Term
What are the two drugs in this category?
Dopamine Precursor/Decarboxylase Inhibitors
MOA: provide body with a precursor to dopamine (L-dopa) |
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Definition
-Carbidopa/Levodopa
(Sinemet, Parcopa)
-Carbidopa/Levodopa/ Entacapone
(Stavelo) |
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Term
PCOL
Carbidopa/Levodopa
(Sinemet, Parcopa) |
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Definition
• Carbidopa inhibits peripheral conversion of L-dopa and doesn’t cross BBB
• Less peripheral DA than levodopa alone, so fewer SEs |
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Term
Therapeutics
Dopamine Precursor/Decarboxylase Inhibitors
MOA: provide body with a precursor to dopamine (L-dopa) |
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Definition
• Used to confirm PD diagnosis
• CIs: narrow-angle glaucoma, melanoma, undiagnosed skin lesions, use of MOAI within 14 days
• DDI: anti-hypertensives, selegiline, D2 antagonists, iron salts, metoclopramide
• Usually only get 5 good years of txt with levodopa, so don’t start younger patients (> 65 years) on it initially
• More effective for txt of motor sx than DA agonists |
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Term
Medchem/PK
Dopamine Precursor/Decarboxylase Inhibitors
MOA: provide body with a precursor to dopamine (L-dopa) |
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Definition
• Levodopa crosses BBB, but is metabolized in periphery to DA
• Carbidopa is a hydrazine derivative that does not cross BBB; it inhibits peripheral DOPA decarboxylase (also called L-AAD) and allows L-dopa to enter the brain
• L-dopa overdose is treated with Vitamin B6 (pyridoxine) to ↑ decarboxylation |
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Term
Side effects
Dopamine Precursor/Decarboxylase Inhibitors
MOA: provide body with a precursor to dopamine (L-dopa) |
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Definition
• Hypotension/ orthostasis
• Arrhythmias
• Nausea
• Hallucinations
• Peak-dose dyskinesia
• End-of-dose deterioration of fxn
• On/off oscillations
• Vivid dreams |
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Term
PCOL
Carbidopa/Levodopa/ Entacapone
(Stavelo) |
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Definition
| • Adding entacapone to carbidopa & levodopa gets more DA to the CNS |
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Term
Two drugs for This category
COMT Inhibitors
MOA: reversible inhibition of COMT → prevent deactivation of dopamine |
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Definition
Entacapone (Comtan)
Tolcapone (Tasmar) |
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Term
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Definition
| • Does NOT cross BBB; only has peripheral effects |
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Term
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Definition
• Adjunct to carbidopa/levodopa in pts with end-of-dose deterioration
• DDI: non-selective MAOIs (phenelzine, tranylcypromine) |
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Term
Medchem/PK
Entacapone (Comtan) |
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Definition
Mainly inhibits peripheral COMT
• 98% PPB
• t1/2 ~ 2 hrs due to isomerization to cis
• Also undergoes O-glucuronidation |
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Term
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Definition
• Does cross BBB, so it has central and peripheral effects
• Not used as much due to hepatotoxicity |
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Term
Therapeutics
Tolcapone (Tasmar) |
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Definition
• Adjunct to carbidopa/levodopa therapy to decrease fluctuations
• Not used much anymore due to hepatotoxicity → must monitor ALT/AST & educate patient on signs of liver disease |
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Term
Medchem/Pk
Tolcapone (Tasmar) |
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Definition
• Acts in brain and periphery
• t1/2 = 8-12 hrs
• Rapidly absorbed
• Met by O-glucuronidation |
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Term
Side effects
COMT Inhibitors
MOA: reversible inhibition of COMT → prevent deactivation of dopamine |
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Definition
• Nausea
• Dyskinesias
• Orthostasis
• Diarrhea
• Brownish-orange urine discoloration
• **Hepatotoxicity |
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Term
Side Effects
MAO-B Inhibitors
MOA: selective, irreversible inhibition of MAO-B → extend the DOA of dopamine |
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Definition
• Hypotension
• Confusion
• Hallucinations
• Insomnia (selegiline)
• Dyskinesias
• Headache
• Serotonin Syndrome
• Major DDI with tyramine-containing foods
• BBW: suicidality in teens/young adults |
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Term
PCOL
Selegiline (Eldepryl, Zelapar)
Zelapar (ODT): NPO for 5 min after admin |
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Definition
• Prolong the effects of DA and L-dopa in the CNS
• Irreversible and selective at low doses
• Mild antidepressant effects
• May provide neuroprotection against Parkinson’s → slows DA metabolism to toxic species |
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Term
Therapeutics
Selegiline (Eldepryl, Zelapar) |
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Definition
• Adjunct therapy when carbidopa/levodopa therapy is deteriorating; can decrease wearing off time by 1 hour
• DDI: sympathomimetics, tyramine
• CI: meperidine, trazodone, dextromethorophan, morphine
• Do not DC abruptly; taper off |
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Term
Medchem/PK
Selegiline (Eldepryl, Zelapar) |
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Definition
• A propagylamine
• N-deakylated via 2B6/2C19 to vasoactive amphetamines
• Transdermal patch reduces 1st pas effect |
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Term
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Definition
• Prolong the effects of DA and L-dopa in the CNS
• Irreversible and selective at low doses
• Mild antidepressant effects
• May provide neuroprotection against Parkinson’s → slows DA metabolism to toxic species |
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Term
Therapeutics
Rasagiline (Azilect) |
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Definition
• Initial monotherapy or adjunct to levodopa in txt of advanced PD; can ↓ wearing off time by 1 hour ; can ↓ carbidopa/levo dose
• DDI: antidepressants, tyramine
• CI: cyclobenzaprine, dextromethorophan, methadone, mirtazapine, St. John’s Wort, tramadol, meperidine |
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Term
Mechem/PK
Rasagiline (Azilect) |
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Definition
• A propagylamine
• N-deakylated via 1A2 (implications for inhibitors/inducers)
• Rapidly absorbed
• More potent than selegiline |
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Term
Side effects
Dopamine Agonists
MOA: mimic the effects of dopamine at its receptors |
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Definition
• Hypotension
• Edema of lower extremities
• Dizziness
• Nausea
• Confusion
• Hallucinations
• Dyskinesias
• Compulsive behavior
• Possible psychosis |
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Term
5 drugs in this category, what are they?
Dopamine Agonists
MOA: mimic the effects of dopamine at its receptors |
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Definition
Bromocriptine (Parlodel)
Pramipexole (Mirapex)
Ropinirole (Requip)
Rotigotine (Neupro)
Apomorphine (Apokyn) |
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Term
| The PCOL for the category Dopamine Agonists are the same for what drugs? |
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Definition
Pramipexole (Mirapex)
Ropinirole (Requip)
Rotigotine (Neupro)
Apomorphine (Apokyn) |
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Term
The PCOL for
Pramipexole (Mirapex)
Ropinirole (Requip)
Rotigotine (Neupro)
Apomorphine (Apokyn) |
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Definition
• Non-ergot (more specific)
• Agonist primarily at D2, so less vasoconstriction |
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Term
Therapeutics
Pramipexole (Mirapex)
Ropinirole (Requip) |
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Definition
• Used as monotherapy in early PD and as adjunct to levodopa
• SQ injection may cause dose-related ↓ in BP → watch for orthostasis and BP drop |
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Term
Medchem/PK
Pramipexole (Mirapex) |
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Definition
• Selective D2 & D3 agonist
• Renally eliminated unchanged
• t1/2 = 8-10 hrs |
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Term
medchem
Ropinirole (Requip) |
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Definition
• Selective D2 & D3 agonist
• t1/2 ~ 6 hrs
• Also for Restless Leg Syndrome |
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Term
Therapeutics
Rotigotine (Neupro) |
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Definition
• Early PD monotherapy or adjunct to levodopa in later stages to improve overnight symptomatic control
• Transdermal patch is once daily |
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Term
Mechem/PK
Rotigotine (Neupro) |
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Definition
• Selective D2 & D3 agonist
• Low PO BA, so used in a patch
• Transdermal delivery has t1/2 = 5-7 hrs
• Contains sulfur
• Major metabolite is an O-conjugate |
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Term
Therapeutics
Apomorphine (Apokyn) |
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Definition
| • Rescue txt for advanced PD pts in a “freezing” episode → triggers “on” response in 20 min |
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Term
Medchem/PK
Apomorphine (Apokyn) |
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Definition
• pKa = 9, so + @ phys pH, but crosses BBB
• Extensive 1st pass met; t1/2 = 30-60 min
• R(-) isomer is potent D1/D2 agonist
S(+) isomer is postsynaptic D2 antagonist and presynaptic D2 autoreceptor agonist |
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Term
Side effects
Anticholinergics
MOA: antagonists at muscarinic cholinergic receptors |
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Definition
• Memory impairment
• Confusion
• Anti-SLUDE
• May increase intraocular pressure (CI: closed-angle glaucoma) |
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Term
Two drugs for this category
Anticholinergics
MOA: antagonists at muscarinic cholinergic receptors |
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Definition
Benztropine (Cogentin)
Trihexiphenidyl (Artane) |
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Term
PCOL
Benztropine (Cogentin) |
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Definition
• MOA: ↓ mACh activity → ↑ DA activity
• Arrhythmias |
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Term
Therapeutics
Benztropine (Cogentin) |
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Definition
• May be effective for tremor
• Better tolerated in younger pts
• Dose adjustments may be needed in elderly |
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Term
Medchem/PK
Benztropine (Cogentin) |
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Definition
• ↓ striatum neuron hyperactivity & involuntary motions
• Relieves tremors & rigidity |
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Term
PCOL
Trihexiphenidyl (Artane) |
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Definition
• MOA: ↓ mACh activity → ↑ DA activity
• Arrhythmias |
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Term
Therapeutics
Trihexiphenidyl (Artane) |
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Definition
• May be effective for tremor
• Better tolerated in younger pts
• Dose adjustments may be needed in elderly |
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Term
Medchem/PK
Trihexiphenidyl (Artane) |
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Definition
• An aminoalcohol
• Similar activity to Cogentin |
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Term
Side effects
NMDA Receptor Antagonist
MOA: promotes dopamine release, prevents dopamine reuptake |
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Definition
• Confusion
• Dizziness
• Hallucinations
• Nightmares
• Dry mouth
• Livedo reticularis (skin condition) |
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Term
PCOL
Amantadine (Symmetrel) |
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Definition
• MOA not entirely understood NMDA antagonist: ↑ DA release, ↓ DA reuptake, stimulates DA receptors
• Effects are modest and short-lived |
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Term
Therapeutics
Amantadine (Symmetrel) |
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Definition
• Originally developed to treat flu
• Manages levodopa-induced dyskinesias
• Provides modest benefit of motor sx
• Dose adjustment needed in renal dysfxn |
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Term
Amantadine (Symmetrel)
Medchem/PK |
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Definition
• pKa ~ 11
• Crosses BBB due to cage-like structure (adamantyl group)
• Metabolized via N-acetylation |
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