Flashcards in Drugs of Abuse Deck (65):
What is drug tolerance?
- a state at which there is no longer the desired response to the drug
Progressive model: to achieve the desired response, more drug is required
- development of tolerance is not necessarily an addiction
- tolerance is typically lost in 10-14 days
What is reverse tolerance?
What is functional tolerance?
- aka pharmacodynamic tolerance
- change in the post synapses of the CNS
- stimulatory and inhibitory pathways
- exposure to psychoactive drugs (could also mean hormone)
- desensitization of receptors (short term)
- down regulation of receptors/signalling pathways (long term)
- cross tolerance
What are examples of post synapse receptors?
G protein, ionotropic, extrasynaptic proteins
What is metabolic tolerance?
- aka pharmacokinetic tolerance
- adaptation of the metabolic machinery to repeated exposure to a drug
- similar to drug resistance mechanism
- enzyme induction
- drug metabolism:
-- CYP P450, glucuronidation
- cross tolerance: drug metabolized similarly
What is drug 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
- after developing unpleasant withdrawal symptoms, the person is likely to take the substance to relive or to avoid these symptoms
What are some common drug classes and bring physiological sx of withdrawal?
What is the definition of dependence?
- a state at which the user functional normally only when taking the drug
Withdrawal symptoms ____ dependence and are a response of the body to less drug
What kind of dependence implied addition?
What is addition characterized by? (the ABCDE's of addiction)
- Inability to ABSTAIN
- impairment in BEHAVIOURAL control
- CRAVING or increased hinger for drugs or rewarding experiences
- DIMINISHED recognition of significant problems with one's behaviours and interpersonal relationships
- a dysfunctional EMOTIONAL response
Opiates can be what? (synthetic, plant extracts or semi-synthetic) What are opioids? What is heroin? Morphine? Fentanyl?
- opiates: plant extracts and semi-synthetic
- opioids: semi-synthetic
- heroin: semi-synthetic
- morphine: plant extract
- fentanyl: synthetic
What are the 3 types of endogenous opioids?
- enkephalins, endorphins and dynorphins
When is there a euphoric effect associated with opioids?
- when there is recreational use of them
What are the other effects that opioids produce?
- respiratory depression
- variable euphoric effect (the high)
- prominent affect on the GI tract
Opioids are all similar in pharmacology but differ in what regard?
- duration of action
- oral availability
- relative potency
- adverse effect profile
What are the different opioid receptors?
mu, kappa and delta
(most opioids are selective for the Mu receptor)
What are the desirable effects of opioids?
- relief on anxiety
- cough suppression
What are the undesirable effects of opioids?
- biliary tract spasm
- urinary retention
- respiratory depression
What are the most common findings associated with opioid overdose on an autopsy?
- pulmonary congestion and frothing of the mouth
____ affects distribution of opioids and CNS levels
What are the stages of first pass metabolism in opioids?
glucuronidation (liver) and active metabolites
_____ recirculation happens with opioids?
What are the CNS effects of opioid tonicity?
- convulsions (delta receptor dependent and targets to hippocampal pyramidal cells)
- meperidine metabolism to normeperidine
What are the respiratory effects of opioid toxicity
- depression of rate, volume and exchange
- decreased respiratory responsiveness
What are the cardiovascular effects of opioid toxicity?
- orthostatic hypotension
- ECG abnormalities
What are the GI effects of opioids toxicity?
- decreased motility
- intestinal obstruction
- increased biliary tract pressure
What happens in the first 8-12 h of opioid abstinence syndrome?
- lacrimation, perspiration, yawning and rhinorrhea
What happens in the first 12-14 h of opioid abstinence syndrome?
- irritability, piloerection, restlessness, weakness, mydriasis, tremor, anorexia
What happens in the first 48-72 hours of opioid abstinence syndrome?
- irritability, insomnia, marked anorexia, sneezing, hyperthermia, hyperpnea, aching muscles, increased heart rate, hypertension, hot and cold flashes, nausea/vomiting, piloerection, abdominal cramps
How many days does opioid abstinence syndrome last for?
What percentage of marijuana users become addicted?
9% (this number increases in those that start young and also in those that use it daily)
What is the long term risk associated with marijuana use?
- overall decrease in cognitive performance
- higher chance of lifetime addiction
What is the major psychoactive component of cannabis?
What is the mechanism of action of cannabis?
cannabinoid receptors: CB1, CB2
- endogenous cannabinoids: anadamide and 2-arachidonyl glycerol
- CB1: MAP kinase/adenylyl cyclase/K channel-linked
What is the THC % of leaves? Hashish? High potency oil?
- leaves: 2-5%
- Hashish: 5-15 % TH
- high potency oil: up to 98%
What are the CNS effects of cannabis?
- lack of concentration
- motor function impairment (reaction time): driving under the influence
- impaired attention, memory and learning
- users at a heightened anxious state
What are the coronary effects of cannabis?
- increased HR
- decreased BP (vasodilation)
What are the respiratory effects of cannabis?
- decreased respiratory effects
- lung damage
What are the drug interactions that can be observed with cannabis?
- cocaine and amphetamines: increased hypertension, tachycardia and possible cardiotoxicity
- CNS depressants: impaired driving enhanced with alcohol
What is the onset bioavailability of cannabis in smoking? When you take it orally?
- smoking: rapid onset-minutes
- oral: slower onset (1-5h)
When dosing cannabis orally, the liver makes it hard to make bioavailable due to the ____
first pass effect
THC is lipophilic and undergoes ______ circulation
What is the urinary t1/2 of the 11-carboxy-THC (as glucuronide)
3 days in chronic users
What are the desirable effects of cocaine?
- locomotor stimulation
- elevation of mood
- increased energy
- alertness, sociability
- sexual arousal
- decreased need for food
What are the undesirable effects of cocaine?
- drug craving
- assaultive behaviour
What is the effect of cocaine?
works as a stimulant (inhibits reuptake of NE, DA and serotonin)
- DA - localized in the striatum (reward and control of motivation) some side effects, hyperthermia
- NE - adrenergic (tachycardia)
- 5HT - dysphoria; depression and craving seen in withdrawal
What is the route of administration of cocaine?
hydrochloride salt vs free base (crack)
What is the purity of cocaine HCl vs crack cocaine?
cocaine HCl: 20-95%
crack cocaine: 20-80%
What is the peak effect in cocaine blood level after IV? After smoking? After intranasal use?
- 5 min after IV
- 7 min after smoking
- 20 minutes after intranasal use (dose dependent)
What is the duration of action of cocaine? What does this lead to?
- short t1/2 of 10-30 minutes and this leads to a binge use for hours or days
What causes the crash in cocaine?
depletion of NE, DA
What are the most common signs of cocaine withdrawal?
fatigue, irritability, loss of sexual desire, muscle pain, etc
What are the toxic symptoms that high doses and chronic use of cocaine can lead to?
- anxiety, insomnia, irritability, paranoia, suspiciousness (toxic paranoid psychosis)
What are the symptoms of acute cocaine toxicity
- increased muscular activity and vasoconstriction (hyperthermia), pronounced CNS stimulation (psychosis, grand-map convulsions, coma), cardiovascular overstimulation (vasoconstriction, ventricular arrhythmia, MI), respiratory dysfunction (paralysis)
What are the toxicity symptoms associated with chronic cocaine use?
- psychiatric disturbance
(violent behaviour, hyperkinetic behaviour)
- shortness of breath
- cold sweats
- cardiovascular toxicity
(tachycardia, vessel rupture, MI, stroke, tolerance to cardiovascular affects does not occur during a cocaine run)
What is the action of amphetamines and methamphetamine?
stimulants- promotes synthesis and release of DA, serotonin and NE
What are some examples of toxicity induced by methamphetamines and amphetamines?
- meth mouth
- cardiac toxicity, endocarditis, aortic dissection, dilated cardiomyopathy, aneurisms
What are the respective half life of amphetamine and methamphetamine?
Amphetamine: 7-34 hours
Methamphetamine: 12-34 hours
What are the 3 other drugs that get metabolized to amphetamine and methamphetamine?
What effect does ecstasy have on the NT in the brain?
- increases 5HT, DA and NA release
- inhibits serotonin transporters, neurotoxic to serotonin neurons
What are the positive effects of
empathy, well being, reduced anxiety
What are the adverse effects of ecstasy?
hyperthermia, dehydration, increased blood pressure, depression, risk of serotonin syndrome
MDMA is considered to be _____ because it causes damage to the serotonin nerve terminals