Dopaminergic Drugs

Authors: Flaherty, Alice W.; Rost, Natalia S.

Title: Massachusetts General Hospital Handbook of Neurology, The, 2nd Edition

Copyright 2007 Lippincott Williams & Wilkins

> Table of Contents > Drugs > Dopaminergic Drugs

Dopaminergic Drugs

A. Dopamine

Used to increase heart rate, contractility, and SBP. Can cause arrhythmias. See ICU Drips, p. 172.

B. Dopamine (DA) receptors

• D1 receptors: Cause vasodilation.

• D2 receptors: Inhibit sympathetic transmission, inhibit prolactin release, cause vomiting.

• D3, 4, 5 receptors: Less well characterized; limbic more than motor effects.

C. Agonists

Used mostly for Parkinson's dz.

• Levodopa: A precursor to dopamine. Given with carbidopa, which blocks peripheral, but not central, levodopa use.

  • Start: 25/100 (carbidopa/levodopa) qd, bring to tid. If necessary, give up to total 1000 mg qd of levodopa, dosing q2-4h. Carbidopa dose should be >75 mg/d, but >125 mg/d may itself cause nausea.

  • Food interactions: Pts. first starting levodopa should take it with meals to minimize nausea. Advanced pts. should take it >30 minutes before or >60 minutes after protein-rich meals because protein blocks CNS levodopa absorption.

  • Side effects: N/V, low BP, confusion, dyskinesias, hallucinations.

• Receptor agonists: Side effects are like levodopa, but agonists are less likely to cause dyskinesias, more likely to cause confusion.

  • D2 agonists: E.g., bromocriptine (Parlodel), ropinirole (Requip).

  • D3 agonists: E.g., pramipexole (Mirapex). Start 0.125 mg tid, max. 1.5 mg tid. Or pergolide (Permax). Start 0.05 mg qd, max. 1.5 mg tid.

• Inhibitors of DA metabolism:

  • Monoamine oxidase inhibitors (MAOIs):

    • Nonspecific MAOIs: Used as antidepressants. Many dietary and drug contraindications, notably meperidine, SSRIs, tyramine-containing foods (red wine, hard cheese).

    • MAO-B inhibitors: E.g., selegiline (Eldepryl), rasagiline (Azilect). They slow dopamine degradation. Start 2.5 mg bid to 5 bid. SEs are few; sometimes N/V. Avoid opiates, TCAs, and SSRIs (can cause hyperthermia, rigidity, autonomic instability).

  • Carboxy-o-methyltransferase (COMT) inhibitors: E.g., tolcapone (associated with fulminant liver failure). For end-stage Parkinson's.

• Amantadine: DA agonist, mechanism unclear, also anticholinergic and antiviral. Used for Parkinson's dz, fatigue in multiple sclerosis.

  • Side effects: Rare confusion, depression, edema.

D. Antagonists

Neuroleptics, e.g., haloperidol, Compazine. Used for sedation, psychosis, vomiting. Extrapyramidal side effects are proportional to D2 binding. Clozapine is underused because it requires WBC tests q 1-4 wk. Its risk of aplastic anemia is very low with testing.

P.170

Table 48. Neuroleptic effects.

Drug	Anti-psych	Extra-pyram	Sedation	Low BP	Weight Gain	Receptor Effect
Typicals
Haloperidol (Haldol)	+++	++++	+	+	+	D2, high
Pimozide (Orap)	+++	++++	++	+	++	D2, high
Perphenazine (Trilafon)	++	++	+++	++	+++	D2, med
Thioridazine (Mellaril)	++ +	++++	+++	++++	D2, low
Atypicals
Risperidone (Risperdal)	+++	++	+	+	++	D2 [congruent] 5HT
Olanzapine (Zyprexa)	+++	++	+++	+	+++	5HT>D2
Ziprasidone (Geodon)	++	+	+	+	+	5HT > D2
Aripiprazole (Abilify)	++	+	+	+	+	D2 ag/ antag
Quetiapine (Seroquel)	+	+	+++	++	++	> D2
Clozapine (Clozaril)	++++	++++	+	++++	5HT >D2

E. Neuroleptic-induced movement disorders

• Neuroleptic malignant syndrome (NMS): An emergency. Happens in response to a neuroleptic or to sudden withdrawal of an antiparkinsonian drug. Caused by a sudden release of calcium from sarcoplasmic reticulum.

  • H&P: Recent drugs. See tachycardia, then acidosis, tachypnea, arrhythmias, muscle stiffness, and fever.

  • DDx of NMS: Malignant hyperthermia, drug interactions with monoamine oxidase inhibitors, central anticholinergic syndromes, catatonia .

  • Tests: ABG, electrolytes, CBC, CPK, EKG.

  • Rx of NMS:

    • Transfer to ICU, maintain ventilation.

    • Surface and core cooling.

    • Dantrolene: Start 1 mg/kg IV, repeat prn to 10 mg/kg qd. Watch for hepatotoxicity, CHF.

    • Bromocriptine: Start 2.5-10 mg IV/pNGT q4-6h.

    • Methylprednisolone: 1 g/d 3 d may speed recovery.

• Acute dystonia: Within a few days of drug initiation. Rx with diphenhydramine 50 mg IM/PO.

• Akathisia: See Movement Disorders, p. 74.

P.171




• Subacute parkinsonian sx: Days to weeks after drug initiation. Add an anticholinergic drug (prophylactic use does not help), switch to clozapine, and use benztropine 0.5-4.0 mg bid it has better compliance than trihexyphenidyl because bid.

• Tardive dyskinesia: Choreoathetosis, dystonia, orobuccal dyskinesia as late (>6 mo) effect of chronic neuroleptic or antiemetic use. Highest risk in mood disorders, women, children.

  • Beware rebound: TD may greatly worsen if you suddenly stop the neuroleptic. Restart it if necessary and taper slowly.

• Rx: Switch to clozapine. Avoid anticholinergics. Consider tetrabenazine (from England), reserpine.