ENDO

Question 1

A drug that is purified from the urine of postmenopausal women and is used to promote spermatogenesis in infertile men

Answer 1

UROFOLLITROPIN
Spermatogenesis in males requires the action of FSH and LH
Urofollitropin – used clinically to provide FSH activity

Question 2

A 3-year-old boy with failure to thrive and metabolic disturbances was found to have an inactivating mutation in the gene that encodes the growth hormone receptor. Which drug is most likely to improve his metabolic function and promote his growth?

Answer 2

MECASERMIN
This child’s condition is due to the inability of GH to stimulate the production of insulin-like growth factors, the ultimate mediators of GH effects. Mecasermin, a combination of recombinant IGF-1 and the binding protein that protects IGF-1 from immediate destruction, will help correct the IGF deficiency. Because of the inactive GH receptors, somatropin will not be effective

Question 3

An important difference between leuprolide and ganirelix is that ganirelix

Answer 3

Leuprolide is an agonist of GnRH receptors, whereas ganirelix is an antagonist. Although both drugs can be used to inhibit gonadotropin release, ganirelix does so immediately, whereas leuprolide does so only after about 1 wk of sustained activity.

Question 4

A 27-year-old woman with amenorrhea, infertility, and galactorrhea was treated with a drug that successfully restored ovulation and menstruation

Answer 4

BROMOCRIPTINE
Bromocriptine, a dopamine receptor agonist, is used to treat the amenorrhea-galactorrhea syndrome, which is a consequence of hyperprolactinemia. Because of its central dopaminergic effects, the drug should not be used in patients with a history of schizophrenia or other forms of psychotic illness.

Question 5

A 3-year-old girl was referred to the genetic counselor by her pediatrician. Cytogenetic testing reveals an XO karyotype. Which of the following drugs will allow her to achieve a higher adult height?

Answer 5

SOMATROPIN
Somatropin, recombinant human GH, promotes growth in children with Turner’s syndrome (an XO genetic genotype) or chronic renal failure. It also helps combat the AIDS-associated wasting syndrome

Question 6

Most appropriate drug for treatment of precocious puberty

Answer 6

LEUPROLIDE
In precocious puberty, the hypothalamic-pituitary-gonadal axis becomes prematurely active for reasons that are not understood. Treatment involves suppressing gonadotropin secretion with continuous administration of a long-acting GnRH agonist such as leuprolide.

Question 7

A 47-year-old man exhibited signs and symptoms of acromegaly, which drug is most likely to be used as pharmacologic therapy?

Answer 7

OCREOTIDE
Octreotide, a somatostatin analog, has some efficacy in reducing the excess GH production that causes acromegaly.

Question 8

A 37-year-old woman with infertility due to obstructed fallopian tubes was undergoing ovulation induction in preparation for in vitro fertilization. After 10 d of treatment with leuprolide, the next step in the procedure is most likely to involve 10–14 d of treatment with which of the following?

Answer 8

FOLLITROPIN
Once the patient’s endogenous gonadotropin production has been inhibited through continuous administration of the GnRH agonist leuprolide, the next step in ovulation induction is the administration of a drug with FSH activity to stimulate follicle maturation. Follitropin is recombinant FSH. The only other drug listed that is used in ovulation induction is hCG, but this is an LH analog.

Question 9

Pituitary diabetes insipidus is likely to be treated with

Answer 9

DESMOPRESSIN
Pituitary diabetes insipidus results from deficiency in vasopressin. It is treated with desmopressin, a peptide agonist of vasopressin V2 receptors.

Question 10

In Graves’ disease, the cause of the hyperthyroidism is the production of an antibody that does

Answer 10

Activates the thyroid gland TSH receptor and stimulates thyroid hormone synthesis and release
Their effects mimic those of TSH

Question 11

Methimazole reduces serum concentration of T3 primarily by

Answer 11

Preventing the addition of iodine to tyrosine residues on thyroglobulin
The thioamides (methimazole and propylthiouracil) act in thyroid cells to prevent conversion of tyrosine residues in thyroglobulin to MIT or DIT.

Question 12

Though rare, a serious toxicity associated with the thioamides is

Answer 12

AGRANULOCYTOSIS
Rarely, the thioamides cause severe adverse reactions that include agranulocytosis, vasculitis, hepatic damage, and hypoprothrombinemia.

Question 13

A 65-year-old man with multinodular goiter is scheduled for a near-total thyroidectomy. Which of the following drugs will be administered for 10–14 d before surgery to reduce the vascularity of his thyroid gland?

Answer 13

LUGOL’S SOLUTION
Iodides inhibit the synthesis and release of thyroid hormone and decrease the size and vascularity of the hyperplastic gland. Lugol’s solution contains a mixture of potassium iodide and iodine.

Question 14

A sign or symptom that would be expected to occur in the event of chronic overdose with exogenous T4

Answer 14

WEIGHT LOSS
In hyperthyroidism, the metabolic rate increases, and even though there is increased appetite, weight loss often occurs.

Question 15

When initiating T4 therapy for an elderly patient with longstanding hypothyroidism, it is important to begin with small doses to avoid

Answer 15

OVERSTIMULATION OF THE HEART
Patients with longstanding hypothyroidism, especially those who are elderly, are highly sensitive to the stimulatory effects of T4 on cardiac function. Administration of regular doses can cause overstimulation of the heart and cardiac collapse.

Question 16

What hormone is produced in the peripheral tissues when levothyroxine is administered?

Answer 16

T3
The thioamides (methimazole and propylthiouracil) act in thyroid cells to prevent conversion of tyrosine residues in thyroglobulin to MIT or DIT. Levothyroxine (T4) is converted into T3 in the periphery.

Question 17

An iodine-containing antiarrhythmic drug with complex effects on the thyroid gland and thyroid hormones

Answer 17

AMIODARONE
One of its actions is to inhibit peripheral conversion of T4 to T3. Note that propranolol also reduces conversion of T4 to T3.

Question 18

A drug that produces a permanent reduction in thyroid activity?

Answer 18

131I
Radioactive iodine is the only medical therapy that produces a permanent reduction of thyroid activity. Anions such as thiocyanate (SCN–) and perchlorate (ClO4–) block the uptake of iodide by the thyroid gland through competitive inhibition of the iodide transporter. Their effectiveness is unpredictable and ClO4– can cause aplastic anemia, so these drugs are rarely used.

Question 19

Pharmacologic effect of exogenous glucocorticoids

Answer 19

Glucocorticoids inhibit the production of both leukotrienes and prostaglandins via inhibition of phospholipase A2. This is a key component of their anti-inflammatory action.

Question 20

A toxic effect associated with long-term glucocorticoid treatment

Answer 20

OSTEOPOROSIS
One of the adverse metabolic effects of long-term glucocorticoid therapy is a net loss of bone, which can result in osteoporosis.

Question 21

Which drugs would be expected to reduce the signs and symptoms of Cushing’s syndrome due to an adrenal tumor

Answer 21

KETOCONAZOLE
Ketoconazole inhibits many types of cytochrome P450 enzymes. It can be used to reduce the unregulated overproduction of corticosteroids by adrenal tumors.

Question 22

Most potent anti-inflammatory steroid

Answer 22

DEXAMETHASONE
Of the drugs listed, cortisol has the lowest and dexamethasone the highest anti-inflammatory activity

Question 23

A drug that, in high doses, blocks the glucocorticoid receptor

Answer 23

MIFEPRISTONE
Mifepristone is a competitive antagonist of glucocorticoid and progesterone receptors. Ketoconazole and aminoglutethimide also antagonize corticosteroids; however, they act by inhibiting steroid hormone synthesis.

Question 24

Postcoital contraception

Answer 24

MIFEPRISTONE
Mifepristone, an antagonist at progesterone and glucocorticoid receptors, has a luteolytic effect and is effective as a postcoital contraceptive. When combined with a prostaglandin, it is also an effective abortifacient.

Estrogen-containing hormonal contraceptives increase the risk of episodes of migraine headache.

Question 25

Men who use large doses of anabolic steroids are at increased risk of

Answer 25

Cholestatic jaundice and elevation of aspartate transaminase levels in the blood

Question 26

A 60-year-old man is found to have a prostate lump and an elevated prostate-specific antigen (PSA) blood test. Magnetic resonance imaging suggests several enlarged lymph nodes in the lower abdomen, and an x-ray reveals 2 radiolucent lesions in the bony pelvis. This patient is likely to be treated with

Answer 26

LEUPROLIDE
Leuprolide is a GnRH agonist used in the treatment of men with prostate cancer. Continuous use leads to downregulation of testosterone production. Initially, the agonist action increases testosterone, causing a tumor flare. To prevent this, flutamide, a competitive antagonist of the androgen receptor, is added until downregulation of testosterone is complete.

Question 27

A young woman complains of abdominal pain at the time of menstruation. Careful evaluation indicates the presence of significant endometrial deposits on the pelvic peritoneum. Which is the most appropriate medical therapy for this patient?

Answer 27

Medroxyprogesterone acetate by intramuscular injection

In endometriosis, suppression of ovarian function and production of gonadal steroids are useful. Intramuscular injection of relatively large doses of medroxyprogesterone provides 3 months of an ovarian suppressive effect because of inhibition of pituitary production of gonadotropins.

Question 28

Diethylstilbestrol (DES) should never be used in pregnant women because it is associated with

Answer 28

Infertility and development of vaginal cancer in female offspring

Question 29

Finasteride has efficacy in the prevention of male-pattern baldness by virtue of its ability to do

Answer 29

Reduce the production of dihydrotestosterone

Question 30

Raloxifene

Answer 30

In patients with a strong family history of breast cancer, raloxifene may be a better choice than a full estrogen agonist because it will not further increase the woman’s risk of breast cancer and may even lower her risk.

Question 31

Which agents should be administered to achieve rapid control of the severe ketoacidosis in this diabetic boy?

Answer 31

Crystalline zinc insulin – a rapid-acting insulin preparation that can be given intravenously

Question 32

Most likely complication of insulin therapy?

Answer 32

Hypoglycemia

Because of the risk of brain damage, the most important complication of insulin therapy is hypoglycemia.

Question 33

A 24-year-old woman with type 1 diabetes wishes to try tight control of her diabetes to improve her long-term prognosis. Which regimens is most appropriate?

Morning injections of insulin glargine, supplemented by small amounts of insulin lispro at mealtimes

Answer 33

Insulin regimens for tight control usually take the form of establishing a basal level of insulin with a small amount of a long-acting preparation (eg, insulin glargine) and supplementing the insulin levels, when called for by food intake, with short-acting insulin lispro.

Less tight control may be achieved with 2 injections of intermediate-acting insulin per day. Because intake of glucose is mainly during the day, long-acting insulins are usually given in the morning, not at night.

Question 34

Drugs promotes the release of endogenous insulin?

Answer 34

SULFONYLUREAS
E.g., glipizide is a second-generation sulfonylurea that promotes insulin release by closing potassium channels in pancreatic B cells.

Question 35

An important effect of insulin?

Answer 35

Increased glucose transport into cells

Insulin lowers serum glucose concentration in part by driving glucose into cells, particularly into muscle cells.

Question 36

Combination of metformin and ethanol increases the risk of

Answer 36

LACTIC ACIDOSIS

Biguanides, especially the older drug phenformin, have been associated with lactic acidosis. Thus, metformin should be avoided or used with extreme caution in patients with conditions that increase the risk of lactic acidosis, including acute ethanol ingestion.

Question 37

Which drugs is taken during the first part of a meal for the purpose of delaying the absorption of dietary carbohydrates?

Answer 37

ACARBOSE
To be absorbed, carbohydrates must be converted into monosaccharides by the action of α-glucosidase enzymes in the gastrointestinal tract. Acarbose inhibits α-glucosidase and, when present during digestion, delays the uptake of carbohydrates.

Question 38

The PPAR-γ receptor that is activated by thiazolidinediones increases tissue sensitivity to insulin by which mechanisms?

Answer 38

Regulating transcription of genes involved in glucose utilization
The PPAR-γ receptor belongs to a family of nuclear receptors. When activated, these receptors translocate to the nucleus, where they regulate the transcription of genes encoding proteins involved in the metabolism of carbohydrate and lipids.

Question 39

Which drug is most likely to cause hypoglycemia when used as monotherapy in the treatment of type 2 diabetes?

Answer 39

The insulin secretagogues, including the sulfonylurea glyburide, can cause hypoglycemia as a result of their ability to increase serum insulin levels.

Question 40

A 62-year-old man with severe bradycardia and hypotension resulting from ingestion of an overdose of atenolol

Treated with intravenous glucagon

Answer 40

Glucagon acts through cardiac glucagon receptors to stimulate the rate and force of contraction of the heart. Because this bypasses cardiac β-adrenoceptors, glucagon is useful in the treatment of β-blocker-induced cardiac depression.

Question 41

Which drug is routinely added to calcium supplements and milk for the purpose of preventing rickets in children and osteomalacia in adults?

Answer 41

Cholecalciferol

The 2 forms of vitamin D—cholecalciferol and ergocalciferol—are commonly added to calcium supplements and dairy products. Calcitriol, the active 1,25-dihydroxyvitamin D3 metabolite, would prevent vitamin D deficiency and is available as an oral formulation. However, because it is not subject to the complex mechanisms that regulate endogenous production of active vitamin D metabolites, it is not suitable for widespread use.

Question 42

Drugs is most useful for the treatment of hypercalcemia in Paget’s disease?

Answer 42

Paget’s disease is characterized by excessive bone resorption, poorly organized bone formation, and hypercalcemia. Bisphosphonates and calcitonin are first-line treatments.
Pamidronate is a powerful bisphosphonate used parenterally to treat hypercalcemia.

Question 43

The active metabolites of vitamin D act through a nuclear receptor to produce which effects?

Answer 43

Increase the absorption of calcium from the gastrointestinal tract

The active metabolites of vitamin D increase serum calcium and phosphate by promoting calcium and phosphate uptake from the gastrointestinal tract, increasing bone resorption, and decreasing renal excretion of both electrolytes. They inhibit, rather than stimulate, PTH formation.

Question 44

Teriparatide

Answer 44

Teriparatide increases bone formation and bone resorption; during the first 6 months, it causes a net gain in bone. Teriparatide should not be used longer than 2 yr due to risk of osteosarcoma

Question 45

In the treatment of patients with secondary hyperparathyroidism due to chronic kidney disease, cinacalcet is an alternative to vitamin D-based drugs. Cinacalcet lowers PTH by which mechanisms?

Answer 45

Activating the calcium-sensing receptor in parathyroid cells

Cinacalcet is a member of a novel class of drugs that activate the calcium-sensing receptor in parathyroid cells. When this receptor is activated by cinacalcet or free ionized calcium, it activates a signaling pathway that suppresses PTH synthesis and release.