67: Antidiabetic Agents Flashcards
alpha cell –>
beta cell –>
glucagon
insulin and amylin
d cell - somatostatin
g cell - gastrin
F cell - pancreatic polypeptide
+ regulation of insulin release
glucose amino acids incretins epi/B2 adrenergic stimulation vagus stimulation
- regulation of insulin release
NE/a2 adrenergic stimulation
amylin
which glucose transported is associated with insulin mediated uptake of glucose?
glut 4
found in muscle and adipose tissue
\+ or - with insulin: gluconeogenesis glycogenolysis glcogenesis glycolysis
+
+
s/s type I DM
polyuria/nocturnal enuresis thirst blurred vision WL/polyphagia weakness/dizziness paresthesia level of consciousness
s/s type II DM
asymptomatic initially infections neurpathy severe insulin deficiency signs obesity and metabolic syndrome
FPG – DM range
greater than 126 mg/dL
pre-diabetes is 110-125
CPG greater than 200
oral glucose tolerance test greater than 200
insulin is absolutely required for…
type I DM
therapeutic goal with insulin
FPG between 90-120
28 U equals =
1 mg
rapid acting insulins
lispro
aspart
glulisine
inhaled insulin
short acting insulin
regular insulin (pump type)
intermediate acting insulin
NPH
long acting insulin
glargine
determir
key feature rapid acting insulins
aa alteration in c-terminal tail of B peptide preventing insulin complex formation
key feature short acting insulins
identical to human insulin, forms complexes
key feature intermediate acting insulin
protamine-insulin complex
key feature long acting insulin
aa substitiutions that result in precipitate formation at more neutral pH in the body
duration of insulins: rapid short intermediate long
3-5 hr
4-12 hr
10-20 hr
12-20 h (glargine) r or 22-24 hr (detemir)
most common adverse effect to insulin therapy
hypoglycemia
tx: give glucose or give glucagon
s/s tahcycardia, sweating, tremors, nausea, hunge, coma, loss of consciousness
adverse effects of insulin therapy
hypoglycemia (insulin therapy too effective)
hypersensitivity (immune response to noninsulin prtn contaminants)
resistance (anti-insulin antibodies)
lipohypertrophy (fat deposition at injection site)
lipoatrophy (fat loss at injection site)
MOA glucagon and use
treat hypoglycemia
injected peptide
catabolism of stored glycogen to increase blood glucose levels
key points metformin
- first line agent
- doesn’t produce hypoglycemia
- not dependent upon B cell function
MOA metformin
decreases hepatic glucose output [via activation of AMPK] and increases peripheral glucose utilization
adverse effects metformin
GI disturbances
vit B12 deficiency
sulfonylureas
glimepiride
glipizide
glyburide
meglitinides
repaglinide
nateglinide
MOA sulfonylureas and meglitinides
inhibition of ATP sensitive K channel of B cell –> insulin release
adverse effects sulfonylureas and meglitinides
weight gain
hypoglycemia
glucosidase inhibitors
acarbose
miglitol
key points glucosidase inhibitors
- taken with a meal
- contraindicated for pts with GI diseases
- hypoglycemia can occur if in combo with other drugs
- treat hypoglycemia with oral glucose
MOA glucosidase inhibitors
inhibition of brush border glucosidase enzyme and subsequent absorption of glucose
adverse effects glucosidase inhibitors
abdominal pain
diarrhea
flatulence
due to unabsorbed carbs
MOA TZD thiazolidinediones
increase transcription of GLUT 4
- decrease peripheral resistance by activation peroxisome proliferator activated receptor gamma
- effect on glucose metabolism, insulin signaling
adverse effects TZDs
**cardiovascular
also peripheral edema, WG, hepatotoxicity, bone fractures, hypoglycemia
TZD thiazolidinediones (2)
pioglitazone
rosiglitazone
amylinomimetic drug =
MOA?
pramlintide
inhibits glucagon release
inhibits gastric emptying
anoretic effect
adverse effects pramlintide
anorexia nausea vomiting hypoglycemia delayed drug absorption
incretin example; MOA
exenatide
- potentiate insulin secretion
- inhibit glucagon release
- inhibit gastric emptying
- anorectic effect
adverse effects exenatide
*acute pancreatitis nausea/vomiting diarrhea hypoglycemia delayed drug absorption
dipeptidy peptidase inhibitor example; MOA
sitagliptin
inhibit incretin degradation
adverse effects sitagliptin
- pancreatitis