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Antipsychotics
N/A
89
Pharmacology
Post-Graduate
04/05/2010

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Cards

Term
What is a psychosis?
Definition
disorder of the mind with delusions, hallucinations, disordered thinking
Term
What is markedly disrupted with schiz?
Definition
thought processes
Term
Who does Schiz affect?
Definition
young adults- "dementia precox" as oppposed to senile dementia
Term
What are the 3 Hypotheses of Schiz?
Definition
Dopamine, serotonin, and glutamate hypothesis. mainly first 2
Term
Based on the Dopamine Hypothesis, what is the "seat of the mind?"
Definition
D2 receptor
Term
What is the neurotranmsitter change with Schiz?
Definition
increased Dopamine
Term
What is the aim of treatment with Schiz?
Definition
the Dopamine receptor is blocked, instead of reuptake
Term
What Dopamine receptors work via Gi?
Definition
D2*, 3, 4
Term
What Dopamine receptors work via Gs?
Definition
D1, 5
Term
What Serotonin recepotr has involvement in Schiz and what G protein does it work by?
Definition
5HT2A, Gq
Term
What 2 receptors play a role in Schiz?
Definition
D2 and 5HT2A
Term
Do D1,3,4,5 blockers affect schizophrenia?
Definition
No
Term
Wehre is D2 located?
Definition
caudate/putamen, nucleus accumbens, an olfactory tubercle
Term
What is the effect of D2 stimulation
Definition
decreaseed cAMP, blocks Ca channels, opens K channels. D2 Block treats schizophrenia.
Term
What Dopamine receptors are involved in Nigrostriatal system?
Definition
D1-5
Term
What disease is a/w Decreased Dopamine?
Definition
parkinsons
Term
What Dopamine recepotrs are found in the Mesolimbic System?
Definition
D2,3,4
Term
what are the functions affected by the Mesolimbic System?
Definition
Food, Sex, and Drug Abuse
Term
Does Mesolimbic D2 block treat schizophrenia?
Definition
yes
Term
What Dopamine Receptors are found in the Mesocortical System?
Definition
D1, 5
Term
What functions are carried by the Mesocortical System?
Definition
short term memory, planning, strategic thinking, and problem solving
Term
What is the function of the tuberoinfundibular system?
Definition
arises in arcuate nuclei and periventricular neurons, and release dopamine into pituitary portal circulation.
Term
What is the effect of Dopamine on pituitary?
Definition
decreased prolactin secretion
Term
What is the effect of antipsychotics on pituitary?
Definition
by blocking Dopamine, they increase prolactin secretion- galactorrhea
Term
What is the medullary-periventricular pathway?
Definition
a Dopaminergic system associated with the motor nucleus of the vagus. very unclear. Eating disorders are involved with this.
Term
What is the Incertohypothalamic pathway involved in?
Definition
Motivational phase of copulatory behavior.
Term
What are the 6 Dopaminergic Systems in the CNS?
Definition
Nigrostriatal System, Mesolimbic System, Mesocortical System, Tuberoinfundibular System, Medullary Periventricular Pathwya, Incertohypothalamic Pathway.
Term
What is the effect of Dopamine on hypothalamic-pituitary endocrine system?
Definition
inhibits Prolactin secretion, which normally directly acts on target tissues
Term
What are the 2 uses of D-Amphetamine?
Definition
1.Anorexigenic- weight loss and 2-ADHD
Term
What effect of D-amphetamine and Levodopa serves as evidence for the Dopaminergic Hypothesis of Pscyhosis?
Definition
Both achieve the same effect as Dopamine and both produce Psychosis
Term
What is a drug that blocks dopamine packaging? And its anti-dopamine effect blocks psychosis
Definition
Reserpine; treats psychosis so it serves as evidence that dopamine is involved
Term
What is a 5HT2a agonist that produces hallucinations?
Definition
LSD- Lysergic acid diethylamide
Term
Atypical antipsychotics have what MOA?
Definition
5HT2a antagonists
Term
What is the basis of the Glutamate Hypothesis?
Definition
PCP, Ketamine, and some other NMDA antagonists produce positive and negative symptoms of Psychosis/Schiz.
Term
What are the positive symptoms of Schiz/psychosis?
Definition
things they normally dont have that surface with Schiz: delusions, hallucinations, illusions, dpersonalization, disorganized speech, formal thought disorders, grossly disorganized/catotonic behavior
Term
What is the mechanism behind the casue of Positive Symptoms of Schizophrenia?
Definition
increased D2 Dopaminergic activity (decreased cAMP in the Mesolimbic system)
Term
are positive symptoms alleviated with antipsychotics?
Definition
yes, pharmacotherapy is effective against Positive Symptoms with all antipsychotics
Term
what are negative sympotms of Schiz/Psychosis?
Definition
deficits of normal function: apathy, asociality, alogia, anhedonia, anergia, avoliton
Term
what is alogia?
Definition
poverty of speech
Term
What is the mechanism behind the negative symptoms?
Definition
decreased D1 activity (decreased cAMP in mesocortical system). May be mediated by increased 5HT2a agonism
Term
What drugs work on the negative symptoms of psychosis?
Definition
Pharmacotherapy is less effective with classical antipsychotics. Atypical (2nd generation) drugs work though
Term
What is a synonym for antipsychotic meds that produce extrapyramidal symptoms?
Definition
Neuroleptics
Term
What drug calss dissociate antipsyhotic effect and Extrapyramidal Symptoms?
Definition
atypical drugs/2nd generation
Term
What symptoms of Schiz/Psychosis do the atypical drgus treat?
Definition
both positve and negative
Term
are adverse effects of atypical drugs more or less than first generation?
Definition
less
Term
is treatment of Schiz/Psychosis started with atypical or first generation?
Definition
atypical
Term
All the antipsychotics have some effect on what 2 receptors?
Definition
5HT2a and D2
Term
what other receptors are acted on by antipsychotics?
Definition
alpha 1, H1, and M1. H1>M1
Term
Is there a relationship of the action of drug dosage and efficacy for D1 receptors?
Definition
No, but there is a linear relationship for D2 action
Term
What are the impt atypical antipsychotics?
Definition
Clozapine, Quetiapine, Olanzapine, Aripiprazole, Risperiodne. In order of potency
Term
What are the 4 important 1st generation antipsychotics?
Definition
Chlorpromazine, Thioridazine, Fluphenazine, Haloperidol. In increasing potency
Term
Which 1st generation can be used IM?
Definition
Flupehnazine-Decanoate can be given IM.
Decanoate ester produces a long lasting (up to 3 wks) parenteral drug for compliance in maintenance therapy
Term
What are the adverse autonomic effects of antipsychotic drugs?
Definition
M block: loss of accomodation, dry mouth, difficulty urinating, constipation. alpha 1 block: orthostatic hypotension, impotence, failure to ejaculate
Term
What are the adverse CNS effects of Antipsychotics caused by D block?
Definition
parkinson's syndrome, Akathisia, dystonias
Term
What Adverse CNS effect of antipsychotics results from D-Hypersensitivity?
Definition
Tardive Dyskinesia
Term
What adverse CNS effect results from M block?
Definition
Toxic-Confusional state
Term
What endocrine adverse effects result from Antipsychotic D block?
Definition
Amenorrhea/galactorrhea, infertility, impotence
Term
What adverse effect of Antipsychotics results form H1 and 5HT2 block?
Definition
weight gain
Term
What are specific side effects of Chlorpromazine?
Definition
photosensitivity, retinopathy, hyperpigmentation
Term
What is the specific side effect of Thioridazine?
Definition
prolonged QT
Term
What is the specific side effect of Haloperidol?
Definition
Decreased Libido
Term
What is the atypical antipsychotic with the least side effects?
Definition
Aripiprazole
Term
What are the 4 extrapyramidal symptoms?
Definition
Tardive dyskinesia (chorea-like), akathisia (restlessness), acute dystonia (spastic), Parkinsons Syndrome
Term
When does Tardive Dyskinesia occur?
Definition
can be many years after treatment; can be predisposed by smoking, DMellitus
Term
What is an impt sign of Tardive Dyskinesia?
Definition
Pineal Calcification
Term
What is a desire to be in constant motion?
Definition
Akathisia; can be accompanied by suicide thoughts, insomnia
Term
What increases incidence of akathisia?
Definition
cigarette smoking in women
Term
What drugs are used to treat Akathisia?
Definition
Trihesyphenidyl and Benztropine mesylate. ( Anti-parkinson Drugs)
Term
What are acute dystonias?
Definition
bizarre muscle spasms of head neck and tongue such as torticollis
Term
What drugs treate Acute Dystonias?
Definition
Diphenhydramine, Benztropine mesylate
Term
What patients are susceptible to extrapyramidal side effects?
Definition
AIDS patients
Term
What is the difference between Parkinsons Syndrome and Dz?
Definition
receptor antagonism with the syndrome as opposed to decreased Dopamine with the disease. the syndrome is also reversible.
Term
What is a partial D2 agonist that is a dopamine stabilizer?
Definition
Aripiprazole
Term
Why is Aripiprazole a PARTIAL D2 agonist?
Definition
it functions as an antagonsit or agonist, depedning on the levels of Dopamine at the receptors
Term
What is the MOA of CLozapine?
Definition
inverse agonist of 5HT2A- blocks consitutive activity
Term
What are the side effects of Clozapine?
Definition
seizures, agranulocytosis, myocarditis, blurry vision. Agranulocytosis risk requires WBC counts
Term
When is Clozapine contraindicated?
Definition
Heart Disease becasue of risk of Myocardiits
Term
What is the unique anti-M effect of Clozapine?
Definition
paradoxical increase in salivary secretion
Term
What is the important side effect of Quetiapine?
Definition
Cataract and lens change; need to have eye exam every 6 months
Term
What is the important side effect of Ziprasidone?
Definition
Arrhythmia. QT prolongation; ECG indicated in these patients
Term
What is the imporant side effect of Olanzapine?
Definition
weight gain and related new onset type 2 Diabetes
Term
What is the impt side effect of Prisperidone?
Definition
Prolactinemia
Term
What is an uncommon potentially fatal reaction to neuroleptic/antipsychotic drugs?
Definition
neuroleptic Malignant Syndrome
Term
What are the features of Neuroleptic Malignant Syndrome?
Definition
HTN, tachycardia, hyperthermia, Mxl rigidity, stupor, Elevated CK, myoglobinemia, Nephrotoxicity
Term
What is the Pathogenesis of Neuroleptic Malignant Syndrome?
Definition
increased Ca2+ release from SR leading to the increased contractility, hyperthermia, rigidity, rhabdomyolysis. D2 receptor block in the hypothalamus, Nigrostriatum, and Spinal Cord lead to rigidity, tremor, and increased Temperature set point
Term
What 2 drugs are used to treat Neuroleptic Malignant Syndrome?
Definition
Dantrolene and Bromocriptine
Term
What is the basis of Dantrolene use to treat Neuroleptic Malignant Syndrome?
Definition
inhibits Ca2+ entry in skeletal myocytes
Term
What is the basis of Bromocriptine use for Neuroleptic Malignant Syndrome?
Definition
Ergot Derivative D2 agonist
Term
[image]
Definition
Receptor Blockade effects of Antipsychotics
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