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Drugs of Abuse Flashcards

1
Q

What is drug tolerance?

A
  • 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
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2
Q

What is reverse tolerance?

A

Sensitization

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3
Q

What is functional tolerance?

A
  • 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
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4
Q

What are examples of post synapse receptors?

A

G protein, ionotropic, extrasynaptic proteins

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5
Q

What is metabolic tolerance?

A
  • 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
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6
Q

What is drug withdrawal?

A
  • 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
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7
Q

What are some common drug classes and bring physiological sx of withdrawal?

A
  • alcohol
  • hypnotics
  • anxiolytics
  • opioids
  • sedatives
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8
Q

What is the definition of dependence?

A
  • a state at which the user functional normally only when taking the drug
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9
Q

Withdrawal symptoms ____ dependence and are a response of the body to less drug

A

re-inforce

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10
Q

What kind of dependence implied addition?

A

psychological dependence

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11
Q

What is addition characterized by? (the ABCDE’s of addiction)

A
  • 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
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12
Q

Opiates can be what? (synthetic, plant extracts or semi-synthetic) What are opioids? What is heroin? Morphine? Fentanyl?

A
  • opiates: plant extracts and semi-synthetic
  • opioids: semi-synthetic
  • heroin: semi-synthetic
  • morphine: plant extract
  • fentanyl: synthetic
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13
Q

What are the 3 types of endogenous opioids?

A
  • enkephalins, endorphins and dynorphins
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14
Q

When is there a euphoric effect associated with opioids?

A
  • when there is recreational use of them
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15
Q

What are the other effects that opioids produce?

A
  • respiratory depression
  • variable euphoric effect (the high)
  • dependence
  • prominent affect on the GI tract
  • miosis
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16
Q

Opioids are all similar in pharmacology but differ in what regard?

A
  • duration of action
  • oral availability
  • relative potency
  • adverse effect profile
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17
Q

What are the different opioid receptors?

A

mu, kappa and delta

most opioids are selective for the Mu receptor

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18
Q

What are the desirable effects of opioids?

A
  • analgesia
  • euphoria
  • sedation
  • relief on anxiety
  • cough suppression
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19
Q

What are the undesirable effects of opioids?

A
  • dysphoria
    • dizziness
    • nausea
  • vomiting
  • constipation
  • biliary tract spasm
  • urinary retention
  • withdrawal
  • respiratory depression
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20
Q

What are the most common findings associated with opioid overdose on an autopsy?

A
  • pulmonary congestion and frothing of the mouth
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21
Q

____ affects distribution of opioids and CNS levels

A

lipid solubility

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22
Q

What are the stages of first pass metabolism in opioids?

A

glucuronidation (liver) and active metabolites

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23
Q

_____ recirculation happens with opioids?

A

enterohepatic

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24
Q

What are the CNS effects of opioid tonicity?

A
  • convulsions (delta receptor dependent and targets to hippocampal pyramidal cells)
  • meperidine metabolism to normeperidine
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25
What are the respiratory effects of opioid toxicity
- depression of rate, volume and exchange | - decreased respiratory responsiveness
26
What are the cardiovascular effects of opioid toxicity?
- orthostatic hypotension - stroke - ECG abnormalities
27
What are the GI effects of opioids toxicity?
- decreased motility - intestinal obstruction - increased biliary tract pressure
28
What happens in the first 8-12 h of opioid abstinence syndrome?
- lacrimation, perspiration, yawning and rhinorrhea
29
What happens in the first 12-14 h of opioid abstinence syndrome?
- irritability, piloerection, restlessness, weakness, mydriasis, tremor, anorexia
30
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
31
How many days does opioid abstinence syndrome last for?
7-10 days
32
What percentage of marijuana users become addicted?
9% (this number increases in those that start young and also in those that use it daily)
33
What is the long term risk associated with marijuana use?
- overall decrease in cognitive performance | - higher chance of lifetime addiction
34
What is the major psychoactive component of cannabis?
THC (delta-9-tetrahydrocannabinol)
35
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
36
What is the THC % of leaves? Hashish? High potency oil?
- leaves: 2-5% - Hashish: 5-15 % TH - high potency oil: up to 98%
37
What are the CNS effects of cannabis?
- euphoria - lack of concentration - motor function impairment (reaction time): driving under the influence - impaired attention, memory and learning - users at a heightened anxious state - paranoria
38
What are the coronary effects of cannabis?
- increased HR | - decreased BP (vasodilation)
39
What are the respiratory effects of cannabis?
- decreased respiratory effects - bronchodilation - lung damage
40
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
41
What is the onset bioavailability of cannabis in smoking? When you take it orally?
- smoking: rapid onset-minutes 18-50% bioavailability - oral: slower onset (1-5h) 6-18% bioavailability
42
When dosing cannabis orally, the liver makes it hard to make bioavailable due to the ____
first pass effect
43
THC is lipophilic and undergoes ______ circulation
enterohepatic
44
What is the urinary t1/2 of the 11-carboxy-THC (as glucuronide)
3 days in chronic users
45
What are the desirable effects of cocaine?
- locomotor stimulation - euphoria - elevation of mood - increased energy - alertness, sociability - confidence - sexual arousal - decreased need for food
46
What are the undesirable effects of cocaine?
- dysphoria - irritability - drug craving - paranoia - assaultive behaviour - hallucinations - hyperthermia - psychosis - death
47
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
48
What is the route of administration of cocaine?
hydrochloride salt vs free base (crack)
49
What is the purity of cocaine HCl vs crack cocaine?
cocaine HCl: 20-95% | crack cocaine: 20-80%
50
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)
51
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
52
What causes the crash in cocaine?
depletion of NE, DA
53
What are the most common signs of cocaine withdrawal?
fatigue, irritability, loss of sexual desire, muscle pain, etc
54
What are the toxic symptoms that high doses and chronic use of cocaine can lead to?
- anxiety, insomnia, irritability, paranoia, suspiciousness (toxic paranoid psychosis)
55
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)
56
What are the toxicity symptoms associated with chronic cocaine use?
- malnutrition - psychiatric disturbance (violent behaviour, hyperkinetic behaviour) - rhinitis - shortness of breath - cold sweats - cardiovascular toxicity (tachycardia, vessel rupture, MI, stroke, tolerance to cardiovascular affects does not occur during a cocaine run)
57
What is the action of amphetamines and methamphetamine?
stimulants- promotes synthesis and release of DA, serotonin and NE
58
What are some examples of toxicity induced by methamphetamines and amphetamines?
- parasitosis - meth mouth - cardiac toxicity, endocarditis, aortic dissection, dilated cardiomyopathy, aneurisms
59
What are the respective half life of amphetamine and methamphetamine?
Amphetamine: 7-34 hours Methamphetamine: 12-34 hours
60
What are the 3 other drugs that get metabolized to amphetamine and methamphetamine?
- selegeline - faprofazone - benphetamine
61
What effect does ecstasy have on the NT in the brain?
- increases 5HT, DA and NA release | - inhibits serotonin transporters, neurotoxic to serotonin neurons
62
What are the positive effects of | ecstasy?
empathy, well being, reduced anxiety
63
What are the adverse effects of ecstasy?
hyperthermia, dehydration, increased blood pressure, depression, risk of serotonin syndrome
64
MDMA is considered to be _____ because it causes damage to the serotonin nerve terminals
neurotoxic
65
What are the common effects of bathsalts?
- paranoia and violent behaviour - hallucinations - delusions - suicidal thoughts - seizures - panic attacks - chest pain - nausea and committing - increased heart rate - increased bp - increased body temperature - rhabdomyolysis (skeletal muscle tissue breakdown) - multiple organ failure - coma - death

Pharmacology (23 decks)

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