Diabetes Drugs DSA Flashcards
which pathway has direct effect on increased glut-4 expression
CBL
PI3K/AKT
insulin effects on MEK/ERK–> increased ___ and effects
ELK1
cell growth and differentiation
cell proliferation and increased survival
insulin and increased AP-1
cell growth and differntiation
cell proliferation and apoptosis
insulin and FOX01
decreased FOX1–> increased PPAR-y =lipogenesis
decreased glycogenolysis
decreased gluconeogenesis
inhibition of gluconeogenesis
PI3K/AKT—-> ^PDE —>decrease cAMP which
reduced expression glucose-6 phosphatase
decreased fructose 1,6 bisphosphatse
reduced PEPCK
clinical use of aspart, lispro, glulisine
duration
postprandial hyperglycemia
-take before meal
1-3 hrs
clinical use of regular insulin
duration
basal insulin maintenance
overnight coverage
if for postprandial hyperglycemia, inject 45 min before the meal
10 hrs
NPH, protamine has to what before what
be digested by tissue proteolytic enzymes before insulin can be absorbed
clinical use of NPH
basal insulin maintenance and or overnight coverage
duration is 10-12 hrs
loop diuretics on K+
K+ wasting
AE of insulin
hypoglycemia
lipodistrophy (hypertroph/atrophy of subcut fat at site of injection, change site to prevent)
resistance: IgG Abs can develop to neutralize exogenous insulin
allergic reactions
hypokalemia
common causes of hypoglycemia
delay of meal or missed meal
exercise
overdose of insulin
treatment for hypoglycemia
glucose: juice, candy, IV glucose
diazoxide-> K+ channel opener, inhibits insulin release
glucagon
MOA of glucagon
Gs coupled GPCR
activates AC–>PKA–>glycogen phosphorylase = glycogenolysis
increased PEPCK and Glu-6-phosphatase = gluconeogenesis
glucagon effects
hepatocytes: increased glucose output, glycogen depletion (no depletion in skeletel muscle)
potent inotropic and chronotropic effect on heart
GI smooth muslce relaxation
increase insulin release by beta cells
increase release of catecholamines by chromaffin cells
what pts is glucagon contraindicated in
pts with pheochromocytomas
clinical uses of glucagon
mod to severe hypoglycemia
beta blocker overdose
radiology of the bowel
clinical use of pramlintide
type 1 diabetes
type 2 diabetes as adjunt to insulin therapy before meal
onset
duration
pramlintide
rapid
3 hr
AE pramlintide
nausea, vomiting, diarrhea, anorexia
severe hypoglycemia
drug interactions of pramlintide
enhances effects of anticholinergic drugs in GI tract (constipation)
long acting GLP-1 receptor agonists and half life
exenatide =2.4hrs
liraglutide = 11-15 hrs
clinical use of long acting GLP-1 receptor agonists
GLP-1 inhibits glucagon secretion and excesive hepatic glucose output postprandially
- this is diminished in type 2 diabetic pts
- approved for these pts who can’t control diabetes with metformin/sulfonylureas/thiazolidineodiones
GLP receptor against and weight
can induce some weight loss
AE long actinv GLP-1 receptor agonists
GI disturbance
acute pancreatitis and pancreatic cancer
possible link to thyroid cancer
DDP-4 inhibitor clinical use
alone or in combo?
approved as adjunctive therapy in DM2
monotherapy and in combo with metformin/sulfonylureas/TZDs
AE of DDP-4 inhibitor
URI
nasopharyngitis
acute pancreatitis
hypoglycemia
adverse effects of sulfonylureas
hypoglycemia
weight gain
secondary failure- respond initially then later cease to respond = hyperglycemia again
disulfiram-like effect of alcohol induced flushing
dermatological and gen hypersens rxns
clinical use of sulfonylureas
type 2 diabetes as monotherapy or in combo with insulin or other anti-diabetic drugs
drug interactions of sulfonylureas
enhancing hypoglycemic effect
displace from binding with plasma proteins: sulfonamides, clofibrate, salicylates
enhance effect on KATP channel: ethanol
inhibiting CYP enzymes: azoles, gemfibrozil, cimetidine
drug interactions of sulfonylureas decreaseing glucose lowering effect
inhibiting insulin secretion: beta blocker, CCB
antagonizing effect on Katp channel: diazoxide
inducing hepatic CYP enzymes: phenyotoin, griseofulvin, rifampin
side effects of meglitinides
hypoglycemia
secdonary failure
weight gain
clinical use of meglitinides
take how
combo or alone?
control postprandial hyperglycemia in pts with DM2
take orally before meal
use alone or in combo with other antidiabetic drugs
MOA biguanides (metformin)
activation of AMP-dep protein kinase
inhibit respiratory complex I in mitochondria
clinical use of metformin
-advantages
most common oral agent for DM2, first line
advantages:
-taken orally, no hypoglycemia, no weight gain, decreased risk of micro and macro vascular complications, superior glucose lowering efficacy
AE and contraindications of metformin
GI complications
decreased B12 absorption
lactic acidosis, especailly with hypoxia, renal and hepatic insufficiency
contraindicatied in pts with HF and copd, renal fialure, alcholism and cirrhosis
MOA thiazolidinediones
effects of MOA
ligand of PPAR-y nuclear receptor which dimerizes with RXR binds to PPRE
effects of PPARy activation
increased GLUT4 in skeletal muscle and adipocytes
increased IRS1,2, PI3K = increased insulin sensitivity
increased adiponectin = increased insulin sensitivity
decreased: NFK-B, AP-1, PEPCK (RL step gluconeogensis)
pk of thiazolidinediones
-taken how
effects when and persist how long
orally
takes 1-3 months for full effect
effects persist after drugs elminated for weeks-months
metabolization of thiazolidinediones
- pioglitazone
- rosiglitazone
metabolized by liver
pioglitazone by CYP2C8 and CYP34A
rosiglitazone by CYP2C8 and CYP2C9
(rosie from lake was a 2 from neck up and 8-9 from neck down)
clincial use TZDs
type 2 diabetes alone or in combo delay progression of prediabetes to DM2 euglycemi drugs (no hypoglycemia when used alone)
AE TZDs
exacerbation heart failure
link to increased risk bladder cancer
osteoporisis
increased TC and LDL-C
other effects of SGLT2 inhibitors
osmotic diuresis weight loss reduced BP reduced plasma uric acid no hypoglycemia when used alone
how should flozins (SGLT2 inhibitors) be taken
and clinical use
orally before first meal once a day
adjunct to diet and exerceise in adults with DM2
AE SGLT2 inhibitors
hypotension
hypoveolemia (orthostatic HTN, dizziness, syncope)
UTI (can lead to urosepsis and pyelonephritis)
increased LDL-C
renal function impairment
ketoacidosis
hyperkalemia
hyperkalemia can form in which pts taking SGLT2 inhibitors
pts with impaired renal fnct
htose taking ACEIs, ARBs, and K+ sparing diuretics
MOA of miglitol and acarbose
competivie inhibtion of a-glycosidases
clinical use of miglitol and acarbose
does not cause
DM2 monotherapy or in combo
take orally at mealtime
no hypoglycemia or weight gain
AE of miglitol and acarbose
malabsorption, flautulence, diarrhea, abdominal bloating
drug interactions of miglitol
decrease absorption of propranolol and ranitidine
Miggy ran the game proper
drug interaction of acarbose
decrease absorption of digoxin
dont dial phone digits in ACAR(bose)
