Pharmacokinetic - The Study of What the Body Does to the Drug

Define the common terms used in pharmacology o Pharmacokinetic- the study of what the body does to the drug; involves the processes of absorption, distribution, metabolism, and excretion; the study of what happens to a drug from the time it is put into the body until the parent drug and all metabolites have left the body; represent the drug absorption into, distribution and metabolism within, and excretion from the body o Pharmacodynamics- the study of what the drug does to the body; involves drug– receptor relationships. o First-pass effect- initial metabolism in the liver of a drug absorbed from the GI tract before the drug reaches systemic circulation through the bloodstream; reduces the bioavaibility of less than 100%, whereas drugs administered by the intravenous route are 100% bioavailable o Bioavaibility- a measure of the extent of a drug absorption for a given drug and route (from 0% to 100%) o Protein-binding o Onset of action- time required for a drug to elicit a therapeutic response after dosings o Peak Effect – the time required for a drug to reach its max. therapeutic response o Duration of action- the length of time the concentration of a drug in the blood or tissues is sufficient to elict a response o Half-life – in pharmacokinetics, the time required for half of an administered dose of drug to be eliminated by the body, or the time it takes for the blood level of a drug to be reduced o Therapeutic index- ratio btwn toxic and therapeutic concentrations of a drug o Trough level- lowest blood level; the lowest concentration of a drug reached in the body after it falls from its peak level, usually measured in blood sample for therapeutic drug monitoring o Peak level- highest blood level; done usually at 12th level after 3rd dose; the max. concentration of a drug in the body after administration, usually measured in a blood sample for therapeutic drug monitoring o Agonist- drug that binds to and stimulates the activity of one or more receptors in the body o Antagonist- drug that binds to and inhibits the activity of one or more receptors in the body; also called inhibitors Type of therapy: o Acute therapy- often involves more intensive drug treatment and implemented in acutely ill (those with rapid onset of illness) or critically ill; often needed to sustain life or treat disease  Ex: vasopressors to maintain BP and cardiac output after open heart surgery  Ex: intensive chemotherapy for pt with newly diagnosed cancer o Maintenance therapy- doesn’t eradicate problems the pt may already have but will prevent progression of a disease or condition; used for treatment of chronic illnesses   Ex: HTN it will maintain the pt’s BP within given limits which prevents certain end-organ damage Ex: oral contraceptives for birth control o Supplemental therapy- or replacement therapy; supplies body with a substance needed to maintain normal function; substance may be needed bc it cannot be made by the body or bc it is produced in insufficient quantity  Ex: administration of insulin to diabetic pt’s  Ex: iron to pts w/ iron-deficiency anemia o Palliative therapy- make pt as comfortable as possible; focuses on providing pts w/ relief from symptoms, pain, and stress of a serious illness; goal is to improve quality of life for both pt and family; typically used in the end stages of an illness when attempts at curative therapy have failed; it can be provided along with curative treatment  Ex: use of high dose opioid analgesics to relieve pain in the final stages of cancer o Supportive therapy- maintains integrity of body functions while the pt is recovering from illness/trauma  Ex: provision of fluids and electrolytes to prevent dehydration in a pt w/ influenza who is vomiting and has diarrhea  Ex: administration of fluids, volume expanders, or blood products to a pt who lost blood during surgery o Prophylactic therapy- drug therapy provided to prevent illness or other undesirable outcome during planned events  Ex: preoperative antibiotic therapy for surgical procedures. Antibiotic given before incision is made so antibiotic can kill any potential pathogens  Ex: administration of disease-specific vaccines to individuals traveling to geographic areas where a given disease is known to be endemic o Empiric therapy- based on clinical probabilities; involves drug administration when certain pathologic condition has an uncertain but high likelihood of occurrence based on the pt’s initial presenting symptoms  Ex: use of antibiotics active against the organism most commonly associated with specific infection before results of C+S reports are available Drug interaction: o Additive effect- (1+1=2) when two drugs with similar actions are given together bc their additive effects so smaller doses of each drug can be given  Ex: combinations of analgesic products antihistamine and opioid combinations (promethazine and codeine) for treatment of cold symptoms  Ex: acetaminophen and opioid combinations (acetaminophen and oxycodone) for treatment of pain o Synergistic effect- when two drugs administered together interact in such a way that their combined effects are greater than the sum of the effects for each drug given alone (1+1 = greater than 2)  Ex: combination of hydrochlorothiazide with lisinopril for treatment of HTN o Antagonistic- occur when the combination of two drugs results in drug effects that are less than the sum of the effects for each drug given separetly (1+1 = less than 2)  Ex: antibiotic ciprofloxacin is given simultaneously with antacids, vitaminsm iron, or dairy products (these drugs reduce absorption of ciprofloxacin and lead to decreased effectiveness of the antibiotic) o Incompatibility- commonly used to describe parenteral drugs; occurs when two parenteral drugs or solutions are mixed together and result is chemical deterioration of one or both of the drugs or the formation of physical precipitate; combination of two such drugs usually produces a precipitate, haziness, or color change in the solution; before administering an IV med always inspect back for precipitate and if bag appears cloudy or visible flecks are seen it must be discarded and not given to pt.  Ex: combination of parenteral furosemide and heparin Adverse drug reaction (ADR)- any reaction to a drug that is unexpected and undesirable and occurs at therapeutic drug dosages; caused by processes inside pts body; may or may not be preventable; mild ADR usually doesn’t require change in pt’s drug therapy or other interventions; more severe ADR are likely to require changes to a pts drug regimen; Severe ADR can be permanently or significantly disabling, life threatening, or fatal o Pharmacologic reactions- extension of a drug’s normal effects in the body; predictable, well known ADR resulting in minor or no changes in pt management; have predictable frequency and intensity and occurrence is related to dose; usually resolve upon d/c of drug therapy  Ex: drug that used to lower BP in a pt causes pharmacologic adverse drug reaction when it lowers the BP to the point that the pt becomes unconscious o hypersensitivity reaction (allergic reaction)- pt’s immune system is involved; immune system proteins (immunoglobulins) recognize drug molecule (metabolites) or another ingredient in a drug formulation as dangerous foreign substance and an immune response can occur in which the immunoglobulin proteins bind to drug substance to attempt to neutralize drug; result in mild (skin erythema or mild rash) to life threatening reactions (constriction of bronchial airways and tachycardia) o idiosyncratic reaction- not the result of known pharmacologic property of a drug or of a pt allergy but occurs unexpectedly in particular pt; genetically determined abnormal response ot normal dosages of a drug Other Drug Effects o Teratogenic- result in structural defects in fetus; drugs capable of crossing the placenta causes drug induced teratogensis; drugs administered pregnancy can produce diff types of congenital anomalies; most vulnerable 3rd week of development till after 3rd mo. o Mutagenic- permanent changes in genetic composition of living organisms and consist of alterations in chromosome structure, the number of chromosomes, or genetic code DNA molecule; radiation, viruses, chemicals, and drugs can all act as mutagenic agents in humans; drugs that affect genetic processes are active primarily during cell reproduction (mitosis) o Carcinogenic- effects are cancer causing effects of drugs, chemicals, radiation, and viruses Chapter 3 Major drug related concern during the pregnancy and lactation o First trimester of pregnancy is generally period of greatest danger of drug-induced developmental defects. o Fetal gestational age is an important factor in determining potential for harmful drug effects to the fetus. o Maternal factors also play a role in determining drug effects on the fetus. Any change in mother’s physiology can affect the amount of drug to which the fetus may be exposed. Maternal kidney and liver function affect drug metabolism and excretion. Impairment in kidney or liver function can result in higher drug levels or prolonged drug exposure which leads to increased fetal transfer. o Avoid breastfeeding/pump and dump o Pregnancy Safety Categories CATEGORY Category A Category B Category C Category D Category X DESCRIPTION Studies indicate no risk to human fetus Studies indicate no risk to animal fetus; information for humans is not available Adverse effects reported in the animal fetus; information for humans is not available Possible fetal risk in humans has been reported; however, in selected cases consideration of potential benefit vs risk may warrant use of these drugs in pregnant women. Fetal abnormalities have been reported and positive evidence of fetal risk in humans is available from animal and/or human studies. These drugs are not o be used in pregnant women Pharmacokinetic change in the life span o Polypharmacy o Everything decreases as you age Chapter 7 What do we need to teach the patient about OTC medications and herb o OTC medications treats symptoms only o Herbs are not FDA regulated o Herbs are not considered medications Chapter 38 & 39, Major Concepts: Antiseptics- one of two types of topical antimicrobial agents; a chemical that inhibits the growth and reproduction of microorganisms without necessarily killing them; aka static agents Disinfectants- one of two types of topical antimicrobial agents; a chemical applied to nonliving objects to kill microorganisms; aka cidal agents Where Used Potency Activity against organisms Antiseptics Living Tissue Lower Primarily inhibits growth (bacteriostatic) Disinfectants Nonliving Objects Higher Kills (bactericidal) Subtherapeutic- generally refers to blood levels below therapeutic levels due to insufficient dosing. Also refers to antibioitic treatment that is ineffective in treating a given infection; possible causes include inappropriate drug therapy, insufficient drug dosing, and bacterial drug resistance Superinfection- 1. An infection occurring during antimicrobial treatment for another infection, resulting from overgrowth of an organism not susceptible to the antibiotic used. 2. A secondary microbial infection that occurs in addition to an earlier primary infection, often due to weakening of the pts immune system function by the first infection Empiric therapy- administration of antibiotics based on the practitioner’s judgment of the pathogens most likely to be causing an apparent infection; it involves the presumptive treatment of an infection to avoid treatment delay before specific culture information has been obtained Definite therapy- the administration of antibiotics based on known results of culture and sensitivity testing identifying the pathogen causing infection Prophylactic antibiotic therapy- antibiotics taken before anticipated exposure to an infectious organism in an effort to prevent the development of infection Bactericidal antibiotics- antibiotics that kill bacteria Bacteriostatic antibiotics- antibiotics that do not actually kill bacteria but inhibit their growth Community-associated infection- an infection that is acquired by persons who have not been hospitalized or hag a medical procedure recently Health care–associated infection- an infection that is acquired during the course of receiving treatment for another condition in a health care facility; infection is not present or incubating at the time of admission; aka nosocomial infection Pseudomembranous colitis- a potentially-necrotizing inflammatory bowel condition that is often associated with antibiotic therapy; often caused by the bacteria Clostridium difficile; a more general term is antibiotic associated colitis. Slow acetylation- a common genetic host factor in which the rate of metabolism of certain drugs is reduced Multidrug resistance Therapeutic drug monitoring- decrease in S/S of infection; return to normal VS; negative results on C+S tests; normal CBC results; improved appetite, energy level, sense of well-being. Minimum inhibitory concentration Peak and Trough level Post-antibiotic effect Major categories of medication: you will need to know the following for each of these category drugs: Mechanism of Action Implications Adverse effects Contraindications Interactions (both drug and food interactions) Nursing Implications (assessment, monitoring, administration and patient teaching) Chapter 38 Antibiotics Part I • • Sulfonamides “Sulf” ▪ Mechanism of Action- Bacteriostatic: prevents synthesis of folic acid which is needed for DNA. Does not affect human cells only bacterial cells ▪ Indications • Effective against both gram-positive and gram-negative bacteria • Treatment of UTIs caused by susceptible strains of: Enterobacter spp., Escherichia coli, Klebsiella spp., Proteus mirabilis, Proteus vulgaris, Staphylococcus aureus • Pneumocystis jirovecii pneumonia (PJP) o Co-trimoxazole • Upper respiratory tract infections • Sulfamethoxazole/trimethoprim is commonly used for outpatient Staphylococcus infections, due to the high rate of community-acquired MRSA infections ▪ Adverse effects- Hemolytic and aplastic anemia, agranulocytosis, thrombocytopenia, Photosensitivity, exfoliative dermatitis, Steven Johnson syndrome, epidermal necrolysis, Nausea, vomiting, diarrhea, pancreatitis, Hepatotoxicity, convulsions, crystalluria, toxic nephrosis, headache, peripheral neuritis, urticaria, cough ▪ Contraindications • Allergy to sulfonamides • Pregnant women • Infant younger than 2 months of age ▪ Interactions- Sulfonamides may potentiate the hypoglycemic effects of sulfonylureas in diabetes treatment, the toxic effects of phenytoin, and the anticoagulant effects of warfarin, which can lead to hemorrhage. Sulfonamides may increase the likelihood of cyclosporine-induced nephrotoxicity. Patients receiving any of the above drug combinations may require more frequent monitoring. Sulfonamides, and all antibiotics, may also reduce the efficacy of oral contraceptives. Instruct patients taking these drugs to use additional contraceptive methods. ▪ Nursing Implications • Take with 2000 to 3000 mL of fluid/24 hr • Assess RBCs prior to beginning therapy • Take oral doses with food Betalactam: • o Penicillins “cillin” ▪ Mechanism of Action- Penicillins enter the bacteria via the cell wall, bind to penicillin-binding protein- normal cell wall synthesis is disrupted. Result: bacteria cells die from cell lysis. Penicillins do not kill other cells in the body ▪ Indications- Prevention and treatment of infections caused by susceptible bacteria, such as: Gram-positive bacteria, including Streptococcus spp., Enterococcus spp., Staphylococcus spp. ▪ Adverse effects • Allergic reactions to the penicillins occur in 0.7% to 4% of treatment courses o Urticaria, pruritus, angioedema • Those allergic to penicillins have an increased risk of allergy to other betalactam antibiotics • Only those patients with a history of throat swelling or hives from penicillin should not receive cephalosporins • Common adverse effects- Nausea, vomiting, diarrhea, abdominal pain • Other adverse effects are less common ▪ Contraindications- known drug allergy ▪ Interactions • NSAIDs • Oral contraceptives • Warfarin • Others ▪ Nursing Implications • Take oral doses with water (not juices) as acidic fluids may nullify drug’s antibacterial action • Monitor patients taking penicillin for an allergic reaction for at least 30 minutes after administration o Cephalosprins “cef” “ceph” ▪ Mechanism of Action- bacteriocidal -> same as penicillin ▪ Indications▪ Adverse effects • Similar to penicillins- Mild diarrhea, abdominal cramps, rash, pruritus, redness, edema • Potential cross-sensitivity with penicillins if allergies exist ▪ Contraindications ▪ Interactions- alcohol, antacids, iron, oral contraceptives ▪ Nursing Implications • Assess for penicillin allergy; may have cross allergy • Give orally administered forms with food to decrease GI upset, even though this will delay absorption • Some of these drugs may cause a disulfiram (Antabuse)-like reaction when taken with alcohol Macrolides “thromycin” : Erythromycin/Azithromycin o Mechanism of Action ▪ Prevent protein synthesis within bacterial cells ▪ Considered bacteriostatic ▪ Bacteria will eventually die ▪ In high enough concentrations, may also be bactericidal • o Indications ▪ Strep infections- Streptococcus pyogenes (group A beta-hemolytic streptococci) ▪ Mild to moderate URI and LRI- Haemophilus influenzae ▪ Spirochetal infections- Syphilis and Lyme disease ▪ Gonorrhea, Chlamydia, Mycoplasma ▪ azithromycin and clarithromycin- Approved for Mycobacterium aviumintracellulare complex infection (opportunistic infection associated with HIV/AIDS) ▪ Clarithromycin- Recently approved for use in combination with omeprazole for treatment of active ulcer disease associated with Helicobacter pylori infection o Adverse effects ▪ GI effects, primarily with erythromycin- Nausea, vomiting, diarrhea, hepatotoxicity, flatulence, jaundice, anorexia ▪ Azithromycin and clarithromycin: fewer GI adverse effects, longer duration of action, better efficacy, better tissue penetration o Contraindications- known drug allergy o Interactions- These drugs are highly protein-bound and will cause severe interactions with other protein-bound drugs o Nursing Implications ▪ The absorption of oral erythromycin is enhanced when taken on an empty stomach, but because of the high incidence of GI upset, many drugs are taken after a meal or snack Tetracyclines “cycline” o Mechanism of Action- Bacteriostatic- Inhibit protein synthesis. Stop many essential functions of the bacteria. In high enough concentrations, may also be bactericidal o Indications- Wide spectrum ▪ Gram-negative and gram-positive organisms, protozoa, Mycoplasma, Rickettsia, Chlamydia, syphilis, Lyme disease, acne, others ▪ Demeclocycline is also used to treat SIADH by inhibiting the action of ADH o Adverse effects ▪ Strong affinity for calcium- Discoloration of permanent teeth and tooth enamel in fetuses and children, or nursing infants if taken by the mother ▪ May retard fetal skeletal development if taken during pregnancy ▪ Alteration in intestinal flora may result in: • Superinfection • Diarrhea • Pseudomembranous colitis • Vaginal candidiasis ▪ Other effects--photophobia o Contraindications- Should not be used in children under age 8 or in pregnant/lactating women because tooth discoloration will occur if the drug binds to the calcium in the teeth o Interactions ▪ Bind (chelate) to Ca+++ and Mg++ and Al+++ ions to form insoluble complexes ▪ Dairy products, antacids, and iron salts reduce oral absorption of tetracyclines o Nursing Implications ▪ Avoid milk products, iron preparations, antacids, and other dairy products because of the chelation and drug-binding that occurs ▪ Take all medications with 6 to 8 ounces of fluid, preferably water ▪ Because of photosensitivity, avoid sunlight and tanning beds Chapter 39 Antibiotics Part II • Aminoglycosides- end in “cin”: Gentamycin o Mechanism of Action: Bactericidal; prevent protein synthesis o Indications- Kill mostly gram-negative bacteria; some gram-positive ▪ Used to kill gram-negative bacteria, such as Pseudomonas spp., Escherichia coli, Proteus spp., Klebsiella spp., Serratia spp. ▪ Often used in combination with other antibiotics for synergistic effects ▪ Used for certain gram-positive infections that are resistant to other antibiotics ▪ Aminoglycosides are poorly absorbed through the GI tract, and given parenterally • Exception: neomycin o Given orally to decontaminate the GI tract before surgical procedures o Also used as an enema for this purpose o Used to treat hepatic encephalopathy o Adverse effects ▪ Ototoxicity and nephrotoxicity are the most significant ▪ Headache ▪ Paresthesia ▪ Fever ▪ Superinfections ▪ Vertigo ▪ Skin rash ▪ Dizziness o Contraindications- known drug allergies, pregnancy and lactation o Interactions- The risk for nephrotoxicity can be increased with concurrent use of other nephrotoxic drugs such as vancomycin, cyclosporine, and amphotericin B. Concurrent use with loop diuretics increases the risk for ototoxicity. In addition, because aminoglycosides, like many other antibiotics, kill intestinal bacterial flora, they also reduce the amount of vitamin K produced by these gut bacteria. These normal flora normally serve to balance the effects of oral anticoagulants such as warfarin (Coumadin). Therefore, aminoglycosides can potentiate warfarin toxicity. Concurrent use with neuromuscular blocking drugs may prolong the duration of action of the neuromuscular blockade. o Nursing Implications ▪ Assess baseline renal and auditory functioning ▪ Monitor drug levels ▪ Monitor BUN/Creatinine ▪ Assess potential drug interactions • Quinolones “floxacin”: ciprofloxacin ( Cipro)/ levofloxacin ( Levaquin) o Mechanism of Action- Bactericidal: Alter DNA of bacteria, causing death. Do not affect human DNA o Indications▪ Gram-negative bacteria such as Pseudomonas ▪ Complicated urinary tract, respiratory, bone and joint, GI, skin, and sexually transmitted infections ▪ Anthrax (ciproflaxin) o Adverse effects CNS Headache, dizziness, insomnia, depression, restlessness, convulsions GI Nausea, vomiting, diarrhea, constipation, thrush, increased liver function studies, others Cardiac Prolonged QT interval Integumentary Rash, pruritus, urticaria, flushing Other Ruptured tendons,* tendonitis,* fever, chills, blurred vision, tinnitus *Black box warning: Increased risk of tendonitis and tendon rupture o Contraindications- known drug allergy o Interactions ▪ Antacids, calcium, magnesium, iron, zinc preparations or sucralfate causes a reduction in the oral absorption of the quinolone. Patients need to take the interacting drugs at least 1 hour before or after taking quinolones. ▪ Dairy products also reduce the absorption of quinolones and should be separated as stated previously for interacting drugs. ▪ Enteral tube feedings can also reduce the absorption of quinolones. ▪ Oral anticoagulants are to be used with caution in patients receiving quinolones because of the antibiotic-induced alteration of the intestinal flora, which affects vitamin K synthesis. o Nursing Implications ▪ Monitor for cardiac dysrhythmias especially if the patients are taking antidysrhythmic medications ▪ Do not take with antacids, zinc, iron, multivitamins, calcium due to impaired absorption ▪ Monitor for joint pain and inflammation • Vancomycin (Vancocin) o Mechanism of Action o Indications ▪ Treatment of choice for MRSA and other gram-positive infections ▪ Oral vancomycin is indicated for the treatment of antibiotic-induced colitis (C. difficile) and for the treatment of staphylococcal enterocolitis o Adverse effects ▪ Ototoxicity ▪ Nephrotoxicity ▪ Red man syndrome may occur • Flushing/itching of head, neck, face, upper trunk • Antihistamine may be ordered to reduce these effects ▪ Additive neuromuscular blocking effects in patients receiving neuromuscular blockers ▪ Hypotension if infused too quickly (should be infused over 60 min) o Contraindications ▪ Known drug allergy ▪ Impaired renal function ▪ Impaired hearing ▪ Elderly and newborns o Interactions o Nursing Implications ▪ Must monitor blood levels to ensure therapeutic levels and prevent toxicity • • • • Clindamycin ( Cleocin) o Used for chronic bone infections, GU infections, intraabdominal infections, other serious infections o May cause pseudomembranous colitis (also known as antibiotic-associated colitis, Clostridium difficile diarrhea, or C. difficile infection) o Potential interaction with vecuronium Linezolid (Zyvox) o New class: oxazolidinones o Used to treat vancomycin-resistant Enterococcus faecium (VREF, VRE), hospitalacquired, and skin structure infections, including those with MRSA o May cause hypotension, serotonin syndrome if taken with SSRIs, and reactions if taken with tyramine-containing foods Metronidazole (Flagyl) o Used for anaerobic organisms o Intraabdominal and gynecologic infections o Protozoal infections o Several drug interactions Nitrofurantoin ( Microdantin) o Primarily used for urinary tract infections (UTIs) (E. coli, Staphylococcus aureus, Klebsiella spp., Enterobacter spp.) o Use carefully if renal function is impaired o Drug concentrates in the urine o May cause fatal hepatotoxicity Chapter 40 Antiviral Drugs • Antivirals (Non HIV) • Acyclovir (Zovirax) o Synthetic nucleoside analog o Used to suppress replication of HSV-1, HSV-2, VZV o Drug of choice for treatment of initial and recurrent episodes of these infections o Oral, topical, parenteral forms • Ganciclovir o Synthetic nucleoside analog o Used to treat infection with cytomegalovirus (CMV) o Oral, parenteral forms o CMV retinitis o Ophthalmic form surgically implanted (Vitrasert) o Bone marrow toxicity • Oseltamivir (Tamiflu) Zannamivir ( Relenza) • Active against influenza types A and B • Reduce duration of illness • Oseltamivir: causes nausea and vomiting • Zanamivir: causes diarrhea, nausea, sinusitis • Treatment should begin within 2 days of influenza symptom onset • Antiretrovirus (HIV) o Zidovudine Zidovudine (Retrovir), also known as azidothymidine or AZT, is a synthetic nucleoside analogue of thymidine that has had an enormous impact on the treatment and quality of life of patients who have AIDS. It was the very first and, for a long time, the only anti-HIV medication. Zidovudine, along with various other antiretroviral drugs, is given to HIV-infected pregnant women and even to newborn babies to prevent maternal transmission of the virus to the infant. Chapter 41 Antitubercular Drugs • • • • Isoniazid o Drug of choice for TB o Resistant strains of Mycobacterium emerging o Metabolized in the liver through acetylation—watch for “slow acetylators” o Used alone or in combination with other drugs o Contraindicated with liver disease o Adverse effects: Peripheral neuropathy, hepatotoxicity o Perform liver function studies in patients (especially in elderly patients or those who use alcohol daily) o Pyridoxine may be needed to combat neurologic adverse effects associated with INH therapy Rifampin o Adverse effects: Hepatitis; discoloration of urine, stools, and other body fluids o Perform liver function studies in patients (especially in elderly patients or those who use alcohol daily) o Rifampin causes oral contraceptives to become ineffective; another form of birth control will be needed o Patients who are taking rifampin should be told that their urine, stool, saliva, sputum, sweat, or tears may become reddish orange; even contact lenses may be stained MDR/MDX-TB o Prevention of the development of multidrug-resistant (MDR-TB) o Perform drug-susceptibility testing on the first Mycobacterium spp. that is isolated from a patient specimen o Begin a regimen with multiple antitubercular drugs (to reduce chances of development of resistance) Adjust drug regimen once the results of susceptibility testing are known o Monitor patient compliance closely during therapy Nursing Implications: o Obtain a thorough medical history and assessment o Perform liver function studies in patients who are to receive INH or rifampin (especially in elderly patients or those who use alcohol daily) o Assess for contraindications to the various drugs, conditions for cautious use, and potential drug interactions o Patient education is critical o Therapy may last for up to 24 months o Take medications exactly as ordered, at the same time every day o Emphasize the importance of strict adherence to regimen for improvement of condition or cure o Remind patients that they are contagious during the initial period of their illness—instruct in proper hygiene and prevention of the spread of infected droplets o Teach patients to take care of themselves, including adequate nutrition and rest o Patients should not consume alcohol while on these medications or take other medications, including over-the-counter medications, unless they check with their prescriber o Oral preparations may be given with meals to reduce gastrointestinal upset, even though recommendations are to take them 1 hour before or 2 hours after meals o Monitor for adverse effects o Instruct patients on the adverse effects o These include fatigue, nausea, vomiting, numbness and tingling of the extremities, fever, loss of appetite, depression, jaundice o Monitor for therapeutic effects o Decrease in symptoms of TB, such as cough and fever o Lab studies (culture and sensitivity tests) and chest x-ray should confirm clinical findings o Watch for lack of clinical response to therapy, indicating possible drug resistance Chapter 42 Antifungal Drugs • Amphotericin B o Mechanism of Action- Bind to sterols in cell membrane lining. Result: fungal cell death. Do not bind to human cell membranes or kill human cells o Contraindications ▪ Liver failure ▪ Renal failure ▪ Drug allergy o Adverse effects ▪ Cardiac dysrhythmias ▪ Neurotoxicity; tinnitus; visual disturbances; hand or feet numbness, tingling, or pain; convulsions ▪ Renal toxicity, potassium loss, hypomagnesemia ▪ Pulmonary infiltrates ▪ Fever, chills, headache, nausea, occasional hypotension, gastrointestinal upset, anemia o Nursing implications ▪ To reduce the severity of the infusion-related reactions, pretreatment with an antipyretic (acetaminophen), antihistamines, antiemetics, and corticosteroids may be given ▪ Use IV infusion pumps and the most distal veins possible ▪ Follow manufacturer’s directions carefully for reconstitution and administration ▪ Monitor vital signs of patients receiving IV infusions every 15 to 30 minutes ▪ During IV infusions, monitor I&O to identify adverse effects ▪ • Fluconazole o Mechanism of Action- Inhibit fungal cell cytochrome P-450 enzymes, resulting in cell membrane leaking. Result: altered cellular metabolism and fungal cell death o Adverse effects ▪ Nausea, vomiting, diarrhea, stomach pain, ▪ Increased liver enzymes ▪ Use with caution in patients with renal and liver dysfunction o Contraindications ▪ Liver failure ▪ Renal failure ▪ Drug allergy o Interactions-Many antifungal drugs are metabolized by the cytochrome P-450 enzyme system. Coadministration of two drugs that are metabolized by this system may result in competition for these enzymes, and thus higher levels of one of the drugs Nystatin o Adverse effects:  Nausea  Vomiting  Anorexia  Diarrhea  Rash o Nursing Implications:  Nystatin given as an oral lozenge or troche should be slowly and completely dissolved in the mouth (not chewed or swallowed whole)  Nystatin suspension should be swished thoroughly in the mouth as long as possible before swallowing  Monitor for therapeutic effects Easing of symptoms of infection Improved energy levels Normal vital signs, including temperature  Monitor carefully for adverse effects Chapter 45, 46 (focusing on nursing implications relate to the toxicity) Antimetabolite: methotrexate (MTX) Mechanism of action o Antimetabolites: Folic acid antagonism- Interferes with the use of folic acid as a result, DNA is not produced, and the cell dies Indications o Used in combination with other drugs to treat various types of cancer, such as solid tumors and some hematologic cancers  Acute and chronic lymphocytic leukemias  Leukemias (several types)  Colon, rectal, breast, stomach, lung, pancreatic cancers o Methotrexate is also used to treat severe cases of psoriasis and rheumatoid arthritis Adverse effects o Hair loss, nausea and vomiting, myelosuppression o Neurologic, cardiovascular, pulmonary, hepatobiliary, GI, genitourinary, dermatologic, ocular, ottic, and metabolic toxicity o Tumor lysis syndrome o Palmar-plantar dysesthesia (also called hand-foot syndrome), Stevens-Johnson syndrome, toxic epidermal necrolysis Antidote o Leucovorin “rescue” is prescribed to reduce the bone marrow suppression that is associated with high-dose methotrexate therapy. Alkylating drugs (cisplatin) Mechanism of action o Work by preventing cancer cells from reproducing o Alter the chemical structure of the cells’ deoxyribonucleic acid (DNA) o Bifunctional or polyfunctional Indications- Used in combination with other drugs to treat various types of cancer o Recurrent ovarian cancer o Brain tumors o Lymphomas o Leukemias o Breast cancer o Bladder cancer o Others Adverse effects o Dose-limiting adverse effects  Nausea and vomiting, myelosuppression o Alopecia o Nephrotoxicity, peripheral neuropathy, ototoxicity o Hydration can prevent nephrotoxicity o Extravasation causes tissue damage and necrosis Nursing implications o Monitor for expected effects of bone marrow suppression o Expect nausea, vomiting, diarrhea, stomatitis o Hydration is important to prevent nephrotoxicity o Report ringing/roaring in the ears—possible ototoxicity o Report tingling, numbness, or pain in extremities— peripheral neuropathies may occur Cytotoxic antibiotics (doxorubicin) Mechanism of action o Natural substances produced by the mold Streptomyces o Synthetic substances also used o Used to treat cancer; too toxic to treat infections o CCNS drugs are active in all phases of the cell cycle o Act by intercalation, resulting in blockade of DNA synthesis Indications o Used in combination chemotherapy regimens o Used to treat a variety of solid tumors and some hematologic malignancies o Leukemia, ovarian, breast, bone, others o Squamous cell carcinomas o AIDS-related Kaposi’s sarcoma (when intolerant to other treatments) Adverse effects o All can produce bone marrow suppression, except bleomycin o Hair loss, nausea and vomiting, myelosuppression o Heart failure (daunorubicin) o Acute left ventricular failure (doxorubicin) o Pulmonary fibrosis and pneumonitis (bleomycin) o Liver, kidney, and cardiovascular toxicities o Many others o Cardiomyopathy is associated with large amounts of doxorubicin  Routine monitoring of cardiac ejection fraction with multiple-gated acquisition (MUGA) scans  Cumulative dose limitations  Cytoprotective drugs such as dexrazoxane can decrease the incidence of this devastating toxicity Nursing Implications o Expect bone marrow suppression, nausea, vomiting, diarrhea, stomatitis o Monitor pulmonary status, since pulmonary fibrosis may occur o Monitor for nephrotoxicity, liver toxicity o Monitor cardiovascular status o Daunorubicin may turn the urine a reddish color Chemotherapy Common adverse effect o Hair loss, nausea and vomiting, myelosuppression o Neurologic, cardiovascular, pulmonary, hepatobiliary, GI, genitourinary, dermatologic, ocular, otic, and metabolic toxicity o Tumor lysis syndrome o Palmar-plantar dysesthesia (also called hand-foot syndrome), Stevens-Johnson syndrome, toxic epidermal necrolysis o Hair loss, nausea and vomiting, myelosuppression o Liver, kidney, lung toxicities o Convulsions o Extravasation  Leaking of an antineoplastic drug into surrounding tissues during IV administration  Can result in permanent damage to nerves, tendons, muscles; loss of limbs  Skin grafting or amputation may be necessary  Several specific antidotes can be used  Prevention is essential  Continuous monitoring of the IV site is essential  If suspected, stop the infusion immediately and contact the prescriber, but leave the intravenous catheter in place  Aspirate any residual drug and/or blood from the catheter  Consult guidelines or the pharmacist regarding antidotes, application of hot or cold packs and/or sterile occlusive dressings, and elevation and rest of the affected limb  Thoroughly document the extravasation incident  Consult facility protocol and guidelines Nursing implication o Assess baseline blood counts before administering antineoplastic drugs o Follow specific administration guidelines for each antineoplastic drug o Remember that all rapidly dividing cells (both normal and cancer cells) are affected  Mucous membranes  Hair follicles  Bone marrow component o Monitor for effects on these tissues or complications o Monitor for complications  GI mucous membranes: stomatitis, altered bowel function with high risk for poor appetite, nausea, vomiting, diarrhea, and inflammation and possible ulcerations of GI mucosa  Hair follicles: loss of hair (alopecia)  Bone marrow components: dangerously low (life-threatening) blood cell counts o Monitor for adverse effects specific to the type of antineoplastic drug given o Implement measures to monitor for and prevent infection in patients with neutropenia or leukopenia o Implement measures to monitor for and prevent bleeding in patients with thrombocytopenia and anemia o Keep in mind that anemia may result in severe fatigue o Monitor for stomatitis (oral inflammation and ulcerations), and implement measures to reduce the effects if it occurs o Anticipate nausea and vomiting, and implement measures to reduce these effects o Antiemetics often work better if given 30 to 60 minutes before chemotherapy is started o Women of childbearing age will need to use a nondrug form of contraception during therapy o In addition to physical measures, keep in mind the need for emotional support during this time for both the patient and family o Monitor for therapeutic responses to antineoplastic therapies and the many possible adverse effects o Monitor closely for anaphylactic reactions  Keep epinephrine, antihistamines, and antiinflammatory drugs on hand o Monitor closely for complications associated with bone marrow suppression  Anemia, thrombocytopenia, neutropenia o Cytoprotective drugs may be used to reduce toxicities  IV amifostine to reduce renal toxicity associated with cisplatin  IV or PO allopurinol to reduce hyperuricemia o Monitor for oncologic emergencies         Infections Pulmonary toxicity Allergic reactions Stomatitis with severe ulcerations Bleeding Metabolic aberrations Bowel irritability with diarrhea Renal, liver, cardiac toxicity Bleomycin? Cant find this one on the ppt Please use this study guide as a reference only. Reading the book, PPTs and Quia games are important for the exam. There are about 50 questions in the first exam with 200 points. The test questions may not be limited in this study guide.