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Pharm Block 2 > Pharmacology of abused substances > Flashcards

Pharmacology of abused substances Flashcards

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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?

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A

Excreted urine/feces

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

What are the IV effects of opiates?

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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?

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

What is the treatment for opiate OD?

Study These Flashcards
A

Narcan/naloxone

24
Q

What are the symptoms of early opiate withdrawal?

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A
  • Lacrimation
  • Yawning
  • Rhinorhea
  • Sweating
  • Sense of anxiety and doom
  • Leads to desperate measures to obtain “fix”
25
What are the symptoms of middle phase opiate withdrawal?
``` Restless sleep Dilated pupils (mydriasis) Anorexia Gooseflesh Irritability Tremor ```
26
What are the symptoms of late phase opiate withdrawal?
``` 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
Describe heroin withdrawal.
Withdrawal begins 8-12 hrs after last dose - Peaks 48 hrs - Lasts about 3-5 days
28
What is cocaine?
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
Describe the metabolism of cocaine.
Metab: CYP 3A4 to benzoylecgonine, excreted in urine (measured in urine drug screens)
30
What are the desired effects of cocaine?
``` 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
What are the CNS toxic effects of cocaine?
CNS Stimulation: - Anxiety, Restlessness - Paranoia including frank delusions - Hallucinations, Seizures - Hyperpyrexia
32
What are the adrenergic toxic effects of cocaine?
Adrenergic effects - Tachyarrythmias, increase blood pressure - Tremor
33
What are the vasoconstrictive toxic effects of cocaine?
Vasoconstrictive | - Heart attacks, strokes
34
What are the neuroadaptive effects of cocaine?
- Decrease in dopamine transporters - Decrease in dopamine receptors - Tolerance/increased doses - “Withdrawal” (abstinence syndrome) - Anhedonia, dysphoria/depression - Low energy High risk for relapse
35
How is crystal meth consumed?
Oral, IN, IV, smoked
36
What are the effects of crystal meth?
Euphoria, well-being, confidence Sexual confidence, enhancement Alertness, hyperactivity, increased energy increased heart rate, blood pressure, body temperature, tremors, and RR
37
What is methamphetamine medically approved for?
ADHD and obesity
38
What are the psychiatric effects of crystal meth?
- 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
What is the effect of chronic methamphetamine use?
Chronic MA use leads to a reduction in dopamine transporter levels (DAT) which leads to depletion of dopamine in presynaptic terminal
40
Describe the effects of meth withdrawal.
- “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
What are the long term cognitive effects of meth?
- Neuropsychiatric effects problems w/ manipulating information, set shifting, divided attention and perseveration - Problems with psychomotor speed, concentration, learning and memory
42
What are the short term effects of meth use?
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
Where is majority of the THC of cannabis delivered?
20 to 70% of THC is delivered in the smoke
44
How is THC metabolized?
CYP 2C9, eliminated in the feces and (33%) in the urine, ~80 inactive metabolites
45
What are the desired effects of cannabis?
``` Sense of well being, relaxation, euphoria Modified level of consciousness Altered perceptions, time sense Intensified sensory experiences Sexual disinhibition ```
46
What are the medical uses of cannabis?
Anxiety, insomnia Pain HIV wasting syndrome, MS spasticity
47
What are the psychomotor effects of cannabis?
``` Object distance distortion Object outlines distorted Inability to make rapid judgment Slowed reaction time Impaired tracking behavior Slowed time perception ```
48
What are the adverse psychiatric effects of cannabis?
``` 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 ```

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