Endocrine Pharm from FA

Question 1

General strategies for treatment of T1DM?

T2DM?

Gestational DM?

Answer 1

T1DM: low-sugar diet, insulin replacement

T2DM: dietary modification and exercise for wt loss, oral agents, non-insulin injectables, insulin replacement

GDM: dietary change, exercise, insulin replacement if diet/exercise fail

Question 2

Lispro, Aspart, Glulisine

Class? Action? Clinical use? Tox?

Answer 2

Rapid acting Insulin

Action: bind insulin receptor (tyrosine kinase activity). In Liver, incr glucose stored as glycogen. In Muscle, increase glycogen and protein synth, incr K+ uptake. Fat: Incr TG storage.

Use: T1DM, T2DM, GDM (postprandial glucose control)

Tox: hypoglycemia, rare hypersens reactions

Question 3

Regular insulin, short-acting: Clinical use?

Answer 3

T1DM, T2DM, GDM, DKA (IV), hyperkalemia (+ glucose), stress hyperglycemia

Question 4

NPH

Class? Use?

Answer 4

Intermediate-acting insulin

(NPH = neutral protamine Hagedorn, something about how it is chemically packaged to be medium-acting)

Use: T1DM, T2DM, GDM

Question 5

Glargine, Detemir

Class? Use?

Answer 5

Long-acting insulin

Use: T1DM, T2DM, GDM (basal glucose control)

Question 6

Metformin

Class? Action? Use? Tox?

Answer 6

Class: Diabetes/Biguanide

Action: exact mech unknown. decr gluconeogenesis, incr glycolysis, incr peripheral glucose uptake (insulin sensitivity)

Use: oral. First line therapy in T2DM. Can be used in patietns without islet cell function

Tox: GI upset, lactic acidosis (CI in renal failure)

Question 7

Tolbutamide, Chlorpropamide

Class? Action? Use? Tox?

Answer 7

First generation sulfonylureas (diabetes)

Action: close K+channel in Beta cell membrane -> cell depolarizes -> triggers insulin release via C2+ influx

Use: Stimulates release of endogenous insulin in T2DM. requires some islet function (useless with T1DM)

Tox: risk of hypoglycemia increased in renal failure, Disulfiram-like effects.

Question 8

Glyburide, Glimepiride, Glipizide

Class? Mech? Use? Tox?

Answer 8

Second generation sulfonylureas (diabetes)

Action: close K+channel in Beta cell membrane -> cell depolarizes -> triggers insulin release via C2+ influx

Use: Stimulates release of endogenous insulin in T2DM. requires some islet function (useless with T1DM)

Tox: risk of hypoglycemia increased in renal failure, Hypoglycemia

Question 9

Pioglitazone, Rosiglitazone

Class? Mech? Use? Tox?

Answer 9

Glitazones/Thiazolidinediones (diabetes)

Mech: increased insulin sensitivity in peripheral tissue. Binds to PPAR-gamma nuclear transcription regulator

Use: monotherapy in T2DM or in combination with insulins, metformin, sulfonylureas

Tox: weight gain, edema, hepatoxicity, heart failure

Question 10

Acarbose, Miglitol

Class? Mech? Use? Tox?

Answer 10

Diabetes/alpha-glucosidase inhibitors

Action: inhibits intestinal brush-border alpha-glucosidases; delayed sugar hydrolysis and glucose absorption decreases postprandial hyperglycemia

Use: Monotherapy for T2DM or im combination with other agents

Tox: GI disturbances

Question 11

Pramlintide

Class? Action? Use? Tox?

Answer 11

Diabetes/Amylin analog

action: decreases gastric emptying, decreases glucagon

Use: T1DM, T2DM

Tox: hypoglycemia, nausea, diarrhea

Question 12

Exenatide, Liraglutide

Class? Mech? Use? Tox?

Answer 12

Diabetes/GLP-1 analogs

Action: increases glucose, decreases glucagon release

Use: T2DM

Tox: N/V, pancreatitis

Question 13

Linagliptin, Saxagliptin, Sitagliptin

Class? Mech? Use? Tox?

Answer 13

Diabetes/DPP-4 inhibitors

Action: increase insulin, decr glucagon release

Use: T2DM

Tox: mild urinary or resp infections

Question 14

What do genes activated by PPAR-gamma do?

Answer 14

regulate fatty acid storage and glucose metabolism.

Activation of PPAR-gamma increases insulin sensitivity and levels of adiponectin

Question 15

What drug is first-line therapy in T2DM? when is it contraindicated?

Answer 15

Metformin

(biguanide class)

CI with renal failure because it can cause lactic acidosis. can also cause GI upset.

Question 16

Which diabetes drugs require some islet cell function and are therefore not useful with T1DM? (3 classes)

Answer 16

Sulfonylureas (Tolbutamide, Chlorpropramide, Glyburide, Glimepiride, Glipizide)

GLP-1 analogs (Exenatide, Liraglutide)

DPP-4 inhibitors (Linagliptin, Saxagliptin, Sitagliptin)

Question 17

Propylthiouracil, Methimazole

Mech? Use? Tox?

Answer 17

Block thyroid peroxidase, inhibiting the oxidation of iodide and the organification (coupling) of iodine, leading to inhibition of thyroid hormone synthesis. Propylthiouracil also blocks 5’deiodinase, which decreases peripheral conversion of T4 to T3.

Use: Hyperthyroidism. “PTU blocks Peripheral conversion, used in Pregnancy”

Tox: Skin rash, agranulogytosis (rare), aplastic anemia, hepatotoxicity (PTU). Methimazole is a possible teratogen (can cause aplasia cutis)

Question 18

Of the two drugs that are used for hyperthroidism, which one is possibly teratogenic?

Which drug do we use for preg women? tox of that drug?

Answer 18

Methimazole is a possible teratogen (can cause aplasia cutis - derm condition, absence of a patch of skin/hair)

For preg women, use Propylthiouracil (PTU) instead

“PTU blocks Peripheral conversion, used in Pregnancy”

PTU may cause hepatotoxicity.

Question 19

Levothyroxine, Triiodothyronine

Mech? Use? Tox?

Answer 19

Mech: Thyroxine replacement

Use: hypothyroidism, myxedema (mucopolysaccharide deposition in the dermis –> results in swelling. ie pretibial myxedema in Graves’ Disease)

Tox: Tachycardia, heat intolerance, tremors, arrythmias

Question 20

Growth Hormone

Use?

Answer 20

Hypothalamic/pituitary drug

Use: GH deficiency, Turner syndrome

Question 21

Somatostatin/Octreotide

Use?

Answer 21

Hypothalamic/pituitary drug

Acromegaly, carcinoid, gastrinoma, glucagonoma, esophageal varices

Question 22

Oxytocin

Use?

Answer 22

Hypothalamic/pituitary drug

Stimulates labor, uterina contractions, milk let-down; controls uterine hemorrhage

Question 23

ADH (DDAVP)

Use?

Answer 23

Hypothalamic/pituitary drug

Pituitary (central, not nephrogenic) DI

vWF d/o - stimulates vWF release from endothelial cells

Question 24

Demeclocycline

Mech? Use? Tox?

Answer 24

ADH Antagonist (member of the tetracycline family)

Use: SIADH

Tox: nephrogenic DI, photosensitivity, bone/teeth abnormalities

Question 25

Glucocorticoids

Mech?

Use?

Tox?

Answer 25

Mech: metabolic, catabolic, anti-inflammatory, and immunosuppressive effects mediated by interactions with glucocorticoid response elements and inhibition of transcription factors such as NF-KB

Use: Addison’s disease, inflammation, immune suppression, asthma

Tox: Iatrogenic Cushing syndrome (buffalo hump, moon facies, truncal obesity, muscle wasting, thin skin, easy bruisability, osteoporosis, adrenocortical atrophy, peptic ulcers, diabetes (if chronic). Adrenal insufficiency when drug stopped abruptly after chronic use.

Question 26

Osteoporosis due to glucocorticoid use: what is treatment?

Answer 26

bisphosphonates

Question 27

List the glucocorticoids (6)

Answer 27

Hydrocortisone

Prednisone

Triamcinolone

Dexamethasone

Beclomethasone

Fludrocortisone (mineralocorticoid and glucocorticoid activity)

Question 28

(From UWorld)

Pheochromocytoma: treatment?

Answer 28

-Irreversible alpha-blockers (ex: phenoxybenzamine) and beta-blockers followed by tumor resection.

Alpha blockade must be achieved before giving beta-blockers to avoid a hypertensive crisis.