Diabetic and antidiabetic drugs

Bangladesh Agricultural University

DIABETIC AND ANTIDIABETIC DRUGS

Department of Pharmacology

Dr. MD. YOUSUF ALI SARKER

Course No. : VPHA 611Course Title: Endocrine and Nutritional Pharmacology

Talk Plan

Background Antidiabetic drug Insulin Oral antidiabetic drugs References

Talk Plan


Background

Background

Diabetes Mellitus (DM) Metabolic and vascular disorder Characterized by Hyperglycemia and glucosuria Two type

Type I: Insulin dependent Type II: Non=insulin dependent

Diabetes Insepidus (DI) kidney fail to prevent excretion of water due to

lack of ADH or loss of sensitivity of to ADHDepartment of Pharmacology

Antidiabetic drugs

Antidiabetic drugs


Insulin Oral anti-diabetic agents

Sulfonylureas

Biguanides

α-Glucosidase inhibitors

Meglitinides

Thiazolidinediones


Insulin

Produces from beta

cell of pancreas

Release of insulin


Insulin mediated glucose uptake

Fig.: Insulin binding to the insulin receptor induces a signal transduction cascade which allows the glucose transporter (GLUT4) to transport glucose into the cell

INSULIN (CNTD)

Insulin

Pharmacokinetic

Destroyed in the GIT therefore it is given by injection,

usually S/C

t1/2 of about 10 minutes.

It is inactivated in the liver and kidney, and 10% is excreted

unchangedSource of Insulin

For clinical use most of the derived from beef and pork


PREPARATIONS OF INSULINType Name Onset (hr) Duration (hr)

Intermediate Isophane insulinLente insulin

22

2424

Long actingPZI

Ultralente insulinInsulin glargine

77

2-4

3635

>24

Short actingSoluble insulinNeutral insulin

Semilente insulin

0.5-10.5-1

1

6-86-814

Ultrashort acting Insulin lispro 5 min 3-4


Adverse effect of insulin therapy

Adverse effects Hypoglycemia

Skin reactions

Immunological reactions

Hypokalemia


Oral Antidiabetic Drugs

Treatment of type 2 diabetes

There are five classes of oral antidiabetic drugs (OADs)

are available:

Sulfonylureas (e.g. Clorpropamide, Gliclazide &

Glimepiride)

Biguanides (e.g., Metformin),

α-Glucosidase inhibitors (e.g. Acarbose)

Meglitinides (e.g. Repaglinide),

Thiazolidinediones (e.g. Pioglitazone)Department of Pharmacology

Sulphanylureas

Sulphonylureas binds to KATP

channel of beta cell

Potassium ions efflux causing

depolarization of the ß cell

Depolarization causes Ca2+

influx, which triggers insulin

release by exocytosis


Pharmacokinetics, use, dosage & relative potency of Sulphonylureas

Name Generation

1st generation 2nd generation 3rd generation

Tolbutamide Chlorpropamide Glibenclamide Gliclazide Glimepiride

Duration 6-12 hrs >24 hrs 24 hrs 6-12 hrs 24 hrs

Metabolism By the liver 80% by liver By the liver 80% by

liver

By the liver

Excretion Urine Urine Urine Urine Urine

Dose/day 500mg/2-

3times/day

250-500mg/day 3-20mg/day 80-

250mg/

day

1-8mg/day

Potency 1 6 100 100 100

Adverse effects of Sulphonylureas

Mild G.I. disturbance, which can be minimized by taking

the drug after meals or by antacids

Skin rash

Blood dyscrasis

Hypothyroidism


BIGUANIDES

Increase glucose

uptake and utilization by

tissues

Decrease hepatic

gluconeogenesis

Decrease glucose

absorption

Increase binding to

insulin receptors


BIGUANIDES (CNTD)

Preparation and Dosage Metformin: (Glucophage), tablets, Dose: 1.5-3 gm/2-3 times daily with meals.

Pharmacokinetics Readily absorbed from G.I.T. Not metabolized and excreted unchanged by the kidney

Therapeutics uses In NIDDM together with SU, when SU failed alone

Adverse Effects Metallic taste and G.I.T. upsets and lactic acidosis Long term use may lead to vitamin B12 malabsorption and

folate deficiency


Alpha-Glucosidase Inhibitors Alpha-glucosidase inhibitors inhihits alpha-glucosidase enzyme


Alpha-Glucosidase Inhibitors (cntd)

Pharmacokinetics Broken down by amylase in the small intestine and by

bacteria in the large intestine excreted by the kidney

Natural alpha glucosidase inhibitors

Fig. Grifola frondosa


MEGLITINIDES

Pharmacodynamics

Bind to an ATP dependent KATP channel of beta cells

a weaker binding affinity and faster dissociation from the SUR1 binding site

concentration of intracellular potassium

Depolarization

Rise in intracellular calcium

Increase secretion of (pro) insulin


MEGLITINIDES (CNTD)

Adverse effects Weight gain Chance of formation of tumor of thyroid gland & liver

Pharmacokinetics Well absorbed from the GIT Peak concentration after 1 hr. from ingestion Cleared by the liver Plasma t1/2 = 1hr.

Preparation and Dosage Tablets form Dose: 0.25 – 4 mg before meals.


THIAZOLIDINEDIONES (TZD)

TZDs act by

activating PPARs a group

of nuclear receptor, with

greatest specificity

for PPARy (gamma).

Liganda for these receptors

are free fatty acids(FFAs) and

eicosanoids

Transcription and repression

of specific genes Increase storage of FFAs in adipocytesDepartment of Pharmacology

THIAZOLIDINEDIONES (TZD) (CNTD)

Pharmacokinetics Well absorbed from the GIT Metabolized through the hepatic cytochrome P450

Adverse effects Edema Hypoglycaemia (if used together with insulin or SU) May affect other medications, which are metabolized by

cytochrome P450 as e.g. oral contraceptives Liver failure (only Troglitazone

DosageTroglitazone: 200 – 600 mg once daily with food. Pioglitazone: 15 – 45 mg once daily. Rosiglitazone: 2 –8 mg once daily.


REFERENCES

Cottez, M. L. (1986). Antidiabetic drugs. Revue de L’infirmiere, 36(5), 33–36. http://doi.org/10.1016/j.mpmed.2007.08.016

Day, C. (1999). Thiazolidinediones: A new class of antidiabetic drugs. Diabetic Medicine. http://doi.org/10.1046/j.1464-5491.1999.00023.xPhung, O. J., Sood, N. A., Sill, B. E., & Coleman, C. I. (2011).

Cowan, S. M., & Bunch, S. E. (2001). Oral Antidiabetic Drugs for Cats. Compendium on Continuing Education for the Practicing Veterinarian, 23(7), 633–642.


Oral anti-diabetic drugs for the prevention of Type 2 diabetes. Diabetic Medicine : A Journal of the British Diabetic Association, 28(8), 948–964. http://doi.org/10.1111/j.1464-5491.2011.03303.x

Waisbourd, M., Goldstein, M., & Loewenstein, A. (2011). Treatment of diabetic retinopathy with anti-VEGF drugs. Acta Ophthalmologica. http://doi.org/10.1111/j.1755-3768.2010.02010.x

Waring W.S. (2012). Antidiabetic drugs. Medicine, 98–99. http://doi.org/10.1016/j.mpme.

REFERENCES (CNTD)


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Diabetic and antidiabetic drugs

Health & Medicine

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