Drugs of Abuse Flashcards
Addiction is characterized by what? (3)
- Compulsive behavior
- Reinforcing behavior (rewarding/pleasurable)
- Loss of control
How do behavioral abnormalities of addiction develop? how long do they last?
Develop progressively during repeated exposure
Can persist for months/years after discontinuation of drug
3 steps of addiction
- Repeated exposure which alters gene expression in certain brain areas
- Altered expression mediates altered neural function
- Result - behavioral changes
Which reward pathway does addiction affect?
reward pathway
MOA of the reward pathway? (areas and neurons involved)
Noradrenergic neurons (locus ceruleus) send info of novelty and arousal to dopaminergic neurons in ventral tegmental area (VTA) VTA projects to nucleus accumbens (NAc) and cortex
Multiple inputs modify signaling in the ________ pathway and modulate which perception?
Mesolimbic dopamine pathway
Perception of pleasure
VTA output is modulated by what? and which functions are these involved in? (3)
- Glutamatergic input from prefrontal cortex - executive function and cognitive control
- Excitatory input from amygdala signals - stress and anxiety
- Glutamatergic input from hippocampus - memory
Which receptors are decreased with addiction?
Dopamine D2 receptors
Do all drugs lead to dependence and are they all addictive?
No
What is dependence?
Development of adaptive responses that lead to symptoms of withdrawal (abstinence syndrome) when drug is discontinued. This drives repeated exposure to avoid withdrawal
4 short-term effects of drugs and their withdrawal symptoms?
- Loss of inhibition - Irritability, tremor
- Reduction in anxiety - Anxiety
- Sedation - Sleep disturbances
- Decreased motor coordination - Seizures
3 main types of tolerance?
Acquired tolerance
Cross-tolerance
Reverse-tolerance
3 types of acquired tolerance?
Pharmacokinetic tolerance
Pharmacodynamic tolerance
Behavioural tolerance
5 types of drugs of abuse
Stimulants Hallucinogens Cannabinoids Opioid Analgesics Sedative-Hypnotics
3 stimulant drugs?
Cocaine
Amphetamines
MDMA
Form of administration of cocaine is important in determining what? (3)
Intensity of effects
Abuse liability
Toxicity
4 types of cocaine administration?
Oral
Inhaled
Injected
Smoked
Is cocaine addictive? Especially in which form?
Yes
smoke-able free-base form (crack)
Cocaine mainly blocks what?
2 others mechanisms it blocks and physical effects?
Reuptake of monoamines
Blockade of DA reuptake in the CNS related to rewarding effects
Others:
1. Reuptake of norepinephrine in sympathetic nervous system : Increased pressure, tachycardia
2. Blocks sodium channels : arrhythmias
4 toxicities of cocaine?
Psychosis
CV complications
Hepatotoxicity
Convulsions
Cocaine increases _____, ______ and ______
Cocaine decreases _______ by inducing _______. This leads to ______
HR, BP, Myocardial oxygen demand
Oxygen supply by inducing coronary vasoconstriction
This leads to Myocardial Ischemia
What is the major CV complication observed in cocaine use?
Myocardial ischemia
Which route of cocaine administration increases plasma concentration the fastest? slowest?
IV
Oral
Which two cocaine administration cause quick intoxication?
IV
Smoked
How does cocaine affect glucose metabolism? Where in the brain does this mainly happen and which functions are affected?
It decreases glucose metabolism
Frontal lobes - Planning, abstract thinking and impulse behavior regulation
3 amphetamine administration forms?
Orally
IV
Smoked
MOA of amphetamines?
Transported like dopamine
Transported into cell, inhibits vesicular monoamine transporter (VMAT)
Increases dopamine in presynaptic terminal
Physiological actions of amphetamines? (5)
- Fight-or-flight response
- Alertness
- Anxiety, apprehension, panic
- Potent effects on DA
- Behavioral stereotypy (meaningless repetition of a single activity)
Drug that is structurally similar to amphetamines and DA?
Metamphetamine
Is meth addictive? What does it look, smell and taste like?
Yes
White, odorless, bitter tasting crystalline powder
Is meth more or less potent than amphetamine? Longer or shorter duration?
More
Longer
MOA of meth?
Blocks DA re-uptake and increases DA release
MOA of MDMA? (3)
Block 5-HT transporter
Causes release of biogenic amines - reverses transporters
Long-term depletion of intracellular 5-HT
Acute toxic effects of MDMA? (2)
Long-term? (2)
Acute : hyperthermia, dehydration
Long : Neurotoxicity, cognitive impairment
What is a syndrome that can occur if combining MDMA with other drugs that increase serotonin levels?
What are the many symptoms? (10)
Serotonin syndrome
- Agitation
- Diarrhea
- Fast HR
- Hallucinations
- Increased body temp
- Loss of coordination
- Nausea
- Overactive reflexes
- Rapid changes in BP
- Vomiting
Cannabinoids interact with ____ receptor
CB1
MOA of cannabinoids?
Inhibiting release of GABA, which causes disinhibition of dopamine neurons
5 effects of cannabinoids?
Euphoria Relaxation Increase appetite Prevent nausea Lower intraocular pressure
How does CB1 distribution change with age?
Decreases
Designer Marijuana :
Other name for it?
What does it contain and their effect? (2)
Spice, K2
Contains synthetic cannabinoids the potently activate CB1 receptors
Contains other unknown compounds, constantly changing
5 opioid analgesics?
Morphine Heroin Oxycodone Meperidine Fentanyl
Opioids work on which receptor in which region?
What does this do?
u k delta opioid receptors (Gi/o couple GPCR)
VTA
Activation of u opioid receptors selectively expressed on GABA neurons results in disinhibition of DA neurons and euphoria
When opioids act on GABA neurons in the VTA, what the affects on neurotransmission?
Efflux of K+
Hyperpolarization
Difficulty of neuron to fire
Dependence on opioids leads to which syndrome and what are the symptoms? (7)
Abstinence syndrome
Yawning, sweating, weakness, nausea/vomiting, tremors, muscle jerks
How do you treat opioid withdrawal? Why is it more efficient?
Replacement with pharmacological equivalent agent
-Doesn’t reach “high” or “withdrawal symptom” levels (peaks arent as fast or as high)
What drug precipitates opioid withdrawal and abstinence syndrome?
Naloxone - opioid receptor antagonist
Example of a partial agonist in the treatment of addiction?
Buprenorphine
What is the MOA of buprenorphine?
Competes with morphine, binds with more affinity on the opioid receptor and decreases cAMP levels.
Prevents lower affinity full agonists (morphine) from binding
What causes opioid withdrawal symptoms
Large increase in cAMP production following discontinuation of opioid agonist or administration of antagonist
3 sedative hypnotics
Do they produce tolerance and/or dependence aka withdrawal symptoms?
Barbiturates
Benzodiazepines
Ethanol
Yes both
Sedative hypnotics relieve ____ and ____
stress
anxiety
Higher doses of sedative hypnotics produce what state? What is this called
Sleep-like state
Hypnosis
5 Hallucinogens
LSD Mescaline Psilocybin PCP Ketamine
Hallucinogens alter _______ and distort ______
Consciousness
Perceptions
Hallucinogens are also called ______
psychomimetics
Do hallucinogens induce addiction?
No
Do hallucinogens stimulate DA release?
No
MOA of LSD?
Half-life?
Acts as agonist at 5-HT2A receptors
Modulates glutamate-mediated sensory, perceptual, affective and cognitive processes (compete with serotonin, increases glutamate release)
Half-life : 2,5-4 hr with inactive metabolites
What areas of the CNS does LSD act (2)
Deep cortical layers
Cortical layer V
PCP and Ketamine cause _____ state and _____
Chronic exposure leads to long-lasting ______
Dissociative, hallucinations
Psychosis
MOA of PCP and Ketamines?
Bind to NMDA-receptors as non-competitive antagonist
Affects glutamate-mediated cortical neuron signaling
