Diabetes Mellitus Type 2 Flashcards
Biguanides- Available Drugs
Metformin
Metformin- Mech of Action
INHIBIT COMPLEX I OF MITOCHONDRIAL OXIDATIVE PHOSPHORYLATION–> INCREASE AMP/ATP RATIO–> ACTIVATE AMP DEPENDENT KINASE (AMPK)–> REDUCE HEPATIC GLUCONEOGENESIS/INCREASE IN INSULIN SENSITIVITY IN MUSCLE AND ADIPOSE–> INCREASE GLUCOSE UTILIZATION–> LOWER FASTING PLASMA GLUCOSE
Metformin- Kinetics
HbA1c decrease= 1.5%
duration= 6 hr
Metformin- Clinical Use
DOC FOR ALL TYPE II DM THAT ISN’T CONTROLLED BY DIET AND EXERCISE ALONE
LOWERS FASTING GLUCOSE
requires the presence of insulin for its effects
improves lipid profiles (decreases FFA, TGs, LDL, increases HDL)
Metformin- Side Effects/Contraindications
DOES NOT CAUSE WEIGHT GAIN
generally well tolerated
can inhibit absorption of B12
POTENTIALLY FATAL LACTIC ACIDOSIS (DEEP, RAPID BREATHING, VOMITING, ABDOMINAL PAIN, WEAKNESS OF LEGS AND ARMS)–> USUALLY SEEN IN RENAL INSUFFICIENCY, CHF, MI, HYPOXIC STATE
CONTRAINDICATED in: pregnancy IMPAIRED LIVER OR RENAL FUNCTION elderly patients taking iodinated contrast agent other conditions predisposing to lactic acidosis- CHF, MI, shock, septicemia, hypoxic/ischemic state, serious illness
Thiazolidinediones- Available Drugs
Pioglitazone
Rosiglitazone
Pioglitazone, Rosiglitazone- Mech of Action
AGONIST FOR PPAR-G TRANSCRIPTION FACTOR–> INCREASE GLUT4 EXPRESSION, ADIPONECTIN, FFA UPTAKE, ADIPOSE REMODELING AND DECREASE TNF-A/RESISTIN–> INCREASE INSULIN SENSITIVITY IN ADIPOSE, MUSCLE, LIVER–> INCREASE GLUCOSE UTILIZATION
Pioglitazone, Rosiglitazone- Kinetics
HbA1c decrease= 0.5%
duration= weeks
Pioglitazone, Rosiglitazone- Clinical Use
LOWERS FASTING GLUCOSE
lowers TGs
monotherapy or in combination with metformin, sulfonylureas, or insulin for DM 2
Pioglitazone, Rosiglitazone- Side Effects/Contraindications
SUB-Q WEIGHT GAIN
FLUID RETENTION–>PERIPHERAL EDEMA–>RISK OF HEART FAILURE
ROSIGLITAZONE CAN CAUSE MI AND CARDIOVASCULAR DEATH = not on the market anymore
decrease bone density–> fracture risk in women
hepatotoxicity
CONTRAINDICATED IN LIVER DISEASE, HEART FAILURE, CVD, preganancy
Sulfonylureas- Available Drugs
2nd Gen:
Chlorpropamide
Tolbutamide
3rd Gen:
Glimepiride
Glyburide
Glipizide
Sulfonylureas- Mech of Action
INHIBIT K CHANNELS IN B-CELLS–> INCREASED [K]INTRACELLULAR–> MEMBRANE DEPOLARIZATION–> OPEN CA CHANNEL–> INCREASE [CA]INTRACELLULAR–> INCREASE SECRETION OF INSULIN
Sulfonylureas- Kinetics
LONG DURATION OF ACTION
metabolized by liver and excreted in kidney
HbA1c decrease= 1.5%
duration= 14-24 hrs
Sulfonylureas- Clinical Use
LOWERS FASTING GLUCOSE
dependent on B-cell function- most effective in patients that have had diabetes for less than 10 years, still have functional B cells
Sulfonylureas- Side Effects/Contraindications
HYPOGLYCEMIA especially in liver/renal dysfunction and the elderly
weight gain
CONTRAINDICATED IN: IMPAIRED RENAL/HEPATIC FUNCTION elderly DM 1 pregnancy lactation sulfa allergies
Sulfonylureas- Drug Rxns
High protein binding- interaction with other protein binders (Salicylates, B-blockers, warfarin, fibrates)