Antipsychotics/AntiParkinsons

Question 1

Describe the mechanism of action of antipsychotics.

Answer 1

They block dopamine receptors (D2).

Question 2

What is unique about the mechanism of action of clozapine?

Answer 2

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

Question 3

Describe the primary physiologic problems that occur with schizophrenia.

Answer 3

There is too much DA activity in the nucleus accumbens, and not enough in the frontal cortex

Question 4

What area of the brain is responsible for negative symptoms in schizophrenia?

Answer 4

The frontal cortex, where there is too little DA activity.

Question 5

What area of the brain is responsible for the positive symptoms of schizophrenia?

Answer 5

The nucleus accumbens where there is too much DA activity

Question 6

What is the primary physiologic process behind Parkinson’s?

Answer 6

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.

Question 7

Blockage of D2 receptors in what area of the brain in treatment of schizophrenia can cause Parkinsonian-like effects?

Answer 7

Blockage of D2 receptors in the striatum. Results in extrapyramidal sx (EPS, aka Parkinsonian sx)

Question 8

Name the antipsychotics.

Answer 8

AC CHORZ - Aripiprazole, chlorpromazine, clozapine, haloperidol, olanzapine, risperidone, ziprasidone

*Having to do chores without air conditioning makes me crazy!

Question 9

What is the primary aim for Parkinson’s treatment?

Answer 9

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.

Question 10

What are the early side effects of antipsychotics?

Answer 10

Acute dystonia, akasthesia (motor restlessness), parkinsonism, neuroleptic malignant syndrome (catatonia, stupor, fever, unstable BP - this can be fatal so stop drug), sedation, seizure

Question 11

What are the late side effects of antipsychotics?

Answer 11

Perioral syndrome (Rabbit syndrome), tardive dyskinesia (will develop in 20% of patients as result of DA receptor supersensitivity)

Question 12

Describe the main physiologic disposition characteristics of antipyschotics.

Answer 12

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.

Question 13

How long does it take to achieve long-term tx of psychosis?

Answer 13

4-6 weeks

Question 14

Describe the primary drug interactions associated with antipsychotics.

Answer 14

They potentiate CNS depressants, barbiturates enhance their metabolism, and anticholinergics can exacerbate confusion

Question 15

What is the major drug in tx of schizophrenia?

Answer 15

Haloperidol

Question 16

What drug is sometimes used in the acute treatment of psychotic episodes?

Answer 16

Chlorpromazine

Question 17

Which drugs have minimal extrapyramidal symptoms (aka parkinsonian sx)

Answer 17

The atypicals (clozapine, risperidone, olanzapine)

Question 18

Which antipsychotic was temporarily withdrawn for widened QT intervals?

Answer 18

Ziprasidone

*Hey QT I wanna zip you open wide

Question 19

Which antipsychotics increase your risk for diabetes?

Answer 19

Pretty much all of them. Also can cause weight gain.

Question 20

Which antipsychotic increases risk of agranulocytosis?

Answer 20

Clozapine

Question 21

Describe the mechanism of action of aripiprazole and its clinical use.

Answer 21

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

Question 22

Which antipyschotic increases serum prolactin most markedly?

Answer 22

Haloperidol

Question 23

Describe the mechanism of action of L-Dopa.

Answer 23

It is DA replacement (L-Dopa is the precursor to dopamine)

Question 24

What are the side effects associated with L-Dopa?

Answer 24

Psychosis from overdose. In periphery conversion to DA causes nausea, palpitations, and arrhythmias, dyskinesias (from increased DA in striatum), on-off phenomenon

Question 25

Explain the on-off phenomenon in parkinson treatment.

Answer 25

It is where response will rapidly stop, caused by variable CNS metabolism of DA

Question 26

What drug interactions are significant with L-Dopa?

Answer 26

MAOIs, pyridoxine (Vitamin B6 - enhances peripheral metabolism of L-Dopa causing worsening of peripheral sx), and antipsychotics (because these block DA receptors)

Question 27

How can you reduce the on-off phenomenon?

Answer 27

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

Question 28

Describe the mechanism of action of carbidopa.

Answer 28

It inhibits peripheral L-Dopa metabolism by L-AAD.

*Lad, you need to lay off the carbs.

Question 29

Describe the mechanism of action of tolcapone and entacapone, and side effects.

Answer 29

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.

Question 30

Describe the mechanism of action of benztropine for parkinsons and when it would be useful.

Answer 30

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)?

Question 31

Describe the mechanism of action of ropinirole and pramipexole, and when they would be most useful.

Answer 31

They stimulate CNS D2 receptors directly. Most useful for L-Dopa refractory patients

Question 32

Describe the mechanism of action of amantadine and when it would be useful.

Answer 32

Enhances DA release from remaining terminals and inhibits reuptake. Useful as initial therapy with relatively mild side effects

Question 33

Describe the mechanism of action of selegiline and rasagiline.

Answer 33

They inhibit metabolism of DA by MAO-B in the CNS

Question 34

What is unique about selegiline?

Answer 34

It is suggested that it may alter progression of idiopathic parkinsons disease by preventing conversion of endogenous/exogenous substances to neurotoxic metabolites.

Question 35

What is the relationship between nicotine and parkinsons?

Answer 35

Nicotine is neuroprotective and releases DA. Smokers are at 40% lower risk for Parkinsonism possibly d/t MAO-B inhibition