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Pharm Block 2 > Pharmacology of abused substances > Flashcards

Pharmacology of abused substances Flashcards

1
Q

What are the pharmacokinetic and pharmacodynamic influences on tolerance?

A

Pharmacokinetic => reduced drug availability
- Increased hepatic enzymes in degradation

Pharmacodynamic => Reduced drug effect
- Downregulation of receptor

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2
Q

Define withdrawal.

A

Physiologic adaptation due to chronic exposure to substance leads to negative physical symptoms upon abrupt discontinuation or dosage reduction.

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3
Q

Most addictive opiods act on which receptors?

A

Act mostly on m (mu) opioid receptors

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4
Q

What is opium?

A

Opium is a fluid obtained from the poppy plant

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5
Q

What is an opiate?

A

A substance derived from opium

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6
Q

What is an opioid?

A

A substance with morphine-like actions, synthetic or semi-synthetic

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7
Q

What is heroin?

A

Heroin is a short acting opiate prodrug.

-Prodrug→6MAM→MS

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8
Q

Why can heroin affect the brain?

A

Heroin is lipid soluble

- when given IV it can rapidly penetrate the BBB

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9
Q

Compare the heroin potency to morphine.

A

2x potency to morphine

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10
Q

What is the half life of heroin?

A

half life => 3 min when given IV

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11
Q

Describe the metabolism of heroin.

A
  • First pass metabolism

- Not bioavailable by mouth

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12
Q

What is the general age group of heroin users?

A

12-25 yo

- usage has been increasing since 2005

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13
Q

What are the primary modes of consumption for heroin?

A

Mostly IV, increasing IN and smoked

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14
Q

What are the treatments for heroin addiction?

A

Methadone maintenance, Suboxone maintenance, heroin IV

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15
Q

What are the unique aspects of methadone?

A

Methadone is a fully synthetic opioid that is a full mu agnoist, with slow development of tolerance. Methadone is also highly protein bound

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16
Q

What is the bioavailability of methadone?

A
  • Methadone has high bioavailability by mouth (>90%)
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17
Q

What is the half life of methadone?

A

24 hours

- Delayed onset of actions tin long duration of effect

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18
Q

Where is methadone stored in the body?

A

With chronic use methadone is stored and accumulates in the liver
- Slow release into the blood: extends duration

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19
Q

How is methadone metabolized?

A

Metabolized CYP3A4, 2B6

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20
Q

How is methadone excreted?

A

Excreted urine/feces

  • ↓GFR: excreted mostly GI
  • Not detected standard UDS
21
Q

What are the IV effects of opiates?

A
  • Warm skin rush
  • Pruritis, especially morphine: releases histamines
  • Pleasure, relaxation, satisfaction: 45 sec
  • Miosis; except Demerol (paralysis of the ciliary body and pupils dilate)
  • “Nodding off”
  • Hypotension
  • Depressed respiration
  • Bradycardia
  • Euphoria
  • Floating feeling
22
Q

What are the symptoms of opiate OD?

A 
Classic Triad:
   - Miosis
   - Coma
   - Respiratory depression
Pulmonary edema
Seizures
23
Q

What is the treatment for opiate OD?

A

Narcan/naloxone

24
Q

What are the symptoms of early opiate withdrawal?

A
  • Lacrimation
  • Yawning
  • Rhinorhea
  • Sweating
  • Sense of anxiety and doom
  • Leads to desperate measures to obtain “fix”
25
Q

What are the symptoms of middle phase opiate withdrawal?

A 
Restless sleep
Dilated pupils (mydriasis)
Anorexia
Gooseflesh
Irritability
Tremor
26
Q

What are the symptoms of late phase opiate withdrawal?

A 
Increase in all previous signs and symptoms
Increase in heart rate and BP
Nausea, vomiting, diarrhea
Abdominal cramps
Depression
Muscle cramps
Weakness
Bone pain
27
Q

Describe heroin withdrawal.

A

Withdrawal begins 8-12 hrs after last dose

  • Peaks 48 hrs
  • Lasts about 3-5 days
28
Q

What is cocaine?

A

Cocaine is a cystalline (IV or IN)
- Freebase or crack smoked

Cocaine blocks the dopamine reuptake transporter located on the presynaptic membrane, thereby increasing synaptic dopamine.

29
Q

Describe the metabolism of cocaine.

A

Metab: CYP 3A4 to benzoylecgonine, excreted in urine (measured in urine drug screens)

30
Q

What are the desired effects of cocaine?

A 
Increased alertness
Increased sense of well-being
Euphoria
Increased energy and motor activity
Self-confidence
Increased sexuality
Possible increased athletic performance
Minor withdrawal symptoms
31
Q

What are the CNS toxic effects of cocaine?

A

CNS Stimulation:

  • Anxiety, Restlessness
  • Paranoia including frank delusions
  • Hallucinations, Seizures
  • Hyperpyrexia
32
Q

What are the adrenergic toxic effects of cocaine?

A

Adrenergic effects

  • Tachyarrythmias, increase blood pressure
  • Tremor
33
Q

What are the vasoconstrictive toxic effects of cocaine?

A

Vasoconstrictive

- Heart attacks, strokes

34
Q

What are the neuroadaptive effects of cocaine?

A
  • Decrease in dopamine transporters
  • Decrease in dopamine receptors
    • Tolerance/increased doses
    • “Withdrawal” (abstinence syndrome)
      • Anhedonia, dysphoria/depression
      • Low energy
        High risk for relapse
35
Q

How is crystal meth consumed?

A

Oral, IN, IV, smoked

36
Q

What are the effects of crystal meth?

A

Euphoria, well-being, confidence
Sexual confidence, enhancement
Alertness, hyperactivity, increased energy
increased heart rate, blood pressure, body temperature, tremors, and RR

37
Q

What is methamphetamine medically approved for?

A

ADHD and obesity

38
Q

What are the psychiatric effects of crystal meth?

A
  • At higher doses: hypomania, grandiosity,
  • Extreme insomnia, irritability
  • 24-72+hrs without sleep,
  • Appetite suppression, weight loss, skin picking
    ~10% : frank psychosis,
    • Presentation similar to paranoid schizophrenia
  • Violent behavior (physical and sexual)
39
Q

What is the effect of chronic methamphetamine use?

A

Chronic MA use leads to a reduction in dopamine transporter levels (DAT) which leads to depletion of dopamine in presynaptic terminal

40
Q

Describe the effects of meth withdrawal.

A
  • “terrible Tuesday”: depression, irritability, suicidal ideation
  • Carbohydrate craving
  • Long-term use (1-2 yrs?): chronic depression
  • 62% remain depressed 2-5 yrs after abstinence
    • exceptionally high risk for relapse
41
Q

What are the long term cognitive effects of meth?

A
  • Neuropsychiatric effects problems w/ manipulating information, set shifting, divided attention and perseveration
  • Problems with psychomotor speed, concentration, learning and memory
42
Q

What are the short term effects of meth use?

A

Mediated through release of DA and NE:

  • Tachycardia, HTN, tachypnea, hyperthermia, CNS excitation
  • Rhabdomyolysis and cardiovascular events
  • CV responses include vasoconstriction, vasculitis and focal myocyte necrosis
  • Cardiovascular events associated with long-term use include MI and stroke
43
Q

Where is majority of the THC of cannabis delivered?

A

20 to 70% of THC is delivered in the smoke

44
Q

How is THC metabolized?

A

CYP 2C9, eliminated in the feces and (33%) in the urine, ~80 inactive metabolites

45
Q

What are the desired effects of cannabis?

A 
Sense of well being, relaxation, euphoria
Modified level of consciousness
Altered perceptions, time sense
Intensified sensory experiences
Sexual disinhibition
46
Q

What are the medical uses of cannabis?

A

Anxiety, insomnia
Pain
HIV wasting syndrome, MS spasticity

47
Q

What are the psychomotor effects of cannabis?

A 
Object distance distortion
Object outlines distorted
Inability to make rapid judgment
Slowed reaction time
Impaired tracking behavior
Slowed time perception
48
Q

What are the adverse psychiatric effects of cannabis?

A 
Transient panic and anxiety
Depersonalization
Delusions (inc paranoia), hallucinations
Acute mania, depression (possibly)
Aggression
Cognitive effects:
   - Impaired short term memory
   - Decreased verbal IQ
   - Decreased attention, focus
   - Decreased executive functioning

Pharm Block 2 (15 decks)

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