Parkinson's and Alzheimer's Diseases

Question 1

Parkinson’s Disease Gene, Protein Errors and Other

Answer 1

Weak - Gene link
Protein Errors - Alpha-synuclein parkin, ubiquitin-proteome errors
Other - Many environmental causes, Substantia Nigra lesion

Question 2

Alzheimer’s Disease Gene, Protein Errors and Other

Answer 2

Weak - Gene link
Protein Errors - Beta-amyloid protein, Tau protein in numerous plaques, presenillins, IL33 disorder
Other - Cerebrovascular component frequent, environment BSE

Question 3

Huntington’s Disease Gene, Protein Errors and Other

Answer 3

Strong - Gene link; 4 Chromosome mutation
Protein Errors - Huntington protein has extra Glutamines
Other - In early disease basal ganglia most affected

Question 4

Levodopa (Larodopa)

Answer 4

Helps replace dopamine in brain - Reduces bradyknesia and rigidity (Less helpful for tremor)

Question 5

Levodopa Side Effects

Answer 5

AIMS - Abnormal Involuntary Movements; Cardiovascular side effects - Orthostatic hypotension, Sensitizes heart; GI Effects - Nausea and Vomit (L-dopa associated with dose related dry mouth), Contraindicated if melanoma, Avoid in closed angle glaucoma, Psychosis like reaction, Carbidopa blocks peripheral dopa decarboxylase and helps reduce adverse effects

Question 6

L-Dopa Drug Interactions

Answer 6

Possible sensitization of heart to epinephrine arrhythmias (Catecholamines) - Cautious vasoconstrictor use; Avoid phenothiazine (DA blockers), promethazine (Phenergan) or hydorxyzine as antiemetics; Don’t use general anesthetic without physician; Anticholinergics may increase visual hallucinations dry mouth and constipation; MAO-A Inhibitors (Hypertensive crisis), Vit B6 (L-Dopa antagonism)

Question 7

COMT Inhibitors

Answer 7

Tolcapone (Tasmar) and Entacapone (Comtan) - May reduce dose requirement for L-Dopa, Reduce 3-methoxydopamine transport inhibition;
Tolcapone-serious hepatotoxicity (Use Entacapone more); Signs of dyskinesias, hallucinations, orthostatic hypotension, sleep disorders, GI nausea and vomiting

Question 8

COMT Inhibitors Drug Interactions

Answer 8

Vasoconstrictors, Increased sedative effect, Ampicillin and Erythromycin (Reduce elimination of Entacapone); Stalevo (Levodopa/Carbidopa/Entacapone)

Question 9

Drugs that Reduce Dopamine Toxicity

Answer 9

Direct Dopamine Receptor Agonist - Ergot/Non-Ergot/Opiate derived
Dopamine Antagonists - May reduce dyskinesias, anti-psychotic, clozapine
Block MAO-B - Selegiline, Rasagiline
Anti-Oxidants - Vit E, Ascorbic acid, Melatonin
Block NMDA Receptors - Amatidine, Memantine reduce dyskinesias
Inverse 5HT2 agonists - Primavanserin

Question 10

D 2,3,4 Dopamine Agonists

Answer 10

Pramipexole (Mirapex), Ropinrole (Requip), Rotigotone (Neupro) - FALL ASLEEP SUDDEN AND GAMBLING ADDICTION
Used for initial mono therapy or adjunct to l-Dopa to reduce “on-off” phenomenon

Question 11

D 2,3,4 Dopamine Agonists Side Effects

Answer 11

Postural hypotension and edema, Fatigue, Drowsiness, Dyskinesia, Nausea and Constipation
Older may fall asleep - Hyper-addictive behavior (Lack of impulse control, Increase gambling, Sex, Eating)
Monotherapy may need supplement after few years

Question 12

Apomorphine

Answer 12

Serious side effects but may be needed for severe “off episodes,” More effective than newer agents, Vomiting, Priapism, Prolinged QT etc

Question 13

Centrally Acting Anticholinergics

Answer 13

Helps balance neurotransmitters in basal ganglia and reduce tremor; Tertiary nitrogen structure allows drugs to center CNS - Benzotropine mesylate, Biperiden, Procyclidine, Trihexyphenidyl, Ethproperizine, Orphenadrine, Diphenhydramine