181 Pharmacology

Question 1

What drug is a synthetic long acting analog of vasopressin?

Answer 1

desmopressin

Question 2

What is the mechanism of vasopressin?

Answer 2

binds to GPCR –> V1/Gq activates phospholipase C, V2/Gs activates cAMP

phospholipase C causes calcium influx, leading to vasoconstriction

cAMP leads to increased water permeability and water resorption in the collecting duct

Question 3

How are vasopression and its analogs metabolized?

Answer 3

metabolized through hepatic and renal metabolism

Question 4

What are the major therapeutic uses of vasopressin and desmopressin?

Answer 4

treat central diabetes insipidus and to stop bleeding (vasopressin for esophageal varices, desmopressin for hemophilia and von willebrand’s disease)

Question 5

What are the major adverse effects of vasopressin and analogs?

Answer 5

uterine rupture and fetal distress at high doses

Question 6

Growth hormone secretion is stimulated by _________ and inhibited by _________.

Answer 6

Growth hormone secretion is stimulated by GNRH and inhibited by somatostatin.

Question 7

What analogs of growth hormone are used pharmacologically?

Answer 7

somatotropin and somatatrem

Question 8

What is the mechanism of growth hormone?

Answer 8

acts on a tyrosine kinase membrane receptor –> activates JAK and STAT

also works through IGF-1

Question 9

What are the therapeutic uses of growth hormone analogs?

Answer 9

growth hormone deficiency in children, short stature in children, Turner syndrome, Prader Willi syndrome, chronic renal insufficiency, idiopathic short stature, AIDS-associated wasting, malabsorption (due to short bowel)

Question 10

What are the adverse effects of growth hormone analogs?

Answer 10

arthralgias, myalgias, carpal tunnel syndrome, slipped epiphyses, scoliosis progression, intracranial hypertension

Question 11

What are clinically used IGF-1 analogs? What is it used for?

Answer 11

mecasermin –> promotes growth and normalizes metabolism in cases of IGF-1 deficiency

Question 12

What are the adverse effects of mecasermin?

Answer 12

hypoglycemia, lipohypertrophy

mecasermin = IGF-1 recombinant form

Question 13

What are clinically used growth hormone antagonists?

Answer 13

octreotide –> analog of somatostatin (inhibitor of growth hormone secretion)

pegvisomant –> growth hormone receptor antagonist

bromocriptine and cabergoline –> mimics of dopamine with D2 selectivity

Question 14

What hormones have secretion inhibited by somatostatin?

Answer 14

growth hormone, thyroid stimulating hormone, glucagon, gastrin, insulin

Question 15

What are the adverse effects of octreotide?

Answer 15

nausea, bloating, bradycardia

Question 16

What is pegvisomant used for?

Answer 16

used to treat acromegaly

Question 17

What are the adverse effects of pegvisomant?

Answer 17

increase in LFTs, worsening of growth hormone secreting adenomas, compulsive behaviors

Question 18

What are the adverse effects of bromocriptine and cabergoline?

Answer 18

nausea and vomiting, headache, orthostatic hypotension, headache, nasal congestion, vasospasm, hallucinations, psychoses, nightmares, insomnia

Question 19

What is the mechanism of thyroid hormones?

Answer 19

nuclear receptors and phosphatidylinositol-3-kinase receptors

nuclear –> activate transcription factors and gene expression

also provide feedback inhibition at the hypothalamus and pituitary

Question 20

How are thyroid hormones metabolized?

Answer 20

metabolized in the liver by deamination, decarboxylation, glucuronide/sulfate conjugation

Question 21

What are the therapeutic uses of thyroid hormone?

Answer 21

to treat hypothyroidism (ex. Hashimotos)

Question 22

What are the adverse effects of therapeutic thyroid hormone?

Answer 22

headaches, weight loss, diarrhea, anxiety, palpitations, angina, coronary and cerebral thromboses

basically hyperthyroidism

Question 23

What agents are used to treat hyperthyroidism?

Answer 23

radioactive iodine, thionamides (ex. propylthiouracil and methimazole), sympatholytic agents (like beta blockers), iodides (ex. potassium iodide)

Question 24

What is the mechanism of thionamides?

Answer 24

enzymes preferentially iodinate the drugs, reducing the amount of activated thyroid hormone

Question 25

What are side effects of thionamides?

Answer 25

dermatits, hepatitis, arthralgias, lymph node enlargement, agranulocytosis

Question 26

What is the mechanism of glucocorticoids?

Answer 26

they interact with receptors in the cytoplasm, leadign to release of heat shock protein --\> leads to translocation of ligand bound receptors to the nucleus

Question 27

What are the metabolic actions of glucocorticoids?

Answer 27

liver --\> production and conservation of glucose through increased gluconeogenesis (insulin antagonist) and increased glycogen synthesis connective tissue --\> decreased synthesis and increased breakdown of proteins adipose tissue --\> fat redistribution, truncal obesity

Question 28

What are the actions of glucocorticoids on the kidneys, immune system, GI, CNS, and stress response?

Answer 28

kidney --\> Na retention, K excretion, H excretion, Ca excretion Immune --\> decreased antibodies, antigen processing, lymphocytes, and inflammatory reaction GI --\> thinning mucosa, increased acid/pepsin, decreased Ca absorption CNS --\> euphoria, depression, sleep disturbances, psychoses stress response --\> increased CO, increased GFR

Question 29

What is the mechanism of mineralocorticoids?

Answer 29

they act on epihelial tissues involved in electrolyte transport, leading to increased trans-epithelial NaCl transport and increased lumen-negative trans-epithelial voltage --\> driving force for potassium and hydrogen ion movement into the tubular lumen

Question 30

What are the major uses of glucocorticoids for replacement therapy?

Answer 30

chronic hypoadrenalcorticism (Addison's disease) - with mineralocorticoids loss of adrenal function - with salt and water replacement treatment of congenital adrenal hyperplasias

Question 31

\_\_\_\_\_\_\_\_\_\_\_\_\_ deficiency is treated by mineralocorticoid and glucocorticoid replacement, ____________ deficiency is treated with only glucocorticoids.

Answer 31

**21-hydroxylase** deficiency is treated by mineralocorticoid and glucocorticoid replacement, **11-hydroxylase** deficiency is treated with only glucocorticoids.

Question 32

What is the mechanism of mifepristone?

Answer 32

it blocks glucocorticoid receptors and is a progestin antagonist ## Footnote *used to treat hyperglycemia in patients with hypercortisolism and type 2 diabetes*

Question 33

Which drugs are glucocorticoids synthesis inhibitors?

Answer 33

metyrapone - inhibits 11-hydroxylase ketoconazole - blocks several steps of pathway aminoglutethimide - blocks cholesterol side chain cleavage Mitotane *used to treat adrenal hyperfunction (ex. adrenocorticol carcinoma)*

Question 34

What are the possible outcomes of an ACTH test?

Answer 34

positive --\> suggests that the deficiency is from inadequate ACTH from the pituitary negative --\> suggests that the deficiency is from primary adrenal insufficiency

Question 35

What is the utility of a metyrapone test?

Answer 35

it assesses the extent to which the pituitary can be stimulated in the case of pituitary stimulation problems

Question 36

How can dexamethasone be used to assess adrenal hyperfunction?

Answer 36

it is a glucocorticoid that elicits feedback inhibition of pituitary ACTH - used to determine if high cortisol/metabolites derive from a supressible or non-supressible source

Question 37

What is the mechanism of the anti-inflammatory and immunosuppressive activity of glucocorticoids?

Answer 37

inhibition of synthesis of prostaglandins and proinflammatory cytokines also decrease the numbers of immune cells

Question 38

What are the major side effects of glucocorticoids?

Answer 38

hypokalemic alkalosis, glycosuria (diabetogenic), susceptibility to infection, ulcers, myopathy, osteoporosis, hypercoagulability, psychoses, glaucoma, reproductive disturbances, adrenal insufficiency

Question 39

Octreotide: a) inhibits secretion of growth hormone b) is an antagonist peptide analog of growth hormone c) is a dopamine receptor analog that inhibits secretion of hypothalamic hormones d) acts through tyrosine kinase-linked receptors e) side effects include stimulation of secretion of glucagon and gastrin

Answer 39

a) inhibits secretion of growth hormone ## Footnote *octreotide is an analog of somatostatin*

Question 40

All of the following are symptoms of excessive thyroid hormone except: a) elevated heart rate b) decreased TSH c) increased glycogenolysis d) increased basal metabolic rate e) increased cholesterol

Answer 40

e) increased cholesterol ## Footnote *thyroid hormone lowers cholesterol*

Question 41

Prednisone has the advantage over hydrocortisone that prednisone: a) is less likely to increase blood glucose b) doesn't suppress the immune response c) has a longer duration of action d) is orally effective e) has greater glucocorticoid/mineralocorticoid activity

Answer 41

e) has greater glucocorticoid/mineralocorticoid activity ## Footnote *the glucocorticoid/mineralocorticoid ratio for prednisone is 5X that for hydrocortisone*

Question 42

Which of the following is true? a) vasopressin decreases the fluid volume in the circulation b) thiazide diuretics are used to treat central diabetes insipidus c) desmopressin activates V1 receptors more potently than V2 receptors d) both oxytocin and vasopressin are polypeptides with 9 amino acid residues

Answer 42

d) both oxytocin and vasopressin are polypeptides with 9 amino acid residues

Question 43

Which of the following is true? a) GH stimulates metabolism of IGF-1 in the liver b) Mecasermin is an IGF-1 antagonist c) Somatostatin is a physiological inhibitor of GH secretion d) Cabergoline inhibits GH production via somatostatin receptor

Answer 43

c) Somatostatin is a physiological inhibitor of GH secretion

Question 44

Which of the following is true about therapy for hyperthyroidism? a) Methimazole inhibits peripheral conversion of T4 to T3 b) 131-I kills follicular cells by beta emission c) Dose of methimazole should be increased when treating pregnant hyperthyroid patients d) KI suppresses thyroid function by inhibiting peripheral conversion from T4 to T3

Answer 44

b) 131-I kills follicular cells by beta emission

Question 45

Which of the following is true? a) Addison's disease is treated with glucocorticoids only b) 11-hydroxylase deficiency is treated with mineralocorticoids c) dexamethasone test is used to determine etiology of adrenal hyperfunction d) steroid withdrawal syndrome results from chronic excess of ACTH synthesis

Answer 45

c) dexamethasone test is used to determine etiology of adrenal hyperfunction