M5: Drugs of Abuse Flashcards
Define the Following:
1. Tolerance
2. Addiction
3. Psychological Dependence
4. Physical (Physiological) Dependence
- Tolerance: the diminishing effect of a drug resulting from repeated administration at a given dose
- Addiction: brain disorder characterized by compulsive engagement in rewarding stimuli despite adverse consequences
- Physiological Dependence: dependence that involves emotional–motivational withdrawal symptoms (e.g., dysphoria and anhedonia)
- Physical (Physiologic) Dependence: dependence that involves persistent physical–somatic withdrawal symptoms (e.g., fatigue and delirium tremens)
Neurobiology of Drug Abuse
- Mesolimbic System = Reward Pathway
- Dopaminergic neurons
- GABAergic neurons
- Glutamatergic neurons - All Addictive Drugs Activate The Mesolimbic DA System
(6) Classification of Drugs of Abuse: Pharmacology
- Stimulants: amphetamines, cocaine, xanthines & nicotine
- Depressants: opioids, alcohol, barbiturates, benzodiazepines, GHB
- Anti-depressants: SSRI, SNRI, MAOI…
- Anti-psychotics: typical & atypical
- Cannabis
- Inhalants: nitrous oxide, ketones, hydrocarbons
Nonaddictive Drugs of Abuse
They don’t target the mesolimbic system
- Hallucinogens:
- Lysergic acid diethylamide (LSD) – mescaline – psilocybin - Dissociative anaesthetics (NMDAR antagonists):
- Phencyclidine (PCP) – ketamine
AMPHETAMINES
- Mechanism of Action
- Pharmacokinetics
- Pharmacological Effects
- Adverse Effects
- Indications and Contraindications
- Alpha-methylphenethylamine
- Synthetic sympathomimetics
- Derivatives:
Amphetamine, methamphetamine
MECHANISM OF ACTION:
Increase DA release through:
1. Competitive decrease of DA transport back to the presynaptic neuron
- Decrease VMAT → decrease DA reuptake by synaptic vesicles
PHARMACOKINETICS:
1. Weak base = oral bioavailability varies with GI pH
- t1/2: relatively short (9-14h)
- Metabolism:
In the liver – hydroxylation, deamination, conjugation - Excretion:
In urine – 30-40% unmetabolized - Administration:
Oral, smoked, IV
PHARMACOLOGICAL EFFECTS:
1. Euphoria & excitement
2. Cognitive enhancement
3. Anorexia
4. Increase motor activity
5. Fatigue resistance (physical & mental)
6. Improved performance of tedious, repetitive tasks
7. Sympathomimetic actions:
E.g., vasoconstriction, increase BP, tachycardia, decrease GI motility
ADVERSE EFFECTS :
1. CVS: dysrhythmias, hypertension, Raynaud’s phenomenon
- CNS: tremors, agitation, confusion
- Respiratory: tachypnea
- GI: anorexia, weight loss
- Urinary: dysuria, retention
- Eye: mydriasis, blurred vision
- Tolerance, addiction & dependence:
- Withdrawal symptoms: dysphoria, irritability, drowsiness, insomnia
- Sympathetic Stimulation
INDICATIONS & CONTRAINDICATIONS:
Indications:
1. Attention Deficit Hyperactivity Disorder (ADHD)
2. Narcolepsy
3. Obesity
Contraindications:
1. CVS disease
2. Anxiety & agitation
3. History of drug abuse
MDMA (ECSTASY - MOLLY)
- Properties
- Mechanism
- Pharmacological Effects
DRUG = 3,4-Methylenedioxymethamphetamine
PROPERTIES:
1. Ecstasy = euphoria, overwhelming feeling of great joy or happiness
2. Amphetamine-related compound.
3. Was used in psychotherapy – now, only recreational.
MECHANISM: as amphetamines +
1. High affinity to serotonin transporter (SERT) → decrease serotonin reuptake → increase serotonin concentration
- Prolonged use → intracellular serotonin depletion
PHARMACOLOGICAL EFFECTS:
1. Increased empathy, euphoria, and heightened sensations
2. Hyperthermia, tachycardia, hallucinations, panic attacks, agitation
- Augmented by dehydration → fatal
COCAINE
- Properties
- Mechanism of Action
- Pharmacokinetics
- Pharmacological Effects
- Adverse Effects
DRUG = aka coke
PROPERTIES:
1. Alkaloid isolated from Erythroxylum coca leaves
2. Strong stimulant
3. Was used as: Local anaesthetic, Mydriatic
MECHANISM OF ACTION:
1. Decrease of DA transporter (DAT) → decrease DA reuptake → increase DA concentration
- Decrease of NE transporter (NET) → decrease of NE reuptake → increase NE concentration
PHARMACOKINETICS:
1. Absorption: lungs & GI (stomach)
- Distribution: rapidly into the brain
- t1/2: short ( 1 hour)
- Metabolism: by cholinesterase enzymes (liver & plasma)
- Excretion: In urine
- Administration: snorting, smoke inhalation, IV, topical
PHARMACOLOGICAL EFFECTS:
1. Euphoria & excitement
2. Cognitive enhancement
3. Anorexia
4. Increase motor activity
Fatigue resistance (physical & mental)
5. Peripheral sympathomimetic actions:
E.g., vasoconstriction, BP, tachycardia, GI motility
ADVERSE EFFECTS:
1. CVS: dysrhythmias, hypertension, CAD
- CNS:
- Repeated use: tremors, agitation, paranoid delusions, stroke
- Overdose: seizures, hyperthermia, hallucination, coma, death - Skin: pruritus (itching)
- Respiratory: tachypnea, hemoptysis, bronchospasm, nasal septum atrophy
- GI: anorexia, dry mouth, gingivitis, dental caries
- Eye: mydriasis, blurred vision
- Tolerance, Addiction & Dependence
- Tolerance may develop
- Reverse tolerance: sensitivity to small doses
Addiction:
High – develops after only few exposures
Dependence:
Withdrawal symptoms: < opioids
Fatigue, dysphoria, anxiety, irritability, sleepiness & agitation
LYSERGIC ACID DIETHYLAMIDE (LSD)
- Properties
- Mechanism of Action
- Pharmacokinetics
- Pharmacological Effects
PROPERTIES:
- Ergot alkaloid
- Hallucinogen
- Psychotomimetic (mimics the symptoms of psychosis)
- Was used in psychotherapy
- Now, only recreational
MECHANISM OF ACTION:
5-HT2A receptor agonist in thalamus → increase glutamate in cortex
PHARMACOKINETICS:
1. Onset of Action: 30 minutes
2. Duration: 6 – 12 hours
3. Typical Dose: 25 mcg
PHARMACOLOGICAL EFFECTS:
1. Psychosis-like manifestations:
Depersonalization, hallucinations, distorted time perception
- Somatic manifestations:
Dizziness, nausea, paresthesia, blurred vision - Uterine contractions → abortion
RAPID tolerance
NO addiction or dependence (doesn’t target mesolimbic system)
(2) Other Hallucinogens
- Mescaline → Peyote cactus (Lophophora williamsii)
- Psilocybin → psilocybin mushrooms
CANNABINOIDS
- Sources
- Mechanism of Action
- Pharmacokinetics
- Pharmacological Effects
- Addiction and Dependence
SOURCES:
1. Endogenous (endocannabinoids):
DRUG = 2-arachidonyl glycerol (2-AG)
- Exogenous:
Plants (phytocannabinoids): cannabis (marijuana)
Synthetic: chemical substances
Main psychoactive constituent of cannabis:
Triangle9-tetrahydrocannabinol (THC)
MECHANISM:
Act on cannabinoid-1 receptor (CB1R) →
Presynaptic decrease of GABA neurons in VTA →
Disinhibition of DA neurons
PHARMACOKINETICS:
1. Absorption: respiratory system
2. Onset of action: few minutes
3. Peak: 1 – 2 hours
4. t1/2: 4 hours
PHARMACOLOGICAL EFFECTS:
1. CNS:
- Euphoria, relaxation, sense of well being & grandiosity
- Disorientation to time & space
- Visual distortion, drowsiness, diminished coordination
- Psychotomimetic, depressant effect & pain relief
- Others:
- Increase appetite & decrease nausea
- Decrease intraocular pressure (IOP)
- Tachycardia, vasodilation & bronchodilation
ADDICTION & DEPENDENCE
- Relatively low risk of addiction
- Withdrawal Symptoms:
Mild & short-lived
Restlessness, irritability, mild agitation, insomnia, nausea, cramps
