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NURS660 PSYCHOPHARM 660 EXAM 1
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Major neurotransmitters involved in schizophrenia - ANS ✓-Dopamine
- Glutamate Dopamine and Schizophrenia - ANS ✓Major neurotransmitter in schizophrenia Some atypical psychotics block dopamine receptors Increased in schizophrenia Glutamate and schizophrenia - ANS ✓Considered the "master switch" of the brain. Glutamate is the major excitatory neurotransmitter of the CNS as it can turn on nearly all of the CNS neurons Decreased in schizophrenia Neuroleptic Malignant Syndrome - ANS ✓-Adverse reaction to antipsychotics with severe "lead pipe" rigidity, FEVER, and mental status changes
- Lab findings- increased CK, leucocytosis, low serum iron
- Caused by dopamine antagonists
- Slower in onset, 1-2 weeks after starting/changing therapy.
- Manage by stopping causative agent, supportive care, ECT, Dantrolene, bromocriptine, and amantadine. Serotonin Syndrome - ANS ✓-Caused by serotonergic agents
- Hyperreflexia, myoclonus, ocular clonus
- Manage by stopping all serotonergic agents, supportive care aimed at normalization of vitals, sedation with benzos, administration of serotonergic antagonists, and antidote therapy with cyproheptadine
- Assess need to resume use of causative serotonergic meds after resolution of symptoms
- Symptoms seen within 24 hours of starting/changing therapy. The "-pine" family - ANS ✓Have 5-HT2A and D2 antagonism. Strong potency for H1 and muscarinic receptors Clozapine, Olanzapine, Quetiapine, Clozapine - ANS ✓Atypical Antipsychotic SE: AGRANULOCYTOSIS- ANC blood testing prior, during. Can be very sedating, excessive salivation, Increased risk of myocarditis, Greatest degree of weight gain and possibly greatest cardiometabolic risk Indications- treatment resistant schizophrenia, reducing suicidal behaviour Drug interactions with Clozapine - ANS ✓Potential to increase levels: SSRIS, cipro, cimetidine, macrolides, caffeine Potential to decrease levels: Carbamazepine, rifampicin, SJW, Omeprazole, Phenytoin, Phenobarbital Olanzapine (Zyprexa) - ANS ✓class: Antipsychotic, mood stabilizers Indication: schizophrenia, mania, depression, anorexia nervosa, Action: Strongest of the pines at the H1 and 5HT2a receptors SE: Obesity, dyslipidaemia, insulin resistance Baseline labs: BMI, fasting glucose, lipid panel Drug interactions with Olanzapine - ANS ✓Contraindicated to use IM Olanzapine with IM benzos- increases likelihood of respiratory depression and excessive sedation.
Conventional Antipsychotics - ANS ✓First-Generation drug for Schizophrenia
- Pure D2 antagonism
- Treats pos. symptoms ONLY (dopamine receptors)
- Less expensive, more side effects Disadvantages: Extrapyramidal side effects, Anticholinergic side effects, tardive dyskinesia, lower seizure threshold*
- Chlorpromazine, Haloperidol, thiordazine, perphenazine Chlorpromazine (Thorazine) - ANS ✓Indications: schizophrenia, psychoses, manic-depression, and severe behavioral problems in children ages 1-12. Chlorpromazine is also used to treat nausea and vomiting, anxiety before surgery, chronic hiccups, acute intermittent porphyria, and symptoms of tetanus. SE: photophobia, lightheadedness, dizziness, drowsiness, blurred vision, weight gain, trouble sleeping Interactions: Food, alcohol, and benztropine can reduce absorption. Antacids can slow absorption. Lithium and barbituates can lead to increased clearance. TCAs decrease clearance Serious adverse effects: postural hypotension, EKG changes, respiratory depression Haloperidol - ANS ✓More selective for D2 receptor, less anticholinergic effects, less antihistamine, and anti-adrenergic effect SE: EPS, neuroleptic induced syndrome, akathisia, TD with high doses, amenorrhea, galactorrhea Interactions: decreases effects of levodopa, dopamine agonists. Serious adverse events: If given IV, pt needs to be on cardiac monitor. Can prolong qtc interval and lead to torsades and cause sudden cardiac death. Indications: acute agitation, Tourette's, delirium Thioridazine (Mellaril) - ANS ✓Dopamine receptor antagonist.
SE: Retinal deposits, RPE hyperpigmentation, dry eye, mydriasis, increased IOP (watch in narrow angle), hypotension, weight gain QTc prolongation. Interactions: levodopa, dopamine agonists, CNS depressants, antihypertensives Indications: schizophrenia pts who fail to respond to other antipsychotics. Perphenzaine (Trilafon) - ANS ✓Potent D2 antagonist SE: neuroleptic induced deficit syndrome, akathisia, EPS, parkonsonism, TD, galactorrhea, urinary retention, sexual dysfunction Interactions: Fluoxetine, paroxetine, and bupropion can increase levels. Antihypertensives have synergistic interaction, increasing risk for hypotension. Serious adverse events: NMS, jaundice, seizures, CV death in elderly The "Done" family - ANS ✓Bind more potently to 5HT2A than D2, have less affinity to 5HT1A than the pines, lower 5HT2C potency than pines. Risperidone, Lurasidone, paliperidone Second generation antipsychotics Lurasidone (Latuda) - ANS ✓Treats schizophrenia and depression. SE: must be taken with 350 calories of solid food for max absorption. Low risk of weight gain Paliperidone (Invega) - ANS ✓If patient has a lot of SE from risperidone, will most likely have a lot of SE with this med. Interactions: Can enhance risk of QT prolongation in other medications with SE. Increases effects of antihypertensivies. Serious adverse effects: hyperglycemia/ DKA, NMS, increased risk of death in elderly pts with dementia indications: oral or LAI (monthly and every 3 month doses)
Acute dystonia - ANS ✓Sustained muscle contraction in the face, neck, trunk, or extremities, can affect the larynx. Oculogyric crisis can be a dystonic reaction. Painful. Onset- quickly, within hours. Reversible with treatment of an anticholinergic, benadryl, benzotropine, or congentin. Akathisia - ANS ✓Uncontrollable motor restlessness. Pace, fidget, rock back and forth. Often misdiagnosed as anxiety, difficult to diagnose Onset: typically occurs within days to weeks but within a month. Reversible with beta blockers, benzos, can switch pt's medication. First generation antipsychotics with high potency are highly likely to produce akathisia. pseudo-parkinsonism - ANS ✓Rigidity, pill-rolling tremors, bradykinesia (top 3), masked face, and shuffling gait. Does not progress to Parkinson's, usually reversible. Onset- Months to years (weeks but within a month-Langford) Treat with amantadine and benzos Tardive dyskinesia (TD) - ANS ✓Late-onset (6 months to years) Irreversible neurologic side effect, only 50% reversible characterized by abnormal, involuntary movements such as lip smacking, tongue protrusion, chewing, excessive blinking, grimacing, irregular finger movements, and choreiform movements of the limbs and feet Older adults are at higher risk Treatment- valbenazine, deutetrabenazine, benzos Do not treat with anticholinergics. Can test severity with AIMS test
Upregulation of dopamine 2 receptors - ANS ✓Long term blockade of D receptors in the nigrostritrial dopamine pathway can cause upregulation of those receptors. May lead to TD as well as quick, jerky, limb movements. Upregulation may be the consequence of the neuron's futile attempt to overcome drug induced blockade of its dopamine receptors Downregulation of dopamine 2 receptors - ANS ✓Process wherein the postsynaptic neuron can make itself less sensitive to stimulation. If a neuron is being activated too often, it can reduce the number of receptors available on it's membrane, making itself less sensitive to acitvation. Dopamine D2 - ANS ✓Possible benefits- reduced positive symptoms SE: EPS, akathisia, endocrine effects such as prolactin secretion, menstrual changes, sexual dysfunction Serotonin - ANS ✓5HT2A- benefits: reduced EPS. SE: sexual dysfunction 5HT2C- benefits: unknown. SE: weight gain Histamine H1 - ANS ✓Benefits: sedation Se: sedation, increased appetite, weight gain, hypotension Muscarinic cholinergic - ANS ✓Benefits: reduced EPS SE: autonomic side effects such as blurred vision, dry mouth, constipation, urinary retention, tachycardia, memory dysfunction. Adrengeric receptors - ANS ✓Benefits unknown. possible side effects: a1- orthostatic hypotension, dizziness, reflex tachycardia a2- drug interactions
Greater risk for EPS, NMS, tardive dyskinesia, QTC prolongation. Haldol, fluphenazine. Low potency first generation antipsychotics - ANS ✓1st gen antipsychotics that have a lower affinity for dopamine receptors have a lower potency (need more of a drug to get an effect). More anticholinergic effects. High H1 (weight gain, sedation) and M1 (dry mouth, tachycardia, urinary retention, constipation, visual changes, visual changes, or blurred vision) More antiadrenergic (A1) effects (orthostatic hypotension, cardiac problems, sexual dysfunction (priapism). More antihistamine effects Decreased incidence of EPS. Positive Symptoms of Schizophrenia - ANS ✓Delusions, hallucinations, distortions, agitation, disorganized speech, disorganized behavior Where do positive symptoms originate? - ANS ✓Mesolimbic dopamine pathway Medications to treat positive symptoms - ANS ✓Antipsychotics Negative symptoms of schizophrenia - ANS ✓Flat affect, alogia, affective blunting, asociality, anhedonia, avolition. Where do negative symptoms originate? - ANS ✓Mesocortical dopamine pathway. May also involve mesolimbic regions such as nucleus accumbens Medications to treat negative symptoms - ANS ✓Vraylar, amisulpride
Hypotheses of Schizophrenia - ANS ✓-Mesolimbic pathway is hypothesized to be hyperactive resulting in excess dopamine at the synapse.
- The gluatamate activity at NMDA receptors is hypofunctional Mesolimbic Pathway Theory of Schizophrenia - ANS ✓Mesolimbic pathway is hyperactive, resulting in excess dopamine at the synapse which leads to positive symptoms. Hyperactivity of mesolimbic dopamine neurons may also play a role in aggression and hostile symptoms. Five Different Dopamine Pathways in the brain - ANS ✓-Nigrostriatal Dopamine Pathway
- Mesolimbic dopamine pathway
- Mesocorticol dopamine pathway
- Tuberoinfundibular dopamine pathway
- Thalamic dopamine pathway Nigrostriatal pathway - ANS ✓Projects from the substantia nigra to the basal ganglia or striatum.
- Part of the extrapyramidal nervous system
- Controls motor function and movement
- When dopamine is deficient, can cause parkinsonism with tremor, rigidity, and akinesia/bradykinesia
- Excess dopamine- can cause hyperkinetic movements, such as tics and dyskinesias Mesolimbic dopamine pathway - ANS ✓Projects from the midbrain ventral tegmental area to the nucleus accumbens (part of limbic system) where many behaviors such as pleasurable sensations, the powerful euphoria of drug abuse as well as delusions and hallucinations. Mesocortical pathway - ANS ✓Projects from the ventral tegmental area to the prefrontal cortex and is important for cognition
