Sulfonylureas for Diabetes: A deep insight

PRESENTED TO: DR.SASWATI SINHA
PRESENTED BY:
VISHNU.R.NAIR,
PHARM.D INTERN,
NATIONAL COLLEGE OF PHARMACY(AMRI HOSPITAL ACADEMIC
TRAINEE)

Sulfonylureas(SUs)  come under the class of “antidiabetic drugs”,
under the sub-heading “Insulin secretagogues”
Insulin secretagogues  refer to those drugs, that PROMOTE
INSULIN SECRETION
Effectiveness of SU  directly proportional to functional status of
pancreatic beta-cells
SUs  not effective for patients with severe insulin deficiency!
iAmerican Diabetes Association. Standards of medical care in diabetes-2016 abridged for primary care providers. Clin Diabetes. 2016;34:3-21.

 Classified into the following generations:
A. 1ST GENERATION SULFONYLUREAS:
- Tolbutamide
- Chlorpropamide
- Tolazamide
B. 2ND GENERATION SULFONYLUREAS:
- Glyburide
- Glipizide
C. 3RD GENERATION SULFONYLUREAS:
- Glimepiride.

SUs  bind to SUR1 (Sulfonylurea subunit of ATP-sensitive K+-
channel)  block ATP-sensitive potassium conductance  causes
partial depolarization of membrane  results in activation of voltage-
sensitive Calcium channels
Activation of Calcium channels  increases calcium influx 
increases cytosolic calcium conductance  promotes exocytosis of
secretory granules containing insulin
iAmerican Diabetes Association. Standards of medical care in diabetes-2016 abridged for primary care providers. Clin Diabetes. 2016;34:3-21.
Sterett JJ, Bragg S, Weart CW. Type 2 diabetes medication review. Am J Med Sci. 2016; 351: 342-55.

 SUs  used for Type-2 DM Management(provided patient does not exhibit severe
insulin deficiency)
 Also effective for “neonatal diabetes”!
 Initially during SU therapy  insulin plasma levels should be sufficient enough
for drugs to show hypoglycemic effects
 After prolonged therapy  although magnitude of insulin returns to pre-
treatment values, hypoglycemic effect of drug persists!
 From above statement  we can understand that “with long-term SU therapy,
there is increment in insulin sensitivity in target tissues, by activating glucose
transport & metabolic enzymes in liver, skeletal muscles & adipose cells”.
https:/www.cdc.gov/diabetes/home/index.html

Drug Route of
administratio
n
Half-life(in
hrs)
PPB(in %) Duration of
action(in hrs)
Metabolite
activity
Elimination
GLIPIZIDE Oral 3-7 >90% 24 None 90%
metabolized,
renal
excretion
GLYBURIDE Oral 10-16 >90% 24 Weak 50%
metabolized,
renal
excretion
GLIMEPIRID
E
Oral 5-9 >99% 24 Weak 99%
metabolized,
renal
excretion

 According to multiple clinical trials :
“Sulfonylureas have maximum potency to cause mild, moderate or severe
hypoglycemia, as compared to other drug classes”
 Hypoglycemia  attributed to:
a. Increased insulin sensitization
b. Dietary pattern changes
c. Increased energy expenditure
 For mild hypoglycemic response  reduce drug dose
 In case of severe hypoglycemia  hypoglycemia may persist for days  warrants
glucose infusions!

 SUs  increase insulin synthesis  triggers TG(triglyceride) production 
leads to weight gain!
 In a small percent of patients taking SUs  the following were observed :
a. GI disturbance(anorexia, N&V, epigastric disturbances, heartburns)
b. Allergic reactions
c. Dermatological issues
d. Mild anemia
e. Transient leukopenia
f. Vague neurological manifestations(weakness, numbness of extremities)

 1st generation SUs  contraindicated in patients with:
- CAD
- Renal dysfunction
- Hepatic dysfunction.
 Liver dysfunction  prolongs drug’s hypoglycemic effects  thus, other
generation SUs should be used with caution!

Sulfonylureas  have similar structure as that of
SULFONAMIDES(sulfa structure)  high risk of cross-sensitivity!
(watch out for furosemide as well!)
If SUs(especially chlorpropamide) are taken with alcohol  there are
chances of disulfiram-like interactions(flushing, nausea & headache)
 avoid alcohol consumption !

SUs + (Anticoagulants/ clofibrate/ fluconazole/ H2-receptor blockers/
methyldopa/ MAO-Inhibitors/ NSAIDs/ Salicylates/ Sulfonamides/
TCAs)  enhanced hypoglycemic effects!
SUs + (Beta-blockers/ CCBs/ Cholestyramine/ Corticosteroids/
Estrogens/ Hydantoins/ INH/ Oral contraceptives/ Phenothiazines/
Rifampin/ Thiazides)  reduced hypoglycemic effects!

DRUG USE DOSAGE
Chlorpropamide T2DM, Diabetes insipidus 100-250 mg/day, orally
Tolazamide T2DM 100-1000 mg/day, orally
Tolbutamide T2DM 0.25-3 g/day, orally
Glipizide T2DM, monotherapy 5-40 mg/day, orally
Glyburide T2DM, monotherapy 1.25-20 mg/day, orally
Glimepiride T2DM, mono/combo therapy 1-4 mg/day, orally.

 Glimepiride  only SU, that can be safely used as combination therapy with
other OHAs!
 Avoid alcohol consumption while taking SUs!
 SUs  cause lowering of HbA1C by 1-2%
 1st generation SUs  rarely used nowadays, owing to:
a. Long duration of action
b. High risk of ADRs
c. Higher propensity for drug interactions
 Never ever skip breakfast when taking 2nd generation SUs!(to prevent
hypoglycemia)
 Consider renal and liver functional status while providing SUs.

How to remember the names of drugs, that enhance the hypoglycemic effects of
Sulfonylureas?
Remember the code: “FACT- DOUBLE MS”!!
F: Fluconazole
A: Anticoagulants
C: Clofibrate
T: TCAs
M: MAO-inhibitors
S: Salicylates
M: Methyldopa
S: Sulfonamides!!!

How to remember the names of drugs that block the hypoglycemic effects of
sulfonylureas??
Remember the code: “RIB- POCCET”!!
R: Rifampin
I: INH
B: Beta-blockers
P: Phenothiazines
O: Oral contraceptives
C: CCBs
C: Cholestyramine
E: Estrogens
T: Thiazides!!!

Sulfonylureas for Diabetes: A deep insight

More Related Content

What's hot

Similar to Sulfonylureas for Diabetes: A deep insight

More from RxVichuZ

Recently uploaded

Sulfonylureas for Diabetes: A deep insight