CNS Drugs Flashcards
(11 cards)
MoA of Benzodiazepines
- Facilitate opening of GABA-activated Cl channels
- Bind to regulatory site (benzodiazepine receptor) on GABA(A) receptor (distinct from binding site for GABA)
- Allosterically increase the affinity of GABA(A)-receptor for GABA with an increase in the frequency of GABA-stimulated Cl conductance..results in hyperpolarization and inhibition
* *No action in the absence of GABA**
Metabolism of long vs. short/medium-acting benzodiazepines
Long-acting are biotransformed to active metabolites from phase I hepatic microsomal oxidation by CYP#a4 or acid hydrolysis in stomach extends half life and leads to hangover
Short-medium acting are biotransformed by ring hydroxylation and/or direct glucuronidation to inactive metabolites followed by renal clearance
Benzodiazepines sensitive populations
Elderly and patients with liver disease (long-acting, especially)
Benzodiazepine use for seizures
Benzos elevate the seizure threshold
IV lorazepam and diazepam may be used for inital treatment of status epilepticus
Levodopa MoA
Isomer of dopa that is decarboxylated in CNS to DA in corpus striatum where it interacts with postjunctional DA D2 and D3 receptors –> activation of inhibitory G proteins –> inhibition of adenylyl cyclase –> decrease cAMP –> open K channels
Carbidopa MoA
L-amnio acid decarboxylase inhibitor that acts peripherally to reduce the amount of levodopa decarboxylated peripherally
Therapeutic effects of Carbidopa/Levodopa
70% of patients experience improvement in functional capacity and quality of life
Tremor and behavioral effects resistant
Effects diminish in 2-5 years
Adverse effects of Carbidopa/Levodopa
- Dyskinesias (80% of patients), akinesia paradoxica
- End-of-dose akinesias, “on-off” akinesias
- Behavioral effects: anxiety, insomnia, early-onset psychosis; late-onset: dream alterations, visual hallucinations, drug-induced psychoses
- Nausea/vomiting
- Cadriovascular effects: postural hypotension, hypertension; rarely tachycardia, arrhythmias, a-fib (increased circulating catecholamines
- Mydriasis
Drug Interactions of Carbidopa/Levodopa
- Therapeutic action reduced by antiemetic or antipsychotic drugs that block DA receptors
- Natural aromatic AAs decrease absorption
- DO NOT use with MAO(A) inhibitors –> hypertensive crisis
- Vitamin B6 increases dopa decarboxylase activity in periphery
Contraindications for Carbidopa/Levodopa use
- Psychosis
- Narrow-angle glaucoma
- PUD
Trade name for Carbidopa/Levodopa
Sinemet
