endocrine Pharmacology 1

Ant diabetic drugs

By: Berhanu T. (B.pharm,MSc in clinical pharmacy)

9/18/2023
 Ant diabetics cont…
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 Upon ingestion of carbohydrates, insulin is released into

the blood and promotes uptake and utilization of glucose
in specific organs
 namely, the heart, adipose tissue, and skeletal muscle

 Diabetes Mellitus is a a group of metabolic disorders

characterized by hyperglycemia
 It occurs as a result of absolute or relative deficiency of

insulin
 results in metabolic and vascular abnormalities

endocrine Pharmacology 9/18/2023

 Criteria for the diagnosis of DM
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 HbA1c ≥ 6.5 percent OR

 FBG ≥ 126 mg/dL (7.0 mmol/L)

 Fasting is defined as no caloric intake for at least 8h, OR

 Two-hour plasma glucose ≥ 200 mg/dL, OR

 In a patient with classic symptoms of hyperglycemia or

hyperglycemic crisis, a random plasma glucose ≥ 200
mg/dL
endocrine Pharmacology 9/18/2023
 The etiologies (causative factors)
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 Obesity(BMI > 25 kg/m2 ): chronic calorie intake and prolonged

stimulation of β cell causes a decrease in insulin receptor and also
adipose tissue and muscle are less sensitive

 Abdominal obesity: Waist circumference

 Men > 102 cm (> 40 inches)

 Women > 88 cm (>35 inches)

 Hypertension (BP >140/90 mmHg)

endocrine Pharmacology 9/18/2023

 The etiologies (causative factors)…
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 Hereditary (from family)

 damage of pancreatic tissue
 diabetogenic hormones (like growth hormone, thyroid,
epinephrine)
 diabetogenic drugs like Thiazide diuretics, epinephrine,
phenothiazines
 Pregnancy

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 The common signs and symptoms

 3p

Polydipsia

Polyphagia

Polyuria

 dehydration due to glucosuria

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 Types of Diabetes mellitus
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 Type I (Juvenile type)-occurs predominantly in children and young

adults who have no insulin secretion
 It is also called insulin dependent diabetes mellitus (IDDM)

 Insulin replacement therapy is necessary to sustain life

 Type II (maturity onset type)-usually occur after the age of 40years

 It is also known as non-insulin dependent diabetes mellitus
(NIDDM)
 Characterized by tissue resistance to the action of insulin combined
with a relative deficiency in insulin secretion
 Gestational Diabetes Mellitus-Defined as any abnormality in glucose
levels noted for the first time during pregnancy
endocrine Pharmacology 9/18/2023
 complications of diabetes mellitus
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 Ketoacidosis (in types I): is serious complication of diabetes

due to insulin deficiency
 Management includes Regular (soluble) insulin IV infusion

 Hypoglycemic coma (in type II): due to excess dose of insulin

 Management includes giving glucose or glucagon

 Cardiovascular disorders: Hypertension, atherosclerosis

(cholesterol deposits plaques), myocardial infarction,
peripheral arterial insufficiency, Anemia, stroke, nephropathy,
retinopathy, neuropathy

endocrine Pharmacology 9/18/2023

 Drugs used for treatment of DM
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 Insulin: the goal of insulin therapy is to replicate normal

physiologic insulin secretion and replace the background
or basal (overnight, fasting, and between-meal) as well as
bolus or prandial (mealtime) insulin
 Sources of insulin: naturally from pork or beef, and also
human
 Actions: lower blood glucose level through increasing

utilization of glucose by peripheral tissue and promoting

synthesis and storage of glycogen

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 Four principal types of injected insulins are available:

1. Rapid acting, with very fast onset and short duration
 Insulin lispro, insulin aspart, and insulin glulisine
2. short-acting, with rapid onset of action
 Regular Insuline
3. intermediate-acting
 NPH (neutral protamine Hagedorn, or isophane) insulin;
Lente insulin
4. long acting, with slow onset of action
 Insulin glargine; Protamine Zn insulin, Insulin detemir
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 Insulins: PK of SC administration
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Examples of recommended insulin regimens

 Short acting insulin mixed with intermediate - acting
insulin: twice daily (before meals)
 Short-acting insulin: three times daily (before breakfast,

midday and evening meal)

 Intermediate-acting insulin with or without short-acting

insulin once daily either before breakfast or at bedtime

 suffices for some patients with type II diabetes who
need insulin, sometimes in combination with oral
hypoglycemic drugs
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Indication of insulin

 Treatment of type I DM

 Treatment of type II DM not controlled by other agents

 Management of diabetic ketoacidosis

 Control of diabetes in pregnancy, during surgery and in

infections

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Adverse Reaction and complication

 Hypoglycemia (reduced blood glucose)

 Hypertrophy (increase size) at site of injection

 Hypersensitivity reaction (insulin allergy)

endocrine Pharmacology 9/18/2023

 Oral hypoglycemic drugs
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 These are antidiabetic drugs administered orally

 They lower blood glucose level and used in mild diabetes

 They are grouped as: Sulphonylureas and Biguanides

endocrine Pharmacology 9/18/2023

 Sulphonyl ureas
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Preparations and their dosage

 Tolbutamide (Tablet, 500mg): 500 mg before each meal
and once or twice per day
 Chlorpropamide (Tablet, 100mg, 250mg): 250 mg daily;

single dose in the morning

 Glibenclamide (Tablet, 5mg): 2.5 mg/d-20 mg/d

 Glipizide: Tablet, 2.5mg, 5mg, 10mg

 Gliclazide:Tablet, 30mg, 40mg, 80mg (sustained release)

 Glimperide: Tablet, 1mg, 2mg, 4mg

endocrine Pharmacology 9/18/2023

 Sulphonyl ureas …
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 Indication: diabetes mellitus (type II)

 Side effects:
 Gastric irritation
 prolonged hypoglycemia (esp. chlorpropamide)
 Confusion

 defect to fetus (contra-indicated in pregnancy)

endocrine Pharmacology 9/18/2023

 Biguanides
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 work by preventing the production of glucose in the liver

 improving the body’s sensitivity towards insulin and reducing the
amount of sugar absorbed by the intestines
 They potentiate the hypoglycemic action of insulin and sulphonyl

ureas
 The only commercially available biguanides is metformin

 Metformin is effective as monotherapy (alone) and in

combination with nearly every other therapy for type 2 diabetes

 Side effects: Nausea, vomiting, anorexia, diarrhea, abdominal

cramp
endocrine Pharmacology 9/18/2023
 Drugs that affect absorption of glucose (α-
glucosidase inhibitors):
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 They delay the digestion and absorption of starch and

disaccharides
 Acarbose

 Dosage of 50 mg twice daily up to 100 mg three times

a day
 It lowers postprandial glucose levels by 30–50%
 adverse effects: flatulence, diarrhea, and abdominal
pain

endocrine Pharmacology 9/18/2023

 Short-acting insulin secretagogues
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Nateglinide and repaglinide

 stimulate insulin secretion from the β-cells of the pancreas similar to
sulfonylureas
 Both require the presence of glucose to stimulate insulin secretion

 Are rapid-acting insulin secretagogues

 Are rapidly absorbed (~0.5 -1 hour) and have a short half-life (1 - 1.5
hours)
 Adverse Effects :

 Weight gain of 2 -3 Kg has been noted with repaglinide, whereas

weight gain with nateglinide appears to be <1 Kg
 Hypoglycemia

endocrine Pharmacology 9/18/2023

 Thiazolidinediones (Glitazones)
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 Pioglitazone and rosiglitazone

 Enhance insulin sensitivity at muscle, liver, and fat tissues indirectly
 Well absorbed with or without food
 Both are highly protein bound to albumin (>99%)
 The half-life of pioglitazone and rosiglitazone is 3 - 7 hours and 3 - 4
hours, respectively
 Adverse Effects
 Elevated liver enzymes

 Fluid retention: edema, dilutional anemia

 Contraindicated for pts with stage III and IV CHF
 Weight gain

endocrine Pharmacology 9/18/2023

 Female Sex Hormones and Hormonal
Contraception
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Estrogens
 These drugs can be classified into three groups

 Natural – estradiol, esterone, estriol

 Estradiol is most potent

 Semisynthetic – Ethnylestradiol

 Highly potent, effective orally

 Synthetic: Diethylstibosterol

 Estrogen inhibit release of gonadotrophins (FSH, LH)

 Estrogen causes the growth of gland and duct system

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Therapeutic uses
 contraceptive in combination with progestogens

 Functional uterine bleeding

 Dysmenorrhea

 Alleviation of menopausal disorder

 Osteoporosis

 Replacement therapy in ovarian failure

 Prevents senile and atrophic vaginitis

 Side effects: Thromboembolism, Sodium and water retention,

Withdrawal bleeding, nausea, endometrial carcinoma

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Progestogens
 Progestrone is natural occuring progestational hormone

 It is synthesized by corpus luteum, placenta, adrenal

cortex, and testis

 It is given through intramuscular route

 Progestogens inhibits ovulation

 It also causes relaxation of the uterus in late pregnancy

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 Synthetic /Semisynthetic progestogens:

 Derivative of progestrone: Hydroxyprogesterone
capriot/medroxyprogestrone
 Derivative of testestrone: Dimethisterone

 Nortestrone: Norethisterone

 Therapeutic use: they are indicated for purpose of:

 Contraception (pregnancy prevention)

 Stopping of functional uterine bleeding

 Relief from dysmenorrhea, and Amenorrhea

 Reduction of Endometrial Carcinoma

endocrine Pharmacology 9/18/2023

 Hormonal contraceptives: Oral Contraceptives
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 These are drugs taken orally to prevent conception

1. Combined regimen: involves the administration of pills
containing combination of Estrogen and Progestogen
 They are administered starting 5th day of menstrual cycle
for 21 days
 Fixed dose combination: the commonest procedure is to
administer one pill containing both an estrogen and
progestin daily at bed time for 21 days

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MOA

 Changing the body's hormonal balance so that

ovulation does not occur

 Causing the mucus made by the cervix to thicken and

form a 'mucus plug' in the cervix

 Making the lining of the uterus thinner

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2. Single Entity preparation

 Continuous progestrone: it makes cervical mucus thick

and also alter endometrial wall
 Oral progesterone: Norethindone (Norgestril)
 Depot (IM injection) e.g. Medroxyprogestrone acetate
(Depoprovera®)
 Subcutanous implant: L- norgestril (Norplant®)
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 Post coital “morning after” pill: used within 72 hrs

after unsafe sexual intercourse

 Levonorgestrel: 0.75 mg twice daily for 1 day is

commonly used or 1.5mg stat

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 CHCs: adverse effects
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Contraindication of OC:

 patients with cardiovascular diseases (hypertension,

coronary heart disease); breast Cancer

 Thromboemolic disease, diabetes mellitus, liver disease

endocrine Pharmacology 9/18/2023

 Obstetric and gynecological medications
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 Mifepristone: its major use thus far has been to terminate early
pregnancies (abortion) in combination with misoprostol
 OXYTOCICS : are oxytocin, Prostaglandins, and Ergometrin
which are used to cause contraction of the uterus and milk
ejection
 Oxytocin: used to induce labor by stimulating the uterus
contraction
 It also causes ejection of milk through contraction of the
mammary gland

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 Dinoprostone (prostaglandin E2): Terminate pregnancy

and evacuate uterus in cases of missed abortion or
intrauterine fetal death
 Ergometrine: Prevent bleeding after delivery of placenta if

bleeding is severe by causing sustained uterine

contraction

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Thank you
endocrine Pharmacology 9/18/2023