Endocrine / MSK SketchyPharm

Question 1

What are the first generation sulfonylureas?

Answer 1

Think of the “maid” Goose = “-amide”

Tolbutamide, Chlorpropamide

Question 2

What are the meglitinides? What is their claim to fame?

Answer 2

Repaglinide
Nateglinide

“Nate be Rapping cuz he so fly”

• > non-sulfa drug sulfonylureas, but more short-acting.
• > think of the goose “gliding” / flying in the air

Question 3

What are the three sulfonylureas primarily being used today?

Answer 3

1. Glimepiride
2. Glipizide
3. Glyburide

Think of the two ducks “riding” mother goose, and a smaller goose making a “z” in the ice for glipiZide

Question 4

What are the actions of exenatide and liraglutide? Benefits? Main side effect of concern?

Answer 4

Induces insulin release, depresses glucagon release, and delays gastric emptying (like amylin + insulin release) -> good for post-prandial surge

• > associated with significant weight loss!
• > liraglutide even approved for obesity
• > probably due to feeling of satiety from delayed gastric emptying

Side effect: Think of the -Tide cleaning witch holding the sponge (acute pancreatitis)

Question 5

What drug is a DPP-4 inhibitor, and what is its primary benefit over the GLP-1 homologs? What is its main side effect?

Answer 5

Sitagliptin (Januvia)
- think of the gliptin clips (4 clips for DPP-4)

Can be taken orally, does not show GI disturbances.

However, no associated weight loss :/

Side effect: upper respiratory tract infections (think of the clothespin on the lady’s nose)

Question 6

What is the current first line treatment for diabetes and what is its mechanism of action?

Answer 6

A biguanide called metformin

Lowers blood glucose levels without stimulating insulin release.

1. Reduces gluconeogenesis (reduced liver output)
2. Enhances insulin action on peripheral tissues (reduces resistance)

Modifies mitochondrial enzymes to do this

Question 7

What are the adverse effects of metformin use and who is it contraindicated in?

Answer 7

GI disturbances -> dose-related, especially at start of therapy -> girl about to puke

Lactic acidosis (from decreased usage of lactate in gluconeogenesis)

-> avoid in renal insufficiency (Decreased clearance of metformin, not metabolized hepatically)

Spilled milk in broken kidney tray

Also avoid in liver disease, or alcoholics

Question 8

What is the mechanism of action of the TZDs and what drug are they similar to?

Answer 8

Similar to metformin, in that they reduce insulin resistance without posing hypoglycemia risk

Mechanism:

1. Activate PPARy (Remember this guy’s shirt is the life of the party (PPARy), don’t get confused with PPARa of the fibrates) receptor, expressed in white adipocytes which is a nuclear transcription factor. This upregulates ADIPONECTIN! (Think adiponectin turtle neck).
2. Also think of the open candy mailbox nearby -> also increases insulin sensitivity.

Question 9

What are the adverse effects of glitazones? How does this relate to their usage

Answer 9

This keeps them from being used alot, only used as second line in combination:

1. Congestive heart failure from 2. Edema -> baggy pants and heart failure ballon
2. Weight gain -> significant, due to induced differentiation of hepatocytes (guy holding donuts)
3. Bone loss -> broken chair leg banging into heart failure balloon

Question 10

What drug is an amylin analog again? How does it work? What types of diabetes can it be used in?

Answer 10

Pramlintide (think lynn) -

Amylin - think of empty glucose packets (suppressed glucagon) and the decreased gastric emptying (gastric water cooler)

Can be used in both Type 1 and Type 2 diabetes, think of the girls holding up one and two fingers.

Think of Amy and Lynn, the twins he asked to be his valentine. Damn you braden!

Question 11

What are the risks of SGLT2 inhibitors?

Answer 11

1. Urinary tract yeast infections -> due to glucose in urine. Think of the Canada flag and kid throwing snowball.
2. Diabetic ketoacidosis (rare, perhaps from hypoglycemia)
3. Dehydration - from diuresis

Avoid in renal insufficiency

Question 12

What is a relative contraindication of radioactive thyroid ablation in Graves disease?

Answer 12

pre-existing Graves ophthalmopathy -> can acutely worsen this condition.

Question 13

What drugs inhibit thyroperoxidase and which one is different / how is it different?

Answer 13

Methimazole (MMI)

Propylthiouracil (PTU)
-> also useful in thyroid storm by inhibiting 5’ deiodinase.

Question 14

What is the treatment for thyroid storm?

Answer 14

1. Hydroxycortisone - steroids block peripheral conversion of T4 to T3 -> think of the moon faces shurikens being thrown
2. Propylthiouracil - Blocks TPO and peripheral conversion of T4 to T3
3. Beta blockers - treats SANS (stops cardiac issues)
4. Iodine - stuns the thyroid from releasing more T3/T4
5. Antipyretics - bring down th e fever
6. Cooling blanket / supportive care

Question 15

What are the adverse effects of PTU and MMI?

Answer 15

Maculopapular rash - think of the dude with lab chemicals on him
Lupus-like syndrome - MMI specifically, think of the lupus wolf
Aplastic anemia - blue bones on ground
Agranulocytosis - hourglass in back
Hepatotoxicity - especially PTU
Vasculitis - ANCA-associated, think of the red leash on the lupus wolf

Question 16

What is the preferred pregnancy regimen for hyperthyroid patients and why?

Answer 16

1st trimester: PTU, since methimazole is a teratogen (think of the tarantula) -> cause cutis aplasia

2nd/3rd trimesters: Use MMI since PTU is more hepatotoxic

Question 17

What is the mechanism of action of bisphosphonates?

Answer 17

Reduce osteoclast activity by mimicking pyrophosphate and interfering with farnesyl pyrophosphate synthase.

Question 18

What is one reason to use bisphosphonates in the acute treatment of a condition?

Answer 18

Give IV to treat hypercalcemia of malignancy (due to PTHrP or osteolytic lesions) which may be very aggressive

Remember PTHrP = Squamous cell+ urinary tract + BRCA

Question 19

What are the side effects of bisphosphonates?

Answer 19

Dyspepsia, acid reflux, esophagitis

Can cause osteonecrosis of the jaw (osteoclastic turnover needed to maintain structural integrity of high-stress bones)

They should be taken without food and with 8 oz of plain water only. Do not ingest other foods for at least 60 minutes (poorly absorbed) and must sit upright after taking (otherwise GI damage may occur).

Question 20

What is the contraindication of bisphosphonates and what could be used instead in this case?

Answer 20

Contraindicated in renal insufficiency (<30 ml/min)

Can use denosumab instead

Question 21

Does Teriparatide increase or decrease blood calcium levels?

Answer 21

Actually increases them, despite causing bone formation. This because it still acts like PTH to improve kidney Ca+2 reabsorption, and increases 1-alpha hydroxylase activity (unlike PTHrP).

Question 22

What effect does vitamin D have on PTH?

Answer 22

Inhibits PTH release -> negative feedback mechanism.

Question 23

What is the mechanism of action of sevelemer?

Answer 23

Think sevelemer shoveler -> phosphate binding resin the GI tract
-> prevents phosphate absorption in those with hyperphosphatemia due to chronic renal failure

Question 24

What is the mineralocorticoid used in the treatment of primary adrenal insufficiency (vs secondary which would not required mineralocorticoid supplementation)?

Answer 24

Fludricortisone

Question 25

What effect do corticosteroids have on circulating WBC levels?

Answer 25

1. Neutrophilia - downregulation of P-selectin causes detachment of the Sialyl-Lewis receptors (involved in rolling).
2. Lymphopenia / Eosinopenia - Leads to direct apoptosis of other WBCs or sequestration within lymph nodes, decreasing the circulating count

Eosinopenia = useful in asthma

Question 26

How does adhesion occur in the WBC recruitment pathway?

Answer 26

Integrins are upregulated on WBCs (think of Integrins as being the things which need to bind the basement membrane, which is in this case the endothelial cell)

They will bind ICAM/VCAM from the endothelial cell.

Question 27

What are the side effects of corticosteroids?

Answer 27

Cushing syndrome
Adrenal insufficiency - negative feedback causes atrophy
Hyperglycemia / diabetes - insulin resistance and increased gluconeogenesis
Psychosis - insomnia first
Cataracts
Hypokalemia - via mineralocorticoid effects
Osteoporosis - direct inhibition of osteoblast bone-forming activity
Avascular necrosis of femoral head - due to increased lipolysis -> triglyceride emboli (like alcohol)
Skin thinning / bruising with streaks from capillary atrophy

Question 28

Treatment of what conditions are most likely to precipitate tumor lysis syndrome? What is the treatment?

Answer 28

T/B lymphocyte diseases
-> think of the T cell swordsmen in the stained glass window

Lymphomas / acute lymphoblastic leukemias are most likely:

Treatment: Rasburicase (uric acid to allantoin), allopurinol, aggressive hydration

Question 29

What are the possible side effects of allopurinol?

Answer 29

Allopurinol hypersensitivity syndrome (AHS): progression to SJS (tengu mask) or DRESS syndrome (slingshot shooter in dress).

Question 30

What is probenecid’s role in gout therapy? Where else is it used clinically?

Answer 30

Generally used second line as an adjunctive agent to xanthine oxidase inhibitors for patients who were unable to get uric acid levels <6 mg/dL.

Also used clinically to increase serum levels of penicillin and cidofovir by inhibiting their excretion

Question 31

What should be given before giving pegloticase, and what is the one definite contraindication?

Answer 31

Give corticosteroids and antihistamines to prevent infusion reaction

Contraindication: G6PD deficiency -> precipitates hemolytic anemia

Question 32

What is the effect of aspirin on uric acid at high and low doses?

Answer 32

High doses -> blocks the renal reabsorption of uric acid (adult empire working just like probeneCID)

Low doses -> blocks the renal excretion of uric acid -> hyperuricemia (Little kid blocking the excretion of uric acid yarn)

Question 33

What are the direct effects of GH on skeletal muscle / adipose tissue? Glucose levels?

Answer 33

Anabolic effects on muscle - think of muscle leaf
Catabolic effects on adipose tissue - think of the jar of donuts toppling over

GH causes insulin resistance, which is supposed to work out because IGF-1 is insulin-like, so it increases insulin sensitivity. In cases of GH adenoma -> insulin sensitivity is greatly decreased -> diabetes.

Question 34

What are the approved indications for growth hormone treatment?

Answer 34

1. Pituitary dwarfism
2. Genetic disorders of Noonan syndrome, Prader-Willi (paternally imprinted 15q11 is lost, often due to maternal UPD, think Padre Willi) and Turner syndrome
3. Idiopathic short stature
4. Adult GH deficiency - due to pituitary adenoma / head trauma
5. Muscle wasting in AIDs

Question 35

What is recombinant IGF-1 called? When is it used?

Answer 35

Mecasermin - Make a sermon!

1. Laron syndrome
2. When anti-GH antibodies are present
3. Growth failures unresponsive to GH

Question 36

Where does necrolytic migratory erythema commonly affect?

Answer 36

The limbs, intertriginous areas, and the skin surrounding the lips

Question 37

What bleeding condition can octreotide treat?

Answer 37

Esophageal varices due to portal hypertension. Mechanism is poorly understood.

Question 38

What are the non-octreotide and non-surgery treatments for GH-secreting adenoma?

Answer 38

Think of the burglar climbing the beanstalk with his broomstick
Dopamine agonists:
1. Cabergoline - burglar
2. Bromocriptine - broomstick
Not nearly as effective in the treatment of GH adenoma as PRL adenoma.

3. Pegvisomant - JAK-STAT growth hormone receptor tyrosine kinase antagonist.