By inhalation to liquefy mucous EXAMPLE: mucomyst (acetylcysteine) mucosolvan (ambroxol)  may be used in treating acetaminophen overdose COLD REMEDIES 40 | P h a r m a c o l o g y  Contain antihistamine, decongestant, and an analgesic Examples: chlorpheniramine Pseudoephedrine acetaminophen dextromethorphan guiafenesin   decongestants can cause stasis of secretions Tamiflu can be used to limit spread of virus in respiratory tract DRUGS AFFECTING THE RESPIRATORY SYTEM KEY TERMS       Ventilation Perfusion Diffusion Pulmonary Circulation Surfactant Pneumocytes Drugs for Asthma and other Bronchoconstrictive Disorders    Asthma – Inflammation, hyperreactivity, and bronchoconstriction GERD – May cause microaspiration / resultant night time cough Antiasthma – Medications can also excacerbate GERD ASTHMA        May be triggered by Viruses, irritants, allergens. Can develop at any age Seen more often in children who are exposed to airway irritants during infancy Bronchoconstriction Inflammation Mucosal edema Excessive mucuos Pathophysiology of Asthma    Mast cells Chemical mediators such as Histamine, prostaglandins, acetylcholine, cGMP, interleukins, leukotrienes are released when triggered. Mobilization of eosinophils. All cause movement of fluid and proteins into tissues Bronchoconstrictive substances antagonized by cAMP Chronic Obstructive Pulmonary Disease (COPD)     Combination of chronic bronchitis and emphysema Bronchoconstriction and inflammation are more contant, less reversibility Anatomic and physiologic changes occur over the years Leads to increasing dyspnea and activity intolerance Drug therapy   Bronchodilators Anti-inflammatories Bronchodilators    Adrenergics- stimulate beta II receptors in smooth muscles of bronchi and bronchioles Receptors stimulates cAMP= bronchodilation Cardiac stimulation is an adverse effect of these medications Bronchodilators- Adrenergics    Cautious use in hypertension and cardiac disease Selective beta II agonists by inhalation are drugs of choice Epinephrine subcutaneous in acute bronchoconstriction Short Acting Bronchodilators 41 | P h a r m a c o l o g y       Treatment of first choice to relive acute asthma Aerosol or nebulization May be given by MDI Overuse will diminish their bronchodilating effects= tolerance Proventil (albuterol) Xopenex (levalbuterol) Other bronchodilators       Foradil (formoterol) and serevent (salmeterol) are long acting beta II adrenergic agonists used only for prophylaxis Serevent (salemeterol)- used in deteriorating asthma can be life-threatening Alupent (metaprotenerol)- intermediate acting. Useful in exercise induced asthma, treatment for acute bronchospasm Brethine (terbutaline)- selective beta II adrenergic agonist that is a long-acting bronchodilator When give subcutaneous, loses selectivity Also used to decrease premature uterine contractions during pregnancy Xanthines         Theophylline Mechanism of action is unclear Bronchodilate, inhibit pulmonary edema, increase action of cilia, strengthen diaphragmatic contractions, over-all anti-inflammatory action Increases CO, causes peripheral vasodilation, mild diuresis, and stimulates SNS Contraindicated in acute gastritis and PUD Second line Narrow therapeutic window- therapeutic range is 5-15 mcg/mLh Multiple drug interactions Anticholinergics     Block the action of acetylcholine in bronchial smooth muscles when given by inhalation Action reduces intracellular guanosine monophosphate (GMP) which is a bronchoconstrictive substance Atrovent (ipratropium)- caution in BPH, narrow-angle glaucoma Spiriva (tiotropium) Anti-inflammatory agents   Suppress inflammation by inhibiting movement of fluid and protein into tissues; migration and function of neutrophils and eosinophils, synthesis of histamine in mast cells, and production if proinflammatory substances Benefits: decrease mucous secretions, decreases edema, and reduced reactivity DRUGS ACTING ON THE ENDOCRINE Control of Hormone Release - - Blood levels of hormones - Are controlled by negative feedback systems - Vary only within a narrow desirable range Hormones are synthesized and released in response to: 1. Humoral stimuli - Blood 2. Neural Stimuli 3. Hormonal Stimuli PITUITARY AGENTS Desmopressin (DDAVP) - - Classification: Antidiuretic, hemostatic Indications: Diabetes Insipidus Available forms: - Intranasal Spray - IV - Tablet Drug of choice for Diabetes Insipidus 42 | P h a r m a c o l o g y Diabetes Insipidus - The problem is there is a decrease in Antidiuretic Hormone (ADH) causing Polyuria Urine output is increased to 7L-8L/Hour Patients die due to Dehydration To confirm diabetes insipidus an urinalysis test is needed Gravity <1.05 is not good Action of Desmopressin - Increase the flow of Adenosine Monophosphate and water through the kidneys, promoting reabsorption of water and producing concentrated urine. Nursing Process in Desmopressin Assessment: Monitor effectiveness of therapy, be alert for Hypertension. Nursing Diagnosis: Fluid Volume Excess Planning and implementation: 1. Ensure nasal mucosa is intact 2. In cases of Rhinorrhea, report it to the doctor 3. Adjust the dose in coordination with the doctor In relation to the urine output of the patient Patient Teachings: - Instruct patient to clear nasal passages Tell patient to report nasal congestion, allergic rhinitis, and respiratory tract infection Rotate injection when using SQ form Warn patient to drink just enough water to satisfy the thirst Vasopressin (Pitressin) - - Classification: Antidiuretic Hormone Indication: - Diabetes Insipidus - Hypotension - Pulseless arrest, Asystole Available forms: IV Last option for Inotropes Can be a substitute for epinephrine but only once More on hypotension and Cardiac arrest Adverse Reaction: - Arrhythmia - Myocardial ischemia - Bronchoconstriction, Anaphylaxis Nursing Process in Vasopressin Assessment: Monitor the urine specific gravity, Watch out for hypertension, Closely monitor for signs of water intoxication. Nursing Diagnosis: Risk for Fluid Volume Deficit Planning and Implementation: 1. Use minimum effective dose 2. In cardiac emergency, follow the guidelines in ACLs 3. Don’t confuse Vasopressin with Desmopressin ADRENOCORTICAL AGENTS Hydrocortisone (Solu Cortef) 43 | P h a r m a c o l o g y Classification: Glucorticoids (steroids), Anti-inflammatory, immunosuppressant Indication: Severe Inflammation, Septic shock Available forms: Tablet, IV Contraindication: GI Ulcers, Renal disease, Osteoperosis, DM Adverse Effects: Seizures, Arrythmia, Pancreatitis, Peptic Ulceration - Therapy must not exceed 21 days Hypokalemia may occur Action of Hydrocortisone - Not clearly defined May stabilize lysosomal membranes, suppress immune response, and stimulate bone marrow Nursing Process in Hydrocortisone Assessment: Monitor weight, Blood pressure, and Electrolytes level Nursing Diagnosis: Risk for Infection Planning and Implementation 1. Give oral dose with food 2. Give potassium supplements 3. Therapy must not exceed the 21 days Patient Teachings - Tell the patient not to abruptly stop taking hydrocortisone without the doctors content Warn patient about easy bruising Warn patient about Cushingcoid symptoms Methylprednisolone (Medrol) Classification: Glucocorticoids, Anti- Inflammatory, Immunosuppresant Indication: Severe Inflammation, shock, multiple sclerosis, severe lupus nephritis Available Forms: Tablet, IV - The rest of the literatures are the same as hydrocortisone ANTIDIABETIC AGENTS Pancreas - Triangular gland behind the stomach Has both exocrine and endocrine cells - Acinar cells (Exocrine) produce an enzyme-rich juice for digestion - Pancreatic Islets (Islets of Langerhans) contain endocrine cells - Alpha cells produce glucagon (a hyperglycemic hormone) - Beta cells produce insulin (a hypoglycemic hormone) Two Types of Diabetes Type 1 Diabetes - Disease case by lack of insulin Destroys beta cells therefore becoming autoimmune which causes a decrease in insulin and an increase of blood sugar Oral medications cannot be used on Type 1 diabetes patients Type 2 Diabetes - Is a disease of insulin resistance by cells The most common type of diabetes Obesity Decrease in receptors of cells because fats covers the receptors 44 | P h a r m a c o l o g y - Once the use of insulin starts it is used for lifetime Insulin is the last option Insulin Classification: Antidiabetic Agent Indication: Moderate to severe diabetec Ketoacidosis, Control of Hyperglycemia, Hyperkalemia Available Forms: IV, SQ Common Types of Insulin Rapid Acting - - Regular Insulin (Humulin R) - 1 hour onset of action - Appears to be clear - Is used in acute cases (IV) Insulin Lispro Insulin Aspart Intermediate Acting - - Isophane Insulin (Humulin N) - Appears to be cloudy - Onset of action is 4 hours Insuline Zinc (Lente) Long Acting - Insulin Glargine (Lantus) - Is used as maintenance Insulin Determir (Levemir) - You can mix Humulin R and Humulin N for better Longevity and Effectivity - Humulin R is aspirated first before Humulin N to not transfer cloudiness to clear - Give air to Humulin N first Contraindication: HYPOGLYCEMIA Adverse Reactions: - Hypoglycemia Urticaria Itching Anaphylaxis Lipodystrophy - A problem in SQ fats where it appears to be depressed due to the repetition of using the same site over and over or injecting cold insulin - To prevent, rotate the injection site or change places. Insulin must be room temperature Action of Insulin - Increases glucose transport into the muscle and fat cell membranes to reduce glucose level Nursing Process (Insulin) Assessment: 45 | P h a r m a c o l o g y - Assess patients glucose level before starting the therapy Monitor patient glycosylated haemoglobin regulary Monitor urine ketones when glucose level is elevated Nursing Diagnosis: Risk for injury related to drug induced hypoglycaemia Planning and Implementation: - Dose is always expressed in units Don’t shake the insulin to prevent bubbles Rapid acting insulin should be given 15 minutes before meals Regular insulin can be mixed with NPH insulin in any proportions SQ route – 45 to 90 degree injection Don’t rub the site on injection Treat Hypoglycemia with rapid acting glucose or with Glucagon IV, IV Glucose If patient is awake you can give juice Insulin Overdose – Antidote is Glucagon Patient Teachings - Tell patient that insulin relieves symptom but does not cure the disease Tell patient that glucose monitoring and urine ketone test are essential to dosage and success of therapy Hypoglycemia is hazardous – Brain damage Smoking decreases absorption of insulin Advise the patient to carry or wear medical identification at all times ORAL HYPOGLYCEMIC AGENTS Oral Hypoglycemic Drugs 1. 2. 3. 4. 5. 6. Sulfonylurea drugs Meglinitides Biguanides Alpha-Glucosidase Inhibitors Thiazolidinediones Dipeptidyl peptidase-4 (DPP-4) Inhibitors Insulin Secretagogues - Sulfonylurea drugs Meglinitides Insulin Sensitizers - Biguanides Thiazolidinediones Others - Alpha-Glucosidase Inhibotors Gastrointestinal hormones INSULIN SECRETAGOGUES - Are drugs which increase the amount of insulin secreted by the pancreas. Include: Sulfonylureas and Meglinitides Mechanism of Action of SULFONYLUREAS - Stimulate insulin release from functioning B cells of ATP-Sensitive K Channels which causes depolarization and opening of voltage-dependent calcium channels, which causes an increase in intracellular calcium in the beta cells, which stimulates insulin release. 46 | P h a r m a c o l o g y Pharmacokinetics of Sulfonylureas - Orally, well absorbed Reach peak concentration after 2-4 hours All are highly bound to plasma proteins Duration of action is variable Second generation has longer duration than first generation, has lesser side effects and more effective Steven – Johnsons Syndrome a type III is related to sulfonylureas Metabolized in liver Excreted in urine (elderly and renal disease) Cross placents, stimulate fetal B-cells to release insulin – Fetal hypoglycaemia at birth First Generation Sulfonylureas Tolbutamide: - Safe for diabetic patients or pts with renal impairment Second Generation Sulfonylureas Glipzide – Glyburide (Glibenclamide) - More potent than first generation Have longer duration of action Less frequency of administration Have fewer adverse effects Have fewer drug interaction 47 | P h a r m a c o l o g y Unwanted Effects: 1. 2. 3. Hyperinsulinemia and Hypoglycemia Less in tolbutamide More in old age, hepatic and renal diseases Weight gain due to increase in appetite GIT upset Contraindications - Hepatic impairment or renal insufficiency Pregnancy and Lactation Type 1 Diabetes MEGLINITIDES - Repaglinide Are rapidly acting insulin secretagogues Stimulate insulin release from functioning B-cells via blocking ATP-sensitive K-channels resulting in calcium influx and insulin exocytosis Orally, well absorbed Very fast onset of action, peak 1 hour Short duration of action (4 hours) Metabolized in liver and excreted in bile Taken just before each meal (3 times/day) Uses of Meglinitides - Type II Diabetes: Monotherapy or combined with metformin (Better than monotherapy) Specific use in patients allergic to sulfur or sulfonylureas Adverse Effect of Meglinitides - Hypoglycemia Weight gain INSULIN SENSITIZERS - Are drugs which increase the sensitivity of target organs to insulin Include: Biguanides and Thiazolidinediones (Glitazones) Gastrointestinal drugs Acid related pathophysiology The stomach secretes   Hydrochloric acid (HCl)- activates pepsinogen into the enzyme pepsin, which then helps digestion by breaking the bonds linking amino acids, a process known as proteolysis. Bicarbonate- acts to regulate pH in the small intestine. It is released from the pancreas in response to the hormone secretin to neutralize the acidic chyme entering the duodenum from the stomach. 48 | P h a r m a c o l o g y     Pepsinogen- powerful and abundant protein digestive enzyme secreted by the gastric chief cells as a proenzyme and then converted by gastric acid in the gastric lumen to the active enzyme pepsin. Intrinsic factor- glycoprotein secreted by parietal (humans) or chief (rodents) cells of the gastric mucosa. In humans, it has an important role in the absorption of vitamin B12 (cobalamin) Mucus Prostaglandins Acid-controlling agents Glands of the stomach    Cardiac Pyloric Gastric o the cells of the gastric glands are the largest in number and of primary importance when discussing acid control Cells of the gastric gland Hydrochloric acid    Secreted by the parietal cells when stimulated by food Maintains stomach at pH of 1 to 4 Secretion is also stimulated by: o Large fatty meals o Excessive amounts of alcohol Parietal cells   Produce and secrete HCl Primary site of action for many acid-controller drugs Chief cells    Secrete pepsinogen, a proenzyme Pepsinogen becomes pepsin when activated by exposure to acid Pepsin breaks down proteins (proteolytic) Mucoid cells    Mucus-secreting cells (surface epithelial cells) Provide a protective mucus coat Protects against self-digestion by HCl Acid related diseases       Caused by imbalance of the three cells of the gastric gland and their secretions Most common: hyperacidity Clients reports symptoms of overproduction of HCl by the parietal cells as indigestion, sour stomach, heartburn, and acid stomach PUD: peptic ulcer disease GERD: gastroespphageal reflux disease Helicobacter pylori (H. pylori) o Bacterium found in the GI tract of 90% of patients with duodenal ulcers and 70% of those with gastric ulcers o Combination therapy is used most often to eradicate H. pylori Treatment for H. pylori    Eight regimens approved by the FDA H. pylori is not associated with acute perforating ulcers It is suggested that factors other than the presence of H. pylori lead to ulceration Types of acid-controlling agents 49 | P h a r m a c o l o g y    Antacids 𝐻2 antagonists Proton pump inhibitors Antacids: mechanism of action     Promotes gastric mucosal defense mechanisms Secretion of: o Mucus: protective barrier against HCl o Bicarbonate: helps buffer acidic properties of HCl o Prostaglandins: prevent activation of proton pump which results to lower HCl production Antacids do not prevent over production of acids Antacids do neutralize the acid once it’s in the stomach Antacids: drug effects  Reduction of pain associated with acid-related disorders o Raising gastric pH from 1.3 to 1.6 neutralizes 50% of the gastric acid o Raising gastric pH 1 point (1.3 to 2.3) neutralizes 90% of the gastric acid o Reducing acidity reduces pain Antacids: aluminum salts     Forms: carbonate, hydroxide Have constipating effects Often used with magnesium to counteract constipation Examples o Aluminum carbonate: basaljel o Hydroxide salt: alternaGEL o Combination products (aluminum and magnesium)  Gaviscon, Maalox, Mylanta, di-gel ALOH HCl H20 ALCL Antacids: Magnesium salts  Forms: carbonate, hydroxide, oxide, trisilicate  Commonly cause diarrhea; usually with other agents to counteract this effect  Dangerous when used with renal failure—the failing kidney cannot excrete extra magnesium, resulting in hypermagnesemia MgOH HCl H20 MgCl Examples: o Hydroxide salt: magnesium hydroxide (MOM) o Carbonate salt: gaviscon (also a combination product) o Combination products such as Maalox, Mylanta (aluminum and magnesium) Antacids: calcium salts  50 | P h a r m a c o l o g y      Forms: many, but carbonate is the most common May cause constipation Their use may result in kidney stones Long duration of acid action may cause increased gastric acid secretion (hyperacidity rebound) Often advertised as an extra source of dietary calcium o Example: Tums (calcium carbonate) CaCO HCl HCO3 CaCl Antacids: sodium bicarbonate  Highly soluble  Buffers the acidic properties of HCl  Quick onset, but short duration  May cause metabolic alkalosis  Sodium content may cause problems in patients with heart failure, hypertension, or renal insufficiency (fluid retention) NaHCO3 HCl H2CO3 H2O CO2 CaCl Antacids and antiflatulents  Antiflatulents: used to relieve the painful symptoms associated with gas  Several agents are used to bind or alter intestinal gas and are often added to antacid combination products  Over-the-counter antiflatulents o Activated charcoal o Simethicone  Alters elasticity of mucus-coated bubbles, causing them to break  Used often, but there are limited data to support effectiveness Antacids: side effects  Minimal and depend on the compound used o Aluminum and calcium  Constipation o Magnesium  Diarrhea o Calcium carbonate  Produces gas and belching; often combined with simethicone Antacids: drug interactions  Absorption of other drugs to antacids o Reduces the ability of the other drug to be absorbed into the body  Chelation 51 | P h a r m a c o l o g y o Chemical binding or inactivation of another drug o Produces insoluble complexes o Result: reduced drug absorption Antacids: nursing implications  Asses for allergies and preexisting conditions that may restrict the use of antacids such as: o Fluid imbalances o Renal disease o Heart failure o Pregnancy o GI obstruction  Patients with heart failure or hypertension should use low-sodium antacids such as riopan, Maalox, or Mylanta II  Monitor for side effects o Nausea, vomiting, abdominal pain, diarrhea o With calcium-containing products: constipation and rebound  Monitor for therapeutic response o Notify healthcare provider if syptoms are not relieved Histamine type 2 (H2) receptor antagonist  Reduce acid secretion  All available OTC in lower dosage forms  Most popular drug for treatment of acid-related disorders o Cimetidine (Tagamet) o Famotidine (Pepcid) o Ranitidine (Zantac) H2 antagonists: mechanism of action  Blocks histamine 2 (H2) at the receptors of acid-producing parietal cells  Production of hydrogen ions is reduced, resulting in decreased production of HCl H2 antagonists: indications  GERD  PUD  Erosive espphagitis  Adjunct therapy of upper GI bleeding  Pathologic gastric hypersecretory condition (Zollinger-Ellison syndrome) H2 antagonists: side effects  Overall, less than 3% incidence of side effects  Cimetidine may induce impotence and gynecomastia  May see o Lethargy, headaches, confusion, diarrhea, urticaria, sweating, flushing, and other effects H2 antagonists: nursing implications  Assess for allergies and impaired renal or liver function  Use with caution with patients who are confused, disoriented, or elderly (higher incidence of CNS side effects)  Take 1 hour before or after antacids  For intravenous doses, follow administration guidelines H2 antagonists: drug interactions  Smoking has been shown to decrease the effectives of H2 blockers o Increases gastric acid production Proton pump inhibitors  The parietal cells release positive hydrogen ions (protons) during HCl production  This process is called the proton pump  H2 blockers and antihistamines do not stop the action of this pump Proton pump inhibitors: mechanism of action  Irreversibly bind to H*/K* ATPase enzyme  Result: achlrohydria—all gastric acid secretion is blocked Proton pump inhibitors: indications  GERD maintenance therapy  Erosive esophagitis  Short-term treatment of active duodenal and benign gastric ulcers  Zollinger-Ellison syndrome  Treatment of H. pylori- induced ulcers Proton pump inhibitors: drug effects 52 | P h a r m a c o l o g y Total inhibition of gastric acid secretion o Lansoprazole (prevacid) o Omeprazole (prilosec)- the first in this new class of drugs o Rabeprazole (acipHex) o Pantoprazole (protonix) o Esomeprazole (Nexium) Proton pump inhibitors: nursing implications  Assess for allergies and history of liver diseases  Pantoprazole (protonix) is the only proton pump inhibitor available for for parenteral administration, and can be used for patients who are unable to take oral medications  May increase serum levels of diazepam, phenytoin, and cause increased chances for bleeding with warfarin  Instruct the patient taking omeprazole (prisolec): o It should be taken before meals o The capsule should be swallowed whole, not crushed, opened, or chewed o It may be given with antacids o Emphasize that the treatment will be short-term Proton pump inhibitors: side effects  Safe for short-term therapy  Incidence is low and uncommon Other drugs  Sucralfate (Carafate)  Misoprostol (Cytotec) Sucralfate (Carafate)  Cytoprotective agent  Used for ulcers, erosions, PUD  Attracted to and binds to the base of ulcers and erosions, forming a protective barrier over these areas.  Protects these areas from pepsin, which normally breaks down into proteins (making ulcers worse)  Little absorption from the gut  May cause constipation, nausea, and dry mouth  May impair absorption of other drugs, especially tetracycline  Binds with phosphate; may be used in chronic renal failure to reduce phosphate levels  Do not administer with other medications Misoprostol (cytotec)  Used for prevention of NSAID- induced gastric ulcers  Doses that are therapeutic enough to treat duodenal ulcers often produce abdominal cramps, diarrhea  Synthetic prostaglandin analog  Prostaglandins have cytoprotective activity o Protect gastric mucosa from injury by enhancing local production of mucus or bicarbonate o Promote local cell regeneration o Help to maintain mucosal blood flow Vomiting center and chemoreceptor trigger zone  VC and CTZ  Both located in the brain o Once stimulated, cause the vomiting reflex o Found in the medulla oblongata Definitions  Nausea- unpleasant feeling that often precedes vomiting  Emesis (vomiting)- forcible emptying of gastric and, occasionally, intestinal contents  Antiemetic agents- used to relieve nausea and vomiting Indications  Specific indications vary per class of antiemetics  General use: prevention and reduction of nausea and vomiting Mechanism of actions and indications  Many different mechanisms of action  Most work by blocking one of the vomiting pathways, thus blocking the stimulus that induces vomiting  Antihistamine agents (H1 receptor blockers) o Inhibit ACh by binding to H1 receptors o Prevent cholinergic stimulation in vestibular and reticular areas, thus preventing nausea and vomiting o Diphenhydramine (Benadryl), meclizine (antivert, promethazine (Phenergan) o Also used for nonproductive cough, allergy symptoms, and sedation  Anticholinergic agents (ACh blockers) o Binds to and blocks acetylcholine (ACh) receptors in the inner ear labyrinth  53 | P h a r m a c o l o g y o Block transmission of nauseating stimuli to the CTZ o Also block transmission of nauseating stimuli from the reticular formation to the VC o Scopolamine o Also used for motion sickness  Prokinetic agents o Block dopamine in the CTZ o Cause CTZ to be desensitized to impulses it receives from the GI tract o Also stimulates peristalsis in the GI tract, enhancing emptying of the stomach contents o Metoclopramide (reglan) o Also used for GERD, delayed gastric empting  Neuroleptic agents o Block dopamine receptors in the CTZ o Chlorpromazine (thorazine) o Prochlorperazine (compazine) o Also used for psychotic disorders, intractable hiccups  Tetrahydrocannabinoids (THC) o Major psychoactive substance in marijuana o Inhibitory effects on reticular formation, thalamus, and cerebral cortex o Alter mood and body’s perception of its surroundings o Dronabinol (marinol) o Used for nausea and vomiting associated with chemotherapy and anorexia associated with weight loss in AIDS patients  Serotonin blockers o Blocks serotonin receptors in the GI tract, CTZ, and VC o Dolaseltron (Anzemet), granisetron (kytril), ondansentron (Zofran) o Used for nausea and vomiting for patients receiving chemotherapy and postoperative nausea and vomiting Nursing implications  Assess complete nausea and vomiting history, including precipitating factors  Assess current medications  Assess for contraindications and potential drug interactions  Many of these agents cause severe drowsiness; warn patients about driving or performing hazardous tasks  Taking antiemetics with alcohol may cause severe CNS depression  Teach patients to change positions slowly to avoid hypotensive effects  For chemotherapy, antiemetics often give ½ to 3 hours before a chemotherapy agent  Monitor for therapeutic effects  Monitor for adverse effects Side effects  Vary according to agent used  Stem from their nonselective blockade of various receptors 54 | P h a r m a c o l o g y