Drugs of Abuse

Question 1

3.3 Types of Tolerance

Answer 1

Innate
Acquired - Pharmokinetic/dynamic, learned
Cross

Question 2

Rimonabant

Answer 2

Cannabinoid R inverse agonist, potential cessation aid for a lot of substances

Question 3

Key Addiction Pathway

Answer 3

DA neurons from VTA go to inhibit GABA nuclei in NAc, leading to reward in ventral pallidum. Also GABA in VTA that inhibit DA. Opioid in each inhibit GABA as well. Glutamate from cortex excites GABA

Question 4

Opiates Effect

Answer 4

Act to inhibit both GABA in VTA (releases DA inhibition) and NAc

Question 5

Opioid Danger

Answer 5

Tolerance to desirable effects develops quickly, so users quickly require desirable effects and withdrawal avoidance, increasing risk of overdose (usually respiratory depression)

Question 6

Salvia

Answer 6

Activates Kappa-opioid agonist

Question 7

3 Kinds of Effects from Smoking and What They’re From

Answer 7

CV: Primarily nicotine
Carcinogenic: Probably tar then enhanced by nicotine
Respiratory: Tar

Question 8

Titration

Answer 8

Smokers will alter their behavior to get the exact conc of nicotine they like

Question 9

Nicotine Effect

Answer 9

Acts on DA cell bodies and presynaptic terminals both to depol them and make APs more likely

Question 10

Cocaine CV Effects

Answer 10

Bradycardia from vagal stimlation, then tachycardia at higher doses. Tolerance develops to CNS effect but not these, where danger lies

Question 11

Cocaine Treatment (3)

Answer 11

Alpha/beta adrenergic blockers - labetolol
Calcium channel block
Diezepam for calming

Question 12

2 Most Common Cocaine Administrations

Answer 12

Cocaine hydrochloride and cocaine free base (crack)

Question 13

Cocaine Mechs

Answer 13

Blocks NE, DA, and 5HT (higher dose) transporters. Peripheral effects due to block of sympathetic neurons

Question 14

Cocaine Elimination

Answer 14

Primarily by plasma esterases, not much excreted in urine

Question 15

Amphetamine Treatment

Answer 15

Alpha1 blocker - prazosin

Question 16

Amphetamine Tolerance

Answer 16

Develops to CNS effects, so move up to huge amounts until reach psychotoxic effects and become so out of it/schizo that they can’t administer anymore

Question 17

Amphetamine Mech

Answer 17

Taken up by NET/DAT/SERT, blocks VMAT which reloads vesicles, so MA builds up at nerve terminal and effluxes. Also inhibits MAO which breaks down toxic DA buildup products

Question 18

Ecstasy Mech

Answer 18

Acute release of 5HT/action on 5HT transporter

Question 19

Phenethylamine and Tryptamine

Answer 19

Scaffolds for DA/NE and 5HT, respectively. Psychadelics

Question 20

Most Potent Cannabinoids

Answer 20

Delta9-THC and 11-hydroxy-Delta9-THC (metabolite) - any further metabolism inactivates

Question 21

2/3 Clinical Uses for Cannabinoids

Answer 21

Anti-emetic/appetite stimulant for chemotherapy - Marinol and nabilone
Glaucoma - reduces intraocular pressure

Question 22

Notable Feature About LSD

Answer 22

Exceptionally potent

Question 23

Notable Aspect of Psychadelic Tolerance

Answer 23

Can develop after a few daily doses, but returns after a few drug free days. Maybe due to downreg. Also cross tolerance b/w LSD, mescaline, and psilocin

Question 24

Psychadelic Mech

Answer 24

Act on 5HT GPCRs, especially partial agonism at 5HT2, probably responsible for hallucinations

Question 25

PCP Mech

Answer 25

Channel blocker of NMDA glutamate Rs. These have learning/memory effects (also this might be responsible for dependence)

Question 26

Standard Dose of Ethanol

Answer 26

0.5 oz = 14g

Question 27

EtOH Distribution

Answer 27

Everywhere, but very water soluble so really where there’s water. Easily crosses BBB

Question 28

EtOH Elimination via Lungs

Answer 28

1st order, so proportional to BAC in exhalation

Question 29

Saturation Kinetics of EtOH Metabolism

Answer 29

Saturated, so 0 order. Can metabolize 2/3 standard drink/hr

Question 30

EtOH Metabolism

Answer 30

ADH converts to acetaldehyde, ALDH converts to acetate. Each step produces NADH, so produces a lot of reducing capacity that can damage cells

Question 31

2 EtOH Metabolism Polymorphisms

Answer 31

ADH: Slow EtOH metabolism, so it lasts longer and increased risk for alcoholism
ALDH - Asian flush, can’t drink

Question 32

Alcohol Mechanisms

Answer 32

Not quite sure, just kinda generalized effects like GA but with very low affinity. GABAa Rs seem to be a target

Question 33

2 Alcohol Dependence Treatment Drugs

Answer 33

Acamprosate - GABAa activator

Disulfiram - ALDH inhibitor, can’t tolerate EtOH

Question 34

Delirium Tremens

Answer 34

Severe alcohol withdrawal w/ hallucinations and delirium and shit

Question 35

Treatment for Alcohol Withdrawal Syndrome

Answer 35

Benzodiazepines

Question 36

3 Liver Issues w/ Alcohol

Answer 36

Excess reducing capacity
Acute Drug Metabolism: decreased bc enzymes being used/decreased blood flow
Chronic: faster for some drugs bc enzyme induction

Question 37

Methanol

Answer 37

Converted to formaldehyde, then formate which is especially dangerous. Can cause retinal damage/blindness, among other things

Question 38

Best Treatment of Methanol and Ethylene Glycol Poisoning

Answer 38

Ethanol - ADH has higher affinity for it

Question 39

GHB

Answer 39

Looks like GABA, addictive as GABAb agonist (inhibits GABA neurons inhibiting DA ones in VTA)

Question 40

Thujone

Answer 40

GABAa R modulator thought to be special factor in Absinthe, turns out not there.