Alzheimer's and Parkinson's

Question 1

L-Dopa

Answer 1

Dopamine precursor, will cross BBB, well absorbed, rapid effect. Greatly metabolized in GI tract and peripheral tissues so high doses are needed.

Question 2

L-Dopa/Carbidopa (Sinemet)

Answer 2

Carbidopa is dopa decarboxylaase inhibitor, does not cross BBB-allows more L-Dopa to reach brain making dosage smaller. Oral admin, absorption delayed by food, short t1/2. Combination drug will decrease sideeffects. SE: HTN when combined w/MAOIs or other sympathomimetic, dyskinesias. Vit B6 inc peripheral metabolism of L-dopa unles carbidopa also administered. CI: psychosis, closed angle glaucoma, cardiac disease, active peptic ulcer, malignant melanoma.

Question 3

Selegiline (Deprenyl; Eldepryl)

Answer 3

Inhibits MAO-B which is mainly in striatum –> dec striatal metabolism of dopamine. Only affects peripheral breakdown of catecholamines by MAO-A at high doses. Decreases formation of free radicals-may slow progression of parkinsons. Well absorbed orally, taken at breakfast and lunch (insomnia if at night). HTN crisis w/high doses of tyramine. Do not combine w/meperidene, other MAOIs, antidepressents, tramadol, dextromethorphan, mehtadone.

Question 4

Rasalgiline (Azilect)

Answer 4

irreversible MAO-B inhibitor, more selective than selegiline. Dietary tyramine restrictions not required. Not transformed to amphetamine-like compound so less likely to cause insomnia. May produce hallucinations/dyskinesias related to DA.

Question 5

Bromocriptine and Pergolide

Answer 5

DA agonists, bromocriptine is D2 agonist, pergolide D1/2. Both ergot derivatives-vasospasm side effects, will dec release of prolactin. SE: gambling/hypersexuality, anorexia/nausea/vomiting, severe postural hypotension, cardiac arrhythmias. Bromocriptine-erythromelagia and pulmonary fibrosis. Pergolide: sudden sleep.

Question 6

Pramipexole and Ropinirole

Answer 6

DA agonists, Not ergot derivatives: no erythromelalgia/vasospasm/fibrosis. Sudden sleep is rare side effect. Well tolerated, much less likely to produce on-off phenomena. Ropinirole is also used for tx of restless legs syndrome.

Question 7

Amantadine (Symmetrel)

Answer 7

Antiviral drug used for flu: may inc release of DA, less potent than l-dopa and effect is short. Toxic psychosis and convulsions may occur w/overdose. Spotting of skin (clears up when drug is discontinued), peripheral edema are common. Use w/caution in pts w/history of seizures or CHF.

Question 8

Anticholinergic Drugs

Answer 8

Benztropine, Biperiden, Procyclidine, Trihexyphenidyl:

Decrease effects of ACh to match loss of DA-restore NT balance. Used in mild/moderate disease. Improves rigidity/tremor/drooling but little effect on bradykinesia. Discontinue gradually, TCAs/antihistamines will increase effects of anticholinergics.

Question 9

Tolcapone and Entacapone

Answer 9

Inhibit COMT, used as adjunts to l-dopa/carbidopa. Tolcapone has been associated w/death from liver disease: must monitor liver enzymes. Rhabdomyolysis and associated myalgia has been reported w/entacapone. Contraindicated w/antipsychotics, MAOIs, sympathomimetics. Caution w/antidepressants and opioids.

Question 10

Cholinesterase Inhibitors

Answer 10

Donepezil, Rivastigmine, Galantamine:

Used to treat Alzheimer’s. Inhibit breakdown of ACh, improves symptoms at least for a while, may help slow progression of disease. SE: N/D/V and inc in stomach acid/saliva secretion.

Question 11

Memantine

Answer 11

Low affinity antagonist at NMDA receptor, used in more severe Alzheimer’s. Blocks extra extra synaptic NMDA receptor that are involved in neurotoxicity due to excessive glutamate release in pathological situations while allowing normal physiological function of synaptic NMDA receptor. Excreted unchanged in urine-elimination inc w/alkalizing agent. May enhance adverse effects of l-dopa. SE: agitation, urinary incontinence, urinary tract infection, insomnia, diarrhea.