Anti-diabetic medications

Question 1

sulfonylureas

Answer 1

glipizide, glypburide, glimepiride, chlorproamide, tolazamide, tolbutamide
PD: increase in endogenous insulin secretion by beta-cells of the pancreas by closing ATP-sensitive K channels in the beta=cell plasma membrane, initiating a chain of events resulting in insulin release
PK: oral
2nd line therapy in typ2 II DM with patients who have tried diet, exercise, weight control, and metformin
PC: pregnancy category C
ADR: may produce severe hypoglycemia (srecond generation drugs less likely than first generation), weight gain common, gi distrubances, dermatological reactions, SIADH

Question 2

biguanides

Answer 2

metformin (glucophage)
first-line mono-therapy type2 DM
PD: increases peripheral glucose uptake and utilization (insulin sensitivity), decreases hepatic glucose production and decreases intestinal absorption of glucose (does NOT stimulate insulin release from pancreatic beta cells, nor does it produce hypoglycemia except in specific circumstances)
results in patients losing weight
PK: oral, extended, and immediate release, excreted unchanged in the urine
PC: counter-indications: advanced renal disease, acute or chronic metabolic acidosis. risk for lactic acidosis.
black box warning: death, hypothermia, hypotension, resistant bradyarrhythmias have been reported due to metformin-associated lactic acidosis. onset may be subtle and include nonspecific symptoms. increase risk with renal or hepatic impairment, aged >65y or older, having a radiological study with contrast, surgery, or other procedures, hypoxic states, and excessive ETOH intake; monitoring recommended. discontinue if suspected and initiate supportive measures”
withhold 48 hours before radiological studies
adr: gi disturbances, abd bloating, diarrhea nausea, vomiting, unpleasant metallic taste- usually transient and resolve in about 2 weeks without a change in dose

Question 3

thiazolidinesdiones (TZDs)

Answer 3

troglitazone (rezulin, pioglitazone (actos), rosiglitazone (avandia)
PD: improve glycemic control by improving insulin sensitivity, depending on the presence of insulin for their action
PK: oral, expensively bound to plasma proteins. highly metabolized in the liver
therapy for DM2 not controlled by diet alone or diet and an oral antidiabetic agent or insulin ]
black box warning: new or symptomatic heart failure promoting fluid retention and its concerns particularly >65y.
should be d/c during ACS.

Question 4

selective sodium glucose co-transporter

Answer 4

canagliflozin (invokana), dapagliflozin (farxiga), ertugliflozin (steglartro)
PD: inhibition of SGLT-2 lowers reabsorption of plasma glucose concentration in the kidneys, which results in increased urinary glucose excretion and reduction of plasma glucose in DM2. works in proximal tubule to absorb about 90% of glucose in the ultra-filtrate
PK: highly protein-bound
adjunct to diet and exercise in the treatment of adults with DM2, can decrease A1c 1% and contribute to 1-1.5kg of weight loss.
PC: black box warning: patients with hx of amputation, PVD, neuropathy, ulcers or leg infections should discontinue or not start canagliflozin. contraindicated in patients with severe renal impairment, esrd, dialysis, . can cause intravascular volume depletion and symptomatic hypotension

Question 5

alpha-glucosidase inhibitors

Answer 5

acarbose and miglitol
PD: do not act directly on any of the defects in metabolism seen in DM2. competitively inhibit the absorption of complex CHO from the small bowel. their chemical structure is a pseudo-tetrasaccharide that binds to the enzyme alpha-glucosidase
does not cause hypoglycemia
PK: less than 2% of acarbose is systemically absorbed as an active drug, the remainder is active in the GI tract. Miglitol is completely absorbed in the GI tract

Question 6

amylin agonists