Exam (elaborations) PHARMACOLO N5334 Exam 2 Notes

Exam 2 Notes  Psychiatric Drugs  Two Groups: o First Generation  Conventional Anti-psychotics  Block the receptors for dopamine in central nervous system (CNS)  Cause serious movement disorders (extra pyramidal symptoms, EPS)  Classified by potency  Low, Medium, High  Low Potency  Chlorpromazine o Indications  Schizophrenia  Schizoaffective disorder in the manic phase of bipolar disorder  Anti-nausea  Relief of hiccups  Control of severe behavioral problems in children o Adverse effects:  Sedation  Orthostatic hypotension  Anticholinergic effects o Drug interactions  Intensifies responses to CNS depressant  Antihistamines  Benzodiazepines  Barbiturates  Anticholinergic drugs  Antihistamines  Tricyclic antidepressants  Atropine-like drugs  Thioridazine o Adverse effects:  Prolonged QT interval  Cause fatal cardiac dysrhythmias  Sedation  Orthostatic hypotension  Anticholinergic effects  Weight gain o Black Box Warning:  Dysrhythmias o Treats Schizophrenia only when patients have not responded to anything else  High Potency  Haloperidol o Butyrophenone family 1 o Indications:  Schizophrenia  Acute psychosis  Preferred agent for Tourette Syndrome o Adverse effects:  EPS  Neuroendocrine effects  Can prolong QT interval and cause dysrhythmias  Fluphenazine o Phenothiazines subclass o Indications  Schizophrenia  Other psych disorders o Adverse effects:  EPS  Acute dystonia  Parkinsonism  Akathisia  Sedations  Orthostatic hypotension  Anticholinergic effects  Gynecomastia  Galactorrhea  Menstrual irregularities  Mechanism of Action (MOA)  Block a variety of receptors within and outside the central nervous system  Suppress symptoms of psychosis by blocking dopamine 2 receptors in the mesolimbic area of the brain  Adverse Effects  Result of walking receptors for dopamine, acetylcholine, histamine, and norepinephrine  Acute dystonia  Oculogyric crisis  Opisthotonos  Joint dislocation  Impaired respiration  Some anticholinergic meds can help o Benztropine and diphenhydramine  Some are irreversible, so crucial to monitor  Can produce Parkinson-like symptoms o Bradykinesia o Mask-like faces o Drooling o Tremor o Rigidity 2 o Shuffling gait o Cogwheeling o Stopped posture o Possible due to blockade of D2 receptors  Other EPS symptoms: akathisia o Pacing and squirming brought on by uncontrollable need to be in motion  Tardive dyskinesia and choreoathetoid movements of tongue and face o Lip smacking o Tongue flicks in and out o A slow worm like movement of tongue o Involuntary movements of limbs, toes, fingers, trunk  Neuroleptic Malignant Syndrome o Rare but serious (risk of death if not treated) o Lead pipe rigidity o Sudden high fever o Sweating o Autonomic instability o Dysrhythmic o Fluctuations of blood pressure o Altered level of consciousness o Seizures or coma can develop o Death is results of respiratory failure, cardiovascular collapse, dysrhythmias  Anticholinergic effects o Dry mouth, poor vision, photophobia, urinary hesitancy, constipation, tachycardia  Can cause orthostatic hypotension o due to blocking of alpha 1 adrenergic receptor at blood vessels  Other effects: o Sedation, neuro endocrine affects seizures, sexual dysfunction, dermatologic effects agranulocytosis and severe dysrhythmias  BLACK BOX WARNING:  Severe dysrhythmias  Do NOT abruptly withdraw  Can precipitate a mild abstinence syndrome  Schizophrenia is primary indication  Suppress symptoms during psychotic episodes  Continued use does reduce risk of relapse  Medication Interactions  Anticholinergic o Can intensify anticholinergic effects  CNS depressants o Can intensify the depressant effect 3  Levodopa o Indirect/direct dopamine receptor agonists can counteract the antipsychotic effects of neuroleptics  Overall safe and deaths from overdose rare  Overdose can cause: o Hypertension o CNS depression, EPS  Treatment of Overdose: o Fluids o Alpha adrengergic agonists o Gastric lavage o Emetics aren’t effective due to neuroleptics blocking antiemetic action o Second Generation  Atypical-psychotics  Produce only moderate blockade of dopamine receptors and a stronger blockade of serotonin  May have fewer EPS  Increased weight gain  Can cause diabetes and dyslipidemia  Clozapine  MOA o Blocks the dopamine and serotonin  Indications: o Schizophrenia o Levodopa induced psychosis  Pharmokinetics o Orally administered o Metabolized in liver via CYP450 system o 12-hour half life  Adverse effects o Agranulocytosis o Seizures o EPS o Diabetes o Dyslipidemia o Can affect total cholesterol o Weight gain o Affects older adults with dementia  Double the mortality rate  Black Box Warning: o Myocarditis  Risperidone  Binds to multiple receptors  Pharmcokinetics: 4 o Rapid absorption o Antagonist at the 5HT receports o Atagonists at D2 receptors o Blocks H1 and adrenergic receptors  Indications o Schizophrenia o Bipolar disorder  Improves cognitive function  Works in about a week  Adverse effects o Generally infrequent and mild  Can be give orally or IM for schizophrenia  Paliperidone  Approve for acute therapy of Schizoaffective disorder  Acute and maintenance therapy of schizophrenia  Active metabolize if risperidone with same adverse and therapeutic effects  Dosed once a day  Can prolong QT  Olanzaprine (Zyprexa)  Indications o Schizophrenia o Maintenance therapy for bipolar disorder o Acute agitation associated with schizophrenia and bipolar mania o Treatment resistant major depression  Combined with fluoxetine  Low risk of EPS but high risk of metabolic effects  Ziprasidone (Geodon)  Indications o Schizophrenia o Acute bipolar mania  MOA o Blocks multiple receptors including dopamine 5-hydroxytryptamine 2 and histamine 1  Adverse effects o Generally well tolerated o Somnolence o Orthostatic hypotension o Rash  Drug interactions o Drugs that induce CYP3A4 such as rifampin o Phenytoin can accelerate metabolism, decreasing the levels o Do not give with dugs that prolong QT  Trycyclics  Thioridazine  Amiodorone 5  Quetiapine (Seroquel)  Indications o Schizophrenia o Major depression o Acute episodes of mania and depression in patients with bipolar  Black Box Warning o Suicide risk in children, adolescents and adults with major psychiatric disorders  Adverse effects: o Moderate risk of serious metabolic affects o Cataracts o Prolonged QT  Drug interactions o Drugs at induce CYP3A4  Can accelerate metabolism  Aripiprazole (Abilify)  Dopamine system stabilizer  Indications o Schizophrenia o Bipolar mania o Irritability associated with Autism spectrum disorder  Adverse effects: o Headache o Agitation o Nervousness o Anxiety o insomnia o nausea o Vomiting o Dizziness o Somnolence  Drug interactions o Drugs that CYP3A4  Can accelerate the metabolism and hence decrease levels  Asenapine  Indications o Acute and maintenance therapy of schizophrenia in adults o Acute mono therapy or acute adjunctive therapy with lithium or valproate o Manic or mixed manic episodes associated with bipolar disorder  Adverse effects o Drowsiness o Hypotension o Prolonged QT 6  Drug interactions—hardly none  Iloperidone (fanapt)  Equal efficacy to Risperidone and now haloperidol  Adverse effects o Better tolerated than some of the other second generation drugs o Weight gain o Hypotension o QT effects  Drug interactions o CYP2D6 or CYP3A4 inhibitors  Can increase the levels and cause prolonged QT  Depot preparations  Long acting injectable formulations  Used for long term maintenance therapy of schizophrenia  No increased risk of size effects  Schizophrenia o Symptoms  Positive  Exaggeration or distortion of normal function  Example: Hallucinations, delusions, agitation, tension, and paranoia  Negative  Loss of their diminution of normal function  Example: lack of motivation, poverty of speech, blunted affect, poor self care, social withdrawal  Cognitive  Disordered thinking, reduced ability to focus attention, prominent learning and memory difficulties o Subtle changes may appear first, then florid changes where thinking and speech can be completely incomprehensible o Acute Episodes  Delusions are fixed false beliefs  Hallucinations are frequently prominent  Residual symptoms  May have suspiciousness, poor anxiety management, diminished judgement  Lack of insight, motivation and capacity for self-care  Acute exacerbations separated by intervals of partial remission o Maintenance Therapy reduce risk for acute relapse but may prevent long term deterioration o Possible primary factors  Excessive activation of CNS receptors for dopamine and insufficient activation of CNS receptors for glutamate o Treatment goals:  Suppression of acute episodes  Prevention of acute exacerbations  Maintenance of highest possible level of function o Drug selection