Movement Disorders Drugs

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Can you name the Movement Disorders Drugs?

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SE: Ergoline-induced toxicity effects unlikely. Postural hypotension, fatigue, somnolence, peripheral edema, nausea, constipation, dyskinesias, & confusion.
SE: Nausea (pretreat w/ anti-emetic - trimethobenzamide or domiperidone), dyskinesias, drowsiness, sweating, hypotension
Use: alleviation of chorea
MOA: Prevents the metabolism of L-dopa --> 3-O-methyldopa (3OMD) by Catechol-0-methyltransferase
Carbidopa + levidopa (1:10 or 1:4)
Use: Monotherapy for mild Parkinsonism or combo tx for advanced pts. Reduces L-dopa dose & smooths response fluctuations. Putative neuroprotective effects (scavenges free radicals)
Trihexyphenidyl class
Fluphenzaine class
SE: If adverse effects become too severe withdraw gradually. break for 3-21 days, and reinstate gradually
Use: Similar to Pramipexole
Carbamazepine class
SE: GI (L-dopa alone): anorexia, n/v (avoid anti-emetics like phenothiazines d/t their extrapyramidal effects -- dopamine antagonist; carbidopa reduces these effects.
Use: Reduced response to fluctuations w/ L-dopa. Decreased L-dopa clearance. Decreased dopa decarboxylase --> compensatory increase in COMT.
Use: Increases amount of L-dopa able to cross the BBB. Combo with L-dopa allows for L-dopa dose reduction up to 85%.
SE: Other: dry mouth, blurred vision, mydriasis, urinary retention, n/v, constipation, tachycardia, increased IOP.
P-kinetics: Start at low dose & gradually increase
Contraindications: Prostatic hyperplasia, obstructive GI dz, & angle-closure glaucoma
Amantadine class
SE: Asthenia, dizziness, GI disorders, & elevation of liver enzymes.
SE: CNS: drowsiness, mental slowness, inattention, restless, confusion, agitation, delusions, hallucinations, & mood changes.
Interactions: Should not be taken w/ meperidine, TCAs, serotonin reuptake inhibitors, or in combo w/ nonspecific MAOIs
TCA class
Apomorphine class
Use: alleviation of chorea if refractory to atypical
Use: May improve tremor & rigidity in Parkinsons. Little effect on bradykinesia.
P-kinetics: Readily absorbed from intestines (depends on rate of gastric emptying and pH -- delayed by food). Some other AAs can compete for transport across the BBB.
Interactions: Vitamin B6 enhances the extracerebral metabolism of L-dopa. MAOI w/ L-dopa can --> HTNive crisis if given within 2 weeks of each other.
P-kinetics: Response can decline over time or stop completely. Start at small dose & escalate as effects diminish. Wearing off rxs. Toxicity concern is supersensitivity develpmnt -
Olanzapine class
P-kinetics: Note: Antidepressant MAOIs are either nonspecific or inhibit MAO-A more specifically (5-HT & NE)
MOA: Preferential affinity for D3 family of receptors
SE: CV: Increased HR, PVCs, A fib (rare), postural hypotension, HTN (usually in the presence of non-specific MAOI or with large doses).
HintAnswer
P-kinetics: Similar to Pramipexole
SE: May be hepatotoxic - (needs signed pt consent & liver monitoring Q 2 wks x 1 yr)
MOA: Increases dopamine release & reduces dopamine reuptake into dopaminergic nerve terminals of substantia nigra neurons. Unknown MOA.
Use: Similar to Bromocriptine, but more effective. May benefit pts not receiving L-dopa. Aids pt w/ response fluctuations to L-dopa
P-kinetics: Variable absorption from GI, peak plasma levels 1-2 hrs post PO dose. Excreted in bile & feces. Build up dose slowly over 2-3 mo to avoid adverse effects
Use: prolong ALS survival by months
MOA: Pure D2 receptor agonist
Pergolide class
SE: May interfere with uptake - Rx metabolizes L-dopa into 3-methyldopa which competes for active transport across the BBB.
SE: Increased L-dopa toxicity (dyskinesias, nausea, & confusion), diarrhea, abd pain, orthostatic hypotension, sleep disturbances, & orange urine.
Rasagiline class
SSRI class
Group P-kinetics: Advantages: No enzymatic conversion required, crosses BBB w/o competing for amino acid transporter. No potentially toxic metabolites
SE: HA, nasal congestion, increased arousal, pulmonary infiltrates, ergoline-induced s/s, erythromelagia, vasospasm, & pleural or retroperitoneal fibroses.
Benzotropine class
Tolcapone class
Phenothiazine class
Entacapone class
P-kinetics: Given PO. Loses effectiveness over time.
MOA: Somewhat selective MAO-B inhibitors. Retard the breakdown of dopamine
MOA: D2 receptor agonist (partial D1 agonist)
Butyrophenones class
P-kinetics: Well absorbed orally. T1/2 ~ 12 hrs. Hepatic metabolism (cytochrome P450, CYP1A2) -- caution in pts w/ hepatic insufficiency.
P-kinetics: Rapid PO absorption, excreted unchanged in urine, gradually increase dose
MOA: Dopamine precursor able to cross the BBB where it is decarboxylated by dopa decarboxylase to form dopamine.
Use: Huntington's dz pts w/ psychosis or disruptive behavior. Also helpful w/ chorea
P-kinetics: Start with a small dose
Procyclidine class
Use: Gold standard in Parkinson's dz - most efficacious treatment
SE: Insomnia when taken late in the day
Clonidine class
Risperidone class
HintAnswer
Haloperidol class
Contraindications: psychotic illness, MI hx, PVD, peptic ulcers
SE: Mental Disturbances: confusion, hallucinations, delusions, other psychiatric reactions.
P-kinetics: Only helpful for Huntington's dz chorea at very high doses
SE: Dyskinesias: chorea, ballismus, athetosis, dystonia, myoclonus, tics, tremors. Behavioral effects: anxiety/ agitation, insomnia/ somnolence, confusion/ delusions/ hallucination
Pramipexole class
MOA: Central (brain) anti-cholinergic
SE: GI: anorexia, n/v, constipation, dyspepsia, peptic ulcers, symptoms of reflux esophagitis. CV: postural hypotension & cardiac arrhythmias. Dyskinesias.
Carbidopa class
P-kinetics: SQ. Rapid onset ~ 10 min. Duration 2 hrs
Riluzole class
Ropinirole class
Tetrabenxine class
Biperiden class
Quetiapine class
Use: Enhance & prolong the effects of L-dopa; reduce response fluctuations; lowers necessary dose of L-dopa. ?Antioxidant properties?
Bromocriptine class
Use: Most effective drug in tx of Tourette's
Selegiline class
MOA: Not completely known. Inhib effects on glutamate-R, NMDA antag, Inactivation of voltage gated Na+ channels. Interferes w/ intracellular events post excitatory AA-R activation
P-kinetics: 2/3 appears in urine as metabolites within 8 hrs (homovanillic acid - HVA and dihydrocyphenylacetic acid - DOPAC). Best response is in the first few yrs of tx.
Contraindications: psychotic pts, angle closure glaucoma (Increased IOP), active peptic ulcers, hx of melanoma (melanin precursor)
Levodopa class
P-kinetics: Only 1-3% enters the brain across BBB unaltered. Peak plasma levels 1-2 hrs post PO dose. Plasma t1/2 = 1-2 hrs (pts vary -- dosing 3-4x/day).
Orphenadrine class
Use: Can be used as 1st line tx for Parkinson's dz - often in combo w/ Sinemet. Commonly used to tx hyperprolactinemia.
MOA: D1 and D2 receptor agonist
Reserpine class
Clonazepam class
Use: depression associated with Huntington's disease
Use: Temporary relief of off-period akinesia in Parkinsons. Also used to tx ED.
MOA: Inhibits the L-dopa --> dopamine conversion by dopa decarboxylase in the periphery (does not cross BBB).

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