Question | Answer |
What physiologic effects of free radical molecules may result in damage or cell death? | peroxidation of lipids (p. 953)
oxidative damage to DNA (p. 956)
oxidation of LDL cholesterol (p. 956) - forms atherosclerotic plaque
blood vessel injury (p. 198) |
Name three drugs or vitamins that may reduce damage produced by free radicals. | Vitamin C
Vitamin E
Selegiline
Gingko Biloba |
Describe the possible sites of drug action on neurotransmission. | Modulate neurotransmitter release
Modulate neurotransmitter clearance from the synaptic cleft
Modulate effects of the neurotransmitter at the post-synaptic receptor |
Name two neurochemical strategies for drug therapy in Parkinson’s disease. | Increase DA activity
Decrease Ach activity |
Which class of drug may be most useful in mild or early PD? | MAO-B inhibitors |
MAO-B Inhibitors | selegiline and rasagiline |
anticholinergic drugs | trihexyphenidyl
bentztropine
biperiden
diphenhydramine |
Dopamine agonists | ergot derivatives: bromocriptine, pergolide
non-ergot derivatives: pramipesole, ropinirole, apomorphine |
bromocriptine, pergolide | ergot derivatives, DA agonist for PD |
pramipesole, ropinirole, apomorphine | Non-ergot derivatives, DA agonist for PD |
carbidopa and entacapone | used together as a Levodopa (l-dopa) to decrease metabolism |
Name another clinical use for the antimuscarinics trihexyphenidyl and benztropine | reduce tremor and possibly rigidity in PD |
trihexyphenidyl and benztropine | antimuscarinic for PD |
Describe the mechanism of action for levodopa and carbidopa. | inhibits decarboxylation of levodopa in the intestine & peripheral tissues, thereby making more levodopa available to the CNS
cannot pass BBB, therefore, does not prevent the conversion of levodopa to dopamine by decarboxylases in the brain |
L-dopa | ups DA
enters brain via active transport system
once in brain, drug undergoes uptake into the few dopaminergic nerve terminals that remain in the striatum
then l-dopa converts to dopamine |
Describe early and late adverse effects of levodopa. | Early:N/V, postural hypotension
Late: Dyskinesias in 1st yr. Loss of effectiveness,
dysrhthmias, psychosis |
What are some strategies for dealing with loss of effectiveness in L-Dopa problems after 3-5 years of therapy? | ncrease total dosing or dose frequency
Use sustained release formulations
supplement with other PD medications
Take a drug holiday |