Pharmacology of Alzheimers and Parkinson's Dz

Question 1

4. Describe the two major pharmacological approaches used to treat Alzheimer disease: inhibition of acetylcholinesterase and antagonism of the NMDA receptor.

Answer 1

in disease there is a disproportionate decrease in Ach and nicotinic receptors– goal to increase ACh levels by blocking ACh metabolism

counter the decrease in critical mass by decreasing receptor-mediated glutamatergic signaling and decrease cytoxicity

note: future drugs THC binds to activate site of ACh estrase, may inhibit inflammation and decrease Tau formation

Question 2

5. Describe the use and adverse effects of the drugs used to treat Alzheimer’s disease.

Answer 2

most related to excessive ACh effects, concern for succinylcholine use, bradycardia, COPD, asthma, bladder or urinary tract obstruction

Question 3

1. Explain why certain antipsychotic drugs cause Parkinsonism and what drugs can be use to treat this iatrogenic condition.

Answer 3

antipsychotic drugs that increase DA release which can interfere with movement centers

drugs that can help to reduce “extra pyramidal signs”: trihexyphenidyl (antagonize at muscarinic receptors), benztropine (anticholinergic) and diphenhydramine (antimuscarinic)

Question 4

List the drugs that inhibit DOPA decarboxylate and COMT.

Answer 4

drugs that inhibit DOPA decarboxylate: levodopa-carbidopa

COMT inhibitor: entacapone

Question 5

Discuss the indications, mechanisms, adverse effects and precautions of Levodopa-carbidopa.

Answer 5

1st line tx of Parkinson’s, formulation blocks peripheral metabolism of L-DOPA

significant latency, carbidopa does not cross BBB but blocks peripheral metabolism

excess DA can cause movement disorders
contraindications: melanoma, narrow-angle glaucoma, abrupt DC

Concern with cardiac disorder and MAOI

Question 6

Discuss the indications, mechanisms, adverse effects and precautions of Entacapone.

Answer 6

adjunct tx. acts as selective and reversible inhibitor of COMT, prolongs the duration of L-DOPA

metabolized by glucuronidation, care with hepatic impairment, may discolor urine

similar effects of high dopamine levels, potential drug interaction with drugs that are metabolized by COMT

Question 7

Discuss the indications, mechanisms, adverse effects and precautions of Selegline.

Answer 7

MAOI, decreases DA metabolism; noncompetitive irreversible antagonist of MAO-B

metabolite is methamphetamine, can potentiate adverse rxns of levodopa: CNS, CV and GI

caution with dementia, severe psychosis, tradeoff, dyskinesia or excessive tremor, peptic ulcer, sympathomimetics, with other MAOI

Question 8

Discuss the indications, mechanisms, adverse effects and precautions of Pramipexole.

Answer 8

synthetic DA agonist, D2 and D3 full agonist, helps preserve working DA neurons

quite potent, mostly excreted by the kidneys

no effect on other peripheral or central adrenergic or serotonergic receptor families

CNS, GI, CV adverse effects, precaution with sleep attacks, care with low renal clearnace and psychosis

Question 9

Discuss the indications, mechanisms, adverse effects and precautions of Ropinirole.

Answer 9

potent DA full agonist D2, D3; helps remaining DA neurons function, also used in restless leg

no effect on D1, 5-HT, GABA, muscarinic a1, a2, or B receptors

adverse effects: CNS, GI, and CV
Caution with sleep attacks, psychosis, CVD

Question 10

Discuss the indications, mechanisms, adverse effects and precautions of Bromocriptine.

Answer 10

ergot-derived DA agonist, extensively metabolized in the liver

some CNS, psychological, and GI effects, and some CV effects, erythromelalgia

caution with Raynaud’s syndrome caution against driving until aware of effects

Question 11

Discuss the indications, mechanisms, adverse effects and precautions of trihexyphenidyl.

Answer 11

anataongonist of ACh at muscarinic receptors,

works in CNS and SM (lesser), direct antispamodic action on SM

Question 12

Discuss the indications, mechanisms, adverse effects and precautions of Benzotropine

Answer 12

anti-muscarinic, structurally similar to atropine, similar effect to trihex+ anxiety

Question 13

Discuss the indications, mechanisms, adverse effects and precautions of Diphenhydramine.

Answer 13

H1 blocker with significant anti-muscarinic effects

Question 14

Discuss the indications, mechanisms, adverse effects and precautions of Amatadine.

Answer 14

2nd line treatment of Parkinson’s (antiviral)

mechanism unclear, involved DA uptake, DA release, cholinergic/glutamate blockade (NMDA blocking effects)

excreted in urine (active secretion)

CNS, GI and CV adverse effects, adjust dose with reduce clearance

Question 15

Discuss the indications, mechanisms, adverse effects and precautions of Rasagiline.

Answer 15

irreversible MAO-B inhibitor, use with levodopa

10-20x more potent than selegilne, well tolerated

Question 16

Discuss the indications, mechanisms, adverse effects and precautions of Donepezil.

Answer 16

bind competitively to AChE with greater affinity for brain enzyme

metabolism is by CYP2D6 and CYP3A4 (drug interaction);

adverse effects due to excessive ACh, rare CNS effects, greatest GI

increased risk of GI bleed, caution with liver dz. succinylcholine use, bradycardia, COPD, asthma, bladder or urinary tract obstruction

Question 17

Discuss the indications, mechanisms, adverse effects and precautions of Rivastigmine.

Answer 17

pseudo irreversible carbamylation active site, AChE inhibitor, brain selective

food delays absorption but increases the bioavilability by 30% more potent

no drug interaction, generally well tolerated

greater propensity for CNS effects, GI effects more prevalent, same adverse effects, minus liver disease

Question 18

Discuss the indications, mechanisms, adverse effects and precautions of Galantamine.

Answer 18

competitive AChE inhibitor, selective and made from daffodil bulbs, positive allosteric modulator of nicotinic receptors

extended release available for once daily dosing CYP2D6 and CYP3A4 (interaction)

kidney function can be concern CNS and GI effects, response not dose dependent

contraindicated for renal failure, or hepatic dz, bradycardia, succinylcholine COPD, asthma, UT obstruction