Drugs of Abuse

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Drugs of Abuse

Nicotine

Treatment for Dependence

Non-Nicotine Therapies

Selegeline

MAO inhibitor

Bupropion (Zyban)

Nortryptyline

Antidepressant

Clonidine

Alpha adrenoreceptor partial ag

Replacement Therapies

Nicotine inhaler

Nicotine nasal spray

Nicotine transdermal patch

Nicotine polacrilex (gum)

High relapse rate

Withdrawal

Psychological Dependence

Activates brain reward system

Incr. DA levels in nucleus accumbens

Incr NO production

Decr. MAO activity

Tolerance

long-lasting

develops rapidly

Peripheral vascular dz

Coronary artery dz

COPD

Chronic bronchitis

Cancer

Pharmacokinetics

t1/2 = 2hrs

eliminated by the kidney

metabolized mostly in liver, but also in lungs

rapidly absorbed and distributed

MOA

mimics Ach at cholinergic nicotinic receptors

increases the release of neurotransmitters

5HT

DA

NE

ACh

increases the release of adrenal catecholamines

Inhalants

Organic nitrates

Amyl Nitrate

Anesthetic gases

Halothane

Nitrous oxide

found in whipped cream cannisters

Aerosols

Fluorocarbons

Industrial/Household Solvents

marker pen solvents

toluene

correction fluid

solvents in glue

degreasers

paint thinners

Opioids

(see "Opioid" map)

Hallucinogens

phenethylamine hallucinogens (NE/DA/Amphet-like)

Ecstasy (MDMA)

drug-reinforcing properties

from release of DA in brain-reward system

halucinogenic properties

from incr 5HT transmission

anesthetic hallucinogens

Phencyclidine (PCP)

dissociates individuals from themselves

long half-life (d/t enterohepatic circulation)

NMDA antag

indoleamine hallucinogens (serotonin-like)

Lysergic Acid Diethylamide (LSD)

5HT agonist

extreme tolerance develops rapidly

Marijuana

Active constituent: THC (delta-9 tetrahydrocannabinol)

dronabinol (Marinol) is THC analogue

tolerance develops but disappears rapidly

"antimotivational syndrome" (controversial)

chronic lung effects (similar to nicotine)

actions:

reddening of the conjunctiva

depersonalization

relaxed, dreamlike state

increased appetite

pharmacokinetics

high lipid solubility so sequestered and slowly metabolized

can detect in drug screen days later

duration of action 2-3 hrs

onset of action almost immediate

rapidly distributed to CNS

rapidly absorbed in lungs

neuropathic pain

decrease IOP in glaucoma

appetite stimulant in AIDS

prevent n/v during chemo

MOA: unknown

has something to do with CB1 receptors and G proteins

Stimulants

increase DA, NE, 5HT avalability in the synapse

AE:

Post spree crash, withdrawal

sexual d/f

tachycardia and HTN

dangerous, bizzare behavior

anxiety, insomnia

extraordinary tolerance can develop

Acute Actions

increased motor activity

decreased appetite

elevated mood

euphoria

Amphetamine analogues

Phenteramine (Adipex-P)

Methylphenidate (Ritalin)

Methamphetamine (Desoxyn)

long t1/2

Amphetamine (Dexedrine)

ADHD

Narcolepsy

Modafinil is another choice for narcolepsy tx

it has less likelyhood of adiction than amphet.'s

toxicity

see also "Cocaine: Toxicity"

necrotizing arteritis

inhibits MAO (so NE builds up)

increases release of DA

short t1/2

Cocaine

more rapidly absorbed and distributed

metabolized by plasma and liver cholinesterase

toxicity:

Toxic psychosis

Coronary vasospasm, Arrythmia, MI

Cerebrovascular hemorrhage

Seizures

"Crack Baby"

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

perferation of nasal septum

indications:

topical anesthesia

metab to benzoylecgonine and ecgonine methlyester

blocks DA transporters/reuptake sites

Sedative-Hypnotics

aka CNS Depressants

act at GABA-A receptor complex

Incr duration of Cl channel opening

Barbituates

much more risk for abuse than BZ's!!

long acting

Phenobarbital

contraindications:

acute intermittent porphyria

phenobarbital induces delta-ALA synthase, which increases porphyrin biosynthesis

uses:

neonatal jaundice

congenital hyperbilirubinemia

withdrawal syndrome from sed/hyp's

duration of action influenced by pH of urine

25% excreted unchanged

short-intermediate acting

Pentobarbital

less lipid soluble

regional anesthesia

preanesthetic

ultrashort acting

Thiopental

rapid redistribution to less vascular tissues

general anesthesia

highly lipid soluble

Incr frequency of Cl channel opening

Benzodiazepines

Short-Med. duration

Chloridiazepoxide

Incr Cl conductance

Alcohols

Methanol

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

Tx

Ethanol administration

Poisoning

Seizures, coma

Acidosis

Blindness

Ethanol

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 activity

also allosterically inhibits activity of excitatory glutamate receptors (NMDA subtype)

Indications: Antiseptic, solvent for other Rx

Drug therapy

reduces craving

Acamprosate

competitive inhib of NMDA Glutamate receptor

Naltrexone

reduces craving and prevents relapse

opioid recptor antag

causes you to feel bad symptoms earlier

Disulfram

causes "acetaldehyde syndrome"

confusion

hypotension

sweating

HA

flushing

chelates the cofactors necessary for acetaldehyde DH

Drug interactions

phentoin and warfarin

Chronic EtOH

induces liver microsomal enzymes

incr metab

Acute EtOH

inhibs liver microsomal enzymes

decr metab

aspirin, other NSAIDS

GI bleeding

other sedatives (BZ, Antidepress., Antihistam.)

Contraindications

seizure d/o

pregnancy

liver disease

ulcers

Actions

Chronic

FAS

cancer

cardiomyopathy

precipitates DM

pancreatitis

cirrhosis

incr NADH/NAD ratio

thiamine deficiency

Korsakoff's syndrome

Wernicke's encephalopathy

peripheral neuropathy

Acute

n/v

Diuresis

inh ADH release

CNS

high dose

more severe CNS depression (coma, death)

moderate dose

neuronal inhibition (CNS depression)

low dose

neuronal disinhibition (behavioral stimulation)

vasodilation and decr HR