Exam 1 Review Guide Pharmacology Part 2

9 Quiz 3 17. EPS and drugs that cause them a. EPS (extrapyramidal symptoms) i. Serious movement disorders ii. Symptoms 1. Acute dystonia: involuntary muscle contractions that may cause repetitive twisting movements. 2. Oculogyric crisis: prolonged upward deviation of the eyes. 3. Opisthotonos: Muscle spasm causing a backward arching of the head, neck, and spine. 4. Joint dislocation 5. Impaired respiration 6. Anticholinergic medications (benztropine and diphenhydramine): May further complicate by causing dry mouth, blurred vision, photophobia, urinary hesitancy, constipation, and tachycardia. 7. Early a) Rigid muscles b) Fever c) Drowsiness d) Confusion e) Seizures 8. Late a) Tardive dyskinesia b) Gait changes, jerky movements, or shrugging b. Drugs that cause them i. Taking first or second generation antipsychotic drugs that antagonize dopamine receptors. ii. Most common: Chlorpromazine (low potency), Haloperidol (high potency) and fluphenazine c. Strategies and treatments for EPS i. Strategies 1. Stop the causing agent immediately. ii. Treatments 1. Benzodiazepines 2. Beta blockers 3. Anticholinergic drugs 18. Tardive dyskinesia as an adverse effect of meds 10 a. Tardive dyskinesia i. Choreoathetoid movements of the tongue and face ii. Lip-smacking movements iii. Tongue flicks out in a “fly-catching” motion iv. Slow, worm-like movement of the tongue v. Involuntary movements of the limbs, toes, fingers, and trunk b. Side effect of first generation (typical) antipsychotic medications 19. Parkinsonism as an adverse effect of meds a. Parkinsonism (medication-caused Parkinson symptoms) i. Bradykinesia (slow movements) ii. Mask-like facies iii. Drooling iv. Tremor v. Rigidity vi. Shuffling gait vii. Cogwheeling (rigidity and tremor at same time) viii. Stooped posture b. Meds that have this as an adverse effect i. First generation antipsychotics 1. High potency agents a) Fluphenazine c. Primary treatment for this type of parkinsonism is to wean off the offending medication, if possible. 20. Atypical antipsychotic drug administration, time frames, reasons for a. Atypical antipsychotics i. Second generation antipsychotics (SGAs) ii. Patient with PD should take these instead of FGAs because they produce only moderate blockage of dopamine receptors, stronger blockade for serotonin. iii. Less risk of EPS than FGAs/Typical antipsychotics iv. Increased risk of weight gain, diabetes, and dyslipidemia b. Drug administration i. Intramuscular and oral ii. Adherence 1. Withdrawal syndrome a) Wean off/taper off slowly. b) Consult with physician first! 2. Adherence should be assessed before increasing dosage, switching to as different antipsychotic, or prescribing additional medication. c. Time frames i. Takes a few days to start working, takes a few weeks to take full therapeutic effect d. Reasons for use i. Bipolar disorder ii. BPD iii. Schizophrenia iv. Major Depressive Disorder 21. Review therapy discontinuation for depression a. Depression i. Caused by functional insufficiency of monoamine neurotransmitters ii. Main treatment is pharmacotherapy, can also be treated with psychotherapy (CBT and interpersonal psychotherapy), ECT, and transcranial magnetic stimulation 1. ECT a) When drugs and psychotherapy have not worked b) Rapid response is needed 11 c) d) e) f) Severely depressed patients Suicidal patients Elderly patient at risk of starving Targets frontal lobe which is responsible for personality and character b. Meds i. Fluoxetine (antidepressant, SSRI) ii. Mechanism of action: selective inhibition of serotonin reuptake (SSRI), makes more serotonin available at synapse. iii. Adverse effects 1. Serotonin syndrome 2. Insomnia 3. Withdrawal syndrome (don’t stop abruptly, taper off slowly) 4. Teratogenesis (only drug safe for breast feeding is sertraline/Zoloft) 5. EPS 6. Bruxism (clenching/grinding teeth) 7. Bleeding disorders 8. Sexual dysfunctions 9. Weight gain 10. Hyponatremia 11. Suicidal tendencies 12. Mood/behavior changes c. Discontinuation i. Taper off slowly to avoid withdrawal syndrome 22. Lithium therapy (blood testing, therapeutic levels, toxicity levels, side effects) a. Class: Mood-stabilizer b. Mechanism of action i. Lithium excretion will be reduced with decreased sodium, neurotrophic, neuroprotective. Short half-life. Normalizes mood fluctuations. c. Therapeutic uses i. BPD ii. Alcoholism iii. Bulimia iv. Schizophrenia v. Glucocorticoid-induced psychosis d. Long-term maintenance i. Blood level check and kidney function tests throughout therapy. e. Blood testing i. Should be done every 2-3 days at initiation the drug therapy, then every 3-6 months while on the medication. f. Therapeutic levels i. 0.8-1.4 mEq/L ii. Takes a few days to kick in, takes a few weeks to take full therapeutic effect. g. Toxicity levels i. 1.5 mEq/L and above ii. Lithium excretion will be reduced with decreased sodium, if kidneys are not excreting the lithium properly, toxicity will occur. Therefore, kidney functions need to be tested frequently. h. Side effects/Adverse effects at therapeutic level i. Leukocytes increased, tremors, hypothyroidism and goiter, increased urine, moms beware (teratogenesis) ii. GI effects iii. Renal toxicity 12 i. Teaching i. Interacts with diuretics, NSAIDs, anticholinergic drugs 23. BPD patients on Lithium and adjunct meds for mania/depression a. BPD (Bipolar Disorder, formerly known as manic-depressive illness) i. Treated by mood stabilizers (lithium), antipsychotics, antidepressants ii. Mainstays of therapy are lithium and valproic acid 1. Valproic acid: take it with food to protect against GI effects. iii. Lifelong treatment iv. Cause may be disruption of neuronal growth and survival v. Recurrent fluctuations in mood vi. Episodes of mania and depression persist for months without treatment vii. Mood stabilizers (lithium, divalproex sodium, and carbamazepine) 1. Relieve symptoms during manic and depressive episodes 2. Prevent recurrence of manic and depressive episodes 3. Do not worsen symptoms of mania or depression; do not accelerate the rate of cycling. b. Adjunct meds for mania/depression i. Many patients also receive antipsychotic ii. Antipsychotics 1. Given during sever manic episodes iii. Antidepressants 1. Given during depressive episodes c. Drug selection i. Short term for manic episodes: lithium and valproate ii. Short term for depressive episodes: lithium or valproate, bupropion, venlafaxine, or SSRI iii. Long term preventative treatment: antipsychotic agents d. Promoting adherence i. Short-term hospitalization ii. Long-term prophylactic therapy iii. Education for both patient and family 24. Review Paroxetine (class, mechanism of action, adverse effects, teaching, administration/withdrawal, etc) as it relates to anxiety disorder. a. Class: Antipsychotic, SSRI, antidepressant b. Mechanism of action: affects serotonin levels, inhibits neuron reuptake of serotonin, short term and long term use. c. Indications i. Major depression ii. OCD Social Phobia iii. Panic disorder iv. Generalized anxiety v. PTSD vi. Premenstrual dysphoric disorder vii. Postmenopausal vasomotor symptoms d. Adverse effects i. Headache ii. Nervousness iii. Insomnia iv. Drowsiness/dizziness v. Anxiety vi. Tremor vii. Fatigue 13 e. f. g. 25. SSRIs a. viii. GI upset ix. Sedation x. Sweating xi. Visual changes Teaching i. Therapeutic effect may take 1-4 weeks ii. Caution with heavy machinery (driving is a no!) iii. No alcohol iv. Do not discontinue abruptly or without consulting doctor. Admin/withdrawal i. Taper gradually over 1-2 to avoid withdrawal syndrome Acute stages (short term) of anxiety can be treated with Benzodiazepines. (IV is immediate) i. Buspirone can be used for long term treatment! Do not cause hypotension, sedation, or anticholinergic effects (xerostomia, blurred vision, dry eyes, constipation, urinary retention, postural hypotension, cognitive problems/confusion, heart dysrhythmias) b. Fluoxetine most widely prescribed SSRI in world. c. Withdrawal SLOWLY d. Overdose does not cause cardiac toxicity. e. Death by overdose is extremely rare. f. Produce CNS excitation i. Since alcohol is an antidepressant, do not drink alcohol with SSRIs (stimulant/excitant). Will have a counter effect on the body. SSRI will become ineffective. g. Drug interactions: MAOIs!! 26. Sertraline (Zoloft) and nursing infants a. Sertraline i. Blocks reuptake of serotonin and dopamine ii. CNS stimulation iii. Minimal effects on seizure threshold (doesn’t affect whether a patient will have a seizure or not) iv. Therapeutic uses 1. Major depression 2. Panic disorder 3. OCD 4. PTSD 5. Premenstrual dysphoric disorder 6. Social anxiety disorder v. Side effects 1. Headache 2. Nausea 3. Tremor 4. Diarrhea 5. Insomnia 6. Weight gain 7. Agitation 8. Sexual dysfunction 9. Neonatal abstinence syndrome and persistent pulmonary hypertension of the newborn when using during late pregnancy 10. Nervousness vi. Drug interactions 1. MAOIs 14 2. Pimozide b. Breastfeeding i. Only type of antidepressant that is safe for a nursing mother to use because it is safe for the baby. 27. Duloxetine (Cymbalta) and alcohol abuse a. Duloxetine i. SNRI 1. Inhibits serotonin and norepinephrine reuptake 2. Similar to SSRI side effects (8 S’s) a) Sleep disturbance b) Sexual dysfunction c) Stomach upset d) Size increase (weight gain) e) Serotonin syndrome f) Sleep difficulties (insomnia) g) Suicidal ideations h) Stress (agitation, anxiety) 3. SNRI side effects (SHAAT) a) Same as SSRI b) Hypertension c) Adrenergic (awake) d) Anxious, agitated e) Tachycardia 4. Food reduces rate of absorption b. Alcohol abuse i. Do not use alcohol! ii. Used with alcohol can affect the quality of sleep, could contribute to worsening depression. iii. Long-term heavy alcohol abuse can cause antidepressant to be less effective 28. Amitriptyline overdose, side effects (other TCAs) a. TCAs (Tricyclic Antidepressants) i. Antidepressants ii. Block reuptake of norepinephrine and serotonin in the synaptic space, thereby intensifying the effects of these neurotransmitters iii. May take up 10-14 days for TCAs to begin to work, maximum effects might not be seen until 4-8 weeks. b. Amitriptyline overdose i. Resulting in cholinergic blockade and cardiac toxicity evidence by 1. Coma 2. Respiratory depression 3. Tachycardia 4. Sodium channel blockade 5. Prolonged QRS complex 6. Dysrhythmias 7. Mental confusion 8. Agitation 9. Seizures 10. Possible death ii. Nursing actions 1. Obtain baseline EKG 2. Monitor vitals frequently 3. Monitor manifestations of toxicity 15 4. Notify provider if manifestations occur Side effects (TCA’S) i. Thrombocytopenia ii. Cardiac (arrythmias, MI, Stroke) iii. Anticholinergic effects (tachycardia, urine retention) iv. Seizures d. Contraindication i. Do not take within 14 days of MAOIs e. Drug/Drug interactions i. CNS depressants ii. Alcohol iii. Hypnotics iv. Barbiturates v. Sedatives potentiate CNS depression 29. MAOI’s and tyramine a. MAOIs i. Second or third drug choice for antidepressants for most patients ii. Drug of choice for atypical depression iii. Convert monoamine neurotransmitters (NE, serotonin, and dopamine) into inactive products iv. Affected by antidepressants v. Act on MAO in 2 ways 1. Reversible (lasts 3-5 days) 2. Irreversible (lasts about 2 weeks) vi. All MAOIs in current use cause irreversible inhibition vii. Therapeutic uses 1. Depression 2. Bulimia nervosa 3. Agoraphobia (type of anxiety- avoid places or situations that might cause panic) 4. Attention-deficit/hyperactivity disorder 5. OCD 6. Panic attacks viii. Adverse effects 1. CNS stimulation 2. Orthostatic hypotension 3. Hypertensive crisis from dietary tyramine ix. Drug interactions 1. Antidepressants (TCAs and SSRIs) 2. Antihypertensives 3. Meperidine x. Administer 1. Orally only! b. Tyramine i. Foods 1. Aged cheese 2. Chocolate 3. Red meat 4. Cured/smoked meat 5. Salami 6. Fish 7. Soy sauce 8. Red wine c. 16 9. Beer 10. Sauerkraut ii. Hypertensive crisis 1. Severe headache 2. Tachycardia 3. Hypertension 4. N/V 5. Confusion 6. Profuse sweating 7. Stroke 8. Death 30. Benzodiazepines and alcohol withdrawal a. Benzodiazepines i. Diazepam (Valium) ii. Lorazepam and alprazolam iii. Lower potential for abuse iv. Produce less tolerance and physical dependence v. Promote sleep and reduce anxiety vi. Fewer drug interactions and adverse effects are rare vii. May cause withdrawal syndrome if stopped abruptly viii. Therapeutic uses 1. Anxiety 2. Insomnia 3. Seizure disorders 4. Muscle spasm 5. Alcohol withdrawal 6. Perioperative applications ix. Adverse effects 1. CNS depression 2. Anterograde amnesia 3. Sleep driving 4. Paradoxical effects (opposite of intended purpose, opposite of calm) 5. Respiratory depression 6. Abuse 7. Use in pregnancy and lactation b. Alcohol withdrawal i. Symptoms of alcohol withdrawal may occur within 2-72 hours 1. Headache 2. Nausea 3. Tremors 4. Anxiety 5. Hallucinations 6. Seizures ii. Medication to treat physical symptoms iii. Counseling and support groups help with controlling behavior iv. Diazepam and other benzodiazepines may be administered to ease withdrawal from alcohol. Benefits derive from cross-dependence with alcohol, which enables benzodiazepines to suppress symptoms brought on by alcohol abstinence. 31. Diazepam (Valium) for status epilepticus (seizures) a. Diazepam i. Anxiolytics/hypnotics; Benzodiazepines-GABA ii. Side effects/adverse effects (COWARD MARE) 17 1. Confusion 2. Over-sedation 3. Withdrawal symptoms 4. Addiction, amnesia, ataxia 5. Rebound effect 6. Drug abuse, dizziness, drowsiness 7. Memory loss 8. Amnesia 9. Respiratory depression 10. Euphoria iii. Mechanism of action 1. Modulates postsynaptic effects of GABA-A transmission, to increase presynaptic inhibition 2. Appears to act on part of the limbic system, as well as on the thalamus, hypothalamus, to induce a calming effect. b. Status epilepticus (seizures) i. Management of generalized convulsive status epilepticus 1. Continuous series of tonic-clonic seizures that last 20-30 minutes 2. Goals of treatment a) Maintain ventilation b) Correct hypoglycemia c) Terminate seizures i. Benzodiazepine lorazepam is recommended for first-line management. ii. Diazepam may be used if lorazepam is not readily available. d) Initiate or continue long-term suppression drugs such as phenytoin or Fosphenytoin 3. Benzo’s can be given for epileptic episodes to break the seizure. 32. Alprazolam therapy and anxiety a. Anxiety i. Psychologic and physical components, characterized by fear, apprehension, dread, and uneasiness. ii. Types 1. Generalized anxiety disorder 2. Panic disorder 3. OCD 4. Social anxiety disorder (social phobia) 5. PTSD b. Alprazolam therapy i. Benzodiazepine, CNS depressant, reduce anxiety ii. With prolonged use, tolerance develops to some effects but not others iii. Can cause physical dependence but the incidence of substantial dependence is low iv. Withdrawal=taper off slowly v. Reduces anxiety and promotes sleep 33. Treatment of anxiety patients with sedative/hypnotics a. Sedative/hypnotics i. Drugs that depress CNS function ii. Used to treat anxiety and insomnia iii. Antianxiety agents or anxiolytics iv. Distinction between antianxiety effects and hypnotic effects is often a matter of dosage v. Medications 1. Benzodiazepines (reduce anxiety and promote sleep) 18 34. 35. 36. 37. 2. Benzodiazepine-like drugs 3. Barbiturates vi. Drug of choice for insomnia and anxiety 1. Benzodiazepines and benzodiazepine receptor agents 2. Most familiar: Diazepam (valium) 3. Most prescribed: Lorazepam and alprazolam Neuroleptics and PD patients a. Neuroleptics i. Block antiemetic action ii. First generation (typical) antipsychotics 1. Block receptors for dopamine in the striatum and decrease therapeutic effects of levodopa b. Parkinson’s Disease i. Interacts with levodopa and can cause hypertensive crisis if administered to an individual taking a nonselective MAO inhibitor. Neuroleptic malignant syndrome (signs, causing meds and treatment) a. Signs i. “Lead pipe” rigidity ii. Sudden high fever iii. Sweating iv. Autonomic instability v. Dysrhythmias vi. Fluctuations in blood pressure vii. Altered level of consciousness viii. Seizures or coma may develop b. Causing meds i. Typical antipsychotics (block dopamine, make muscles stiff, can cause stiffness in people with Parkinson’s Disease. (for PD, use second generation drugs to avoid this) 1. Haloperidol 2. Fluphenazine 3. Chlorpromazine 4. Trifluoperazine 5. Prochlorperazine c. Treatment i. Risk of death without treatment due to cardiovascular collapse & dysrhythmias ii. Stop causing agent immediately! iii. Drugs that relax tight muscles (dantrolene), PD drugs that make the body produce more dopamine (amantadine or bromocriptine) Lamotrigine indications, adverse effects, etc. a. Lamotrigine (Lamictal) b. Indications i. Broad spectrum antiseizure activity, Epilepsy ii. Bipolar disorder to delay the time to occurrence of mood episodes in adults, help prevent low mood. c. Adverse effects i. Dizziness, diplopia, blurred vision, N/V, headache ii. Severe skin reactions iii. Aseptic meningitis iv. Risk for suicide Lisdexamfetamine adverse effects a. Lisdexamfetamine i. Amphetamines 19 1. 2. 3. 4. 5. Pharmacologic effects a) CNS b) Cardiovascular system Bronchospasm side effects Tolerance a) With regular use, tolerance develops to elevation of mood, suppression of appetite, and stimulation of the heart and blood vessels. Physical dependence a) Abstinence syndrome with abrupt withdrawal Abuse a) High potential for abuse due to euphoric effect b. Adverse effects i. CNS stimulation ii. Weight loss iii. Cardiovascular effects iv. Psychosis 38. Antidotes to common meds... (you should really memorizes all 4 I mentioned in lecture) a. Benzodiazepine overdose = flumazenil b. Phenobarbital (no antidote) but give charcoal to absorb c. Anticholinergics = physostigmine d. Beta blockers = glucagon e. Warfarin = vitamin K Phenobarbital -Barbeque- needs charcoal f. Digoxin = digoxin immune Fab (digibind) Benzodiazepine -Ben has the flu- Flumazenil g. Heparin = protamine sulfate h. Methotrexate = leucovorin Opioids -Nah I can’t open it- Narcan i. Opioids = Narcan Acetaminophen -Ace went to the “Cysteine” Chapel- Acetylcysteine j. Acetaminophen overdose = acetylcysteine Heparin—protamine 39. Drug metabolizing and eliminating organs a. Drug metabolizing (also known as biotransformation) i. Enzymatic alteration of drug structure ii. Most often takes place in the liver iii. Hepatic drug-metabolizing enzymes 1. Most drug-metabolism that takes place in liver is performed by the hepatic microsomal enzyme system, which is known as P450 system. 2. Metabolism does not always result in a smaller molecule. iv. Therapeutic consequences 1. Accelerated renal drug excretion 2. Drug inactivation 3. Increased therapeutic action 4. Activation of prodrugs (a biologically inactive compound that becomes activated with metabolism) 5. Increased or decreased toxicity v. Enterohepatic recirculation 1. Liver metabolism, excretes in bile, gets reabsorbed back. 2. Repeating cycle in which drug is transported a) From liver into duodenum (via bile duct) b) Back to liver via the portal blood 3. Limited to drugs that have undergone glucuronidation vi. Special considerations 20 1. 2. 3. Age Induction of drug-metabolizing enzymes First-pass effect a) drug metabolism whereby the concentration of a drug, specifically when administered orally, is greatly reduced before it reaches the systemic circulation. More barriers to absorption cause the concentration of drug to be less once it reaches the desired area. (IV dose should be less than oral dose of same medication) 4. Nutritional status 5. Competition among drugs b. Eliminating organs i. Kidneys, skin, lungs ii. Drugs and their metabolites can exit the body through urine, sweat, saliva, breast milk, or expired air iii. Renal routes of elimination/excretion 1. Steps a) Glomerular filtration b) Passive tubular reabsorption c) Active tubular secretion 2. Factors that modify renal drug excretion a) pH-dependent ionization b) Competition for active tubular transport c) Age iv. Non-renal routes of elimination/excretion 1. Breast milk 2. Bile a) Enterohepatic recirculation 3. Lungs (especially anesthesia) 4. Sweat/saliva (small amounts) 40. Receptor binding (agonist, antagonist, partial agonist) a. Receptor binding i. The binding of a drug to its receptor is usually reversible ii. Receptor activity is regulated by endogenous compounds iii. When a drug binds to a receptor, it will mimic or block the action of the endogenous regulatory molecules and increase or decrease the rate of physiologic activity normally controlled by that receptor. iv. Drugs can agonize or antagonize when attached to a receptor. b. Agonist i. Molecules that activate receptors ii. Endogenous regulators are considered agonists iii. Have both affinity and high intrinsic activity iv. Dobutamine mimics norepinephrine at cardiac receptors v. Agonists can make processes go “faster” or “slower” c. Antagonist i. Produce their effects by preventing receptor activation by endogenous regulatory molecules and drugs ii. Affinity but no intrinsic activity iii. No effects of their own on receptor function iv. Do not cause receptor activation but cause pharmacologic effects by preventing the activation of receptors by agonists. v. If there is no agonist present, and antagonist will have no observable effect. d. Partial agonist 21 i. There are agonists that have only moderate intrinsic activity ii. The maximal 2effect that a partial agonist can produce is less than that of a full agonist iii. These can act as antagonists as well as agonists 41. Memorize therapeutic levels for Phenytoin, Valproic Acid, Lithium a. Phenytoin i. 10-20 mcg/mL b. Valproic acid i. 50-100 mcg/mL c. Lithium i. 0.8-1.4 mEq/L Dosage Calc Review: 1. 2. 3. 4. 5. Review the basic formula for calculations: (desired/available) * quantity Review abbreviations: PO, BID, TID, Q8hr, Q6hr a. PO: by mouth b. BID: twice daily c. TID: three times daily d. Q8hr: every 8 hours (same as TID) e. Q6hr : ever 6 hours Review how to convert pounds to kilograms and how to calculate dosage based on weight: e.g., 5 mcg/kg (pt. weights 100lbs) a. 1kg=2.2lbs Review how to calculate dosage range based on weight: e.g., 5-10mcg/kg (pt. weights 65lbs) Review how to calculate a daily dose of a medication: e.g., acetaminophen 650mg, q4h (every 4 hours) (24hrs/4hrs * 650mg = 3900mg)