diabetic and antidiabetic drugs
TRANSCRIPT
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
Department of Pharmacology
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
Department of Pharmacology
Insulin Oral anti-diabetic agents
Sulfonylureas
Biguanides
α-Glucosidase inhibitors
Meglitinides
Thiazolidinediones
Department of Pharmacology
Insulin
Produces from beta
cell of pancreas
Release of insulin
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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
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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
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Adverse effect of insulin therapy
Adverse effects Hypoglycemia
Skin reactions
Immunological reactions
Hypokalemia
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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
Department of Pharmacology
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
Department of Pharmacology
BIGUANIDES
Increase glucose
uptake and utilization by
tissues
Decrease hepatic
gluconeogenesis
Decrease glucose
absorption
Increase binding to
insulin receptors
Department of Pharmacology
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
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Alpha-Glucosidase Inhibitors Alpha-glucosidase inhibitors inhihits alpha-glucosidase enzyme
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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
Department of Pharmacology
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
Department of Pharmacology
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.
Department of Pharmacology
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.
Department of Pharmacology
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.
Department of Pharmacology
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)
Department of Pharmacology
Thank You All
Department of Pharmacology