Non-Medical Drug Use Flashcards
Alcohol is absorbed how? Rate of absorption depends on? Distribution? Elimination & Metabolism? What is the overall effect of alcohol on the liver?
Absorbed via diffusion across membranes (mouth, mucus, stomach, small intestine) – it is a very small molecule! Rate depends on concentration & empty/full stomach (a full stomach decreases BAC & delays achievement of peak BAC). Distribution is TBW (again, it is small!) Elimination via urine, breath, sweat; Metabolism mostly in liver & stomach. Metabolized mostly via alcohol dehydrogenase (ADH) & acetaldehyde dehydrogenase (esp. ALDH2 in liver mitochondria) – EtOH via ADH (NAD+ –> NADH) to Acetaldehyde, via ALDH (NAD+ –> NADH) to Acetate. The P450 )CYP2E1) MEOS system is inducible and converts EtOH to Acetaldehyde (NADPH –> NADP+). Effect: dramatic change in redox state, in which all NAD-dependent rxns are affected because all NAD is being used to detox EtOH; the supply of NAD+ is the limiting factor in alcohol oxidation – this is ZERO-ORDER kinetics.
What is the MOA of EtOH? What are effects? What is the LD50 of alcohol? What drug inhibits aldehyde dehydrogenase and is a mode of aversion therapy in alcoholism treatment?
GABAa-ergic. CNS: depressant (though weak compared to most other drugs). Liver: alteration in lipid mets –> fatty liver –> hepatitis –> necrosis –> fibrosis –> cirrhosis –> liver failure and death. GI: irritation, gastritis. Endocrine: Suppress ADH, stress adrenal cortex, decreased testosterone synthesis, suppress uterine motility and milk ejection. Teratogen: FAS. LD50 = 450-500 mg/dl. Disulfiram (Antabuse) – causes toxicity from acetaldehyde.
Besides EtOH, other alcohols? Their toxic metabolites and effects? Treatment?
Methyl alcohol (antifreeze), Formaldehyde/formic acid, Severe acidosis + Retinal damage. Ethylene glycol (antifreeze), Oxalic acid, Acidosis + Nephrotoxicity. Treatment: give ethyl alcohol, ADH inhibitor (fomepizole, though very expensive).
How do CNS stimulants (amphetamine, cocaine) work? How is cocaine metabolized? What is the MOA of caffeine? How is it metabolized? What is the MOA of nicotine?
The most important component of CNS stimulation is dopaminergic potentiation. Cocaine: Rapidly hydrolyzed by plasma cholinesterase (metabolite benzoylecgonine is tested for in urine). Caffeine (& other methylxanthines) are competitive antagonists at adenosine receptors (an inhibitory NT). Metabolized by demethylation & oxidation via liver enzymes. Nicotine: acivates nicotinic ACh receptors in the periphery and in the CNS (thus, it is a ganglionic stimulant & depolarizing ganglionic blocker), probably also hits nACh receptor on VTA & endogenous opiate systems to increase addicton.
Hallucinogens? Which of these are the indole alkyl amines (these look like…)? Which are phenylethylamines (these look like…)? What schedule are these drugs? How is LSD metabolized? It has cross tolerance with…but not with…suggesting? How might these work?
LSD, MDMA (ecstasy), mescaline (peyote), psilocybin (psilocin). Indole alkyl amines (look like 5HT, tryptamine): Psilocybin, LSD. Phenylethylamines (look like NE, E, DA, Amph): Mescaline, MDMA. Schedule I drugs high potential for abuse and no currently accepted medical use. Remarkably small doses can produce hallucinations.
LSD is oxidized by hepatic microsomal enzymes and excreted in feces. Cross tolerance with mescaline and psilocybin but not THC or PCP, suggesting common receptor with the formers. MOA: Agonist at 5HT2Ar of Raphe Nuclei, decreasing the inhibitor activity of the Raphe, resulting in disinhibition, resulting in a flood of sensory and emotional input. Also: partial DA agonist.
Marihuana psychoactive ingredient? MOA? Metabolized by? Possible therapeutic uses of marihuana? What is the FDA approved form called?
THC: delta-9-tetrahydrocannabinol. Hits cannabinoid receptors (CB1, CB2 – GPCRs, members of the endocannabinoid system). THC metabolized by P450, which with chronic use is inducible. Therapeutic potential: anti-emetic/N, appetite stimulant, analgesis, lower intraoc pressure (glaucoma), bronchodilator (asthma), neurological problems, migraine treatment. Approved forms of synthetic cannabinoids: Dronabinol, Nabilone (w/o psychoactive side effects).
Phencyclidine (PCP) MOA? Effects? What is the half-life?
Antagonist of ion channel associated with NMDA receptor, agonist at mu. Effects: violent behavior, coma, seizures, arrest, psychoses, dissociation, marked nystagmus, confusion, ataxia. LONG half-life due to high lipid solubility and active metabolites.
