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20 Cards in this Set

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What is the dopamine hypothesis of Schizophrenia?
Evidence.
- most antipsychotic drugs block postsynaptic D2 receptors in CNS
- Dopamine agonist drugs (e.g., amphetamine & levodopa) exacerbate schizophrenia
- Increased density of D2 receptors has been found in brains of untreated schizophrenics
- Successful treatment of schizophrenics shows lower levels of the dopamine metabolite -- Homovanillic acid (HVA)) in CSF, Plasma, & urine
What is the dopamine hypothesis of Schizophrenia?
Problems.
- AP drugs are only partially effective in most patients and 20% do not respond to treatment at all
- The Atypical AP drugs have a higher affinity for 5 HT receptors than D2 receptors
- There is a time course difference of about 2-3 weeks between biochemical effects & therapeutic effects
EXTRAPYRAMIDAL EFFECTS
what are they?
What is the MOA.
Parkinson like symptoms: dystonia, akathisia.
MOA: Many older high potency AP drugs like Fluphenazine, Trifluoperazine, & Haloperidol block D2 receptors in the nigrostriatal tract and impairing extrapyramidal function. There is also a concomitant blockage of cholinergic (muscarinic receptors)
EXTRAPYRAMIDAL EFFECTS
What is the treatment
Effects are dose dependent so try to reduce dose. Can also try some of tha less potent or atypical APs that have less affinity to D2 receptors such as Thioridazine, olanzapine, quetiapine and risperidone or Clozapine. EPE can be treated with anticholinergic antiparkinsonism drugs like benztropine (Cogentin) or diphenhydramine (Benadryl).
TARDITIVE DYSKINESIA
What is it?
These side effects usually happen late in treatment. It occurs in 20-40% of population. It is most prevalent in elderly. It is the MOST SERIOUS complication because it is irreversible with little treatment. It involves rhythmic, repetitive involuntary movement of tongue, lips jaws, face, extremities (choreathetosis).
TARDITIVE DYSKINESIA
MOA
D2 receptors upregulate (become supersensitive)
TARDITIVE DYSKINESIA
Treatment.
NONE. Try discontinue, reduce dose, or switch to a newer atypical agent. Avoid drugs with central anticholinergic action with such as antiparkinsonism drugs, TCA because these can exasperate TD. You can try to give a benzodiazepine like diazepam to increase GABA.
Difference between overdose toxicity and neuroleptic malignant syndrome.
OVERDOSE TOXICITY.
Usually NOT fatal.

Drowsiness & agitation that can proceed to coma. Hypotension & HYPOTHERMIA.

Thioridazine can cause cardiac arrhythmia

Treatment is gastric lavage & symptomatic and supportive
Difference between overdose toxicity and neuroleptic malignant syndrome.
NEUROLEPTIC MALIGNANT SYNDROME.
Rare, but LIFE THREATENING

Muscle rigidity, akinesia, HYPERTHERMIA, altered BP & hart rate.

More likely with potent antipsychotics (e.g., fluphenazine, trifluoperazine, & haloperidol.

Treatment is to use mm relaxants like diazepam or dopamine agonist like bromocriptine
List advantages and disadvantages of clozapine for tx of psychosis
Clozapine is an atypical AP that binds to 5HT receptor more so than D2 receptor. Therefore it has a low risk of EP side effects. No tarditive dyskinesia. However it can cause anticholinergic side effects and seizures. It also carries with it a high risk of sever agranulocytosis (1-2%) so it’s use is limited to severely ill patients with refractory psychosis and patients on Clozapine must get weekly CBC.
Cloropromazine (thorazine)
It is a phenothiazine with an aliphatic side chain.

It is the prototype drug.

Low potency (low D2).

High risk of sympathoplegic effects: (a1) orthostatic hypotension & inhibition of ejaculation

Used as an antiemetic
Thioridazine (Mellaril)
Phenothiazine with a piperidine side chain.

Low potency

Low incidence of EPS but can cause sedation and hypotension.

Overdosed can cause ventricular arrythmia and sudden death.

High risk of sympathoplegic effects: (a1) orthostatic hypotension & inhibition of ejaculation

High risk of pigentary retinopathy
Fluphenazine (Permitil, Proloxin)
Phenothiazine with a piperaqzine side-chain.

High potency.

Greatest risk of Neuroleptic Malignant syndrome.

High incidence of EPS. Less incidence of sedation and hypotension

Less risk of ANS effects.
Trifluoperazine (Stelazine)
Phenothiazine with a piperaqzine side-chain.

High potency.

Greatest risk of Neuroleptic Malignant syndrome.

High incidence of EPS. Less incidence of sedation and hypotension

Less risk of ANS effects.
Haloperidol (Haldol)
A butyrophenone. Prototype.

High potency.

Greatest risk of Neuroleptic Malignant syndrome.

High incidence of EPS. Less incidence of sedation and hypotension

Less risk of ANS effects.

Also used for Tourette's syndrome
Pimozide (Orap)
Considered miscelaneous drug

Also used for tourette's syndrome--motor and/or vocal tics.
Clozapine (Clozaril)
Superior to 1st generation drugs.

Considered most effective 2nd generation atypical antipsychotic.

Better at treating "negative symptoms" of schizophrenia (apathy, social withdrawl)

More binding to 5HT receptors.

Less EP side effects, TD, hyperprolactemia. More sedating and more hypotension.

Can also cause siezures.

Agranulocytosis is an allergic rxn that happens in 1-2%. Because of this it's use is limited to severely ill patients with refractory psychosis. In addition weekly CBC must be done.

"Black box" worning for Alzeimers pt's cuz of increased CV risk
Olanzapine (Zyprxa)
Superior to 1st generation drugs.

Considered 2nd most effective 2nd generation atypical antipsychotic (after Clozapine).

Better at treating "negative symptoms" of schizophrenia (apathy, social withdrawl)

More binding to 5HT receptors.

Less EP side effects, TD, hyperprolactemia. More sedating and more hypotension.

Used for Agitation & psychosis of Alzeimers BUT "Black box" warning cuz of increased CV risk in elderly pts w/ dementia.

Side effects are wieght gain and diabetes cuz of hyperglycemia
Risperidone (Risperdal)
Superior to 1st generation drugs.

Considered 3nd most effective 2nd generation atypical antipsychotic (after Clozapine & Olazapine).

Better at treating "negative symptoms" of schizophrenia (apathy, social withdrawl)

Equal binding to 5HT & D2 receptors.

Minimal aticholinergic effects (m)

but hyperprolactinemia & extrapyramidal effects (D2) and some sedation (5HT)

Used for Agitation & psychosis of Alzeimers BUT "Black box" warning cuz of increased CV risk in elderly pts w/ dementia.
Ziprasidone (Geodon)
Superior to 1st generation drugs.

Better at treating "negative symptoms" of schizophrenia (apathy, social withdrawl)

MAY CAUSE PROLONGED Q-T INTEVAL INCREASING RISK OF TORSADES DE POINTES.

"Black box" warning cuz of increased CV risk in elderly pts w/ dementia.