pharm antiparkinsons
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- Central Anticholinergic RX's
- Trihexyphenidyl, Benztropin, benadryl
- S/E of Entacone
- may cause parkinsons like s/e like N,V, hypotn, dreams and DIARRHEA!!!!
- MOA of Apomorphine
- potent lipophilic dopamine agonist
- Uses of Amantadine
- antiviral for type A influenza, tx mild cases alone or severe ases with levodopa or anticholenergic rx. less efficacious than levodopa and tolerance develops more readily but with less side effects than levodopa. has little effect on tremor but more effective than anticholinergics vs rigidity and bradykinesia
- Uses of Levodopa
- decrease regidity and tremors of Park DZ. Decreases severity for inital 1-4 years of tx and then refractoryness develops.
- Uses of pramipexole and ropinirole
- alieviate motor deficits in pts who have never recieved levodopa therapy and with pts with advanced (refractory to levodopa) dz. may delay the need to use levodopa early in dz onset and decreased ds of levodopa in advancing dz. ropinirole is also used for RESTLESS LEG SYNDROM (greater incidence in women)
- MOA of Amantadine
- increase dopamine release form neurons, blocks dopamine reuptake. (inhibits NMDA glutamate receptors
- Uses of Trihexyphenidyl and Benztropin
- less effective than levodopa but recommended in younger pts with early, mild dz and pts with drug induced parkinsons sx. Adjuctive tx with levodopa. Improves tremor and rigidity but less improvement of bradykinesia
- MOA of Selgiline
- SELECTIVELY AND IRREVERSIBLY INHIBITS MAO-B (inhibits MAO metabolization of dopamine in the brain). May have neuroprotective and anti-apoptotic effects-anti-oxidant effects, decreasing Dz progression
- Uses of Apomorphine
- SC injection during hypoactivity (off) episodes in pt with advanced parkinsons dz..in Europe approved for treatment of erectile dysfunction sublingual spray
- pharmacokinetics of Levodopa
- absorbed from small intestine where other AA's (lucine) can compete for absorption (therefore large doses must be give and best to give before or after meals). Rate of absorption dpnds on Ph of gastric contents and rate of gastric emptying. Short half life (1-2 hrs) leads to on/off phenoomenon. Extensive 1st pass metabolism in GI and liver where decarboxylated to Dopamine; only 1% of administered dose enters CNS without peripheral decarboxylase inhibitor is given
- MOA of carbidopa
- decarboxylation inhibitor allowing for increased amount of levodopa to enter the BBB from 1-3% to 10%
- Uses of Bromocriptine
- combinded with levodopa in pts experiencing on-off phenomena or with refractory response to levodopa similar axn to levodopa with different emphasis of S/E
- pharmacokinetics of ropinirole
- metabolized by CYP1A2 therefore drugs metabolized by liver may alter clearance
- pharmacokinetics of Selgiline
- high doses selectiivty is lost
- Ergot Dopaminergic agonists
- Bromocriptine-an ergot alkaloid derivative with dopamine agonist activity used to treat hyperprolactinemia (binds D2 receptor and decreases prolactin release in the pituitary. Is a potent Vasoconstrictor.
- Interactions of Levodopa
- vit B6 (pyridoxine) decreases drug effectiveness by increasing peripheral breakdown of the RX. MAOI's coadministration casues increased catacholamine produciton and increase chance of Hypertensive crisis
- MAO Inhibitors
- Selegiline (selective for MAO B inhibition meaning inhibits MAO metabolization of dopamine in the brain but not the MAO metabolization of serotonin and NE perpherially. Rasegiline nonselective MAOI
- S/E of Carbidopa
- dyskinesias and psychiatric disturbances associated with levodopa as well as peripheral s/e of levodopa/dopamine my develop earlier and may be more severe due to overal increased circulating Dopamine.
- Uses of Entacone
- treat On Off sx: smooth and prolonged on time (PEVENTS PERIPHERAL CONVERSION OF L-DOPA TO 3-O-MD
- S/E of Selegiline
- dyskinesias and metal disturbances, insomnia, anexiety, nausea and hypotension
- pharmacokinetics of Entacone
- rapid absorption, bound to plasma protein, metabolized prior to excretion. t1/2 2 hrs therefore ds q4 or 6 hrs
- S/E of Amantadine
- unusual S/E of Livedo Reticularis due to catecholamine release (vasospastic DZ) with fishnet appearance of reddish blue discoloration in exts, edema and orthostatic hypotn. also mild reversible sx of dizziness, confusion, insomnia, hallucinations, excitement, urinary retention
- S/E of Parmipexole and Ropinirole
- nausea, fatigue, hallucinations, dizzinesss, confusion, post hypotn, uncommon sudden sleep attacks, less dyskinesia than levodopa alone.
- pharmacokinetics of paramipexole
- rapidly absorbed reaching peak plasma level in 2 hrs and is excreted UNCHANGED in urine (THEREFORE IS DEPENDENT ON RENAL FUNCTION FOR ELIMINATION!!!!)
- Use of Selgiline
- along for early dz tx or as adjunctive tx with levodopa for advanced dz: may prolong the effects of levodopa and decrease mild on-off or wearing off AKINESIA (DECREASES DOSE 20-30%)
- MOA of Bromocriptine
- strong agonsit at D-2 receptor but weak antagonist at D-1 receptor
- MOA Levodopa
- Metabolic nonpolar precursor of polar dopamine that can cross BBB to CNS and then activate to Dopamine which interacts with D-2 receptors located on neurons in the striatum and presynaptic terminals of Dopamine nigrostriatal axons. Restores dopamine levels in the extrapyrimidal Center (substantia nigra) that atrophys in Park DZ.
- S/E of Apomorphine
- commonly casuses rxn at injection site, hypersexuality (increased erection), N,V, drowsiness, yawning, orthostatic hypotn, syncope, sudden daytime sleep attacks, confusion and hallucinations
- S/E of Bromocriptine
- ERYTHROMELAGIA (edematous, red LE's), anorexia, NV, constipation + relative to levodopa an increased incidence of hallucinations, orthostatic hypotension, confusion, delirium; decreased incidence of dyskinesias. May lead to retroperitoneal or pulmonary fibrosis. S/E risks higher for pt with psychosis, heart, PVD or peptic ulcer dz
- MOA of Pramipexole and Ropinirole
- selective D-2 agonists
- Interactions of Apomorphine
- 5HT antagonist ondansetron results in severe hypotn and fainting. also react with Dopamine antagonists like prochlorperacizine and metopropaminde
- MOA of Entacaone
- selectively inhibits COMT (blocks the PERPHERIAL conversion of L-Dopa to 3-O-methyl-Dopa and therefore increases L-Dopa levels that can cross the BBB
- S/E of Trihexyphenidyl and Benztropine
- Drowsiness, confusion, hallucinations especially in elderly. peripherally causes dry mouth, cycloplegia, constipation and urinary retention
- pharmacokinetics of Apomorphine
- rapidly absorbed after sc injection with t1/2 of 30-60 min.
- Interactions of Selegiline
- Tricyclicc antidepressants, SSRI's increase risk of serotonin syndrom resulting in htn, tremors, rigidity, agitation, hyperthermia and coma
- S/E of Levodopa
- Decarboxylation in periphery results in increased HR, N,V, Arrythmias, postural Hypotn, increased IOP, abnormal involuntary movements (dyskiesias) such as facial ticks, dystonic movements of arms and legs (usually dyskinesias usually disappear of dosage is decreased), behavioral disturbances such as hallucinations, paranoia, exessive sexual behavior, vivid dreams, and brown urine and feces due to melanin resulting from catacholamine oxidation.
- MOA of Trihexyphenidyl and Benstropin
- blocks central M-1 receptors decreasing excitatory chlinergic activity from striatal neurons
- COMT Inhibitors
- Entacaone
- Nonergot dopaminergic agonists
- pramipexole and ropinirole
- Contraindications of Levodopa and Carbidopa
- closed angle glaucoma, psychosis, malignant melanoma (l-dopa a precursor to melanin)