Term
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Definition
Idiopathic (75%): Genetic factor
Oxidative distress: free radicals
Neurotoxins
Infections, e.g. encephalitis-- Epidemic in 1910
Trauma: Head injury (Ali)
Endocrine, e.g. hypothyroidism, Wilson’s disease -- Altered COPPER Metabolism.
Drugs |
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Term
| Drug-induced Parkinsonism: |
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Definition
Neuroleptics: e.g. haloperidol (blocks DA receptors)
Metoclopramide-- DA Antagonist
Reserpine-- Depletes DA, NE (antipsychotic drug)-depletes storage vesicles of catecholamines
Carbamazepine-- Antiepileptic
MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)-- Neurotoxin; analog of Meperidine. 1-MPP-- toxic metabolite. |
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Term
| 4 Cardinal Features of Parkinson's: |
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Definition
Tremor: first motor sign in 75% of patient, pill rolling, 3-5 cycles per min.
Rigidity
Bradykinesia & Akinesia: mask like or expressionless face, drooling
Disorders of gait and posture |
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Term
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Definition
Pallidotomy, thalamotomy-- Remove Globus Pallidus; VL Thalamus.
Deep brain stimulation
Fetal nigral transplantation |
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Term
| DA 1) the DIRECT pathway via 2) receptors & 3) the INDIRECT pathway via 4) receptors. |
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Definition
| 1)excites 2) D1 3) inhibits 4) D2. Overall effect: movement |
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Term
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Definition
Converted to DA in CNS → **REPLACES the effect of substantia nigra pars compacta
-interacts with dopamine D-2 receptors located on neurons in the striatum and on presynaptic terminals of DA nigrostriatal axons |
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Term
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Definition
Major symptoms of Parkinsonism especially bradykinesia & rigidity
Best results in the 1st 3-4 years |
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Term
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Definition
Short 1/2 life (1-3hrs).
Undergoes first pass (aka prodrug) by GI mucosa and liver=decarboxylated into DA
-can prevent this with Carbidopa (inhibits decarboxylase)
**Major metabolites are 3,4-dihydroxyphenylacetic acid (DOPAC) and 3-methoxy-4 hydroxyohenylacetic acid (homovanillic acid; HVA). Rapidly excreted in urine. |
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Term
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Definition
1) GI: Anorexia, NV (80%)
-- Action of DA on chemoreceptor trigger zone (CTZ-NV center in 4th ventricle). Tolerance gradually ↑.
Start w/ LOW doses ; Given w/ MEALS
-- Carbidopa ↓ incidence-- 20%(decrease formation of DA in plasma)
2) CV: Tachycardia & cardiac arrhythmias
Postural hypotension. (Due to high DA in heart, affect Beta 1-DA receptors), DA receptors in the kidneys can lead to hypotension.
3) Abnormal involuntary movements: Dyskinesias
-Carbidopa tends to ↑ incidence
-usually disappear if dosage ↓ (no tolerance development)
->dose and time related (80% of pts with long tx)
--can have a drug holiday, but this can lead to withdrawal)
4) Behavioral disturbances
Dose-related; more common with levodopa + carbidopa.
5) Fluctuations in response:
• “Wearing-off” effect or “End-of-dose akinesia”
-->End of dose “wearing-off” ↓ with COMT inhibitors or Stalevo, a combination of entacapone with 3 different doses of levodopa/caridopa.
• “On-off phenomenon” → unpredictable, marked dyskinesia during on-periods → ↓ protein intake to limit dyskinesia (competes with AA for transport)
-->MOA: May result from alteration of DA R & post-R changes to plasma levodopa level .
Fluctuations may be ↓ by taking medication more frequently in smaller doses or using a Prolonged- release prep. (Sinemet CR) |
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Term
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Definition
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Term
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Definition
-↓ levodopa dose by 75%
-NV much less frequent (2-5%)
-Less likelihood of tachycardia
-Greater efficacy with smoother control; Sinemet CR may result in less fluctuation.
-Pyridoxine no longer antagonizes effect of L-DOPA= increases L-DOPA metabolism |
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Term
| Sinemet: Contraindications |
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Definition
| - Contraindications---angle-closure glaucoma, psychosis, malignant melanoma--L-DOPA, a Precusor to Melanin |
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Term
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Definition
Start low doses and ↑ gradually
best to administer on an empty stomach.
Caution---peptic ulcer, cardiac disease, open-angle glaucoma—MYDRIASIS |
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Term
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Definition
-Pyridoxine--increases L-DOPA metabolism
-Antipsychotic drugs
-Anticholinergic drugs– Glaucoma
-Non-selective MAO inhibitors, e.g. phenelzine, tranylcypromine --Hypertensive Crisis; ↓↓ Catechol Metabolism
-Other dopamine agonists |
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Term
| Bromocriptine (generic, Parlodel): MOA |
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Definition
DA agonist (ergot)
Bind D2-R → ↓ prolactin release
Strong AGONIST at D-2 R & a weak antagonist at D-1 R. |
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Term
| Bromocriptine: Indications |
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Definition
--Used to treat hyper-prolactinemia; binds D-2 R & ↓ Prolactin release in Pituitary. ↓ galactorrhea (milk flow)
--Combined with levodopa (Sinemet) in patients experiencing on-off phenomena or becoming refractory. |
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Term
| Bromocriptine: Side Affects |
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Definition
-GI: Anorexia, NV, constipation
-CV: Orthostatic hypotension; Cardiac arrhythmias > levodopa (worse than LDOPA)
-Dyskinesias < levodopa (Not as bad as LDOPA)
-Mental disturbances: Confusion, hallucinations, delusions, nightmares, esp.in elderly pts > levodopa (worse than LDOPA)
-Miscellaneous: headache, nasal congestion, erythromelalgia (red, tender, edematous, lower extremities-fluid accum.) |
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Term
| Bromocriptine: Cautions & Contraindications |
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Definition
-History of mental illness
-Cardiovascular disease
-Pregnancy |
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Term
Pramipexole :MOA
Ropinirole
Rotigotine(transdermal 24hr) |
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Definition
| Selective D-2 R Agonists; Pramipexole & rotigotine also activates D-3 R (neuro protective). (Nonergot DA agonists) |
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Term
| Pramipexole: Pharmokinetics |
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Definition
| Rapidly absorbed and excreted UNCHANGED in the urine. |
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Term
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Definition
| metabolized by CYP1A2; drugs metabolized by the liver may alter its metabolism. |
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Term
| Nonergot DA Agonists: Indications |
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Definition
PD:Alone for Mild disease: 1st line
combination with levodopa for advanced disease.
Restless Leg Syndrome (more common in women) |
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Term
| Nonergot DA Agonists: Side Affects |
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Definition
Nausea, fatigue, hallucinations, dizziness, confusion, postural hypotension.
**Sudden sleep attacks-- During DAYTIME activity; Uncommon. |
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Term
| Selegiline(deprenyl)(generic,Eldepryl): MOA |
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Definition
Monoamine Oxidase (MAO) Inhibitor
By Selectively decreasing MAO-B (irreversibly) → decrease DA metabolism & ↑ DA levels. |
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Term
| Monoamine Oxidase (MAO): 2 Types |
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Definition
Type A—primarily for norepinephrine and serotonin (peripheral).
Type B—predominant in brain; metabolizes dopamine. |
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Term
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Definition
-Alone for Early disease: < L-DOPA (not as good as LDOPA)
-Adjunctive therapy with levodopa for Advanced disease: May prolong the effect of levodopa & ↓ mild on-off or wearing off AKINESIA-- also decreases DOSE 20-30 % |
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Term
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Definition
-Dyskinesias and mental disturbances (e.g. confusion; hallucinations) from levodopa -- ↑ in incidence and intensity.
-Insomnia, anxiety, nausea, hypotension |
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Term
| Selegiline: Rx Interactions |
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Definition
-Tricyclic antidepressants, SSRI’s (Selective Serotonin Reuptake Inhibitors): ↑ risk of Serotonin Syndrome--> Hypertension, tremors, rigidity, agitation, hyperthermia,
-Meperidine (Demerol): Rigidity, agitation, delirium, tremors. |
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Term
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Definition
Lack undesirable effects of NONselective MAO inhibitors (e.g. hypertension following ingestion of foods rich in tyramine -- releases NE from sympathetic neurons.)
May have neuroprotective & anti-apoptotic effects -- ANTI-OXIDANT effects → slow Dz Progression. |
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Term
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Definition
| Selective Inhibitors of COMT, which BLOCKS primarily the PERIPHERAL conversion OF L-DOPA to 3-O-Methyl–DOPA → increase in L-DOPA |
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Term
| Catechol-O-Methyltransferase (COMT) does: |
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Definition
| conversion OF L-DOPA to 3-O-Methyl–DOPA |
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Term
| Tolcapone:Pharmacokinetics |
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Definition
| Rapidly absorbed, bound to plasma protein, & metabolized prior to excretion. Half-life of entacapone is about two hrs, but tolcapone has a longer duration –2-3 X/D. |
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Term
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Definition
| Adjunct to levodopa/carbidopa in patients experiencing on-off phenomenon: may produce a smooth response and prolong “on-time”. |
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Term
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Definition
-ND, hypotension, orthostatic hypotension, vivid dreams, hallucinations.
-Hepatotoxicity: Severe; Tolcapone only
BBW: Monitor Liver Enzymes |
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Term
| Amantadine (generic, Symmetrel): MOA |
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Definition
-- ↑ DA release from NEURONS
-- Blocks DA REUPTAKE
-- Blocks NMDA-Glutamte R
=Increased excitation to the cortex
(this is an antiviral drug that used to be for Influ. A) |
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Term
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Definition
Mild cases--alone; < L-DOPA
Severe cases: Adjuctive therapy with levodopa or anticholinergic drugs.
Start w/ low dose and ↑ gradually to 100 mg twice daily. |
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Term
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Definition
-CNS: Dizziness, confusion, insomnia, anxiety, excitement, hallucinations.
-Livedo reticularis – due to local release of catecholamines.--Vasospastic Dz, ”FISHNET” appearance; Reddish, bluish discoloration in legs & arms.
-Edema; orthostatic hypotension |
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Term
Trihexyphenidyl (Artane; generic)--Prototype: MOA
Benztropine mesylate (Cogentin) |
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Definition
Central Anticholinergic Drugs:
-Blocks CENTRAL M-1 R.
-Decreases Excitatory Cholinergic activity from striatal neurons |
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Term
| Anticholinergics: Side Affects |
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Definition
-CNS: Sedation, drowsiness, confusion, delirium, hallucinations, esp. in older patients.
-Peripheral: e.g. dry mouth, cycloplegia, constipation, urinary retention. (Anti-SLUDGE) |
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Term
| Anticholinergics: Indications |
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Definition
-- Less effective than levodopa, but are recommended in younger pts with mild (“early”) disease and pts with drug- induced parkinsonism.
-- Adjunctive therapy with levodopa.
-- Tremor and rigidity are most improved ; bradykinesia less so. |
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