Pharmacology Flashcards
sulfonylureas (SUs)
e. g.,
- gl(i/y)***ide
- glipizide, glimepiride, glyburide
mx:
- stimulate insulin release
- SUR1 AGonists
uses:
- OHA (oral hypoglycemic agent)
- decreases A1c by 1.5-2, fasting blood glucose (FBG) by ~60
- lean type 2 diabetics
- combine w/ other OHAs or basal insulin
- cheap, long history of safety
sFx/AEs:
- hypOglycemia
- weight gain
gl(I/y)***ide
sulfonylureas stimulate insulin release decrease A1c 1.5-2, FBG 60 cheap may cause hypOglycemia
glipizide
sulfonylurea stimulate insulin release decrease A1c 1.5-2, FBG 60 cheap may cause hypOglycemia
glimepiride
sulfonylurea stimulate insulin release decrease A1c 1.5-2, FBG 60 cheap may cause hypOglycemia
meglitinides
e. g.:
- –glinide
- repaglinide
- nateglinide
mx:
- stimulate insulin release
- SUR1 AGonist
uses:
- OHA
- permits dietary variability d/t rapid on and off = good for pts with erratic meal patterns
- hepatic metabolism = can be used in renal disease
- use w/ other OHA or basal insulin
- repaglinide ~ SUs > nateglinide
sFx/AEs:
- hypOglycemia
- relative c/i in liver disease (hepatic metabolism)
repaglinide
meglitinide stimulate insulin release decrease A1c 1.5-2, FBG 60 safe in renal disease, erratic meal patterns may cause hypOglycemia
biguanides
e. g.,
- metformin
mx:
- decrease hepatic glucose output (HGO; mostly glycogenolysis)
- increase GLUT4 translocation (insulin sensitivity)
- may reduce appetite (anorectic)
uses:
- first line OHA when renal fx preserved
- no hypOglycemia
- weight neutral
- similar strength to SU – decrease A1c 1.5-2, FBG ~60
sFx/AEs
- c/i in eGFR <30
- GI discomfort
- reduced B12 absorption
- possible lactic acidosis
metformin
biguanide
first line OHA when renal fx preserved
c/i in eGFR <30
alpha-glucosidase inhibitors
e. g.,
- acarbose
- miglitol
mx:
- delays carbohydrate absorption
- intestinal glucosidase ANTagonist
use:
- normal FBG, high postprandial BG
- decrease A1c 0.5-1
- decrease postprandial BG 50-60
- limited hypoglycemia
sFx/AEs:
- GI - flatulance, diarrhea, discomfort
- hypoglycemia when combined with SU, meglitinides, insulin
acarbose
alpha-glucosidase inhibitor
delays carbohydrate absorption
decrease postprandial BG 50-60
GI side effects
thiazolidinediones
e. g.,
- –glitazone
- pioglitazone
mx:
- PPAR-gamma receptor AGonists
- relocate fat from muscle and liver to peripheral fat
- increases peripheral insulin sensitivity
uses:
- obese T2DM
- lipodystrophy (inability to produce and maintain fat)
- decrease A1c 0.5-1.5
- decrease FBG 15-60
- no hypoglycemia
- safe in renal failure
sFx/AEs:
- weight gain, esp w/ insulin cotherapy
- fluid retention
- edema
- CHF
- in women, fractures, decreased bone mineral density
- caution in liver disease
- c/i class 3-4 CHF
pioglitazone
thiazolidinediones PPAR-gamma-R AGonist move fat from liver/muscle to periphery to increase peripheral insulin sensitivity use in obese T2DM safe in renal failure
DPP-IV inhibitors
e. g.,
- –gliptin
- alogliptin
mx:
- increase glucose-dependent insulin secretion and glucagon suppression
- inhibition of dipeptidyl-peptidase IV
- increase portal GIP and GLP-1
uses:
- mono therapy or combo w/ metformin, –glitazone, basal insulin
- decrease A1c 0.5-0.8
- decrease FBG and postprandial BG
- once daily
- weight neutral
sFx/AEs:
- increased risk of pancreatitis
- hypersensitivity incl SJS
- nasopharyngitis
alogliptin
DPP-IV inhibitor increase portal GIP and GLP-1 to increase glucose-dependent insulin secretion mono or combo decrease A1c 0.5-0.8, FBG, ppBG pancreatitis risk
SGLT2i
e. g.,
- –gliflozin
- empagliflozin
mx:
- renal glucose wasting
- inhibit SGLT2 transporter
uses:
- add-on independent of A1c in CAD, CHF, CKD w/ eGFR >30
- decrease A1c ~1
- once daily
- weight loss
- bp control
- decrease major adverse cardiac events, hospitalization for HF, progression of CKD
sFx/AEs
- genital candiasis
- UTI
- dehydration
- euglycemic DKA
- Fournier’s gangrene
empagliflozin
SGLT2i
renal glucose wasting
T2DM, CAD, CHF, CKD (eGFR>30), weight loss, HTN
risk of euglycemic DKA, Fournier’s gangrene, genital candiasis/UTI, dehydration
indications for basal+bolus insulin
any of:
- FBG >250
- A1c > 10
- ketonuria
- severely symptomatic hyperglycemia
- T1DM
except in T1DM can ween if glucose control improves
indications for bedtime (only) insulin
not at A1c on maximal oral and non-insulin tx
and*
A2c <10 (>10 is analog insulin)
bedtime insulin dosing
10 units starting is “typical”
but more accurately:
- 1 units/kg in small, insulin sensitive, or CKD patients
- e.g. 5 units for 110 lb pt - 2 units/kg if obese AND FBG>200
- e.g., 25 units for 275 lb pt
THEN
check BG daily
if FBG >130 3 days in a row, titrate up by 2 units
(then check again for 3 days, titrate up again 2 more units if still not at goal)
etc until goal is reached
up to 40-50 units or 0.5 units/kg is not uncommon
basal-prandial insulin dosing
total daily dose: 0.3-0.5 units/kg
1/2 at bedtime, 1/2 before meals
split evenly between meals
e.g., 100 kg (220 lb):
30 units total daily dose starting (0.3 units/kg) =
15 units at bedtime (QHS)
5 units before each of 3 meals (TIC AC)
when to titrate insulin
- 10% increase to total daily dose if all BG >200
- 15-20% increase if all BG >300
- if some normal some high, fine tune to carb counts
- be sure to check FBG at least 2-3 days in a row before increasing to avoid overnight hypOglycemia
supplemental/correctional dosing of analog (short-acting) insulins
“fudge factor” = 1700
this helps you calculate their insulin sensitivity i.e. the amount that their BG should drop with a single insulin unit
which helps to make a supplemental/correction scale (how much to add before a meal, based on their BG)
insulin sensitivity = ff / TDD
e.g.,
for patient on 50 units TDD
insulin sensitivity = 1700 / 50 = 34
blood glucose should drop by 34 with each unit of insulin given
so
advise the patient to add 1 unit for each 35 above 150 before a meal (add 1 unit if BG 150-185, 2 units if BG 185-220, etc)
if pre-meal BG is too low (<80-90), reduce dose by 10%
for a patient on 75 units TDD insulin, how much analog insulin should they add if their pre-meal BG is 250?
“fudge factor” = 1700
insulin sensitivity = ff/TDD = 1700 / 75 = 23
round off to 25
150 is max pre-meal goal
(250 - 150) / 25 = ***4 units
or 150-175 1 unit 175-200 2 units 200-225 3 units 225-250 4 units
correctional analog insulin based on carbohydrate to insulin ratio (CIR)
CIR fudge factor = 450
CIR = ff / TDD
CIR tells you g of carb you can eat per unit of insulin (or insulin to add per given amount of carbs)
e.g.,
TDD = 50 units
CIR = 450 / 50 = 7
take 1 unit insulin per 7 g carbs
regular (R) insulin, SQ
PK:
- 0.5-1 h onset
- 2-4 h peak
- 6-8 h duration
uses:
- premeal
advantages:
- inexpensive
- long safety track record
- i.e. insurance
disadvantages:
- take 30-60 min before meal
- long tail = late lows
rapid insulin analogs
e. g.,
- Aspart
- Lispro
PK:
- 15-30 min onset
- 1.5 h peak
- 3-6 h duration
uses:
- premeal
- SQ or pumps
advantages:
- stronger postprandial control with less hypOglycemia
- less variable onset and duration
disadvantages:
- more rapid DKA w/ insulin pump failure
- $$$
faster-acting aspart
PK:
- 15 min onset
- 1 h peak
uses:
- immediately before meal or w/in 20 min of meal
NPH (N) insulin
(neutral protamine haegdorn)
PK:
- 1-4 (~2) h onset
- 6-10 h peak
- 12-20 h duration
uses:
- basal/bedtime insulin
advantages:
- inexpensive
- can mix with R w/ no change in kinetics
disadvantages:
- peaks in afternoon if used in am or at 2-3 am if used before dinner, making it not true flat basal maintenance (lows around those times)
glargine
long-acting insulin analog
PK:
- 1.5 h onset
- 20-24 h duration
- flat/no peak
uses:
- basal/bedtime insulin
- can combine with prandial regimen, OHAs, GLP-1R AGonists
advantages
- long acting
- ~flat
disadvantages
- can’t be combined with other insulins, so more injections
- injection site pain
- $$$
GLP-1R AGonists
non-insulin injectable
e. g.,
- –glutide
- semaglutide (oral also)
- lira, dula, lixi
mx:
- glucose-dependent insulin secretion and glucagon suppressant
- appetite suppressant/satiety enhancement
uses:
- first-line injectable when maxed on oral
- OHA add-on
- appetite suppressant
- weight loss
- limited hypoglycemia
- pp control
- decreased MACE (sema, lira, dula)
- renal protection
- 1 wk duration w/ sema, dula, exen
sFx/AEs:
- GI (nausea, vomiting, diarrhea)
- pancreatitis risk
- possible C-cell neoplasia (rodents)
semaglutide
GLP-1R AGonist oral and SQ 1 week duration glucose-dependent insulin secretion, appetite suppression, weight loss decreased MACE renal protection
