Drugs for Parkinson's Disease Lecture PDF Flashcards
Principles of treatment for parkinson’s disease (2)
- reduce incidence and severity of symptoms
- delay progression of symptoms and complications
Surgical approach to treatment for Parkinson’s
Last resort therapy particularly when drug treatment loses effectiveness, deep brain stimulation of the subthalamic nucleus or globus pallidus with high frequency electrical stimuli from implanted electrodes is a treatment of choice
Levodopa (dopar) function, ADR’s (3), mech of action, drug interactions (1)
- drug of choice for parkinson’s disease at controlling tremor, bradykinesia, and rigidity
- limited duration of efficacy that diminishes over years (on-off effect), acceleration of disease process, cannot stop suddenly
- Promotes synthesis of dopamine in the striatum after being taken across blood brain barrier, is then converted to dopamine by dopa decarboxylase, (dopamine cannot get across BBB on own and has too short half life)
- 1st generation antipsychotics directly decrease therapeutic action
Reasons patients have declined response to levodopa after years of therapy
- progressing disease
- decreased sensitivity of post synaptic receptors to dopamine
2 patterns of acute loss of effect of levadopa
1) gradual loss “wearing off” at end of dosing interval
2) “on-off” phenomenon that can happen any time during dosing interval with off periods lasting minutes to hours and suddenly changing from mobility to immobility
Drug holidays
May benefit some patients taking levodopa, brief 10 day interruption of treatment, when successful, beneficial effects are achieved with lower doses but will not correct “on=-off” phenomenon, must be done in hospital as patient may become immobilized
Carbidopa + levodopa (sinemet) function, mech of action
- Most effective therapy for parkinson disease, more effective than levodopa alone
- Carbidopa which has no therapuetic effects on its own enhances actions of levodopa by inhibitng decarboxylases in periphery making more levodopa available to CNS but carbidopa cannot cross BBB so doesn’t affect it in the CNS (recall only 2% levadopa normally reaches brain, goes up to 10%)
MAO-B inhibitors (selegiline) function
-Selective inhibitors of enzyme that metabolizes dopamine in the brain increasing amount of dopamine that can produce therapeutic effect when used adjunct to levodopa, unfortunately resistance quickly builds within 12-14 months, can delay early progression of parkinson disease when used alone
Recent studies indicate selegiline (MAO-B inhibitor) may actually…
….cause more death than benefit
Amantadine (symmetrel) mech of action, function, ADR (1 big one)
- Developed as antiviral that may be employed alone in early parkinsons disease or in combo with other drugs to improve symptoms modestly and decrease levodopa induced dyskinesias
- improves symptoms in 20-50% of patients but rarely lasts more than 6 months
- Livedo reticularis (rose colored to purple mottling of skin and legs, nonharmful)
Anticholinergics for parkinson disesase and 2 examples
- Can be useful in control of symptoms of PD by blocking ability of acetycholine to reach receptors thereby improving balance between dopamine and Ach
- benztropine and trihexphenidyl
Dopamine receptor agonists for Parkinson’s disease, mech of action, ADR’s (3)
- Effective monotherapy in early mild disease but in few years often require addition of levodopa
- Stimulate effects of dopamine by binding postsynaptic receptors, do not undergo conversion process
- Nausea, confusion, psychosis
What kind of dopamine agonists do we use today?
Nonergoline
COMT inhibitors function
-approved for adjunctive use with levo/carbidopa in parkinson patients who have end dose wearing off symptoms by prolonging half life of levodopa and decreasing parkinsonian disability, but can increase dyskinesia
Tolcapone (tasmar) drug class and mech of action
- COMT inhibitor
- Adjunct to levodopa/carbidopa that prolongs half life of levodopa increasing amount that can cross the BBB
