Week 3 Milestones

mechanism of action for:

I. exenatide
II. glyburide
III. glimepiride
IV. metformin
V. levothyroxine
VI. pioglitazone
VII. colesevelam

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mechanism of action for:

I. exenatide
II. glyburide
III. glimepiride
IV. metformin
V. levothyroxine
VI. pioglitazone
VII. colesevelam

I. GLP-1 agonist; augments insulin secretion, slows gastric emptying

II. stimulates the release of insulin

III. second-gen sulfonylurea, enhances insulin secretion from beta-cells

IV. biguanide; does not affect insulin secretion, but does suppress hepatic gluconeogenesis and increases sensitivity

V. synthetic T3

VI. TZD; PPAR-ɣ agonist (sensitizer)

VII. bile acid sequestrant

dosage forms of exenatide

- SQ solution, IR (5 mcg/0.02 mL, 10 mcg/0.04 mL)
- SQ suspension, ER (2 mg)

dosage forms of glimepiride

- oral tab (1, 2, and 4 mg)

dosage forms of metformin

- oral tab (500, 850, 1000 mg), oral tab ER (500, 750, 1000 mg)
- oral solution (500 mg/5 mL)

dosage forms of levothyroxine

- oral tab (25, 50, 75, 88, 100, 112, 125, 137, 150, 175, 200, 300 mcg)
- oral cap (13, 25, 50, 75, 88, 100, 112, 125, 137, 150, 175, 200 mcg)

dosage forms of pioglitazone

- oral tab (15, 30, 45 mg)

dosage forms of colesevelam

- oral tab (625 mg)
- granules for oral susp (3.75 g/packet)

indications for week 3 drugs

- all T2DM except levothyroxine (hypothyroidism) and colesevelam (primary/familial hyperlipidemia)

Off-Label:
o levothyroxine: toxicity due to radiotherapy
o colesevelam: diarrhea

drug characteristics for:

I. exenatide
II. glyburide
III. glimepiride
IV. metformin
V. pioglitazone

I. no hepatic dosing; renal dosing CrCl 30-50 5 mcg initial dose, increase w/caution; avoid if CrCl <30
II. no G6PD deficiency
III. avoid in hepatic dysfunction; start 1 mg PO daily for renal dysfunction BEER'S AVOID
IV. avoid in severe hepatic dysfunction; eGFR <30 contraindicated, 30-45 not recommended
V. avoid if LFTs are elevated

black box warnings for:

I. exenatide
II. metformin
III. levothyroxine
IV. pioglitazone

I. thyroid C-cell tumors (Bydureon)
II. lactic acidosis
III. not for weight reduction
IV. heart failure risk

drug interactions for exenatide- warfarindrug interactions for glyburide- interacts with CYP2C9drug interactions for glimepiride- beta-blockers - CYP2C9 inducers/inhibitors - FQs - NSAIDs - fenofibrate - SSRIs - somatostatin analogues - MAOIs - psyllium - sulfonamidesdrug interactions for metformin- acetrizoic acid and other contrast media - beta-blockers - cationic drugs - amiloride - cimetidine - cephalexin - FQs - MAOIs - psylliumdrug interactions for levothyroxine- antacids and other cation-containing compounds - estrogens - eltrombopag - imatinib - phenytoin, rifampin, simvastatin - warfarindrug interactions for pioglitazone- CYP2C8 inducers/inhibitors/substrates - corticosteroids - NSAIDs - SSRIs - MAOIsdrug interactions for colesevelam- antidiabetic drugs - diltiazem - ezetimibe - fibrates - levothyroxine - mycophenolate - oral contraceptives - cyclosporine - phenytoin - warfarincommon ADRs of exenatide- hypoglycemia - diarrhea - nausea - injection-site reactioncommon ADRs of metformin- diarrhea - malabsorption - n/v - asthenia - flatulencecommon ADRs of pioglitazone- edema - weight gaincommon ADRs of colesevelam- constipationuncommon/rare ADRs for exenatide- diaphoresis - decreased appetite - GERD - antibody development - HA - asthenia RARE: - pancreatitis - anaphylaxis - ARF - worsening of pre-existing renal diseaseuncommon/rare ADRs for glimepiride- hypoglycemia - nausea - headache - dizziness - asthenia RARE: - cutaneous hypersensitivity - hemolytic anemia - hepatotoxicity - disulfiram reactionuncommon/rare ADRs for metformin- headach - indigestion - cobalamin deficiency - weight loss RARE: - lactic acidosis - hepatotoxicity - hemolytic anemia - hypersensitivityuncommon/rare ADRs for levothyroxine- appetite decreased - anxiety - diarrhea - insomnia RARE: - aggravation of pre-existing CVD - hyperthyroidismuncommon/rare ADRs for pioglitazone- myalgia - bone fractures - sinusitis - headache RARE: - heart failure - anemia - hepatotoxicity - diabetic macular edema - hypoglycemia when used in combination with insulin or sulfonylureas, bladder canceruncommon/rare ADRs for colesevelam- asthenia - nasopharyngitis - myalgia - nausea - HTN - hypertriglyceridemia - hypoglycemia RARE: - pancreatitis - bowel obstructioncounseling/clinical pearls for exenatide- pre-filled pen w/60 doses - use 1 hour before eating - ER product is powder w/diluent in pre-filled syringe - should be opaque and white to off-white - may be added to metformin if HBA1C is bad - may increase risk of pancreatic duct metaplasiacounseling/clinical pearls for glimepiride- take with food/milk in the morning - use sunscreen - do not drink alcohol - hemolytic anemia in G6PD deficiencycounseling/clinical pearls for metformin- take with meals - drink plenty of liquids - avoid alcohol - response typically not seen at doses <1500 mg/d - hold prior to contrast administration and hold for 48h following (may restart if kidney function normal after 48h)counseling/clinical pearls for levothyroxine- may require 6-8 weeks for improvement - take on empty stomach w/water 30 min before food - avoid antacids/iron within 4 hours of dose - not recommended for weight losscounseling/clinical pearls for pioglitazone- may take without regard to food - seek care for bone pain, yellowing of skin/eyes, eye pain, SOB - causes edema - contraindicated in NYHA III/IV heart failure - stimulates ovulationcounseling/clinical pearls for colesevelam- mix packet with 120-240 mL water - take with meal - may be given with HMG-CoA reductase inhibitor