Drugs of Abuse

Sedative-Hypnotics

r

aka CNS Depressants

act at GABA-A receptor complex

Incr Cl conductance

Alcohols

Ethanol

r

MOA: acts w/ specific site on GABA-A Receptor to facilitate opening of Cl channels (by incr conductance) which leads to hyperpolarization and inhibition of neuronal activityalso allosterically inhibits activity of excitatory glutamate receptors (NMDA subtype)Indications: Antiseptic, solvent for other Rx

Actions

Acute

vasodilation and decr HR

CNS

low dose

neuronal disinhibition (behavioral stimulation)

moderate dose

neuronal inhibition (CNS depression)

high dose

more severe CNS depression (coma, death)

Diuresis

r

inh ADH release

n/v

Chronic

thiamine deficiency

peripheral neuropathy

Wernicke's encephalopathy

Korsakoff's syndrome

incr NADH/NAD ratio

cirrhosis

pancreatitis

precipitates DM

cardiomyopathy

cancer

FAS

Contraindications

ulcers

liver disease

pregnancy

seizure d/o

Drug interactions

other sedatives (BZ, Antidepress., Antihistam.)

aspirin, other NSAIDS

GI bleeding

phentoin and warfarin

Acute EtOH

inhibs liver microsomal enzymes

decr metab

Chronic EtOH

induces liver microsomal enzymes

incr metab

Drug therapy

causes you to feel bad symptoms earlier

Disulfram

chelates the cofactors necessary for acetaldehyde DH

causes "acetaldehyde syndrome"

n/v

flushing

HA

sweating

hypotension

confusion

reduces craving

Naltrexone

opioid recptor antag

reduces craving and prevents relapse

Acamprosate

competitive inhib of NMDA Glutamate receptor

Methanol

r

metabolized by ADH to formaldehyde, then oxidized to formic acid (toxic)

Poisoning

Blindness

Acidosis

Seizures, coma

Tx

Ethanol administration

Incr frequency of Cl channel opening

Benzodiazepines

r

Short-Med. duration

Chloridiazepoxide

Incr duration of Cl channel opening

Barbituates

ultrashort acting

Thiopental

r

rapid redistribution to less vascular tissues

highly lipid soluble

general anesthesia

short-intermediate acting

Pentobarbital

preanesthetic

regional anesthesia

less lipid soluble

long acting

Phenobarbital

less lipid soluble

25% excreted unchanged

duration of action influenced by pH of urine

uses:

seizure d/o

withdrawal syndrome from sed/hyp's

congenital hyperbilirubinemia

neonatal jaundice

contraindications:

acute intermittent porphyria

r

phenobarbital induces delta-ALA synthase, which increases porphyrin biosynthesis

much more risk for abuse than BZ's!!

Stimulants

r

increase DA, NE, 5HT avalability in the synapse

short t1/2

Cocaine

r

more rapidly absorbed and distributedmetabolized by plasma and liver cholinesterase

blocks DA transporters/reuptake sites

metab to benzoylecgonine and ecgonine methlyester

indications:

topical anesthesia

toxicity:

perferation of nasal septum

"Crack Baby"

r

b/c cocaine decreases uterine bloodflow, thus causing fetal hypoxia

Seizures

Cerebrovascular hemorrhage

Coronary vasospasm, Arrythmia, MI

Toxic psychosis

long t1/2

Amphetamine (Dexedrine)

increases release of DA

inhibits MAO (so NE builds up)

toxicity

necrotizing arteritis

see also "Cocaine: Toxicity"

l

indications:

Narcolepsy

r

Modafinil is another choice for narcolepsy txit has less likelyhood of adiction than amphet.'s

ADHD

Amphetamine analogues

Methamphetamine (Desoxyn)

Methylphenidate (Ritalin)

Phenteramine (Adipex-P)

Acute Actions

euphoria

elevated mood

decreased appetite

increased motor activity

AE:

extraordinary tolerance can develop

anxiety, insomnia

dangerous, bizzare behavior

tachycardia and HTN

sexual d/f

Post spree crash, withdrawal

Marijuana

r

Active constituent: THC (delta-9 tetrahydrocannabinol)dronabinol (Marinol) is THC analogue

MOA: unknown

r

has something to do with CB1 receptors and G proteins

indications:

prevent n/v during chemo

appetite stimulant in AIDS

decrease IOP in glaucoma

neuropathic pain

pharmacokinetics

rapidly absorbed in lungs

rapidly distributed to CNS

onset of action almost immediate

duration of action 2-3 hrs

high lipid solubility so sequestered and slowly metabolized

r

can detect in drug screen days later

actions:

increased appetite

relaxed, dreamlike state

depersonalization

reddening of the conjunctiva

AE:

chronic lung effects (similar to nicotine)

"antimotivational syndrome" (controversial)

tolerance develops but disappears rapidly

Hallucinogens

indoleamine hallucinogens (serotonin-like)

Lysergic Acid Diethylamide (LSD)

extreme tolerance develops rapidly

5HT agonist

anesthetic hallucinogens

Phencyclidine (PCP)

NMDA antag

long half-life (d/t enterohepatic circulation)

dissociates individuals from themselves

phenethylamine hallucinogens (NE/DA/Amphet-like)

Ecstasy (MDMA)

halucinogenic properties

from incr 5HT transmission

drug-reinforcing properties

from release of DA in brain-reward system

Opioids

(see "Opioid" map)

m

Inhalants

Industrial/Household Solvents

paint thinners

degreasers

solvents in glue

correction fluid

marker pen solvents

toluene

Aerosols

Fluorocarbons

Anesthetic gases

Nitrous oxide

found in whipped cream cannisters

Halothane

Organic nitrates

Amyl Nitrate

Nicotine

MOA

mimics Ach at cholinergic nicotinic receptors

increases the release of adrenal catecholamines

increases the release of neurotransmitters

ACh

NE

DA

5HT

Pharmacokinetics

rapidly absorbed and distributed

metabolized mostly in liver, but also in lungs

eliminated by the kidney

t1/2 = 2hrs

AE:

Cancer

Chronic bronchitis

COPD

Coronary artery dz

Peripheral vascular dz

Tolerance

develops rapidly

long-lasting

Psychological Dependence

Activates brain reward system

Decr. MAO activity

Incr NO production

Incr. DA levels in nucleus accumbens

Withdrawal

High relapse rate

Treatment for Dependence

Replacement Therapies

Nicotine polacrilex (gum)

Nicotine transdermal patch

Nicotine nasal spray

Nicotine inhaler

Non-Nicotine Therapies

Clonidine

Alpha adrenoreceptor partial ag

Nortryptyline

Antidepressant

Bupropion (Zyban)

Antidepressant

Selegeline

MAO inhibitor