Pharmacology - Drugs for movement disorders

Question 1

Parkinson disease treatment

Answer 1

Levodopa
Dopamine recep agonists - bromocriptine, pramipexole, ropinirole
MAO inhibitors - selegiline, rasagiline
COMT inhibitors - tolcapone, entacapone
Apomorphine
Amantadine
Antimuscarinics - benztropine, biperiden, orphenadrine, procyclidine, trihexyphenidyl

Question 2

Levodopa

Answer 2

D2 agonist
PD treatment
Coadmin of carbidopa (DA decarboxylase inhibitor) incr efficacy
Wearing-off phenom
On-off phenom, apomorphine provide benefit during off period

Question 3

Levodopa adverse effects

Answer 3

Anorexia, nausea, vomiting
Postural hypotension, htn, cardiac arrhythmias
Dyskinesia/choreoathetosis
Depression, anxiety, agitation, insomnia, somnolence, confusion, delusion, hallucination, nightmares, euphoria

Question 4

Bromocriptine

Answer 4

D2 agonist
Ergot alkaloid derivative
PD treatment
Approved for endocrine disorder treatment
Extensive first-pass via CYP3A4

Question 5

Pramipexole

Answer 5

D3 agonist
PD treatment
Approved for RLS treatment
Excreted unchanged in urine

Question 6

Ropinirole

Answer 6

D2 agonist
PD treatment
Approved for RLS treatment
Metab by CYP1A2

Question 7

Dopamine recep agonists adverse effects

Answer 7

Anorexia, nausea, vomiting, constipation, dyspepsia, reflux
Postural hypotension, digital vasospasm (bromocriptine), periph edema, arrhythmias
Dyskinesia
Confusion, hallucination, delusion (all worse than levodopa)
Headache, nasal congestion, arousal, pulm infiltrate, pleural/retroperitoneal fibrosis (bromocriptine)
Fall asleep at inappropriate times (pramipexole, ropinirole, rare)

Question 8

Dopamine recep agonist contraindications

Answer 8

Hx of psychosis, recent MI, active peptic ulcer

Bromocriptine contraind in PVD

Question 9

MAO-A vs MAO-B

Answer 9

A - metab NE and serotonin
B - metab phenylethylamine and benzylamine
DA and tryptamine metab equally by the above

Question 10

Selegiline

Answer 10

MAO-B inhib
PD treatment
Slows breakdown of DA–>prolong levodopa efficacy
Adjunctive therapy
Contraind with meperidine, TCAs, serotonin reuptake inhib

Question 11

Rasagiline

Answer 11

MAO-B inhib, irreversible
PD treatment
More potent than selegiline
Neuroprotective, early symptomatic treatment for PD

Question 12

Tolcapone

Answer 12

COMT inhib (COMT metab levodopa to 3-O-methyldopa which competes with levodopa)
PD treatment
Prolong activity of levodopa
Central and peripheral effects
Incr liver enz, may cause death from acute hepatic failure

Question 13

Entacapone

Answer 13

COMT inhib
PD treatment
Prolong activity of levodopa
Peripheral effects

Question 14

COMT inhib adverse effects

Answer 14

Orange urine, diarrhea, abd pain, sleep disturbance

Question 15

Apomorphine

Answer 15

D2 agonist in caudate-putamen
PD treatment
Subcutaneous injection
Quick, transient relief of off-periods
Adverse effects: nausea (can use trimethobenzamide antiemetic), dyskinesia, drowsiness, sweating, hypotension, bruising at injection

Question 16

Amantadine

Answer 16

Antiviral
PD treatment, MOA unknown
Adverse effects: restlessness, depression, irritability, insomnia, agitation, excitement, hallucination, confusion, headache, urinary retention, GI disturbance
Caution in pt with hx of seizure or HF

Question 17

Benztropine, biperiden, orphenadrine, procyclidine, trihexyphenidyl

Answer 17

Antimuscarinics
Centrally acting mAChR antagonists
PD treatment
Improve tremor and rigidity, little effect on bradykinesia
Adverse effect: peripheral antimuscarinic effects

Question 18

Tremor treatment

Answer 18

Metoprolol, propranolol - B1 blockers
Primidone - antiepileptic
Topirimate - serotonin recep agonist
Alprazolam - benzodiazepine
Botulinum toxin A

Question 19

Huntington disease treatment

Answer 19

DA antagonists and/or anxiolytics
Reserpine, tetrabenazine, olanzapine, perphenazine, haloperidol - impair dopaminergic neurotransmission
Reserpine and tetrabenazine - block vesicular monoamine transporter–>deplete cerebral DA

Question 20

Tics treatment

Answer 20

Tetrabenazine, haloperidol, pimozide - neuroleptic antipsychotics, can cause extrapyramidal syndromes, wt gain, sedation, irritability, phobias
Clonidine, guanfacine - a-adrenergic agents
Botulinum toxin A

Question 21

Restless leg syndrome (RLS) treatment

Answer 21

Resolve iron-deficiency anemia
DA agonists, levodopa, diazepam, clonazepam, opiates
Pramipexole and ropinirole - DA agonists, first line treatment

Question 22

Wilson disease treatment

Answer 22

Penicillamine - copper chelator, excrete in kidney, may cause nausea, vomiting, nephritic syndrome, myasthenia, optic neuropathy, blood disorders
Potassium disulfide, zinc acetate, zinc sulfate - decr GI absorption
Trientine - copper chelator

Question 23

Levodopa contraindications

Answer 23

With MAO-A inhib-->htn crisis
Psychotic pts
Angle-closure glaucoma
Hx of melanoma
Active peptic ulcer-->GI bleeding