CNS Pharmocology UCLA
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| 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)
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| Name three drugs or vitamins that may reduce damage produced by free radicals. | Vitamin C
Vitamin E
Selegiline
Gingko Biloba
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| 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
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| Name two neurochemical strategies for drug therapy in Parkinson’s disease. | Increase DA activity
Decrease Ach activity
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| Which class of drug may be most useful in mild or early PD? | MAO-B inhibitors
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| MAO-B Inhibitors | selegiline and rasagiline
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| anticholinergic drugs | trihexyphenidyl
bentztropine
biperiden
diphenhydramine
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| Dopamine agonists | ergot derivatives: bromocriptine, pergolide
non-ergot derivatives: pramipesole, ropinirole, apomorphine
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| bromocriptine, pergolide | ergot derivatives, DA agonist for PD
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| pramipesole, ropinirole, apomorphine | Non-ergot derivatives, DA agonist for PD
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| carbidopa and entacapone | used together as a Levodopa (l-dopa) to decrease metabolism
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| Name another clinical use for the antimuscarinics trihexyphenidyl and benztropine | reduce tremor and possibly rigidity in PD
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| trihexyphenidyl and benztropine | antimuscarinic for PD
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| 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
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| 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
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| Describe early and late adverse effects of levodopa. | Early:N/V, postural hypotension
Late: Dyskinesias in 1st yr. Loss of effectiveness,
dysrhthmias, psychosis
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| 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
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