Drugs of Abuse Flashcards
Mechanism of action of cocaine
Blocks reuptake of monoamines (especially dopamine)
Blockage of DA reuptake in the CNS related to rewarding effects
Along with a drug of abuse, cocaine is a…
Local anesthetic
Blocks sodium channels
Toxicities from cocaine include… (4)
Psychosis
Cardiovascular complications
Hepatotoxicity
Convulsions
Effects of cocaine on the CV system
Increases heart rate, BP, and myocardial oxygen demand
Decreases oxygen supply by inducing coronary vasoconstriction, leading to myocardial ischemia
4 ways to ingest cocaine
Orally
Inhalation
Injected (very fast effects)
Smoked (highly addictive)
Which form of cocaine takes the longest time to onset?
Oral
Which 2 forms of cocaine have the highest anticipated intoxication levels
IV
Smoked
Cocaine causes a decreases in _____ in what part of the brain?
Decrease in glucose metabolism in the brain, especially in the frontal lobes
3 ways amphetamines can be taken
Orally
Intravenously
Smoked
Mechanism of action of amphetamines
At high concentrations it will compete for binding to the transporter but will also be transported into the terminal itself
Can bind to and inhibit the vesicular monoamine transporter
Dopamine cannot be repackaged into the vesicles, the intracellular concentration increases, and the amount of DA in the synapse increases
Amphetamines can cause what symptoms
Fight or flight response
Alertness
Anxiety, severe apprehension, panic
Potent effects on DA in the reward center of the brain
Behavioral stereotypy (meaningless repetition of a single activity)
Methamphetamine mechanism of action
Blocks DA reuptake and increases DA release
Schedule 1 substances
No medical use
Highly addictive
MDMA mechanism of action
Preferentially blocks the 5-HT transporter
Causes release of serotonin
Long term depletion of intracellular serotonin (24 hours - leads to depression, irritability)
Acute toxic effects of MDMA
Hyperthermia
Dehydration
When does serotonin syndrome occur
If MDMA is combined with other drugs that increase serotonin levels
Symptoms of serotonin syndrome
Agitation or restlessness Diarrhea Fast heart beat Hallucinations Increased body temperature Loss of coordination Nausea Overactive reflexes Rapid changes in BP Vomiting
Hallucinogens
Alter consciousness Distort perceptions Also called psychomimetics Do not induce dependence or tolerance Do not stimulate dopamine release
4 ways LSD can be taken
Orally
Inhalation
Injected
Transdermally
LSD mechanism of action
Acts as agonist at 5-HT2a receptors
Modulates glutamate-mediated sensory, perceptual, affective, and cognitive processes
Increase glutamate release at cortical layer 5
Phencyclidine and ketamine mechanism
Bind to NMDA-receptors as non-competitive antagonists and affect glutamate-mediated cortical neuron signaling
Work on interneurons that have NMDA receptors
Block the disinhibition of glutamate release
2 major categories of hallucinogens based on the mechanisms
Partial agonists at 5-HT2a receptors (LSD, psilocybin, mescaline)
Block NMDA receptors (PCP, ketamine)
The main psychoactive ingredient of cannabis is…
Delta 9 tetrahydrocannabinol
4 ways to use cannabis
Smoked
Vaporizer
Oral
Sublingual
First two endocannabinoids discovered
2-arachidonoylethanolamine (Anandamide, AEA)
2-arachidonylglycerol
Which cannabinoid holds the most promise for serious conditions?
Cannabadiol
Cannabinoid binding and mechanism
Lipid soluble compounds that are released from post-synaptic membranes and diffuse back to pre-synaptic CB1 receptors
Cause disinhibition of DA neurons by inhibiting the release of GABA
Cannabinoids cause…
Euphoria Relaxation Increased appetite Prevent nausea Lower intraocular pressure
Designer marijuana
Spice, K2
Do not contain tobacco or cannabis but produce similar effects to those of cannabis
Contain synthetic cannabinoids that potently activate CB1 receptors
What G protein do opioids act at?
Gi/o
Mechanism of opioid action
In the ventral tegmental area
Activation of mu opioid receptors selectively expressed on GABA neurons results in disinhibition of DA neurons and euphoria
What channels are acted on from opioid receptors
- At the presynaptic terminal
- On the cell body
- Cause the inhibition of Ca influx (get less GABA release)
2. Enhance K efflux (hyperpolarization)
Symptoms of opioid withdrawal
Yawning Sweating Weakness Nausea/vomiting Tremors Muscle jerks
Methadone
Way to treat opioid withdrawal
It is pharmacologically equivalent, but has a much longer half life to suppress withdrawal symptoms
Can do slow dose withdrawal
Naloxone
Opioid receptor antagonist
Precipitates withdrawal and abstinence syndrome in a dependent person
Buprenorphine
Partial agonist at opioid receptor with high affinity
Another way to treat opioid addiction (morphine)
It competes at the same site, but still gives some efficacy
Prevents the high, but also alleviates craving and drug seeking behaviour
Which partial agonist is used to treat nicotine addiction
Varenicline
Addiction is characterized by which 3 things?
Compulsive behaviour to take drug despite negative consequences
Reinforcing behaviour (rewarding or pleasurable)
Loss of control
Acute effects of alcohol on
- GABA receptors
- Glutamate (NMDA receptors)
- Activate
2. Inhibit (non competitive antagonist)
6 drugs that work on neurons in the nucleus accumbens
Opioids Cocaine Amphetamines Alcohol PCP Cannabinoids
3 drugs that work in the ventral tegmental area
Nicotine
Opioids
Cannabinoids
