Материал: 2016_Kaplan_USMLE_Step_1_Lecture_Notes_Pharmacology

Section IV λ CNS Pharmacology

8.Answer: B. In addition to blocking reuptake of NE and 5HT, pharmacodynamic actions of the tricyclic antidepressants include block of peripheral adrenergic and muscarinic receptors—the former resulting in postural hypotension and the latter, via mydriasis, exacerbating glaucoma. TCAs may cause arrhythmias in overdose. They have no effect on the absorption of levodopa.

9.Answer: C. Lithium causes goiter in a significant number of patients; however, thyroid dysfunction does not occur in all such patients, and when it does it presents as hypothyroidism (not hyper-T). High-Na diets increase lithium elimination; low Na increases lithium plasma levels. Uncoupling of vasopressin receptors is characteristic of lithium, leading to a nephrogenic diabetes insipidus. Although potential teratogenicity is a concern during pregnancy, lithium does not cause neural tube defects but may cause abnormalities in heart valves. Lithium takes 10 to 20 days for effectiveness, and in acute mania it is often necessary to calm the patient with parenteral antipsychotic drugs such as fluphenazine or haloperidol.

10.Answer: A. Methanol is metabolized by alcohol dehydrogenase to formaldehyde and then further metabolized to formic acid by aldehyde dehydrogenase. Its major toxicity is severe vision damage. Ethylene glycol Ingestion is associated with nephrotoxicity, while ethanol ingestion causes nausea, vomiting, and hypotension.

11.Answer: B. Carbidopa inhibits peripheral dopa decarboxylase which enhances uptake of levodopa into the CNS and therefore, its conversion to dopamine. Carbidopa doesn’t cross the blood-brain barrier and therefore has no direct benefit at dopamine receptors.

12.Answer: C. The patient is probably taking an SSRI such as paroxetine. SSRIs rarely cause sedation and commonly cause agitation and the “jitters,” which sometimes necessitates concomitant use of drugs that are strongly sedating, such as trazodone. SSRIs are best taken in the morning to avoid problems of insomnia, and they appear to cause weight loss, at least during the first 12 months of treatment. Severe drug interactions leading to the “serotonin syndrome” have been reported when SSRIs have been used together with MAO inhibitors, tricyclics, and the opioid meperidine.

13.Answer: C. Drug C appears to be a selective inhibitor of the reuptake of serotonin, and existing drugs of this class (SSRIs) are approved for use in both major depressive and obsessive-compulsive disorders. The tricyclic antidepressant clomipramine, a potent inhibitor of 5HT reuptake, was formerly the drug of choice for OCD until replaced by the SSRIs. Drugs A and E may have value in the treatment of Parkinson disease because they block the reuptake of DA. Drug D may be effective in anxiety and seizure states because it is an effective blocker of GABA reuptake.

14.Answer: D. Atomoxetine is used in attention deficit hyperactivity disorder (ADHD) and works by blocking the reuptake of norepinephrine into nerve terminals. This mechanism is how both cocaine and the tricyclic antidepressants such as amitriptyline work. Amphetamines such as methylphenidate are also commonly used in ADHD and work by displacing norepinephrine from the mobile pool.

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Chapter 9 λ CNS Drug List and Practice Questions

15.Answer: B. Buspirone has selective anxiolytic activity that is slow in onset. The drug has no abuse liability and will not suppress withdrawal symptoms in patients who have become physically dependent on barbiturates, benzodiazepines, or ethanol. Bupropion is an antidepressant, also approved for management of dependence on nicotine. Baclofen is a spinal cord muscle relaxant that

activates GABAB receptors. Buprenorphine is a long-acting opioid analgesic with no effectiveness in GAD, and phenobarbital is a barbiturate that may cause dependence.

16.Answer: E. The patient is experiencing postherpetic neuralgia. While acyclovir is effective at eradicating the herpes virus it is ineffective against the pain of shingles. Appropriate drugs are TCAs like amitriptyline and gabapentin. Patients with long QT syndrome have a genetic flaw in cardiac inward rectifying K current, leading to increased APD. Drugs that accentuate this by inhibiting the repolarizing K current (phase 3), which include thioridazine and the tricyclic antidepressants, are likely to have enhanced cardiotoxic potential in such patients. As a result, this patient should be placed on gabapentin.

17.Answer: D. The signs and symptoms described are typical of withdrawal from physical dependency on an opioid that has efficacy equivalent to a full ago- nist—in this case, meperidine. Although anxiety, agitation, and even muscle jerking may occur in withdrawal from dependence on sedative-hypnotics such as alprazolam and secobarbital, the symptoms of GI distress, rhinorrhea, lacrimation, and yawning are not characteristic (seizures are more typical). Symptoms of withdrawal from high-dose use of CNS stimulants such as amphetamine or cocaine include lassitude and severe depression of mood. The phrase “schedule-controlled” refers to FDA classifications of drugs that have abuse liability, including both licit and illicit drugs.

18.Answer: B. Fentanyl is a full agonist at opioid receptors and provides analgesia in cancer pain equivalent to morphine, so there is no good reason to have morphine on hand, and it would be a danger to the patient in terms of accidental overdose. Apomorphine is an emetic, hardly appropriate given the stimulatory effects of opioids on the emetic center. Likewise, loperamide is used in diarrheal states, and patients on strong opioids are almost certain to be constipated; for this reason, a stool softener like docusate should be available to the patient. The opioid antagonist naloxone is used IV in overdose situations but would not be provided to the patient for use PRN.

19.Answer: C. Orthostatic hypotension occurs with both tricyclic antidepressants and phenothiazines because both types of drug can block alpha-adrenergic receptors in venous beds. Their ability to block M receptors leads to xerostomia (not salivation) and mydriasis (not miosis). Tricyclics and phenothiazines also share a common tendency to decrease seizure threshold and cause weight gain (not loss).

20.Answer: E. Lithium inhibits the dephosphorylation of IP2 (needed for the recycling of inositol), leading to depletion of membrane PIP2. Consequently, the activation of receptors by neurotransmitters such as ACh, NE, and 5HT fails

to release the second messengers IP3 and DAG. Carbamazepine and the local anesthetic procaine block axonal Na channels; ethosuximide may block Ca channels in thalamic neurons. Phenelzine is a nonselective inhibitor of MAO.

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Section IV λ CNS Pharmacology

21.Answer: A. The signs and symptoms are characteristic of a CNS stimulant that facilitates the activity of amines in both the CNS and the periphery. Amphetamines promote the release of NE from sympathetic nerve endings, causing CV stimulation and pupillary dilation. In the CNS, they enhance the actions of DA, NE, and 5HT, causing behavioral excitation and a psychotic state that may be difficult to distinguish from schizophrenia. Ethanol, marijuana, fentanyl, and flunitrazepam (a benzodiazepine that has been used in “date rape”) are all CNS depressants.

22.Answer: A. ACh receptors in the CNS are present on less than 5% of the neu-

ronal population. Most of them are of the muscarinic subtype, M1 (excitatory) and M2 (inhibitory), via G-protein coupled changes in cAMP. Nicotinic receptors are excitatory via direct coupling to cation channels (Na/K), and their activation does not initiate second messenger pathways. Other CNS transmitter receptors that are directly coupled to ion channels include those for GABA and glutamic acid. Almost all CNS receptors for DA, NE, 5HT, and opioid peptides are coupled to ion channels via second messenger systems.

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SECTION V

Antimicrobial

Agents