Drugs of Abuse genreal Flashcards
Drug abuse defenition
- consumption of drugs without medical approval or supervision to acheive strong feelings of EUPHORIA and REWARD
- use of drug in manner DETRIMENTAL TO THE HEALTH
- Chonric exposure may lead to brain alterantions that result in COMPULSIVE DRUG USE = HALLMARK OF DRUG ADDICTION
Tolerance
takes more drug to elicit same effect/response
- Pharmacokinetic tolerance = increase drug metabolism results in decrease in the amount of available drug or duration of drug action at the target site
- Pharmacodynamic tolerance = CNS responds and adapts to presence of drug –> DESENSITIZATION, down-regulation
Withdrawal syndromes
- Onset of WITHDRAWAL SYNDROME when drug is no longer available
- DYSPHORIA, DEPRESSION, ANXIETY< STRONG CRAVINGS, SEIZURES< pSYCHOSIS
ADICTION
- Psychological dependence
- Compulsive drug use to induce pleasure and or escape from reality despite negative consequences
- HIGH RISK OF RELAPSE IF:
–> re-exposure to addictive drug
– exposure to contextual cues that recall prior drug use trigger cravings
–> stress
describe teh mech of addictive drusg
ALL ADDICTIVE DRUGS ACTIVATE MESOLIMBIC DOPAMINE SYSTEM –> REWARD PATHWAY
CNS DEPRESSANTS and SEDATIVES/HYPNOTICS
Releative risk (RR) of addiction = 3
- Alcohol
- Benzodiazepines (diazepam, alprazolam, flunitrazepam)
- Barbiturates (pentobarbital)
- GHB
Most commoly abused benzodiazepines
Diazepam, alprazolam
Flunitrazepam
- Date rape drug
60 hour detection windown
Flumazenil
benzodiazepine receptor antagonist
- useful in tx of overdose and reversing the effects of long-acting benzodiazepines used in anesthesia
MoA of benzodiazpeines and barbiturates abuse
- Benzo and barbiturates are POSITIVE MODULATORS of GABAa-Chloride ion channels
–> potentiate GABAergic inhibiton at all level of the neuraxis
- OVERALL RESULT IS DISINHIbiTION OF THE VTA DOPAMINE (DA) NEURONS AND ACTIVATION OF THE MESOLIMBIC REWARD PATHWAY
Gama-hydroxybutyric acid (GHB)
- low margin of safety, addictive potential
- REWARD PATHWAY: disinhibition of Da neurons in VTA via GABAb receptor (metabotropic)
- causes euphoria, enhanved sensory perception, sedation, feeling of social closeness and AMNESIA
**ODORLESS< TASTELESS, READILY DISSOLVES –> DATE RAPE DRUG
drugs calssified as PSYCHOSTIMULANTS
RR of adicition = 5!!!
- Cocaine
- amphetamine
- methamphetamine
- methylphenidate
- MDMA
Cocaine
- reward effects of cocaine = increased DA release in nucleus accumbens (VTA - mesolimbic pathway
- Induces INTENSE euphoric effect, increased energy and libido
–> LINKED TO CARDIOVASCULAR TOXICITY
- tolerance and withdrawal symptoms
- STRONGEST PSYCHOLOGICAL DEPENDENCE OF ANY DRUG
Cocaethylene
- mixture of ETOH and cocaine, produces an intesnification of cocaines euphroic effects
Methamphetamine
- Amphetamines lead to increase in catecholamines resulting in EUPHORIA, INCREASED AROUSAL, and REDUCED SLEEP
- produce sympathomimetic effects = mydriasis, tachycardia, hypertension
- SERIOUS EFFECTS = MI, cerebrovascular hemorrhage, seizure and death
- VERY ADDICTIVE; TOLERANCE develops with chronic use;
- WITHDRAWAL SYMPTOMS = dysphoria, drowsiness and irritability
MoA of psychostimulant
- Cocaine = blocks DA reuptake transporter (DAT and increase synpatic DA
- AMphetamines
1) taken up into DA and NE terminals
2) cause vesicular release of DA and NE
3) reverse DA transporter (DAT) –> increased release of DA
Methylphenidate
- DA/NE reuptake blocker; sympathomimetic
- Used to tx ADHD and Narcolepsy
- ADVERSE EFFECTS = insomnia, abdominal pain, weight loss and grwoth suppression
- absolute contraindication with MAOI and existing cardiac abnormalities
MDMA
ecstasy
- 5-HT transporter (SERT) to release t-HT from presynaptic terminals
–> significant 5-H% depeltion for 24 hrs following a single use
–> PERMANENT 5-HT DEPELENTION may occur following prolonged, chronic admin
- TOXICITY = ACUTE –> HYPERTHERMIA and DEHYDRATION
- WITHDRAWAL = offset mood (prolonged depression and sometime aggression
Psychedelics
RR of addiction = 1
- Lysergic acid diethylamide
- psilocybin
- ketamine
- phencyclidine
OPIOIDS
- RR of addiction = 4
- Opiates = morphine, codeine, heroin
- Opioids
opioid abstincence syndrome
- cessation of long-term opiate use
- Symptoms
–> dysphoria, nausea, vomiting, rhinorrhea, lacrimation, yawning, chills, flu-like muscular aches, gooseflesh, hyperventilation, hyperthemia etc
