Antidiabetic agents Flashcards
insulin secretion stimulated by
glucose
amino acids
gastrointestinal hormones - incretins
incretin effect
oral glucose results in higher insulin than glucose IV
incretins rleased by gut enhance insulin secretion
insulin lispro
rapid acting
inuslin aspart
rapid acting
insulin glulisine
rapid acting
rapid acting insulins
hexamers - slow absorption
mimic prandial release of insulin - given with longer acting insulin, 15 mins before meal
short acting insulin
soluble crystalline zinc insulin
given 30 mins before a meal
intermediate acting insulins
neutral protamine hagedorn
crystalline zinc insulin + protamine
BASAL CONTROL
insuline glargine
long acting
inuslin detemir
long acting
IV insulin given when
pts with ketoacidosis
peri-operative
during labor
ICU
inhaled insulin
peak reached in 12-15 mins and decline in 3 hours
inhaled insulin AE
cough, throat pain, hypoglycemia
should monitor pulmonary function
contraindicated in asthma, COPD, smokers
basal bolus insulin regimen
1 daily shot of glargine, detemir
doses of lispro, aspart, or glulisine for each meal
insulin pump therapy
glulisine
lispro
insulin
hypoglycemia management
sugar containing food
if severe – IV glucose infusion
insulin AE
allergic reaction - immediate hypersensitivity
lipodystrophy at injection site
drugs that cause hypoglycemia
ethanol - inhibits gluconeogenesis
b blockers - block effects of catecholamines on gluconeogenesis and glycogenolysis
salicylates - enhance beta cell sensitivity to glucose and potentiate insulin secretion
drugs that cause hyperglycemia by countering action of inuslin
epinepherine
glucocorticoids
atypical antipsychotics
HIV protease inhibitors
drugs that cause hyperglycemia by inhibition insulin secretion
phenytoin
clonidine
Ca ch blocker
diuretics can inhibit insulin secretion indirectly via depletion of K+
non-insulin anti-diabetic agents
sulfonylureas, meglitinides biguanides thiazolidinediones alpha-glucosidase inhibitors incretin analogs DPP-IV inhibitors amylin analogs bile-acid sequestrants SGLT-2 inhibitors
sulfonylureas
effective at reducing fasting plasma glucose and HbA1c
sulfonylurea MOA
stimulate insulin release from B cells
bind to SUR1 subunit - blocks ATP sensitive K+ channel in beta cell membrane
1st generation sulfonylurea
chlorpropamide
chlorpropamide
hypoglycemia common in elderly pt
hyperemic flush with alcohol (inhibition of aldehyde dehydrogenase)
can elicit SIADH - potentiates
2nd generation sulfonylurea
glyburide
glipizide
glimepiride
more potent than 1st generation
lack AE of 1st generation
overall have replaced 1st generation
glyburide
2nd generation - worst of three - causes hypoglycemia in users commonly
glipizide
shortest half life of potent agents
less likely to cause hypoglycemia
glimepiride
causes hypoglycemia in very very few pt’s
sulfonylurea AE
hypoglycemia
weight gain
meglitinides
repaglinide
nateglinide
stimulate insulin release by SUR1 binding - inhibition of ATP sensitive K+ channel
(effect not as strong as sulfonylurea in reducing plasma glucose and HbA1c)
meglitinides
rapid onset, short duration
postprandial glucose regulators
must be taken before meal
contain no sulfur - good for pt with sulfa allergy
meglitinides AE
hypoglycemia – repaglinide
(less likely in nateglinide)
both have weight gain
which meglitinide has a higher chance of hypoglycemia
repaglinide
biguanides
metformin
does not increase insulin secretion or hypoglycemia
equivalent effect to sulfonylureas in reducing fasting glucose and HbA1c
metformin MOA
1) inhibits gluconeogenesis inhibits GENE EXPRESSION of gluconeogenic enzymes - not direct inhibition of enzyme
2) increases insulin mediated glucose utilization in muscle and liver
– via activation of AMP-activated protein kinase
= insulin levels decline slightly
metformin additional effects
dec plasma TG
dec body weight
first line in NIDDM
metformin
can be used alone or in combo with sulfonylureas, Tzds, insulin
metformin AE
mainly GI
may interfere with B12 absorption
fatal lactic acidosis
contraindicated with pt with renal disease, hepatic disease, hypoxia, alcoholism
pioglitazone
thiazolidinediones
rosiglitazone
thiazolidinediones
thiazolidinediones
1) pioglitazone
2) rosiglitazone
“insulin sensitizers”
dec insulin resistance
agonist of PPAR-gamma (intracell receptors in muscle, fat, liver)
promotes glucose uptake and utilization
less effective than sulfonylureas and metformin in decreases FPG/HbA1c
TZD PKA
because of gene regulation - slow onset of effect
pioglitazone versus rosiglitazone
pioglitazone = greater improvements in HDL, TG, LDL size and concentration
TZD AE
fluid retention exacerbation of CHF - spec class III or IV
what is required to be monitored with TZD therapy
liver function
severe hepatic toxicity seen with first TZD released
acarbose
alpha-glucosidase inhibitor
only one
alpha-glucosidase inhibitor MOA
competitive inhibitor
1) dec postprandial digestion of starch and disacc
2) dec postprandial hyperglycemia and hyperinsulinemia
3) modest drop in HbA1c, FPG
alpha-glucosidase inhibitor AE
GI
contraindicated in IBS, intestinal conditions
reversible hepatic enzyme elevation = requires LFT monitoring
incretin analog
exenatide
glucagon like polypeptide-1 analog
exenatide
GLP-1 analog
injectable
resistant to dipeptidyl peptidase IV
exenatide MOA
1) enhances glucose dep insulin secretion
2) suppresses post prandial glucagon release
3) slows gastric emptying
used in NIDDM
exentaide AE
n/v/d
acute pancreatitis
should not be used in pt with gastroparesis
sitagliptin
DDP-IV inhibitor
increases circulating GLP-1 and insulin levels
improves glycemic control in adults with NIDDM
oral
sitagliptin AE
pancreatitis
hypersensitivity (angioedema, anaphylaxis, stevens johnson)
pramlintide
amylin analog - secreted with insulin from beta cells
inhibits food intake, gastric emptying, glucagon secretion
adjunct to insulin
colesevelam
bile acid sequestrants
(lowers LDL cholesterol)
also used for NIDDM tx
oral
Canagliflozin
SGLT-2 inhibitor
responsible for most reabsorption in PCT = BLOCKS - causing increased glucose excretion, dec blood glucose levels
oral
canagliflozin AE
genital and UTIs
volume depletion d/t osmotic diuresis
inc serum creatinine
hyperkalemia, hypermagnesemia, hyperphosphatemia, hypotension
contraindicated in pt with GFR <45
initial drug therapy for NIDDM
1st agent - metformin
only started if lifestyle intervention doesn’t reach HbA1c goals
dual combination therapy
if monotherapy doesn’t reach goal at 3 months - second drug could be oral agent, exenatide, or insulin
(higher HbA1c = more insulin)
triple combo therapy
most robust response will be with insulin - progressive beta cell loss - thus need to transition to inuslin
(favored when HbA1c >8.5%)
transition to insulin
single injection of basal insulin
(either NPH, glargine, or detemir insulin can be used)
then uptitirate dose
if high postprandial glucose - add prandial insulin therapy with short acting (lispro, aspart, glulisine)
most effective diabetic meds in lowering glycemia
insulin
severe hyperglycemia
insulin used as initial therapy
1) significant hyperglycemic sxs
2) ketonuria
3) HbA1c >10%
4) random glucose >300
DM and HTN tx
ACE-I or ARB
antiplatelet agents in DM pt
ASA
DM pt with albuminuria
ACE-I or ARB
DM pt with neuropathic pain
amitriptyline pregabalin gabapentin duloxetine venlafaxine valproate opioids
DM pt with gastroparesis
metoclopramide
erythromycin
DM pt with erectile dysfunction
PDE-5 inhibitors
glucagon use
severe hypoglycemia (in pt taking insulin)
bowel radiology (relaxes intestine)
B blocker poisoning antidote
C-peptide test - testing residual beta cell function
DOC for gestational DM
regular insulin
