Материал: 2016_Kaplan_USMLE_Step_1_Lecture_Notes_Pharmacology
Section IV λ |
CNS Pharmacology |
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Table IV-8-1. Properties of Drugs of Abuse (continued) |
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CNS Depressants |
Benzodiazepines |
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Barbiturates and Ethanol |
Neurotransmitters involved |
GABA |
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Mechanism of |
Potentiation of GABA interaction |
Prolongation of GABA, GABA mimetic at high doses, on GABAA |
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action |
with GABAA receptors |
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receptors |
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involves BZ1 and BZ2 binding sites |
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Effects |
Light to moderate CNS depression |
Any plane of CNS depression |
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Toxicity |
Sedation, anterograde |
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Severe CNS depression, respiratory depression, and death |
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amnesia; in severe OD |
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(or IV use), reverse |
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with flumazenil |
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Withdrawal |
Rebound insomnia, rebound |
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Agitation, anxiety, hyperreflexia, and life-threatening |
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anxiety |
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seizures + in ethanol withdrawal delusions/ hallucinations— |
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delirium tremens (DTs) |
Opioids |
Morphine, Heroin, Methadone, Fentanyls, Other Opioids |
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Neurotransmitters |
NE, DA, 5HT, GABA, and many others |
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involved |
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Mechanism of |
Activate opioid µ, κ, and δ receptors. Potent µ receptor activators have the most intense abuse and |
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action |
dependence liability, possibly effected via an increase in dopaminergic transmission in the mesolimbic |
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tracts |
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Effects |
Euphoria, analgesia, sedation, cough suppression, and constipation; strong miosis (except meperi- |
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dine) |
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Toxicity |
Severe respiratory depression (reverse with naloxone), nausea, vomiting |
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Withdrawal |
Lacrimation, yawning, sweating, and restlessness, rapidly followed with centrally |
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originating pain, muscle cramping, and diarrhea; not life-threatening |
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Hallucinogens |
Marijuana |
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Hallucinogens |
Neurotransmitters |
Many |
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5HT |
involved |
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Mechanism of |
Interaction of THC with CB1 and |
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Interaction with several subtypes of 5HT receptors |
action |
CB2 cannabinoid receptors in CNS |
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and periphery |
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Effects |
Sedation, euphoria, ↑ HR, |
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Hallucinogen, sympathomimetic, |
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conjunctival irritation, delusions, |
causes dysesthesias |
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hallucinations |
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Toxicity |
Associated with smoking, possible |
Poorly described, flashbacks likely |
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flashbacks |
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Withdrawal |
Irritability, anxiety |
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Poorly characterized |
Miscellaneous Abused Drugs
1.PCP: NMDA-receptor antagonist; extremely toxic, horizontal and vertical nystagmus, paranoia, rhabdomyolysis; overdose is common, with convulsions and death
2.Ketamine: similar to but milder than PCP, with hallucinations, glutamate-receptor antagonist
3.Anticholinergics: scopolamine, atropine-like
4.MDMA (“Ecstasy”), MDA, MDEA: amphetamine-like with strong 5HT pharmacology and therefore hallucinogenic; generally neurotoxic
5.Inhalants: solvent abuse, multiple organ damage; see Toxicology, section XI
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Chapter 8 λ Drugs of Abuse
Chapter Summary
λTable IV-8-1 summarizes the properties of drugs of abuse. These include the CNS stimulants (cocaine and amphetamines), the CNS depressants
(benzodiazepines, barbiturates, and ethanol), the opioids (morphine, heroin, methadone, fentanyl, and others), the hallucinogens (marijuana and other hallucinogens), PCP, ketamine, anticholinergics (scopolamine), MDMA-MDA- MDEA (all amphetamine-like), and inhalants.
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Section IV λ CNS Pharmacology
1.Lorazepam can be safely used as a preanesthetic medication in a patient undergoing liver transplantation without fear of excessive CNS depression because the drug is
A.excreted in unchanged form
B.actively secreted into the GI tract
C.conjugated extrahepatically
D.a selective anxiolytic devoid of CNS depressant actions
E.reversible by naloxone
2.Midazolam is an effective anesthetic because it acts by
A.increasing functional activity at GABAB receptors
B.enhancing the actions of dopamine
C.blocking the NMDA glutamate receptor subtype
D.acting as a partial agonist at 5HT receptors
E.facilitating GABA-mediated increases in chloride ion conductance
3.Which one of the following is an established clinical use of morphine?
A.Management of generalized anxiety disorders
B.Relief of pain associated with biliary colic
C.Pulmonary congestion
D.Treatment of cough associated with use of ACE inhibitors
E.Suppression of the ethanol withdrawal syndrome
4.A 40-year-old man was given a drug that binds to a subunit of the GABAA receptor. When used at a high dose, the drug can open Cl– channels independent of GABA. What drug was the man given?
A.Diazepam
B.Ethanol
C.Phenobarbital
D.Baclofen
E.Dronabinol
5.Which one of the following is characteristic of both phenytoin and carbamazepine?
A.Inhibition of hepatic cytochrome P450
B.First-order elimination at high therapeutic doses
C.Enhances the effects of oral contraceptives
D.Safe to use in pregnancy
E.Prevent sodium influx through fast sodium channels
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