Insuline and oral antidiabetic agents Flashcards
what affects rate of absorption of insulin
-insulin forms dimers and hexamers in concentrated solutions but these are absorbed slowly when injected subcutaneously. Monomers are absorbed much faster.
insulin lispro
- rapid acting insulin
- modification of the amino acid squence (B28/B29) that promotes absorption by preventing self-association
insulin aspart
- rapid acting insulin
- modification of the amino acid sequence (B28 substitution) that promotes absorption by preventing self association
insulin glulisine
- rapid acting insulin
- modification of the amino acid sequence (B3 and B29 changed( that promotes absorption by preventing self-association
NPH insulin
-wild type amino acid sequence (cloudy suspension with protamine added to give a `1:6 molar ratio to insulin). under these conditions basically all the protamine and insuline are in a complex, slows absorption
insulin glargine
-modification of the amino acid sequence (A21 changed, B31/32) to make insulin soluble at acidic pH but precipitates at neutral pH thus slowing down absorption
insulin detemir
-modification of the amino acid sequence (C terminal Thr B chain was deleted and myristic acid attached to new C terminal Lys) that increases self-aggregation and binding to albumin
inhalable insulin
- regular human insulin
- peaks 12-15 mins, basal in 3 h
- slower than SQ rapid acting, but faster than regular
amylin
- can improve effectiveness of insulin therapy, approved for Type 1 DM
- hormone made in the B cells in pancreas that acts upon the alpha cells to inhibit glucagon secretion. CNS-mediated anorectic effect
drug: pramlintide
adverse reactions to insulin therapy
- hypoglycemia
- lipodystrophy at site of injection
- cough for inhalable insulin, contraindicated in smokers and COPD
- allergy and resistance
sulfonylureas
- increase insulin secretion by decreasing K efflux from B cells in the panreas
- tolbutamide, chorpropramide (1st gen)
- glipizide, glyburide, glimepride (2nd gen, more potent)
SE of sulfonylureas
- hypoglycemia
- sulfonylurea resistance/tachyphylaxis
meglitinides
- like sulfonylureas they prevent K efflux from B cells, ultimately leading to increase insulin secretion
- chemically unrelated to sulfonylureas
- binding affinity of meglitinides for K channels is higher than sulfonylureas
name: repaglinide
repaglinide use and SE
-more potent than second gen sulfonylureas but of shorter duration
-used mostly for control of postprandial glucose
-meglitinide
SE: hypoglycemia, use cautiously with renal/liver insuff
D-phenylalanine analog
- chemically unrelated to meglitinides or sulfonylureas, but stimulates insulin secretion by the same mechanism
- nateglinide
- faster than meglitinide, but less sustained
SE of nateglinide, bonus feature
- hypoglycemia
- safe for use in reduced renal function
biguanides
-inactivate mitochondrial glycerophosphate dehydrogenase, antagonize actions of glucagon and activate AMP-activated protein kinase
-takes place in liver and leads to reduction in gluconeogenesis and hepatic glucose output
1st line for DM II
metformin, type of drug, SE
- biguanide
- GI discomfort, lactic acidosis, B12 deficiency
thiazolidinediones
- agonists for PPAR-gamma, increase insulin sensitivity in target tissues (liver, fat, muscle)
name: pioglitazone and rosiglitazone
SE of pioglitazone and rosiglitazone
- increase risk of CV disease
- fluid retention and edema
- wgt gain
- liver toxicity and bladder cancer
alpha-glucosidase inhibitors
- alpha glucosidase receptors in intestine absorb CHO, drug reduces intestinal absorption of CHO
names: acarbose, miglitol
SE of acarbose, miglitol
- flatulence, diarrhea, abd pain
- not really effective solo
incretins
- hormones secreted after a meal that increase insulin and decrease glucagon release
- exenatide, liraglutide (SQ inj)
- sitagliptin, saxagliptin (oral)
SE of exenatide and liraglutide
- nausea, anorexia, h/a, diarrhea, pancreatitis
- incretin agonists
SE of sitagliptin and saxagliptin
- oral incretin agonists
- h/a, increased infections, pancreatitis
pramlintide use & SE
-useful in DM II alone
-given with insulin in type I DM
SE: hypoglycemia, N/V, anorexia
canaglifozin, MOA & SE
-inhibit glucose reabsorption thus promoting glucose excretion in urine via glucose/sodium cotransporter inhibition
SE: UTI, increased urination
empaglifozin
-inhibit glucose reabsorption thus promoting glucose excretion in urine via glucose/sodium cotransporter inhibition
SE: UTI, increased urination
1st line rx of DM II
-weight loss, exercise, metformin
2nd line rx of DM II
-metformin + another agent
3rd line rx of DM II
-metformin + 2 agents
4th line rx of DM II
-metformin and insulin and non-insulin agents
other drugs that can affect insulin release
- Ca channel blockers (decrease insulin release)
- adrenergic agents (agonists increase insulin & output of glucose from liver, antagonists decrease)
glucocorticosteroids: increase glucose, resistance - progestins, estrogens, etc.
