Drugs of Abuse Flashcards
Drugs with dependence liability (signif) share what property?
-enhance dopamine activity in the nucleus accumbens
DA neuron cell body in ventral tegmental area, nerve terminal in Nucleus Accumbens
drug abuse
Use of a drug for nonmedical reasons that deviates from approved social patterns (alters mood, level of perception, or brain functioning).
metabolic tolerance
a change in pharmacokinetics results in lowered drug concentrations at the active site; metabolism the primary mech (eg more rapid enzymatic degradation of the drug)
Pharmacodynamic tolerance
lessened response at active site to the same drug concentration; achieved via changes in receptor sensitivity or other adaptive changes
learned tolerance
- reduction in the effects of a drug due to learned compensatory mechanisms
- behavioral tolerance: describes skills developed due to repeated experiences in attempting to function despite mild-moderate intoxication
-conditioned tolerance: develops when environmental cues (sights, smells, situations) are consistently paired with drug administration
reverse tolerance
sensitization (increased response) to drug following repeated doses
cross tolerance
after tolerance develops to one drug, it is also seen to other drugs
-used in detox procedures
Ex: heroin and hydrocodone (both @ mu recep)
Ex: ethanol and BDZ (both at GABA recep)
Physical dependece
-repeated drug use alters physiological state such that continued admin is needed to prevent withdrawal sx
cross dependence
ability of drug to suppress the withdrawal assoc w/ physical dependence of another drug
Ex: benzos are often used to suppress alcohol withdrawal sx
psychological dependence
perceived need for a drug (“CRAVING”)
-related to pathologic learning in reward pathway
opioids
Heroin, (oxycodone, hydrocodone)
Action in CNS: interaction w/ endogenous opiate receptors (especiall mu); rush feeling related to histamine release
Major effects leading to abuse: euphoria, analgesia, sedation w/ anxiety reduction
Sx of acute toxicity: coma, respiratory distress, pinpoint pupils
Treatment: naloxone (Narcan)–could precip withdrawal
tolerance develops rapidly to most opioids
physical dependence: develops rapidly
withdrawal: sx are not MEDICALLY dangerous, but bothersome
Which route of admin from psychoactive drugs provides most rapid onset of effects in the brain?
inhalation (smoking)
MOAs of drugs of abuse
opioids: mu opioid receptors (Gi)
CNS depressants: enhance GABA, inhibit glut
CNS stimulants: block DA reuptake or enhance DA release
Nicotine: agonist @ nicotinic neuronal receptors
Hallucinogens: partial agonist at 5HT2 receptors (DA releaser)
Dissociative anesthetics: antagonist at NMDA-Glu receptors
Cannabinoids: agonist at cannabinoid (CB1-CB2) receptors
reinforcing effects of opioids
euphoria, sedation, anxiolytic
reinforcing effects of CNS depressants
euphoria, sedation, loss of inhibition
reinforcing effects of CNS stimulants
euphoria, decreased fatigue, increased arousal
reinforcing effects of nicotine
increased alertness
reinforcing effects of hallucinogens
altered sensory perception, enhanced insight
reinforcing effects of dissociative anesthetics
euphoria, heightened emotionality
reinforcing effects of cannabinoids
euphoria, mellowness, changes in perception
examples of stimulants
cocaine
meth
nicotine
cocaine and meth have highest relative risk of addiction
ex of drug that blocks reuptake of DA and NE into presyn catecholamine neurons and also blocks Na channels in neuronal membranes
cocaine
CNS depressants
-action/acute toxicity
-via GABA activation +/- glu inhibition
-respiratory depression, coma (extremely rare w/ BDZs)
Treatment:
ethanol: supportive plus fluids-electrolytes-thiamine
BDZs: flumazenil
Barbs: supportive
CNS stimulants
-action/acute toxicity
-via activation of NE and DA receptors
-tox: SNS overactivity, increased HR/BP/temp, chest pain/MI, psychosis
Treatment: CVS suport, vasodilators for BP, BDZs for agitation/seizures
Nicotine
-action/acute toxicity
-rare toxicity
-via activation of nicotinic cholinergic receptors
Tox: n/v, diarrhea, CVP collapse, convulsions
Tx: CVS support, emetics, gastric lavage, charcoal
Hallucinogens
-action/acute toxicity
-actions on 5HT receptors
-LSD-Psilocybin: “bad trip”, severe anxiety
Tx: talking down, BDZs for agitation
-MDMA: agitation, hyperthermia, ADH release–>hyponatremia
Dissociative anesthetics
-action/acute toxicity
Phencyclidine (PCP), Ketamine
-via block of NMDA Glu receptors
-delirium, increased RR, HR, BP, temp, agitation, violent behavior
Tx: supportive for BP-hyperthermia, agitation (BDZs)
Cannabinoids action/acute tox
-activation of CB1 receptors
minimal–>possible anxiety, impaired coord-tracking, acute psychosis
Tolerance to drugs of abuse
opioids: rapid (but not to constipation)
CNS dep: rapid to barbs>ethanol, BDZs (signif to sedation/intox, less to lethal dose)
CNS stim: develops to euphoria, anorex/hyperthermia, can see supersensitivity to paranoia
Nicotine: develops to subjective effects and nausea
hallucinogens: not common
dissociative anesthetics: not well studied
cannabinoids: rapid to most effects, but disappears rapidly
Do tolerance and dependence coexist?
-not necessarily
nor do addiction and physical dependence
Dependence on Drugs of abuse
-opioids: develops rapidly (scheduled doses, within 1-2 wks)
-CNS dep: w/in WEEKS
-CNS stimulants: arguable, lack of physiological effects
-Nicotine: moderate devel
-Hallucinogens: does not devel
Dissoc anesthetics: probably none
Cannabinoids: accumulating evidence for dependence
Withdrawal
characterized by rebound effects on the phsyiological sx that have been modified by chronic drug use
- Effects generally opposite of the acute effects of the drug
- Withdrawal sx can be FATAL and may require emergent interventions
Withdrawal from opioids
rarely life threatening**
insomnia, diarrhea, irritability, cramps, muscle aches, increased BP
Tx: clonidine, methadone
CNS depressants withdrawal
-significant risk of mortality due to seizures
Tx: substitution with BDZs: loading dose then taper to prevent sz
CNS stim withdrawal
sleepiness, fatigue, depression, hyperphagia, craving
Tx: largely behavioral
Nicotine withdrawal
-irritability, hostility, anxiety, increased appetite, weight gain
Tx: relapse–>nicotine replacement, bupropion, varenicline
Hallucinogens withdrawal
not known, “flashbacks in some former users
Withdrawal from cannabinoids
not clinically significant (long t1/2)
Tx: usually not needed
