Neuro Pharm Flashcards
Immediate precursor to DA converted in periphery and brain to DA by L-AAD
Replenishes DA stores in the remaining DA terminals in the striatum
Readily absorbed from GI tract but is dependent on gastric emptying
Excreted in urine as HVA and DOPAC
* Single most effective treatment for PD can completely ameliorate all the symptoms of PD particularly during initial treatment
Drug is only effective for 3-5 years delay treatment until symptoms of PD yield functional impairment
Drug?
L-DOPA
Interactions & contraindications w/ L-DOPA
Drug-drug interactions: VitB6 increases L-Dopa metabolism (use decarboxylase inhibitor) and food can impair absorption (give before a meal)
Contraindications: DO NOT GIVE WITH MAO-A INHIBITOR hypertensive crises
L-AAD inhibitor that cannot cross the BBB prolongs L-Dopa t1/2, reduces the amount of L-Dopa needed to be administered by up to 75% and redues side effects due to reduced peripheral [DA
Carbidopa
DA - Receptor Agonist for Parkinsons
activates the D2 receptors to reduce activation of the indirect pathway
do not need to compete with other substances for G.I. absorption or across BBB. They may also be more selective, which reduces ADEs
D2 agonist and partial D1 agonist
Bromocriptine
D1/D2 agonist
Apomorphine
D2 selective agonist + free radical scavenger
Pramipexole
D2 selective agonist + metabolized by CYP1A2
Ropinirole
Antiviral agent that was found to alleviate parkinsonian symptoms by enhancing release and possibly DA synthesis, inhibiting DA uptake and possible interaction with NMDA receptors
Restlessness, depression, agitation, irritability, insomnia, excitement, hallucinations and confusion
Overdose may produce psychosis
Can also produce ADEs similar to those produced by L-Dopa and DA
Contraindication: patients with history of seizures or heart failure
Amantadine
Selective MAO-B inhibitor retards the breakdown of DA
Metabolites include amphetamine and methamphetamine increase DA release, may be neuroprotective and prevent the progression of PD by inhibiting MAO-B generation of free radicals
May potentiate the adverse effects of L-Dopa
Contraindications: DO NOT TAKE WITH meperidine, TCAs or SSRIs
Used primarily in patients whose responsiveness to L-Dopa has declined
Little effect when administered alone
Selegiline
More potent MAO-B inhibitor for combined therapy with L-Dopa in late-stage PD or alone in early PD
Rasagiline
Selective COMT inhibitor prolongs action of L-Dopa, reduces the production of 3OMD, which may compete for transport carriers in GI and BBB & increases bioavailability of L-Dopa
- peripheral effects only and no liver damage so it is the preferred agent
Rapidly absorbed and extensively protein bound
Etacapone
COMT inhibitor, prolongs action of DA / has peripheral and central side effects
Increased liver enzymes and hepatic failure (*Requires signed patient consent)
Rapidly absorbed and extensively protein bound
Tolcapone
locking cholinergic activity was a widely used form of therapy for PD prior to advent of L-Dopa therapy. Currently, these agents are used in early PD or as adjunct to L-Dopa.
ADEs: drowsiness, mental slowness inattention, confusion, delusions, hallucinations, mood changes, dry mouth, blurred vision, mydriasis, urinary retention, N/V, constipation, tachycardia, increased intraocular pressure, palpitations and arrhythmias
Contraindications: prostatic hyperplasia, OBD, glaucoma and avoid with concomitant use of drugs with anti-muscarinic effects (i.e. TCAs of antihistamines)
Benzotropine
Diphenhydramine
Trihexyphenidyl
Huntington’s disease (initially the loss of the indirect pathway, followed by loss of the direct pathway)
VMAT inhibitors - DA depleting agents
Reserpine
Tetrabenazine
Anti-depressants commonly used to tx Huntington’s:
Fluoxetine, carbamazepine
D2 receptor antagonists
Chlorpromazine, Haloperidol
4 endogenous opiates
POMC, B-endorphins, proenkalain, dynorphins
modulate initial signal transduction
NSAIDS
block the signal conduction in nociceptive fibers
Sodium Channel Blockers
block the signal conduction in nociceptive fibers
Allodynia
high intensity stimuli perceived as more painful
Hyperalgesia
arises from transection of mechanical damage to the nerve axon loss of C-fiber and “rewiring” with A fiber proliferation into these areas changes in gene expression and altered sensitivity as well as changes in the Na-channel expression that leads to enhanced cellular excitability, which is the basis for treatment of neuralgia with carbamazepine (Na channel blocker)
Neuropathic pain
Supraspinal/spinal analgesia, sedation, respiration, GI transit, modulation of hormone and neurotransmitter release
endorphins > enkephalins > dynorphins
Mu/ OP-3
