Endocrine Drugs

Question 1

denosumab

Answer 1

RANK-L monoclonal ab used for osteoporosis

Question 2

mechanism of -dronate drugs

Answer 2

bisphosphonates - pyrophosphate analogues that bind hydroxyapatite in bone and inhibit osteoclast activity and bone resorption by blocking apical GTPase that is used to induce bone hydrolysis

Question 3

clinical use of -dronate drugs

Answer 3

• osteoporosis
• hypercalcemia
• Paget’s dz
• corticosteroid-induced osteoporosis

Question 4

SEs of -dronate drugs

Answer 4

• corrosive esophagitis

- jaw osteonecrosis

Question 5

mechanism of teriparatide

Answer 5

recombinant PTH analogue which, if given intermittently, actually stimulates osteoblasts to lay down new bone more than it stimulates osteoclasts to resorb bone

Question 6

clinical use of teriparatide

Answer 6

severe osteoporosis with poor BMD or multiple fractures

Question 7

SEs of teriparatide

Answer 7

• transient hypercalcemia

- do not use for longer than 2 yrs due to osteosarcoma risk

Question 8

thionamides include:

Answer 8

methimazole, propylthiouracil

Question 9

mechanism of methimazole, propylthiouracil (thionamides)

Answer 9

• block thyroid peroxidase to prevent oxidation of I an the organification of I –> inh of thyroid hormone synth
• propylthiouracil blocks 5’-deiodinase and thus peripheral conversion of T4 –> T3

Question 10

clinical use of methimazole, propylthiouracil (thionamides)

Answer 10

• hyperthyroidism

- use PTU in pregnancy

Question 11

SEs of methimazole, propylthiouracil (thionamides)

Answer 11

• itchy skin rash
• agranulocytosis
• aplastic anemia
• hepatotoxicity (PTU)
• teratogen (methimazole)

Question 12

mechanism of levothyroxine

Answer 12

synthetic free T4 replacement

Question 13

clinical use of levothyroxine

Answer 13

hypothyroidism, myxedema

Question 14

SEs of levothyroxine

Answer 14

tachycardia, heat intolerance, tremors, arrythmias (so start low and titrate up esp in older pts)

Question 15

Why do we give levothyroxine but not triiodothyronine?

Answer 15

b/c 85% of T3 comes from conversion of T4 by 5’-deiodinase

Question 16

mechanism and use of -vaptan drugs

Answer 16

ADH antagonists - SIADH

Question 17

mechanism and use of demeclocycline

Answer 17

ADH antagonist - SIADH

Question 18

mechanism and use of cinacalcet

Answer 18

sensitizes CaSR to circulating Ca 2+, so less PTH secretion by PT glands - hypercalcemia due to primary or secondary hyperPTism

Question 19

Lupron Depo-Ped

Answer 19

synthetic LHRH –> causes constant high level of LH that causes the body to stop the LH pulses involved with going through puberty

used to treat precocious puberty - just give this drug until the child is old enough to go through puberty normally

Question 20

mechanism of sulfonylureas and -glinide drugs

Answer 20

closure of B cell K+ channel –> depolarization –> opening of VG Ca 2+ channels –> insulin secretion

Question 21

clinical use of sulfonylureas and -glinide drugs

Answer 21

DM II - require functioning B cells (less and less effective w/ progressive B cell loss)

Question 22

SEs of sulfonylureas and -glinide drugs

Answer 22

hypoglycemia (prevented by taking with food and eating often)

Question 23

mechanism of biguanides (metformin)

Answer 23

• decreases gluconeogenesis
• increases glycolysis
• increases peripheral glucose uptake by muscles
• decreases hepatic steatosis
• increases liver’s insulin sensitivity

Question 24

clinical use of biguanides (metformin)

Answer 24

first-line for DM II

Question 25

SEs of biguanides (metformin)

Answer 25

- diarrhea, nausea | - lactic acidosis (rare)

Question 26

mechanism of acarbose, miglitol

Answer 26

- inhibition of intestinal brush border a-glucosidases - delayed carbohydrate hydrolysis and glucose absorption - decrease in post-prandial hyperglycemia

Question 27

clinical use of acarbose, miglitol

Answer 27

DM II (monotherapy or in combo)

Question 28

SEs of acarbose, miglitol

Answer 28

GI disturbances like flatulence (causes a malabsorption!)

Question 29

mechanism of thiazolidinediones (-glitazone)

Answer 29

increase insulin sensitivity in peripheral tissues by binding to PPAR-y nuclear transcription factor

Question 30

clinical use of thiazolidinediones (-glitazone)

Answer 30

DM II (monotherapy or in combo)

Question 31

SEs of thiazolidinediones (-glitazone)

Answer 31

CHF, weight gain, edema, anemia, hepatotoxicity, risk of fractures, risk of MI

Question 32

mechanism of exenatide, liraglutide

Answer 32

GLP-1 analogues that stimulate insulin secretion and suppress glucagon secretion/gluconeogenesis, contribute significantly to post-prandial glucose control

Question 33

clinical use of exenatide, liraglutide, -gliptin drugs

Answer 33

DM II (usually used with sulfonylurea or metformin in refractory cases)

Question 34

SEs of exenatide, liraglutide

Answer 34

nausea, vomiting, pancreatitis

Question 35

mechanism of -gliptin drugs

Answer 35

DPP4 inh --> prevents breakdown of GLP-1/GIP

Question 36

SEs of -gliptin drugs

Answer 36

urinary or resp. infections

Question 37

mechanism of canagliflozin

Answer 37

SGLT2 inh --> blocks reabsorption of glucose in PCT

Question 38

clinical use of canagliflozin

Answer 38

DM II

Question 39

SEs of canagliflozin

Answer 39

glucosuria --> UTIs, vaginal yeast infxns

Question 40

mechanism of pramlintide

Answer 40

amylin analogue packaged with glucose that delays gastric emptying and decreases glucagon secretion, resembles amylin which is a molecule packaged in granules with natural insulin

Question 41

clinical use of pramlintide

Answer 41

given with insulin in DM I or II, promotes weight loss by delaying gastric emptying and triggering satiety

Question 42

SEs of pramlintide

Answer 42

hypoglycemia, diarrhea, nausea

Question 43

mechanism and duration of action of aspart, glulisine, lispro

Answer 43

- rapid acting insulin (4-6 hrs) | - monomers (active already)

Question 44

mechanism and duration of action of regular insulin

Answer 44

- short acting insulin (6-8 hrs) - hexamers w/ central Zn 2+ - must be broken down into dimers and then monomers to be active

Question 45

mechanism and duration of action of NPH insulin

Answer 45

- intermediate acting insulin (12-20 hrs) | - smaller crystals in protamine, Zn 2+ buffer

Question 46

mechanism and duration of action of detemir, glargine, ultralente

Answer 46

- long acting insulin (18-24 hrs) | - larger crystals in acetate, Zn 2+ buffer