Drugs Of Abuse Flashcards
Definition of dependence
Psychological and physical phenomena associated with drug use
Tolerance definition
Deceased effect or increased dose needed to produce same effect
Withdrawal definition
Signs and symptoms associated with reduced drug intake or withdrawal
Addiction definition
Compulsive relapsing drug use despite negative consequences, triggered by cravings in response to contextual cues
What does dopamine play a role in
Movement, motivation, reward and addiction
Dopamine pathway involved in addiction
Mesolimbic dopamine system
Process of reinforcement
Dopamine-producing projections from the ventral tegmental area extend to prefrontal cortex and limbic system
Limbic system contains nucleus accumbens , hippocampus and amygdala
Limbic system components have D2 sites - stimulated by drug and cause cravings for drugs to replenish dopamine . Receptors likely reduce in number due to repeated over stimulation
Addiction and dopamine interaction
Drugs directly or indirectly increase dopamine in pleasure and motivation pathways –> change normal communications between neurons
Addictive drugs increase dopamine –> strong but inappropriate learning signal -> hijack reward system -> pathological reinforcement with automatic compulsive behaviors
Definition of intoxication
Transient syndrome following recent substance ingestion with physical and psychological impairment
3 classes of activity at ventral tegmental area
Class I and II at VTA alone, class III at VTA and NA Class I: opioids, THC, GHB - at G(io) protein-coupled receptors Class II: BDZs, nicotine, ethanol - at ionotropic receptor/ ion channel Class III: cocaine, amphetamines , ecstasy - at dopamine transporter
Effects of dopamine, norepinephrine and serotonin
DA and NE have sympathomimetic effects
Serotonin has hallucinogenic effect. Normal functions include mood, memory, sleep and cognition
Commonly abused opioids and site of action
Morphine, heroin, codeine
Interact with u-receptor -> inhibits GABA neurons -> euphoria
Features of opioid withdrawal
Nausea and vomiting Muscle aches Rhinorrhoea Lacrimation Piloerection Sweating Diarrhea
Management of opioid overdose and addiction
Naloxone - competitive opioid antagonist -> reverses effects of drug in minutes
Naltrexone - longer duration of action than naloxone, better for LT mx, can also be used in alcohol dependence
Long acting = methadone - substitute for shorter acting, more rewarding opioids; abrupt termination can lead to severe withdrawal
BDZs and loperamide
Effects of exogenous THC
Psychoactive agent with dose-dependent perceptual changes
Presynaptic inhibition of GABA neurons in VTA-> disinhibition of dopamine neurons -> euphoria and relaxation
Half life 4 hours, onset within minutes and max effect 1-2 hours later
Medical uses of marijuana
Increase appetite
Relief of chronic pain
Features of marijuana withdrawal
Restlessness Agitation Irritability Insomnia Nausea Cramping
Management of marijuana withdrawal
BDZs - anxiety and restlessness
Symptomatic relief
Function of endocannabinoids
Regulate pain, appetite, memory and mood
Mechanism of cocaine intoxication
Blocks uptake of DA, NE and 5HT through transporters
Blocks DA transporter –> increased DA in NA-> rewarding effects
Clinical effects of cocaine intoxication
Decreased appetite
Hyperactive
Sleep disturbance
Cocaine intoxication is associated with increased risk of
ICH Ischemic stroke MI Seizures Ventricular arrhythmias
Mechanism of amphetamines
Synthetic indirect-acting sympathomimetics -> release of endogenous biogenic amines, DA and NE
Effect of amphetamines at cellular level
Interferes with vesicular monoamine transporter
Depletes synaptic vesicles of NT content
Increased DA and other amines in the cytoplasm
Clinical effects of amphetamines
Similar to cocaine
Euphoric to a lesser extent but longer lasting
Presentation of opioid intoxication
Reduced consciousness preceded by euphoria
Constipation
Pupillary miosis
Conjunctival injection
Presentation of marijuana intoxication
Agitated
Perceptual disturbances
Psychotic features
Auditory hallucinations
Presentation of alcohol intoxication
Euphoria Social disinhibition Difficulty with balance and muscle coordination Vomiting Comatose
Presentation of cocaine or tik intoxication
Sinus tachycardia Hypertension Hyperthermia Mania Agitation Delusional
Effect of alcohol on neurotransmitters
GABA - increases inhibitory transmission at GABA-A receptor acutely; chorionic consumption causes suppression of GABA activity (=tolerance)
Glutamate - decreases excitatory transmission at glutamate receptor ; brain attempts to restore equilibrium -> increases glutamate -> when alcohol stopped, inhibition stopped, enter into hyper-excitable state
Features of alcohol withdrawal / DTs
ANS hyperactivity Hand tremor Nausea and vomiting Insomnia Transient hallucinations or illusions Psychomotor agitation GTC seizures Anxiety
Management of DTs
Goals- decrease immediate withdrawal symptoms; prevent complications ; LT mx to promote alcohol abstinence
Meds- BDZs; carbamazepine; B-blocker
