M5 L2: CNS Stimulants and Drugs of Abuse Flashcards
physical dependence
dependence involving emotional-motivational withdrawal sympt (ex: dysphoria, anhedonia)
physical (physiologic) dependence
dependence involving persistent physical-somatic withdrawal sympt
all addictive drugs activate the…
mesolimbic system = reward pathway
what are ex of stimulants
amphetamines, cocaine, xanthines and nicotine
what are ex of depressants
opioids, alcohol, barbiturates, benzodiazepines, GHB
ex of anti-depressants
SSRI, SNRI, MAOI
ex of anti-psychotics
typical and atypical
what has its own classification for drugs of abuse
cannibis
what are ex of inhalants
nitrous oxide, ketones, hydrocarbons
what are 2 non-addictive drugs of abuse
- hallucinogens
- dissociative anaesthetics (NMBAR antagonists)
(they don’t target the mesolimbic sys!)
examples of hallucinogens
lysergic acid diethylamide (LSD) - mescaline - psilocybin
ex of dissociative anaesthetics (NMDAR antagonists)
phencyclidine (PCP) - ketamine
what are amphetamines
- alpha-methylphenethylamine
- synthetic sympathomimetics
- derivatives: amphetamine, methamphetamine
what is the mech of action for amphetamines
- increase DA release through: competitive decrease of DA transport back to the presynaptic neuron, and decreased VMAT -> decreased DA reuptake by synaptic vesicles
- increased NE release (sympathomimetic action)
what are amphetamines
weak base (oral bioavailability varies w GI pH
what is the half life of amphetamines
relatively short (9-14h)
what is the metabolism of amphetamines
in the liver - hydroxylation, deamination, conjugation
how are amphetamines excreted
in urine - 30-40% unmetabolized
how are amphetamines administered
oral, smoked, IV
what are the effects of amphetamines
- euphoria and excitement
- cognitive enhancement
- anorexia
- increased motor activity
- fatigue resistance
- improved performance of tedious, repetitive tasks
- sympathomimetic actions* ex: vasoconstriction, increased bp, tachycardia, decreased motility
what are amphetamines CVS adverse effects
dysrhythmias, hypertension, raynaud’s phenomenon
what are amphetamines CNS adverse effects
tremors, agitation, confusion
what are amphetamines respiratory adverse effects
tachypnea
what are amphetamines GI adverse effects
anorexia, weight loss
what are amphetamines urinary adverse effects
dysuria, retention
what are amphetamines eye adverse effects
mydriasis, blurred vision
what are the overall adverse effect of amphetamines
- SNS stim
- tolerance, addiction, dependence
indications of amphetamines
- ADHD
- narcolepsy
- obesity
contraindications of amphetamines
- CVS disease
- anxiety and agitation
- history of drug abuse
what is MDMA (ecstasy-molly)
3,4-Methylenedioxymethamphetamine
- amphetamine-related compound
- was used in psychotherapy - not, only recreational
what is the mech of action for MDMA (ecstasy-molly)
- as amphetamines
- high affinity to serotonin transporter -> increased serotonin reuptake and concentration
- prolonged use causes serotonin depletion
what are the effects of MDMA (ecstasy-molly)
- increased empathy, euphoria, and heightened sensations
- hyperthermia** from dehydration, tachycardia, hallucinations, panic attacks, agitation
what is cocaine
coke!
- alkaloid isolated from Erythroxylum coca leaves
- strong stim
- was used as: local anaesthetic, mydriatic
what is the mech action of cocaine
- cocaine inhibits the reuptake of dopamine (DA) by blocking the dopamine transporter (DAT), leading to an increase in extracellular dopamine concentration
- cocaine also inhibits the reuptake of NE by blocking the NE transporter, resulting in an increase in extracellular concentration
where is cocaine absorbed
lungs and GI (stomach)
where is cocaine distributed to
rapidly into the brain
how is cocaine metabolized and where
by cholinesterase enzymes (liver and plasma)
half time of cocaine
short (1hr)
how is cocaine excreted
in urine
how is cocaine administered
snorting (salt powder), smoke inhalation (crack cocaine), IV (solution), topical (solution)
what are the effects of cocaine
- euphoria + excitement
- cognitive enhancement
- anorexia
- increased motor activity
- fatigue resistance
- peripheral sympathomimetic actions
CVS adverse effects of cocaine
dysrhythmias, hypertension, CAD
CNS adverse effects of cocaine
repeated use:
- tremors, agitation, paranoid delusions, stroke
overdose:
- seizures, hyperthermia, hallucination, coma, death
skin adverse effects of cocaine
pruritus (itching)
respiratory adverse effects of cocaine
tachypnea, hemoptysis, bronchospasm, nasal septum atrophy
GI adverse effects of cocaine
anorexia, dry mouth, gingivitis, dental caries
eye adverse effects of cocaine
mydriasis, blurred vision
can tolerance, addiction, dependence happen w cocaine
YES. obvi
tolerance to cocaine
- may develop
- reverse tolerance: sensitivity to small doses
addiction to cocaine
HIGH - develops after only few exposures
dependence to cocaine
- withdrawal sympt: < opioids
- fatigue, dysphoria, anxiety, irritability, sleepiness, agitation
what is LSD
- ergot alkaloid
- hallucinogen
- psychotomimetic
- was used in psychotherapy
- only recreational
DOES NOT TARGET MESOBOLIC SYS
onset of action, duration, typical dose of LSD
onset of action: 30 min
duration: 6-12 hrs
typical dose: 25 mcg
mech of action in LSD
5-HT2a receptor agonist in thalamus, increases glutamate in cortex
what are the effects of LSD
psychosis-like manifestations:
- depersonalization, hallucinations, distorted time perception
somatic manifestations:
- dizziness, nausea, paresthesia, blurred vision, could cause abortion
- rapid tolerance
- no addiction or dependence
sources of cannabinoids
- endogenous
ex: 2-arachidonyl glycerol (2-AG) - exogenous
- plants: cannabis (marijuana)
- synthetic: chemical substances
what is the main psychoactive constituent of cannabis
Δ ^9 -tetrahydrocannabinol (THC) is the primary psychoactive compound in cannabis.
what is the mech of action of cannabinoids
- activation of cannabinoid-1 receptors leads to an increase in presynaptic GABA neurons in the ventral tegmental area, resulting in the disinhibition of dopamine neurons
how are cannabinoids
absorbed:
onset of action:
peak:
half life:
absorbed: resp sys
onset of action: few min
peak: 1-2 hrs
half life: 4 hrs
CNS effects of cannabinoids
- euphoria, relaxation, sense of well being, and grandiosity
– Disorientation to time & space
– Visual distortion, drowsiness, diminished coordination
– Psychotomimetic, depressant effect & pain relief
can also cause: Tachycardia, vasodilation & bronchodilation
addiction and dependence of cannabinoids
Relatively low risk of addiction
* Withdrawal symptoms:
– Mild & short-lived
– Restlessness, irritability, mild agitation, insomnia, nausea,
cramps
