Antipsychotics/AntiParkinsons Flashcards
Describe the mechanism of action of antipsychotics.
They block dopamine receptors (D2).
What is unique about the mechanism of action of clozapine?
It somehow selectively causes dopaminergic inhibition in the mesolimbic pathway where there is too much DA activity. It also blocks 5HT receptors somehow facilitating DA release.
*Good for refractory patients and is better against negative sx
Describe the primary physiologic problems that occur with schizophrenia.
There is too much DA activity in the nucleus accumbens, and not enough in the frontal cortex
What area of the brain is responsible for negative symptoms in schizophrenia?
The frontal cortex, where there is too little DA activity.
What area of the brain is responsible for the positive symptoms of schizophrenia?
The nucleus accumbens where there is too much DA activity
What is the primary physiologic process behind Parkinson’s?
It is caused by progressive degeneration of DA neurons int he substantia nigra. The loss of cells is correlated to clinical severity.
*Also, ACh and DA balance is disrupted.
Blockage of D2 receptors in what area of the brain in treatment of schizophrenia can cause Parkinsonian-like effects?
Blockage of D2 receptors in the striatum. Results in extrapyramidal sx (EPS, aka Parkinsonian sx)
Name the antipsychotics.
AC CHORZ - Aripiprazole, chlorpromazine, clozapine, haloperidol, olanzapine, risperidone, ziprasidone
*Having to do chores without air conditioning makes me crazy!
What is the primary aim for Parkinson’s treatment?
To treat the imbalance between striatal cholinergic and dopaminergic activity via DA replacement, enzyme inhibitors to enhance CNS deliver, MAO-B inhibition to prolong CNS effects, enhancement of DA release and blocked, and use of anticholinergics to restore balance.
What are the early side effects of antipsychotics?
Acute dystonia, akasthesia (motor restlessness), parkinsonism, neuroleptic malignant syndrome (catatonia, stupor, fever, unstable BP - this can be fatal so stop drug), sedation, seizure
What are the late side effects of antipsychotics?
Perioral syndrome (Rabbit syndrome), tardive dyskinesia (will develop in 20% of patients as result of DA receptor supersensitivity)
Describe the main physiologic disposition characteristics of antipyschotics.
Absorption is decreased by food, antacids, and anticholinergics. They concentrate in fatty tissue (good because the brain is fatty) and they’re highly protein bound.
How long does it take to achieve long-term tx of psychosis?
4-6 weeks
Describe the primary drug interactions associated with antipsychotics.
They potentiate CNS depressants, barbiturates enhance their metabolism, and anticholinergics can exacerbate confusion
What is the major drug in tx of schizophrenia?
Haloperidol
What drug is sometimes used in the acute treatment of psychotic episodes?
Chlorpromazine
Which drugs have minimal extrapyramidal symptoms (aka parkinsonian sx)
The atypicals (clozapine, risperidone, olanzapine)
Which antipsychotic was temporarily withdrawn for widened QT intervals?
Ziprasidone
*Hey QT I wanna zip you open wide
Which antipsychotics increase your risk for diabetes?
Pretty much all of them. Also can cause weight gain.
Which antipsychotic increases risk of agranulocytosis?
Clozapine
Describe the mechanism of action of aripiprazole and its clinical use.
It’s a partial D2 agonist.
Good because it decreases DA activity in accumbens where it’s too high and increases it in the frontal cortex
Which antipyschotic increases serum prolactin most markedly?
Haloperidol
Describe the mechanism of action of L-Dopa.
It is DA replacement (L-Dopa is the precursor to dopamine)
What are the side effects associated with L-Dopa?
Psychosis from overdose. In periphery conversion to DA causes nausea, palpitations, and arrhythmias, dyskinesias (from increased DA in striatum), on-off phenomenon
Explain the on-off phenomenon in parkinson treatment.
It is where response will rapidly stop, caused by variable CNS metabolism of DA
What drug interactions are significant with L-Dopa?
MAOIs, pyridoxine (Vitamin B6 - enhances peripheral metabolism of L-Dopa causing worsening of peripheral sx), and antipsychotics (because these block DA receptors)
How can you reduce the on-off phenomenon?
By inhibiting COMT and MAO-B. These are the enzymes that metabolize DA and remember variable CNS metabolism of DA causes the on-off phenomenon
Describe the mechanism of action of carbidopa.
It inhibits peripheral L-Dopa metabolism by L-AAD.
*Lad, you need to lay off the carbs.
Describe the mechanism of action of tolcapone and entacapone, and side effects.
Both inhibit peripheral L-Dopa metabolism by COMT. *Tolcapone also inhibits central metabolism because it’s the TOTAL package.
Side effects from enhanced DA (pyschosis), hepatotoxicity.
Describe the mechanism of action of benztropine for parkinsons and when it would be useful.
An antimuscarinic used to rebalance DA and ACh. Most useful for very mild Parkinsonism (esp tremor only).
*How much can you benz (bench) (get it, muscles, muscarinic)?
Describe the mechanism of action of ropinirole and pramipexole, and when they would be most useful.
They stimulate CNS D2 receptors directly. Most useful for L-Dopa refractory patients
Describe the mechanism of action of amantadine and when it would be useful.
Enhances DA release from remaining terminals and inhibits reuptake. Useful as initial therapy with relatively mild side effects
Describe the mechanism of action of selegiline and rasagiline.
They inhibit metabolism of DA by MAO-B in the CNS
What is unique about selegiline?
It is suggested that it may alter progression of idiopathic parkinsons disease by preventing conversion of endogenous/exogenous substances to neurotoxic metabolites.
What is the relationship between nicotine and parkinsons?
Nicotine is neuroprotective and releases DA. Smokers are at 40% lower risk for Parkinsonism possibly d/t MAO-B inhibition
