Flashcards in Lecture 13 - Drugs of Abuse Deck (119)
Define recreational drug use
-use of a pharmacologically active agent (drug) for purposes other than its intended medicinal or other purpose
-use of a substance/drug to get high or be in an altered mental state
List some recreational drug classes
Tolerance is a state at which there is no longer the desired response to the drug
Describe the Progressive model
To achieve the desired response, more drug is required
Tolerance typically lost in?
What is reverse tolerance?
sensitization - can resist for years (ex. cocaine and amphetamines)
Functional tolerance also referred to as?
Describe functional tolerance
-change in the post synapses of the CNS
-stimulatory and inhibitory pathways
-exposure to psychoactive drugs (could also means hormones)
-desensitization of receptors (short)
-down regulation receptors/signaling pathways (long)
List the post-synapse receptors
Metabolic tolerance is also referred to as?
What is metabolic tolerance?
-adaptation of the metabolic "machinery" to repeated exposure to a drug
-similar to drug resistance mechanisms
-CYP P450 system
-cross tolerance: drugs metabolized similarly
What is cross tolerance?
drugs metabolized similarly
What is withdrawal?
-a maladaptive behavioural change, with physiological and cognitive concomitants, that occurs when blood or tissue concentrations of a substance decline in an individual who had maintained prolonged heavy use of the substance
What happens after a person develops the unpleasant withdrawal symptoms?
The person is likely to take the substance to relieve or to avoid those symptoms
There are physiological signs available of withdrawal symptoms for?
There are less obvious signs available of withdrawal symptoms for?
The state at which the user functions normally only when taking the drug
How do withdrawal symptoms and dependence work?
Withdrawal symptoms re-enforce dependence and are a response of the body to less drug
withdrawl of alcohol from an alcoholic - life threatening
repeated crack cocaine use - drug seeking habits in spite of risks, repeated dosing related to keep the high
-it implies addiction and pertains to desirable properties or the high
Affects on _____ pathways though to play a role in crave to use the drug again
What is addiction characterized by?
-Inability to consistently abstain
-Impairment in behavioural control
-Cravings or increased "hunger" for drugs or rewarding experiences
-Diminished recognition of significant problems with one's behaviours and interpersonal relationships
-A dysfunctional emotional response
Good data in Canada on recreational drug use is _____
What do you need to consider when discussing recreational use?
-recreational drug use is country-dependent
-source of drug (prescription versus street market)
-scheduled drugs (legal versus illegal highs)
Plant Extracts Opiates?
Why are opioids used recreationally?
Euphoric affect associated with recreational use
Examples of opioids
What are designer drugs?
What contributes to an abuser's drug of choice?
-route of administration
-duration of high
_____ are the most efficacious analgesic drugs available
Opioids also produce??
-Variable euphoric affect (the high)
-Prominent affect on GI tract
Opioids are similar in pharmacology but differ in: ?
-Duration of action
-Adverse side effect profile
Potency related to binding affinity: ??
mu, kappa, delta
Most opioids are selective for ___ receptor
Desirable effects of opioids?
Relief of anxiety
Depress cough reflex
Undesirable effects of opioids?
Dysphoria (dizziness, nausea)
Biliary tract spasm
What is the common autopsy finding associated with opioid overdose?
-pulmonary congestion and frothing of mouth
-witnesses often comment that deceased was heavily snoring prior to death: blockade of respiratory centres to PCO2
Admin routes for opioids?
-Oral: readily absorbed
-Transdermal: increased lipophilicity
Opioids have a prolonged affect
accumulation of drug/formation of active metabolites
First pass metabolism of opioids
glucuronidation (liver) and renal elimination
*also enterohepatic re-circulation
-convulsions (delta receptor dependent and targeted to hippocampal pyramidal cells)
-meperidine metabolism to normeperidine
Respiratory (brain stem)
-depression of rate, volume & exchange
-decreased respiratory responsiveness
-increased biliary tract pressure
Chronology of Opioid Abstinence Syndrome:
Chronology of Opioid Abstinence Syndrome:
Chronology of Opioid Abstinence Syndrome:
-increased heart rate
-hot and cold flashes
-nausea & vomiting
How long is the opioid abstinence syndrome duration?
*encompasses all drugs that have similar pharmacological properties as cannabis
Is marijuana addictive?
*see slide 28
Variable effects of cannabis
dysphoria to hallucination
1 in _ first time users become dependent
Major psychoactive constituent in cannabis leaves?
Cannabis has ____ with chronic use
Can take cannabis ?
oral or smoked
Mechanism of action of cannabis?
Cannabinoid receptors: CB1, CB2
anandamide and 2-arachidonyl glycerol
MAP kinase / adenylyl cyclase / K-channel-linked
Active ingredient in cannabis?
Cannabis leaves are ____%
Sinsemilla cannabis ___%
Hashish cannabis ___%
High potency cannabis oil up to __%
-lack of concentration
-motor function impairment (rxn time): driving under the influence - impairment can persist after the perceived high has dissipated
-impaired attention, memory, and learning
-users at heightened anxious state (CB1 in amygdala)
-decreased BP (vasodilation)
-decreased respiratory rate
-lung damage (smoking)
-use with cocaine and amphetamines may lead to increased hypertension, tachycardia and possible cardiotoxicity
-additive effect with CNS depressants (impaired driving enhanced with alcohol)
Smoking of cannabis
-rapid onset (minutes) 18-50% bioavailability
-smoking dynamics: # puffs, duration and volume inhalation, hold
-slower onset (1-5 hr)
-1st pass effet (liver)
THC is _____
THC undergoes _____ circulation
Urinary t1/2 of 11-carboxy THC (as glucuronide) ?
3 days in chronic users
Cannabis PK follows a ____ curve
__mg is a legal dose of cannabis
What are spice products?
cannabinoids that are structurally related to cannabis
*not pharmacologically equivalent to THC
Desirable effects of cocaine
-elevation of mood
-decreased need for food
Undesirable effects of cocaine
Cocaine is a _____
stimulant (inhibits reuptake of NE, DA, and serotonin)
-localized to striatum (reward and control of motivation)
-some side effects: hyperthermia
depression and craving seen in withdrawal
Route of admin for cocaine
hydrochloride salt versus free base (crack)
Purity of cocaine HCl
Purity of crack cocaine
Smoking cocaine produces similar effects as IV
Peak effect and cocaine blood level
-5 min after IV
-7 min after smoking (bioavailability 32-77%)
-20 min after intranasal (dose dependent?)
t1/2 of intranasal cocaine
t1/2 of IV cocaine
t1/2 of smoking cocaine
Cutters of cocaine
Cocaine duration of action
short half life 10-30 mins and this leads to binge use for hours or days
______ to euphoric effects but also ____ to psychomotor effects
binge to crash
depletion of NE, DA
diminished effect or kindling
fatigue, irritability,, loss of sexual desire, muscle pain, etc.
high doses and chronic use lead to?
toxic symptoms, including anxiety, insomnia, irritability, paranoia, suspiciousness (toxic paranoid psychosis)
cocaine & heroin
cocaine & phencyclidine
cocaine & marijuana
What happens with acute cocaine intoxication?
-Increased muscular activity & vasoconstriction (hyperthermia)
-Pronounced CNS stimulation (psychosis, grand-map convulsions, coma)
-Cardiovascular overstimulation (vasoconstriction, ventricular arrhythmia, myocardial infarction)
-Respiratory dysfunction (Chenyn-stoke breathing, respiratory paralysis)
What happens with chronic use of cocaine?
-Excited delirium (sudden collapse, DIC, renal failure, rhabdomyolysis)
-Death can occur in spite of appropriate medical intervention (1-12 hr)
-Upregulation of kappa receptors in amygdala
Chronic use of cocaine leads to?
-Psychiatric disturbance (violent protective behaviour, hyperkinetic behaviour, distorted perception)
-Rhinitis (nasal septum perforation)
-Shortness of breath
-Cardiovascular toxicity (tachycardia, vessel rupture, MI; stroke, tolerance to cardiovascular affects does not occur during a cocaine run)
Amphetamine and Methamphetamine are ______
stimulants (promote synthesis and release of DA, serotonin and NE)
Rx names of amphetamine?
Adderall, Benzedrine, Dexedrine
Clandestine names of methamphetamine?
crank, crystal, speed, ice 2, rock candy
Rx name of methamphetamine?
Toxicity symptoms of amphetamine and methamphetamine?
-Cardiac toxicity, endocarditis, aortic dissection, dilated cardiomyopathy, aneurisms
Half life of amphetamine?
7 - 34 hours
Half life of methamphetamine?
12 - 34 hours
Route of admin of amphetamine and methamphetamine?
Mechanism of action for amphetamine and methamphetamine?
-Increase synaptic levels of DA, 5-HT, NE
-Displace DA from nerve terminals storage vesicles
-Substrate for 5-HT, DA, and NE transporters lead to transmitter release
-Reduce accumulation in synaptic vesicles (affect proton gradient)
Other drugs metabolized to amphetamine and methamphetamine?
What does ecstasy do?
-increases serotonin, DA, and NA release
-inhibits serotonin transporters, neurotoxic to serotonin neurons
Positive effects of ecstasy?
Adverse effects of ecstasy?
increased blood pressure
risk of serotonin syndrome
Amphetamine-like substances are known as ??