Flashcards in Pharmacology of Substance Use Deck (44):
How do CNS Depressants mostly act?
augment GABA-A receptor complex activity, to increase Cl- influx, hyperpolarizing the cell (inhibitory)
Alcohol is a tiny molecule! What does this mean for how it's absorbed?
small so easy, rapid absorption by DIFFUSION through membranes; including mouth mucous membrane, stomach and MOST at small intestines
What does the rate of alcohol absorption depend on and what does this mean for BAC?
concentration of alcoholic beverage and whether the stomach is empty or full; empty stomach: peak BAC 3/4-1hr after last drink; full stomach: peak BAC 2-3 hrs after last drink
What exactly does food in the stomach do for alcohol?
it dilutes it, delays stomach emptying, increases effective rate of alcohol metabolism
Where is alcohol distributed? how is it eliminated? where is it metabolized?
1) distributed in total body water (it's a tiny molecule)!
2) eliminated by METABOLISM
3) mostly in liver, some in stomach
Tell me about the hepatic pathway of ethanol oxidation
1)ethanol-->acetaldehyde (alcohol dehydrogenase mostly in liver cytoplasm)
2)acetaldehyde-->acetate (acetaldehyde dehydrogenase; ALDH1 in liver cytoplasm and ALDH2 in liver mitochondria)
What's up with Asians and alcohol?
Asians possess atypical Beta2 allele w/enhanced rate of hepatic conversion of ethanol-->acetaldehyde; increased acetaldehyde causes facial flushing! Also, many Asians lack functional forms of ALDH2 so further elevating blood acetaldehyde levels (dizziness, nausea, etc)
Consumed alcohol is a tremendous load for the liver!! What are some metabolic effects?
all NAD dependent reactions are diverted, thus: impaired gluconeogenesis, increased lactic acid production, increased ketone body production, inhibited uric acid excretion, decreased fatty acid oxidation
What is the limiting factor determining the rate of alcohol oxidation (saturation/zero order kinetics)?
supply of NAD+
When do P450 enzymes (ie CYP2E1) come into play with alcohol oxidation?
more important factor at high levels of alcohol and with chronic alcohol consumption; this may enhance metabolism of some other drugs that are also metabolized by P450 (contributes to tolerance)
What three drugs have cross tolerance with their respect to actions on GABA?
alcohol, barbiturates and benzodiazepenes
What is considered the LD(50) for alcohol?
450-500 mg/dl (.45% BAC)
WHat is the progression of liver pathology regarding chronic heavy drinking?
inhibition of tricarboxcylic (TCA) cycle/oxidation of fat-->fatty liver-->hepatitis-->necrosis-->fibrosis -->cirrhosis-->hepatic failure-->death
What's the word on cardiovascular effects of alcohol?
moderate consumption is protective (increases HDL, decreases coronary heart disease); i.e. 1 drink/day (more than that and no longer protective)
What's the word on GI and Endocrine effects of alcohol?
chronic gastritis, decreased ADH secretion, hypogonadism/feminization/gynecomastia, suppreses uterine motility
How does disulfiram (antabuse) work?
Inhibits aldehyde dehydrogenase to cause acetaldehyde toxicity (nausea, vomit, headache etc)
What are some other alcohols that get abused?
methyl acohol (drygas)-->formaldehyde/formic acid-->severe acidosis/retinal toxicity
ethylene glycol (antifreeze)-->oxalic acid-->acidosis, nephrotoxicity
What are the main CNS stimulants and how do they generally act?
amphetamine, cocaine, caffeine, nicotine; most increase CNS catecholamine, especially dopamine activity
What is the MOA of amphetamines and what are its current official therapeutic uses?
indirect sympathomimetic release of biogenic amines from nerve terminals in periphery and in CNS; dopamine potentiation most important
used to treat narcolepsy and ADHD
What are the side effects to taking amphetamines?
Vasospasm leading to possible stroke or MI, arrhythmia, weight loss, tremor, anxiety, irritability, confusion, possible paranoid state
What is the MOA of cocaine and what are its current official therapeutic uses?
blocks uptake transporters for dopamine (most important), norepi, and serotonin (thus increasing activity at those synapses)
used as topical anesthetic for URT (has combined vasoconstrictor/local anesthetic properties to shrink mucosa and provide anesthesia)
How is cocaine broken down in the body?
It's rapidly hydrolyzed by plasma cholinesterase
What is the MOA of caffeine?
competitive antagonist at adenosine receptors (thus preventing adenosine's sedative/anxiolytic etc effects); also inhibit phosphodiesterases (to increase cAMP)
What can caffeine but used to treat?
vascular headaches (constricts blood vessels in the brain), asthma (relieves bronchoconstriction and reduces inflammation)
What is the MOA of nicotine?
ganglionic stimulant and depolarizing ganglionic blocker
What are considered to be the three Schedule I hallucinogens?
LSD, mescaline, psilocybin
What is meant by Schedule I v Schedule II v Schedule III etc
Schedule I: drug has high potential for abuse and not accepted for medical use in US; Schedule II: may have high abuse potential but still accepted medical use (ex morphine); Schedule III "abuse less than Sched I or II)...etc
What are the chemical categories of hallucinogens and what drugs fall under each category?
1) Indole alkyl amines: psilocybin and LSD
2) Phenylethylamines: Mescaline, MDMA
What is the possible mechanism of action of all the hallucinogens?
agonist at 5HT2A receptors on Raphe cell body--> inhibition of Raphe Nuclei firing --> increased sensory input; also a partial dopamine agonist
How is LSD oxidized? Is there cross tolerance between the hallucinogens?
LSD is oxidized int he liver; there is cross tolerance between LSD, mescaline and psilocybin (thus suggesting similar receptors)
What are some of the side effects/toxicities of LSD?
bad trips (anxiety attack, panic attack), flashbacks, "street drug" lifestyle; note that no overdoses, birth defects of chronic psychoses ever linked to LSD
What are some theoretical therapeutic effects of lSD?
helps w/pscyhoanalysis, alcoholism, autistic children, terminal cancer patients (may change attitude toward death)
What is the name of the medication that blocks alcohol dehydrogenase in the treatment of methanol and ethylene glycol poisoning?
What is the mechanism of action for all the cannabinoids (marijuana, anandamide, dronabinol, nabilone)
all act on cannabinoid receptors CB1 and CB2 which are G protein coupled receptors
Classify the cannabinoids and whether they are schedule I, II or III drugs
Marijuana - Cannabinoid - Schedule I
Anandamide - Endogenous Cannabinoid (thus no schedule)
Dronabinol - Synthetic THC - Schedule III
Nabilone - Synethetic THC - Schedule II
What are the therapeutics of the cannabinoids?
anti-emetic, anti-nausea, appetite stimulating for cancer chemo and AIDS patients, analgesic for neuropathic pain;
possible: glaucoma, asthma, anxiolytic, migraine, MS treatment
What are the side effects of cannabinoids?
vasodilation-->tachycardia, dilation of conjunctival vessels, bronchodilation, decreased intraocular pressure, hunger, impaired reproductive function, development, respiratory damage due to tar
What is the active ingredient in marijuana and how is it metabolized?
active ingredient: delta-9-tetrahydrocannabinol
metabolized by P450 (can act as inducing enzyme with chronic use)
What were the synthetic THC drugs (dronabinol and nabilone) created to treat?
anti-emetic, anti-nausea, appetite stimulate for cancer chemotherapy and AIDS patients
Which of the synthetic THC analogs has the therapeutic effects of THC without the psychactive effects?
What type of drug is Phencyclidine (PCP) and what is its MOA?
it's a dissociative anesthetic that acts as an antagonist of ion channels associated w/NDMA receptors; it's also an agonist at mu opioid receptors
What are the effects of taking PCP?
violent behavior, coma, seizures, arrest, inexplicable psychoses, dissociation, confusion, ataxia, marked nystagmus; long half life due to its high lipid solubility and having active metabolites
What type of drug is MDMA (Ecstasy)?
it's a psychoactive substituted amphetamine with characteristics of: amphetamine + LSD + fluoxetine