This presentation deals with DPP-IV inhibitors, that are implicated for use in diabetes mellitus. Generalized pharmacology, including a precise insight into individual drugs have been elucidated.
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Dipeptidyl peptidase inhibitors(DPP-IV): A deep insight
1. PRESENTED TO: DR.SASWATI SINHA, DR.SHARMILA CHATTERJEE
PRESENTED BY:
VISHNU.R.NAIR,
PHARM.D INTERN(AMRI HOSPITAL ACADEMIC TRAINEE),
NATIONAL COLLEGE OF PHARMACY, KERALA.
2. DPP-IV inhibitors(also known as “GLIPTINS”) represent a class of oral antidiabetics.
Principle of action: “Drugs, that prolong incretin action”
Oral glucose intake
Causes release of “gut hormones”(incretins)
Increases glucose-induced insulin secretion
Thus
Oral glucose load provokes higher insulin response (as compared to glucose given i.v)
Katzung B. Basic & clinical pharmacology. 14th ed. San Francisco: McGraw-Hill Education; 2018. Pg: 761-62.
3. Incretins include:
a. GLP-1(Glucagon-like peptide-1)
b. GIP(Glucose-dependent insulinotropic peptide)
GLP-1
Infused in Type-2 DM
Reduces blood glucose levels Stimulates insulin release
Katzung B. Basic & clinical pharmacology. 14th ed. San Francisco: McGraw-Hill Education; 2018. Pg: 761-62.
4. GLP-1 shows “glucose-dependent action”:
a. Increases insulin release only when BGL is high
b. No effect in euglycemia
c. Lower risk of hypoglycemia (as compared to sulfonylureas).
Other effects of GLP-1 include:
a. Suppression of glucagon secretion
b. Reduced gastric emptying
c. Reduced apoptosis of human islets
Katzung B. Basic & clinical pharmacology. 14th ed. San Francisco: McGraw-Hill Education; 2018. Pg: 761-62.
5. d. GLP-1
Reduces “feeding” (via CNS mechanism)
Thus
Type-2 DM patients on GLP-1 therapy tend to be less hungry!
Katzung B. Basic & clinical pharmacology. 14th ed. San Francisco: McGraw-Hill Education; 2018. Pg: 761-62.
10. Bioavailability: 85%
Half-life: 12 hours
Drug undergoes renal excretion requires dosage adjustment in renal dysfunction!
Metabolite activity: Nil
Dosage adjustment for renal dysfunction:
a. If GFR = 30-50 ml/min dose : 50 mg OD
b. If GFR < 30 ml/min dose: 25 mg OD.
Can be given as either “monotherapy”/ in combination with metformin, TZDs or SUs.
Katzung B. Basic & clinical pharmacology. 14th ed. San Francisco: McGraw-Hill Education; 2018. Pg: 761-62.
Tripathi K. Essentials of Medical Pharmacology. 8th ed. New Delhi: Jaypee Brothers Medical Publishers; 2018. Pg: 297-98.
11. ADRs include:
a. Nasopharyngitis
b. URTIs
c. Headache
d. Acute pancreatitis
e. Severe hypersensitivity reactions
If the above PMS reports occur discontinue drug immediately!!
Post marketing
surveillance
reports
Katzung B. Basic & clinical pharmacology. 14th ed. San Francisco: McGraw-Hill Education; 2018. Pg: 761-62.
Tripathi K. Essentials of Medical Pharmacology. 8th ed. New Delhi: Jaypee Brothers Medical Publishers; 2018. Pg: 297-98.
12. Drug interactions:
a. Sitagliptin + OHAs increased toxicity/effects of latter monitor therapy!
b. Drug + ACE-Inhibitors increased toxicity of latter monitor therapy!
c. Drug + diuretics(loop, thiazide); corticosteroids diminished hypoglycemic effect of
former monitor therapy!
Contraindications:
a. Type-1 DM
b. DKA(Diabetic keto-acidosis)
c. Drug hypersensitivity.
Katzung B. Basic & clinical pharmacology. 14th ed. San Francisco: McGraw-Hill Education; 2018. Pg: 761-62.
Tripathi K. Essentials of Medical Pharmacology. 8th ed. New Delhi: Jaypee Brothers Medical Publishers; 2018. Pg: 297-98.
13. Monitoring parameters:
a. Symptoms of pancreatitis
b. RFTs
c. HbA1C levels.
Therapeutic efficacy: Reduction of HbA1C by 0.5-1.0% observed.
Pregnancy category: “B”
Dose: 100 mg OD, orally.
Katzung B. Basic & clinical pharmacology. 14th ed. San Francisco: McGraw-Hill Education; 2018. Pg: 761-62.
Tripathi K. Essentials of Medical Pharmacology. 8th ed. New Delhi: Jaypee Brothers Medical Publishers; 2018. Pg: 297-98.
14. Metabolite activity: Active
Half-life: 3.1 hours
Dosage adjustment required for renal impairment
Can be given as “monotherapy” or as “combination therapy” with biguanides,
TZDs & SUs
Therapeutic efficacy: reduction in HbA1C by 0.4-0.9%
Pregnancy category: “B”
Katzung B. Basic & clinical pharmacology. 14th ed. San Francisco: McGraw-Hill Education; 2018. Pg: 762.
Tripathi K. Essentials of Medical Pharmacology. 8th ed. New Delhi: Jaypee Brothers Medical Publishers; 2018. Pg: 298.
15. ADRs:
a. URTI
b. UTI
c. Headache
d. Hypersensitivity reactions
e. High risk of heart failure!!!
High risk observed with
High levels of NT-pBNP
Renal impairment History of HF
Katzung B. Basic & clinical pharmacology. 14th ed. San Francisco: McGraw-Hill Education; 2018. Pg: 762.
Tripathi K. Essentials of Medical Pharmacology. 8th ed. New Delhi: Jaypee Brothers Medical Publishers; 2018. Pg: 298.
16. Drug interactions: Same as that of sitagliptin.
Contraindications:
a. Same as that of sitagliptin
b. Heart failure(extra addition)
Monitoring parameters: Same as that of sitagliptin
Pregnancy category: “B”
Dose: 2.5-5 mg OD, orally.
Katzung B. Basic & clinical pharmacology. 14th ed. San Francisco: McGraw-Hill Education; 2018. Pg: 762.
Tripathi K. Essentials of Medical Pharmacology. 8th ed. New Delhi: Jaypee Brothers Medical Publishers; 2018. Pg: 298.
17. Usually given in combination with pioglitazone, metformin and sulfonylureas
Therapeutic efficacy: If used as combination therapy drug reduces HbA1C by 0.4-0.6%
Drug mainly excreted through bile no dosage adjustment required in renal dysfunction!
Drug interactions: Same as that of sitagliptin
Contraindication: Same as that of sitagliptin
Monitoring parameters: Same as that of sitagliptin(except RFT)
Pregnancy category: “B”
Katzung B. Basic & clinical pharmacology. 14th ed. San Francisco: McGraw-Hill Education; 2018. Pg: 762.
18. ADRs:
a. Nasopharyngitis
b. Hypersensitivity reactions
c. Pancreatitis.
Dose: 5 mg OD, orally.
Katzung B. Basic & clinical pharmacology. 14th ed. San Francisco: McGraw-Hill Education; 2018. Pg: 762.
19. Given in combination with metformin, pioglitazone and SUs
Dosage adjustment required for renal dysfunction
Dosage adjustment for renal dysfunction:
a. If CrCl = 30-60 ml/min dose: 12.5 mg OD
b. If CrCl = < 30 ml/min dose: 6.25 mg OD
Therapeutic efficacy: If used as combination therapy reduction in HbA1C by 0.5-
0.6%
Drug interactions: Same as that of sitagliptin.
Katzung B. Basic & clinical pharmacology. 14th ed. San Francisco: McGraw-Hill Education; 2018. Pg: 762.
20. Contraindications: Same (in addition, heart failure)
Monitoring parameters: Same(in addition, LFTs prior to starting treatment, and periodically
thereafter)
Pregnancy category: “B”
ADRs:
a. Hypersensitivity reactions
b. Hepatic failure
c. Pancreatitis.
Dose: 25 mg OD, orally.
Katzung B. Basic & clinical pharmacology. 14th ed. San Francisco: McGraw-Hill Education; 2018. Pg: 762.
21. Usually used as combination therapy
Therapeutic efficacy: If used as combination therapy lowers HbA1C by 0.5-1.0%
Drug interactions: Same as that of sitagliptin
Contraindications:
a. Pancreatitis f. DKA
b. Liver failure
c. Heart failure
d. Drug hypersensitivity
e. Type 1 DM
Katzung B. Basic & clinical pharmacology. 14th ed. San Francisco: McGraw-Hill Education; 2018. Pg: 762.
Tripathi K. Essentials of Medical Pharmacology. 8th ed. New Delhi: Jaypee Brothers Medical Publishers; 2018. Pg: 298.
22. Monitoring parameters:
a. Blood glucose levels
b. Lipid profile
c. HbA1C(Baseline & periodically thereafter)
d. LFTs
e. Symptoms of pancreatitis.
Pregnancy category: Uncategorized usage is not recommended.
Dose: 50 mg, OD/BD, orally.
Katzung B. Basic & clinical pharmacology. 14th ed. San Francisco: McGraw-Hill Education; 2018. Pg: 762.
Tripathi K. Essentials of Medical Pharmacology. 8th ed. New Delhi: Jaypee Brothers Medical Publishers; 2018. Pg: 298.
23. ADRs:
a. URTI
b. Nasopharyngitis
c. Dizziness
d. Headache
e. Hepatitis(rare).
Katzung B. Basic & clinical pharmacology. 14th ed. San Francisco: McGraw-Hill Education; 2018. Pg: 762.
Tripathi K. Essentials of Medical Pharmacology. 8th ed. New Delhi: Jaypee Brothers Medical Publishers; 2018. Pg: 298.
24. Patient counselling tips:
a. Can be taken with/without food
b. Avoid alcohol intake
c. Report to physician if the following occur:
Fatigue Right upper abdominal discomfort.
Anorexia
Dark urine
Katzung B. Basic & clinical pharmacology. 14th ed. San Francisco: McGraw-Hill Education; 2018. Pg: 762.
Tripathi K. Essentials of Medical Pharmacology. 8th ed. New Delhi: Jaypee Brothers Medical Publishers; 2018. Pg: 298.
25. Newer molecule
Developed in Japan
Long-lasting (> 24 hours) hypoglycemic effect
With a single morning dose post prandial blood glucose level is reduced significantly at all
3 meals of the day!
Given either as “monotherapy” or as “combination therapy” with metformin ± SUs/ a TZD
Metabolites eliminated by both liver & kidney no dose adjustment required in renal
dysfunction!
Exercise caution, while using drug in patients with/ prone to QT-prolongation!
Dose: 20 mg before breakfast daily increase dose to 40 mg/day(if needed).
Tripathi K. Essentials of Medical Pharmacology. 8th ed. New Delhi: Jaypee Brothers Medical Publishers; 2018. Pg: 298.