Pharmacology/substance abuse

Question 1

What is the progression of alcohol withdrawal?

Answer 1

Anxiety, insomnia, tremors, diaphoresis, palpitations, GI upset, intact orientation (6-24 hrs after not drinking) → single or multiple tonic-clonic seizures (12-48 hrs) → Visual, auditory, or tactile hallucinations; intact orientation; stable vital signs (12-48 hrs) → Delirium tremens: confusion, agitation, fever, tachycardia, HTN, diaphoresis, hallucinations (48-96 hrs).

Question 2

What is the manifestation of Reye’s syndrome?

Answer 2

Hepatic dysfunction: causes hepatomegaly and vomiting. LFTs show increased ALT, AST, ammonia and bilirubin with a prolonged PT and PTT. Hepatocytes show microvesicular steatosis (small fat vacuoles in the cytoplasm of hepatocytes).

Question 3

What fetal heart anomaly can lithium cause if taken during pregnancy?

Answer 3

Ebstein’s anomaly: apical displacement of the tricuspid valve leaflets, atrialization of the right ventricle and a decrease in the volume of the right ventricle. There will be moderate to severe tricuspid regurgitation with a holosystolic murmur heard best in the left sternal border.

Question 4

Which class of lipid lowering drugs can cause an elevation in triglycerides?

Answer 4

Bile acid-binding resins (e.g. cholestyramine, colestipol, colesevelam). They work by binding bile acids in the gut, preventing their reabsorption. This causes a diversion of hepatic cholesterol to be synthesized a new bile acids (causing increased LDL uptake from circulation). They also lead to increased hepatic production of triglycerides.

Question 5

What is the mechanism of action of cromolyn?

Answer 5

Asthma medication. Inhibits mast cell degranulation. For prevention of acute attacks (can replace inhaled glucocorticoids).

Question 6

What is the mechinism of action of colchicine?

Answer 6

Inhibits microtubular polymerization. This prevents functions such as chemotaxis, phagocytosis, and degranulation. Colchicine also reduces the formation of leukotriene B4, which is involved in inflammation. It is used to treat gout.

Question 7

How is bioavailability (F) calculated if shown a curve?

Answer 7

F=(area under oral curve x IV dose)/(area under IV cure x oral dose). If the IV and oral dose are the same, you can eliminate the doses from the calculation.

Question 8

What topical agent is often used for plaque psoriasis?

Answer 8

Topical vitamin D analogs (e.g. calcipotriene, calcitriol, and tacalcitol). These drugs bind and activate the vitamin D receptor, a nuclear transcription factor that causes inhibition of keratinocyte proliferation and stimulation of keratinocyte differentiation.

Question 9

What is a toxicity of overaggressive mannitol administration?

Answer 9

Pulmonary edema (due to the rapid increase in plasma volume thus increasing hydrostatic pressure and pushing fluid into the lungs).

Question 10

What agent can be used to prevent gynecomastia in men taking GnRH analogs for prostate cancer?

Answer 10

Selective estrogen receptor modulators (e.g. tamoxifen).

Question 11

What is the mechanism of action of anastrozole, letrozole and exemestane?

Answer 11

Aromatase inhibitors - used in the treatment of ER-positive tumors (e.g. breast).

Question 12

What is the mechanism of action of phencyclidine (PCP)?

Answer 12

Acts as an N-methyl-D-aspartate (NMDA) receptor antagonist. This secondarily inhibits reuptake of NE, DA, and 5-HT.

Question 13

What enzyme do etoposide and podophyllin inhibit?

What enzyme do irinotecan and topotecan inhibit?

Answer 13

Topoisomerase II

Topoisomerase I

Question 14

How is agitation caused by PCP treated?

Answer 14

Benzodiazepines or haloperidol for severe symptoms.

Question 15

What cardiovascular medication should be used with caution in diabetic patients, especially those taking insulin?

Answer 15

Non-selective beta-blockers (e.g. propranolol, timolol, nadolol). These drugs inhibit NE/epi-mediated (beta 1) compensatory reactions to hypoglycemia (hepatic gluconeogenesis, and peripheral glycogenolysis and lipolysis). Symptoms of NE/epi release include tremulousness, palpitations, and anxiety/arousal. Note that cholinergic symptoms such as sweating, hunger and paresthesias are not affected. Selective beta 1 blockers are preferred in diabetic patients.

Question 16

What is the action of finasteride and dutasteride?

Answer 16

5-alpha-reductase inhibitors. They act by reducing prostate gland size. May take 6-12 months to take effect. Side effects include decreased libido and erectile dysfunction.

Question 17

What is latanoprost?

Answer 17

A topical prostaglandin (drops) used in the treatment of glaucoma. Prostaglandins are the preferred first-line agents for the treatment of glaucoma. Mxn is unknown other than they increase outflow of aqueous humor. It is know to cause pigmentation of the iris and eyelashes.

Question 18

Why do similar drugs which bind to the same target site demonstrate different potencies?

Answer 18

More potent drugs have a higher affinity for the target.

Question 19

What are the affects of inhaling glue (or other volatile hydrocarbons)?

Answer 19

Inhalant abuse is the intentional inhalation of volatile hydrocarbons, such as model glue, correction fluid, spray paint, and gasoline, to achieve an altered mental state. It is a common health problem in adolescence. The effect of inhaling a large quantity of hydrocarbons has been described as “quick drunk” because it resembles alcoholic intoxication. Initially, euphoria develops; then, lightheadedness and agitation. Disorientation, ataxia, and dizziness might develop with increasing intoxication. In extreme cases, generalized weakness, hallucinations, and nystagmus can occur. Abusers often show deterioration in school performance, disturbance of family relationships, and increased risk-taking behaviors. Encephalopathy is the major chronic morbidity following chronic inhalant abuse. Hydrocarbons are highly lipophilic and can easily distribute to the brain. Studies have shown that chronic abusers have radiographic evidence of CNS damage, such as loss of brain mass on CT and white matter degeneration on MRI. Clinically, chronic abusers often have cognitive and cerebellar dysfunction, including peripheral and cranial neuropathy, visual loss, and Parkinsonism.

Question 20

What are the phases of drug trials?

Answer 20

Preclinical: Testing of drug in non-human subjects.
Phase 0: Pharmacokinetics; particularly oral bioavailability and half-life of the drug (dosage is subtherapeutic in 10 human volunteers).
Phase I: Testing of drug in healthy volunteers for dose-ranging (20-100 normal healthy volunteers, exception is cancer patients for cancer drugs).
Phase II: Testing of drug on patients to assess efficacy and side effects (therapeutic dose on 100-300 patients with specific disease).
Phase III: Testing of drug on patients to assess efficacy, effectiveness and safety (therapeutic dose, 300-3,000 patients with specific disease).
Phase IV: Postmarketing surveillance (watching drug in public).

Question 21

What drug is used to reduce the severity of tumor lysis syndrome by converting uric acid into more soluble metabolites?

Answer 21

Rasburicase (recombinant urate oxidase). It can help to reduce the uric acid levels during the breakdown of tumor cells in chemotherapy.

Question 22

What is varenicline used for?

Answer 22

Helps with smoking cessation. Acts as a partial agonists on the nicotinic acetylcholine receptor in the CNS that contributes to addiction. As a partial agonist, it helps reduce the symptoms of nicotine withdrawal by mildly stimulating the receptor, while at the same time limiting the downstream release of dopamine which results in less stimulation of the reward pathway when a patient smokes.

Question 23

If the volume of distribution and clearance of a drug are known, how is half-life calculated?

Answer 23

t1/2=(0.7 x Vd)/CL

E.g. Vd=10L and CL= 7 L/hr so t1/2=1 hr

Question 24

How is maintenance dose calculated?

Answer 24

Dm/𝜏=Cpss x CL

Question 25

How are loading doses calculated?

Answer 25

Loading dose = Vd x Cp

Question 26

What test should be ordered prior to initiating metformin treatment?

Answer 26

Serum creatinine to assess renal function. Metformin is excreted by the kidneys and patients with low GFR are at higher risk for lactic acidosis.

Question 27

What is the mechanism of action of naltrexone?

Answer 27

Blocks mu-opioid receptors

Question 28

What are the risks for infants associated with secondhand smoke exposure?

Answer 28

Prematurity/low birth weight, SIDS, middle ear disease (e.g. otitis media), asthma, and respiratory tract infections (e.g. bronchitis, pneumonia)

Question 29

Why can heavy drinking lead to hypoglycemia?

Answer 29

Gluconeogenesis is inhibited. Alcohol dehydrogenase and aldehyde dehydrogenase reduce NAD+ to NADH. NAD+ is required for some of the steps in gluconeogenesis.

Question 30

What enzyme deficiency is linked to hemolytic anemia when taking dapsone (antibiotic)?

Answer 30

G6PD defiency

Question 31

What is the calculation for plasma drug concentration for a drug if the volume of distribution and drug dose are known?

Answer 31

Cp= (drug dose)/Vd

Question 32

What eye condition can acetazolamide be used to treat?

Answer 32

Relieves intraocular pressures in open-angle and angle-closure glaucoma.

Question 33

What should you give as first line treatment for arsenic poisoning.

Answer 33

Dimercaprol is a heavy metal chelating agent.
Patients with acute arsenic poisoning will have abdominal pain, vomiting, severe watery diarrhea, delirium, and hypotension. They can get QTc prolongation. Patients are noted for having a garlic odor on their breath.
Arsenic may be found in pesticides/insecticides, contaminated water, and pressure-treated wood.

Question 34

What kind of renal damage can calcineurin inhibitors (e.g. cyclosporin, tacrolismus) cause?

Answer 34

Obliterative vasculopathy.

Question 35

What is probenecid?

Answer 35

Blocks organic anion transporters on renal tubular cells to inhibit tubular secretion of certain antibiotics (e.g. penicillin). It can be used to enhance penicillin’s efficacy in certain clinical settings (e.g. penicillin resistance, gonorrhea, neurosyphilis).

Question 36

How do opiate analgesics exert there affect on spinal cord neurons?

Answer 36

Opiates primarily bind to mu receptors on afferent neurons in the spinal chord resulting in closure of voltage-gate calcium channels, reduced calcium influx, and decreased excitatory neurotransmitter release from the presynaptic terminal. They also bind to mu receptors on the postsynaptic membrane, which opens potassium channels and leads to membrane hyperpolarization due to potassium efflux.