Oral Medications in Diabetes Flashcards
T/F all glucose lowering agents are only used for t2d
T
T/F all glucose lowering agents are contraindicated in pregnancy
F –> all except sulfonylurea and metformin
T/F all glucose lowering agents can be used in any combination
F –> any combination except sulfonylurea and meglitinides should not be mixed
T2D first drug of choice
metformin
Metformin/diguanide action and mechanism
activation of ampk –>
- increase muscle glucose tranport
- reduces hepatic glucose production
- sensitizes insulin (via reduced ACC and SREBP expression and consequent reduced hepatic FA production)
–>improves pre meal glucose and modestly affects post-prandial glucose
Thiazolidinendiones (TZD)/PPARgamma agonists MOA/Action
binds nuclear ppar gamma receptor –> increases GLUT4 transporter–> decreases peripheral insulin resistance in skeletal muscle, adipose, liver –> lowers premeal/post meal glucose
Insulin secretagogues
Induce beta cell secretion of insulin (short and long acting) –> suflonylureas and meglitinides
alpha glucosidase inhibitors MOA/action
competitively inhibit enzymes in brush border to breakdown carbohydrates –> delay carbohydrate absorption in gut –> reduce post prandial glucose only
GLP1 agonist
slows gut motility, induces satiety, increased insulin/lower glucagon
Incretin enhancers (DPP-4 inhibitors)
increase duration of action of GLP1 via 80% inhibition of DPP4 –> mostly on post-meal glucose
Advantageous characteristics of a good drug for t2d
weight loss/neutral, no hypoglycemia, oral, frequency of delivery
Disadvantageous characteristics of a good drug for t2d
weight gain (reversal of osmotic diuresis, reversal of relative starvation/normalization, fluid retention), hypoglycemia, frequency of delivery, injectable
T/F metformin is weight neutral and can induce weight loss
T
T/F metformin is metabolized at the liver
F –> renally excreted unexchanged and can accumulate if pt has renal insufficiency
Adverse effects of metformin
anorexia, nausea, diarrhea, lactic acidosis
T/F metformin does not cause hypoglycemia
T
Contraindications of metformin
prone to metabolic acidosis, hypoxic states, renal failure, t1d, cardiac ischemia
T/F metformin requires presence of insulin for its action
T
Sulfonylurea action and MOA
binds to sulfonyl receptor in beta cell –> depolarization of ATP K channels –> pancreatic insulin secretion for 12-24 hours –> mostly premeal glucose effect
T/F Sulfonylurea does not get metabolised
F –> hepatic and excreted in kidney
Contraindications of sulfonylurea
T1d, DKA, sulfa allergy
Adverse effects of sulfonylurea
hypoglycemia, weight gain, hunger
K+ channel in the beta cell
induces calcium current which causes insulin release –> sulfonylurea and meglitinide binding sites
Meglitinide action/MOA
stimualtes K+ channel on beta cells –> pancreatic insulin for 3-4 hours
T/F Meglitinide is fast onset
T
Adverse effects of meglitinide
low glucose after meal, weight gain
Contraindications of meglitinide
T1d, liver failure, DKA, sulfa allergy
T/F meglitinide is metabolized in the kidney
F –> in liver by p450 –> excreted mostly in GI tract
Adverse effects of TZD
weight gain, hepatocellular injury
Contraindications of TZD
active liver disease, heart failure, renal insufficiency
T/F TZD has slow onset of action
T
T/F TZD can induce low blood glucose
F –> no insulin secretory effect
Adverse effects of alpha glucosidase inhibitors
flatulence, abdominal bloating
T/F alpha glucosidase inhibitors are metabolized in the liver
F–> renally excreted unchanged
T/F alpha glucosidase inhibitors can cause low glucose
F
Metabolism of GLP agonists
rapidly degraded by DPP4 in blood
SGLT2
major transporter of glucose in kidney, low affinity/high capacity- -> 90 % of renal glucose reabsorption in proximal tubule
SGLT2 inhibitors
inhibit reabsorption of glucose –> excretion by kidney
