SM159 Pharm

Question 1

Desmopressin

Answer 1

ADH analog, long-acting

Question 2

Vasopressin mechanism

Answer 2

Acts through GPCR
V1 receptors: couples to PLC, releases Ca++, causes vasoconstriction and CNS effects
V2 receptors: couples to AC to increase cAMP, increases water reabsorption in the collecting duct via insertion and stabilization of aquaporins, increases factor VIII and vWF

Question 3

Is desmopressin or vasopressin more potent? Which as a longer half-life?

Answer 3

Desmo has a 4000x greater antidiurietic/pressor activity

Desmo also has a longer half-life

Question 4

Vasopressin pharmacokinetics

Answer 4

Hepatic/renal metabolism

Reduction of disulfide bond

Question 5

Vasopressin indications

Answer 5

Central DI (inadequate release of vasopressin)
Stop esophageal varices bleeding
Stop bleeding in hemophilia A and vW disease

Question 6

Vasopressin adverse effects

Answer 6

Undesired vasoconstriction (like in patients with CAD)
Nausea, cramps, headaches, allergic rxn

Question 7

Nephrogenic DI: etiology, treatment

Answer 7

Impaired renal response to ADH

Treat with thiazides

Question 8

SIADH: etiology, treatment

Answer 8

Malignancy, head injury, drugs

Conivaptan, tolvaptan: vasopression receptor antagonists

Question 9

Oxytocin mechanism

Answer 9

Binds GPCR, releases Ca++ via PLC. Also causes release of prostaglandins and leukotrienes.

Actions: leads to smooth muscle contraction, stimulates uterine contraction, causes milk ejection.

Question 10

Oxytocin indications

Answer 10

Induce labor when early vaginal delivery is indicated (eclampsia) or when labor is protracted or arrested

Postpartum to control uterine hemorrhage

Question 11

Oxytocin adverse effects

Answer 11

Uterine rupture, fetal distress, activation of vasopressin receptors

Question 12

GH analogs

Answer 12

Somatropin: identical
Somatrem: + methionine (extends half life)

Question 13

GH regulation

Answer 13

Stimulated by GHRH

Inhibited by SS and dopamine

Question 14

GH mechanism

Answer 14

Acts through TYK receptors, activates JAKs which activate STAT proteins. Stimulate release of IGF-1.

Actions: stimulates longitudinal growth of bone before plates close, increase muscle mass, decrease central fat, reduce sensitivity to insulin, increase glycolysis

Question 15

GH indications

Answer 15

Replacement therapy for GH deficient kids
Other causes of short stature: Turner, Prader-Willi, chronic renal insufficiency
AIDS wasting
Abuse: antiaging, athletic enhancement

Question 16

GH adverse effects

Answer 16

Joint and muscle pain, peripheral edema, carpal tunnel, insulin resistance, adrenal insufficiency due to inhibition of 11b-hydroxysteroid dehydrogenase

Question 17

IGF-1 agonists

Answer 17

Sometimes GH response is inadequate, so use these

Mecasermin: recombinant form
Mecasermin rinfabate: contains IGF-1 and IGF-1 binding protein (IGFBP-3) that extends the half-life and stimulates uptake into cells

Question 18

Mecasermin indications

Answer 18

Promote growth and normalize metabolism in cases of GH deficiency that are resistant to GH

Question 19

Mecasermin adverse effects

Answer 19

Hypoglycemia, lipohypertrophy, slipped epiphyses, scoliosis

Contraindicated in people with cancer

Question 20

Somatostatin analog

Answer 20

Octreotide

Question 21

Somatostatin analogs indications

Answer 21

Acromegaly: abnormal growth of bone and cartilage

Question 22

Octreotide adverse effects

Answer 22

Nausea and bloating, gall stones, bradycardia

Question 23

Octreotide mechanism

Answer 23

Acts through SS receptors (GPCR), activates K+ channels and protein phosphotyrosine phosphotases

Actions: inhibits GH secretion, inhibits secretion of TSH, ACTH, glucagon, gastrin, and insulin

Question 24

Pegvisomant mechanism

Answer 24

Allows receptor dimerization but blocks signaling in the JAK-STAT pathway

Question 25

Pegvisomant adverse effects

Answer 25

Increase in liver transaminases, lipohypertrophy, compulsive behavior, GH-secreting adenomas

Question 26

Bromocriptine and cabergoline mechanism

Answer 26

Selective dopamine D2 agonists, mimic effects of dopamine to inhibit GH production and secretion Also inhibit prolactin

Question 27

Bromocriptine and cabergoline adverse effects

Answer 27

Nausea, vomiting, headache, orthostatic hypotension

Question 28

Generic names for thyroid hormones, other preparation used

Answer 28

``` T4 = levothyroxine T3 = liothyronine Liotrix = T4/T3 combination ```

Question 29

Thyroid hormones mechanisms

Answer 29

Act as heterodimers through nuclear receptors to regulate genes. Receptors with no ligand bound acts as repressors. 4 major types: a1, a2, b1, b2

Question 30

Thyroid hormone tissue differences

Answer 30

b1 > a1 in liver b2 in hypothalamus a2 is a non-binding inactive form

Question 31

Thyroid hormones role in development

Answer 31

Critical for CNS development (inadequacy gives you cretinism) both during gestation and postpartum Critical for skeleton development

Question 32

Thyroid hormones non-development effects

Answer 32

Metabolic: important for optimal energy metabolism and reproductive function Cardiac: inotropic and chronotropic effects; potentiate effects of sympathomimetic amines Hepatic: increase cholesterol metabolism; effects on glucose metabolism cause insulin resistance Skeletal: excess thyroid hormone can promote osteoporosis, especially in adults

Question 33

Target genes for thyroid hormones

Answer 33

``` Myelin basic protein Ca++ ATPase in skeletal muscle Ion channel protein in pacemaker b-adrenergic receptors IGF-1 ```

Question 34

T4 to T3 conversion

Answer 34

5'-deiodination in the periphery (blocked by beta-blockers)

Question 35

T3 or T4: which is more potent, better cleared, binds less proteins, and cleared faster? Which one is most commonly used and why?

Answer 35

T3 is better in each category | T4 is more commonly used: more convenient dosage and lower risk

Question 36

Thyroid hormone indications

Answer 36

Hypothyroidism: Hashimoto's, destruction by medical treatment, secondary

Question 37

Thyroid hormone adverse effects

Answer 37

Weight loss, sweating, diarrhea, anxiety, headaches Palpitations, angina, thrombosis (due to beta-adrenergic signaling) Chronic: weakness, anemia, infertility, HF, bone loss, insulin resistance

Question 38

T3/T4 production mechanism

Answer 38

Iodide is transported into the follicular cells, peroxidase oxidizes iodide and couples it to thyroglobulin to produce MIT and DIT (target of antithyroid drugs), two DIT get put together and then proteolysis gives you T4 T4 is turned into T3 in the periphery

Question 39

Radioactive iodide (131 I) mechanism

Answer 39

Gamma and beta emitter 131 I gets trapped, incorporated, and deposited into the colloid Released beta particles cause necrosis of follicular cells without damaging nearby cells

Question 40

Methimazole and propylthioruacil mechanism

Answer 40

Thionamides: used for hyperthyroidism | Inhibit thyroid peroxidase (PTU also blocks T4 to T3 conversion in the periphery)

Question 41

Thionamide adverse effects

Answer 41

Pruritic rash, arthralgia Agranulocytosis is rare but fatal Give PTU in pregnancy

Question 42

Role of sympatholytics in hyperthyroidism (beta-blockers)

Answer 42

Controls tachycardia, HTN, A Fib

Question 43

KI mechanism

Answer 43

Inhibits hormone release, antagonizes TSH, inhibits peroxidase

Question 44

KI indications

Answer 44

``` Prior to thyroid surgery Radiation emergencies (block uptake of 131 I) ```

Question 45

KI adverse effects

Answer 45

Rashes, swollen salivary glands, headache | Can cross placenta and cause hypothyroidism

Question 46

Glucocorticoids mechanism

Answer 46

Interacts with receptors in cytoplasm, resulting in release of hsp90. This exposes the DNA binding domain and allows translocation to the nucleus, where they bind as homodimers.

Question 47

Mineralocorticoids mechanism

Answer 47

Act at the distal convoluted tubule and collecting duct, induce the synthesis of proteins that promote transepithelial Na transport Increases the lumen-negative transepithelial voltage that drive K and H into the urine Net result: Na retention and K/H excretion

Question 48

Adrenal steroid indications

Answer 48

Replacement therapy: Addison's disease, ACTH deficiency, acute loss of adrenal function, congenital adrenal hyperplasia (CAH - hydroxylases essential for steroid synthesis are deficient resulting in hypersecretion of either mineralocorticoids or androgens occurs)

Question 49

21-hydroxylase deficiency

Answer 49

Low glucocorticoids and mineralocorticoids, high ACTH, high androgens

Question 50

11-hydroxylase deficiency

Answer 50

Low glucocorticoids, high ACTH, high mineralocorticoids and androgens

Question 51

Adrenal excess treatments: what suppresses ACTH, what suppresses synthesis, what is a receptor antagonist?

Answer 51

SS analogs (suppress ACTH), glucocorticoid synthesis inhibitors (metyrapone and ketoconazole), receptor antagonist (mifepristone RU-486)

Question 52

ACTH test for adrenal hypofunction

Answer 52

Exogenous ACTH will stimulate secretion if problem is secondary but not primary

Question 53

Metyrapone test for adrenal hypofunction

Answer 53

Metyrapone blocks 11-hydroxylase, leading to less glucocorticoids, which leads to less negative feedback, which should lead to more ACTH secretion

Question 54

Dexamethasone test for adrenal hyperfunction

Answer 54

Test whether the adrenal response is suppressible. Pituitary adenomas are suppressible with high levels, ectopic ACTH and cortisol-producing tumors are not suppressible.

Question 55

Antiinflammatory mechanism of glucocorticoids

Answer 55

Decrease synthesis of prostaglandins and inflammatory cytokines, decrease lymphocytes/monocytes/eosinophils/basoils, decrease antibody production and antigen processing, decrease scar formation

Question 56

Chemotherapeutic mechanism of glucocorticoids

Answer 56

Decreases lymphocytes, especially good for hematologic malignancies

Question 57

Pegvisomant

Answer 57

GH receptor antagonist

Question 58

Bromocriptine/cabergoline

Answer 58

Ergots, dopamine agonists | Suppress GH and PRL