Chapter 18: Psychopharm part 2 Flashcards
Antipsychotics- typicals vs atypicals
Used to treat psychotic disorders as well as psychotic symptoms associated with other psychiatric and medical illnesses
Typical/ first-gen = neuroleptics. Classified according to potency and treat psychosis by blocking dopamine (D2) receptors.
Atypicals/ 2nd gen: block both D2 and serotonin (2A) receptors
Most have a number of actions and receptor interactions –> varied efficacy and side-effect profiles.
Both typical and atypical- similar efficacies in treating POSITIVE psychotic sympoms (hallucinations, delusions)
Atypcals- maybe better at negative symptoms
Atypicals- better side-effect profile. However, metabolic syndrome and expensive –> both classes used equally
Choice: base on pt’s presentation, past response, side-effects, patient preference
Typical (first gen) antipsychotics: low-potency
lower affinity for dopamine receptors; higher dose is required. Higher antiadrenergic, anticholinergic, antihistaminic side effects compared to high-potencies
lower incidence of EPS and (possibly) neuroleptic malignant syndrome
more lthality in overdose due to QTc prolongation and the potential for heart blocka nd ventricular tachycardia
Rare risk for agranulcytosis/ seizures
Chlorpromazine- orthostatic hypotension, blue-gray skin, photosensitivity. Also to treat nauseia
Thioridazine - retinitis pegmentosa
Midpotency typical antipsychotics
Loxapine (higher risk of seizures, metabolite is an antidepressant)
Thothixene (can cause ocular pigment changes)
Molindone
Perphenazein
High potency typical antipsychotics
greater affinity for dopamine receptors –> low dose needed to achieve effect
less sedation, orthostatic hypotension, anticholinergic effects
greater risk for EPS and TD
Haloperidol- can be given PO/ IM/ IV. Decanoate available
Fluphenazine- decanoate available
Trifluoperazine - approved for nonpsychotic anxiety
Pimozide - associated with QTc prolongation and ventricular tachycardia
Mesolimic dopamine pathway
treats the positive symptoms of schizophrenia
includes the nucleus accumbens, the fornix, the amygdala, and the hippocampus
why do negative symptoms of schizophrenia occur?
thought to occur due to decreased dopaminergic action in the mesocortical pathway
Extrapyramidal symtoms occur why?
through blockade of of the dopamine pathways in the nigrostriatum
Side effects of antipsychotics
Antidopaminergic Anti-HAM (histaminic, adrenergic, muscarinic) Tardive dyskinesia Neuroleptic malignant syndrome (less common) Elevated liver enzymes, jaundice Ophthalmologic problems Dermatologic problems Seizures
Extra-Pyramidal Symptoms
(anti-dopaminergic)
Parkinsonism- bradykinesia, masklike face, cogwheel rigidity, pill-rolling tremor
Akathisia- subjective anxiety and restlessness, objective fidgetiness. Patients may report a sensation of inability to sit still. Best treated with B-blockers or benzos.
Dystonia- sustained painful contraction of muscles of neck (torticollis), tongue, eyes (oculogyric crisis). It can be life threatening if it involves the airway or diaphragm
Hyperprolactinemia –>
decreased libido glaactorrhea gynecomastia impotence amenorrhea (anti-dopaminergic effect of anti-psychotics)
Anti-HAM effects of antipsychotics
Antihistaminic –> sedation, weight gain
Anti-alpha1 adrenergic–> orthostatic hypotension, cardiac abnormalities, sex dysfunction
antimuscarinic–> dry mouth, tachycardia, urinary retention, blurry vision, constipation, preciptation of narrow-angle glaucoma
Tardive dyskinesia
choreoathetoid (writhing) movements of mouth and tongue (or other body parts) that may occur in patients who have used neuroleptics for > 6 months.
Older age is a risk factor
Women and patients with affective disorders may be at an increased risk
Although 50% of cases will spontaneously remit (without further antipsychotic use), most cases are permanent
Treatment- usually discontinuation of current antipsychotic if clinically possible and changing to a med with less TD
Neuroleptic malignant syndrome
esp in yount males in early treatment w/ high-potency typical antipsychotics
medical emergency– 20% mortality rate if untreated
Fever
Autonomic instability (tachycardia, labile hypertension, diaphoresis)
Leukocytosis
Tremor
Elevated CPK
Rigidity (lead pipe)
Excessive sweating (diaphoresis)
Delirium (mental status changes)
RX- discontinuation of med, administration of supportive care (hydration, cooling, etc.)
Sodium dantrolene, bromocriptine, amantadine may be used but have their own side effects and unclear efficacy
NOT an allergic reaction
Pt is not prevented from restarting the same neuroleptic later; increased risk of another episode, though
Treatment of EPS
reduce the dose of the antipsychotic
administer anticholinergic medication (benztropine = cogentin) or diphenhydramine (Benadryl) or or, less commonly, an antiparkinsonian med such as amantadine.
What atypical antipsychotic is less likely to cause tardive dyskinesia?
Clozapine
chances of developing TD with typical antipsychotic
5% per year
Onset of antipsychotic side effects
NMS- any time, usually early Acute dystonia- hours to days Parkinsonism/ akathisia- days to weeks TD- months to years Abnormal Involuntary Movement Scale (AIMS) can be used to quantify and monitor for TD
Atypical antipsychotics (in general)
block both dopamine and serotonin receptors.
different side effects from typicals
less likely to cause EPS, TD, neuroleptic malignant syndrome
MAY be more effective at negative symptoms
also used for mania, bipolar, adjunctive in unipolar
Also used for borderline, PTSD, psychiatric disorders in childhood (tic disorders, e.g.)
include Clozapine, Risperidone, Quetiapin (=Seroquel), Olanzapine (Zyprexa), Ziprasidone (Geodon), Aripiprazole (Abilify). Paliperidone (Invega) = metabolite of resperidone Asenapine (Saphris)- sublingual Iloperidone Lurasidone (Latuda)- take with food, used in bipolar
Clozapine
= Clozaril
Less likely to cause TD
Only antipsychotic shown to be more efficacious, used in treatment of refractory schizophrenia
Associated with tachycardia and hypersalivation
more anticholinergic side effects than other atypical or high-potency typical antipsychotics
Small risk of myocarditis
1% incidence of agranulocytosis
Clozapine must be stopped if the absolute neutrophil count drops below 1500/microliter
4% incidence of seizures
Only antipsychotic shown to DECREASE the RISK OF SUICIDE
Haldol vs Clozapine
Haldol- increased risk of EPS (dystonia, TD) but does not typially lead to agranulocytosis (associated with clozapine)
Risperidone
atypical antipsychotic
can –> increased prolactin
Orthostatic hypotension and reflex tachycardia
Long-acting infectable form
Quetiapine
(Seroquel) much less likely to cause EPS; common side effects include sedation and orthostatic hypotension
Olanzapine
(Zyprexa) - common side effects include weight gain, sedation
Ziprasidone
(Geodon)
Less likely to cause significant weight gain, associated with QTc prolongation, must be taken with food (50% reduction in absorption without a 300 calorie meal
Aripiprazole
(Abilify)
unique mechanism of partial D2 agonism
Can be more activating (akathisia) and less sedating
less potential for weight gain
