Endocrine
Pharmacology
Beyene Dereje D.
B.Pharm, MA, MSc, PGD
School of Medicine, Dire Dawa University
Learning Objectives
At the end of the module, students will be able to describe the:
• Describe the effects of insulin on different organ systems
• Differentiate types of insulin therapeutic uses & adverse reactions
• Identify MOA, uses and side effects of oral hypoglycemic agents
• Describe the effects of thyroid and antithyroid drugs
• Differentiate the types of antithyroid drugs uses and adverse effects
• Discuss drugs used for contraction of the uterus
Brainstroming
Students will be asked questions about the types of
endocrine hormones and common endocrine disorders.
Introduction to
Endocrine System
Diabetes, Thyroid disorders, PCOS, Contraceptives
Introduction
• Endocrine hormones regulates practically all bodily activities.
• These molecules aid in the coordination of our body processes,
which include metabolism, growth and development, emotions,
mood, sexual function, and even sleep.
• Some common endocrine disorders
• Diabetes, Thyroid disorders, Hypogonadism
• Polycystic ovary syndrome (PCOS), Osteoporosis
Prerequisite Questions?
1. Name the functions of insulin & glucagon?
2. What will you treat in diabetic patients?
3. What are the common contraceptives
currently we are using in Ethiopia?
Diabetes
A group of metabolic
diseases characterized by
high blood glucose levels.
Introduction
• A disease that occur as a result of absolute/relative deficiency
of insulin that results in metabolic & vascular abnormalities.
• The etiologies/ risk factors include:
• Obesity
• Hereditary
• Diabetogenic drugs: thiazides, epinephrine, phenothiazines
• Pregnancy: placenta & placental hormones create
resistance to insulin
Common signs and symptoms
• Polydipsia, Polyphagia, Polyuria
• Dehydration due to glucosuria
• Fatigue/lethargy
• Recurrent infection
• Prolonged wound healing
• Seizure, coma
• Unexplained weight loss
Diagnosis
• Fasting Plasma Glucose (FPG) Test፡ FBG ≥ 126 mg/dl
• Oral Glucose Tolerance Test (OGTT)፡ BGL ≥ 200mg/dl
• HgbA1C Test:
• Measures average blood glucose over the past 2-3
months: Hgb A1c ≥ 6.5%
• Random Plasma Glucose Test: RBS ≥ 200mg/dl
• NB: The diagnosis should be done on more than one
occasion for confirmation.
DM Classifications
1. Type I: IDDM (Juvenile type)
• Occurs predominantly in children and young adults who have
no insulin secretion.
2. Type II: NIDDM (Maturity onset type)
• Usually occur after the age of 40 years
3. Gestational diabetes mellitus
4. Diabetes resulting from other causes
• Diseases and Drugs
Contd…
• Diseases
• Pancreatitis, pancreatic cancer, trauma,
• Drugs
• Glucocorticoids, Oral contraceptives
• Beta blockers, Thiazide diuretics
• Nicotinic acid, Statins
• Protease inhibitors
• Gonadotropin-releasing hormone agonists
Antidiabetogenic Drugs
Insulin Insulin Secretagogues Biguanides
Regular Insulin, Lente Sulfonylureas, Meglitinides, Metformin
Insulin, NPH Insulin Repaglinides
Thiazolidinediones α-Glucosidase Inhibitors
Pioglitazone, Rosiglitazone Miglitol, Acarbose
Insulin
Sources of insulin include:
• Enzyme modification of Pork or beef
• Combination of pork and beef insulin and
• Human insulin (Recombinant DNA technique)
Mechanism of Actions:
• Insulin lowers the blood glucose level by increasing utilization of
glucose by peripheral tissue and promoting synthesis and storage
of glucose in form of glycogen.
Insulin Effects
• The main actions of insulin are exerted on metabolism of
carbohydrate, fat and protein in liver, muscle & adipose tissue.
1. Effect on Carbohydrate Metabolism
• Liver: Increases glycogen synthesis and glucose utilization,
while it decreases gluconeogenesis and glycogenolysis
• Muscle: Increases glucose uptake, glucose utilization and
glycogen synthesis.
• Adipose tissue: glucose uptake and glycerol synthesis
Insulin Effects
2. Effect on Fat metabolism
• Liver: It increases lipogenesis (fatty acid formation)
• Adipose tissue: It increases synthesis of triglycerides and
synthesis of fatty acid
3. Effect on Protein metabolism
• Liver: It decreases protein catabolism
• Adipose tissue: It increases amino acid uptake and protein
synthesis
Insulin Effects
4. Other Metabolic Effects:
• It increases uptake of K+ & Ca++ into cells & synthesis of
nucleic acids
• There are some factors that increase insulin demand:
• Like infection, surgery, pregnancy and
• Drugs (those that antagonize actions of insulin
glucocorticoids, thyroid hormone and/or adrenaline)
Types of Insulin Preparation
• Rapid-acting insulin:
• Injection: Insulin Lispro, Insulin Aspart, Insulin Glulisine, and
• Inhalation: human insulin recombinant inhaled
• Replaces endogenous prandial insulin secretion than does
regular insulin
• Short acting (rapid onset): e.g. Regular Insulin
• Intermediate acting: e.g. Lente insulin, NPH (neutral protamine
Hagedorn) insulin
Contd…
• Long acting
• e.g. Protamine Zn insulin, insulin detemir, insulin glargine
• Insulin Glargine: is not mixed with other insulin since its
solubility is affected due change in PH (soluble at PH is 4.0)
N.B. It is only regular insulin that can be given by intravenous route,
while other preparations are given SC or IM. Why?
Insulin Therapeutic uses
• IDDM
• NIDDM (if not controlled by diet and oral hypoglycemic agents)
• Diabetic ketoacidosis
• For control of diabetes in pregnancy
• During surgery and in infections
• They are also used in the treatment of hyperkalemia due to renal
failure
Adverse Reactions
• Local:
• Atrophy or hypertrophy at site of injection, local hypersensitivity
and secondary infections, common with older animal insulin
preparations
• This may be corrected by avoidance of specific the same
injection site
• Systemic:
• Hypoglycemic coma and Immunologic reactions: hypersensitive
and insulin resistance.
Oral Hypoglycemics
• These are drugs administered orally to lower blood glucose level in
patients with type 2 diabetes.
• Some of the groups are:
• Insulin secretagogues: Sulphonylureas, Meglitinides, Repaglinide
• Biguanides: Metformin, Phenformin
• Thiazolidinediones: Pioglitazone, rosiglitazone
• α-glucosidase inhibitors: Miglitol, Acarbose
Sulphonylureas
• These compounds are chemically related to sulphonamides.
• First generation:
• Tolbutamide, Chlorpropamide, tolazamide, acetohexamide
• Second generation:
• Glibenclamide, Glipizide, glimepiride
• Second generations are highly potent (x100) and more safe on
long term use.
Contd…
Mechanism of Action:
• Hypoglycemic action is due to stimulation of insulin released from cell.
Pharmacokinetics:
• All are absorbed from the GIT: food and hyperglycemia retard absorption
• All the sulfonylureas are metabolized by liver, and metabolites are
excreted in the urine.
• Thus sulfonylureas should be administered with caution to patients with
either renal or hepatic insufficiency.
Therapeutic Uses
• To control hyperglycemia in type 2 diabetes mellitus not managed by
diet and lifestyle changes.
• More effective in patients > 40 years.
• Contraindications to the use of these drugs include type 1 DM,
pregnancy, lactation, and significant hepatic or renal insufficiency.
Adverse Reactions
• Hypoglycemia: the longer the half life of the agent the more likely it is to
induce hypoglycemia.
• Displacement from binding sites by other drugs can exacerbate
hypoglycemia.
• Nausea and vomiting, cholestatic jaundice, agranulocytosis, aplastic &
hemolytic anemia, hypersensitivity and severe skin reactions.
• Cause weight gain
Biguanides
• Metformin, Phenformin, Buformin
• hey potentiate the hypoglycemic action of insulin and sulphonylureas
but they don’t produce clinical hypoglycemia in diabetics.
• Phenformin & Buformin – now withdrawn (Lactic acidosis)
Mechanism of Action:
• Decreases basal hepatic glucose production
• Increased action of insulin on muscle and fat
Pharmacokinetics
• Metformin has a half-life of about 3 hours and is excreted unchanged in
the urine. Not associated with weight gain: even promotes weight loss.
• When added to a sulfonylurea, the effects of both agents are additive.
• Can also be combined with other oral agent
Therapeutic Use:
• Obese diabetics (uncontrolled by diet alone, they cause loss of appetite or
anorexia w/c leads to weight loss),
• Supplement to sulphonylureas
Side effects:
• Nausea, vomiting, anorexia, diarrhea, abdominal cramp, metallic taste,
lactic acidosis (esp. phenformin)
Contraindication:
• Diabetes with renal insufficiency
• In IDDM
• During pregnancy
• Alcoholics
• Cardiac failure
Thiazolidinediones
• Pioglitazone, Rosiglitazone
Mechanism of Action:
• They act as a nuclear transcription regulator and an insulin sensitizer.
• Act by activating PPARs (peroxisome proliferator-activated
receptors), a group of nuclear receptors, specific for PPARγ (PPAR-
gamma, PPARG).
Side Effects
• Edema and congestive heart failure, weight gain, fractures, bladder
cancer, hepatotoxicity, diabetic macular edema, increased
ovulation and teratogenic effects.
• Mostly removed from market in Europe and America.
Alpha-glucosidase inhibitors
• Acarbose, Miglitol
• Alpha-glucosidases are enzymes in the digestive tract that hydrolyze
carbohydrates into glucose.
• These drugs are competitive inhibitors of the enzymes in the brush border
of enterocytes that cleave oligosaccharides to monosaccharides.
• Contraindicated in gastrointestinal conditions like inflammatory bowel
disease (IBD), as well as ileus, colonic ulceration, or intestinal obstruction.
Side Effects
• Flatulence (gas): The most frequently reported side effect, occurring in
about 78% of cases.
• Diarrhea: Undigested carbohydrates ferment in the colon, leading to
increased bowel movements.
• Abdominal Pain/Bloating: These can also result from the fermentation of
undigested carbohydrates.
• Nausea, Stomach Cramps/discomforts
Microvascular Complications
• Diabetic Retinopathy:
• Damage to small blood vessels in the retina, potentially leading to vision loss.
• Diabetic Nephropathy:
• Damage to small blood vessels in kidneys, potentially leading to kidney failure.
• Diabetic Neuropathy:
• Nerve damage, affecting various parts of the body, including the peripheral
nerves (causing pain, numbness, tingling) and autonomic nerves (affecting
functions like digestion, heart rate, and bladder control).
Macrovascular Complications:
• Cardiovascular Disease:
• Increased risk of heart attack, stroke, and peripheral artery
disease.
• Peripheral Artery Disease (PAD):
• Reduced blood flow to the legs and feet, potentially leading to
ulcers and infections.
• Cerebrovascular Disease:
• Increased risk of stroke.
Diabetic ketoacidosis (DKA)
• It is a serious, potentially life-threatening complication of
diabetes that occurs when the body doesn't have enough insulin,
leading to a buildup of harmful ketones in the blood.
• DKA is most common among people with type 1 diabetes.
• Its treatment involves a hospital setting with intravenous fluids,
insulin therapy to lower blood sugar, and electrolyte replacement
to correct imbalances, along with addressing any underlying
causes.
DKA Management
1. Fluid Replacement
• Administering Isotonic Saline: Start with 0.9% sodium chloride at a rate
of 15-20 mL/kg/hour for the first hour ( 1-1.5 liters).
• Monitoring Fluid Status: Continue to assess the patient’s hydration
status, blood pressure, heart rate, and urine output.
• Adjusting Fluid Type: If serum sodium levels are normal or high after
initial resuscitation, switch to 0.45% NS. Once blood glucose levels drop
below 200 mg/, add dextrose to prevent hypoglycemia.
Contd…
2. Insulin Therapy
• Initial Insulin Bolus: Administer a bolus of regular insulin at a dose of 0.1
units/kg.
• Continuous Infusion: Follow with an infusion of regular insulin at a rate
of 0.1 units/kg/hour.
• Monitoring Glucose Levels: Aim for a decrease in blood glucose levels
by approximately 50-70 mg/dL per hour.
• Adjusting Insulin Rate: If glucose does not decrease adequately,
increase the insulin infusion rate as needed.
Contd…
3. Electrolyte Management
• Potassium Monitoring: Check serum potassium levels frequently
(every 2-4 hours).
• If potassium is >5.2 mEq/L, no supplementation is needed.
• For levels between 3.3 and 5.2 mEq/L, administer potassium
replacement at a rate of 20-30 mEq/hour.
• If potassium is <3.3 mEq/L, hold insulin therapy until potassium is
corrected.
Contd…
4. Correction of Acid-Base Balance
• Bicarbonate Use: Sodium bicarbonate should only be used if the
arterial pH is <6.9 and should be administered cautiously due to
potential complications like hypokalemia and cerebral edema.
5. Addressing Underlying Causes
• Common causes include infections (e.g., pneumonia or UTI),
noncompliance with insulin therapy, or new-onset diabetes.
• Initiate appropriate antibiotics if an infection is suspected.
Thyroid and
Antithyroid Drugs
Thyroid Drugs
Replacements Thiourea Compounds Radioactive Iodine
Levothyroxine, Propylthiouracil, Methimazole, 131I
Liothyronine Carbimazole
Iodides Ionic inhibitors
Lugol’s Iodine, Potassium Potassium Perchlorate, Potassium Thiocyanate
Iodide
Introduction
• Thyroid hormones are responsible for optimal growth,
development, function, and maintenance of all body tissues.
• Inadequate secretion of thyroid hormone results in bradycardia,
poor resistance to colds, and mental and physical slowing.
• Excess secretion of thyroid hormone causes tachycardia and
cardiac arrhythmias, body wasting, nervousness, tremor, and
excess heat production.
Thyroid Drugs
1. Levothyroxine (T4): The preparation of choice for thyroid
replacement and suppression therapy because of its stability.
2. Liothyronine (T3): It is 3-4x more potent than levothyroxine
• It is not recommended for routine replacement therapy
• It is used for short term suppression TSH
• T3 has greater risk of cardiotoxicity, it should be avoided
in patients with cardiac disease
Antithyroid Drugs
• Antithyroid drugs inhibit the function of the thyroid gland and are
used in hyperthyroidism
• Antithyroid drugs include:
1. Thiourea Compounds: propylthiouracil, methimazole,
carbimazole
2. Ionic inhibitors: potassium perchlorate, potassium thiocyanate
3. Iodide: Lugol’s iodine, potassium iodide
4. Radioactive iodine: - (131I)
MOA of Antithyroid Drugs
Thiourea Compounds
Reduce formation of thyroid hormone by:
• Inhibit oxidation and organification of iodine
• Inhibit coupling of iodotyrosines to form T4 and T3
Propylthiouracil: inhibits peripheral deiodination of T4 to T3
• Well absorbed from GIT, but have short t1/2 & slow in onset
Carbimazole: is rapidly converted to methimazole
• Both methimazole and PTU cross the placenta and also appear
in the milk, but less with PTU
Pregnancy
• Use smallest possible amount of these drugs specifically PTU in
the first trimester.
• Overtreatment causes fetal goiter.
Breast feeding
• Propylthiouracil is the drug of choice
Side Effects:
• Drug fever, skin rashes, acute hepatic necrosis, cholestatic
jaundice, agranulocytosis.
Ionic Inhibitors
• Potassium perchlorate prevents the synthesis of thyroid
hormones through inhibition of uptake and concentration of
iodide by the gland.
• It has the risk of aplastic anemia, therefore is no longer used in
the treatment of hyperthyroidism.
Iodides
• In pharmacologic doses (>6 mg/d), the major action of iodides
is to inhibit hormone release, possibly through inhibition of
thyroglobulin proteolysis.
• Improvement in thyrotoxic symptoms occurs rapidly: within 2-
7 days: hence the value of iodide therapy in thyroid storm.
• In addition, iodides decrease the vascularity, size, and fragility
of a hyperplastic gland, making the drugs valuable as
preoperative preparation for surgery.
Contd…
Adverse Reactions:
• Allergic reactions (angioedema, rashes, drug fever,
lacrimation, conjunctivitis), pain in the salivary glands
• Chronic use in pregnancy avoided → fetal goiter.
Radioactive Iodine
• It is used orally in hyperthyroidism as sodium 131I.
• It is trapped and concentrated as ordinary iodine, which emits
beta rays that act on parenchymal cells of the gland.
• Used in diffuse toxic goiter (Thyrotoxicosis / Grave’s disease),
toxic nodular goiter, thyroid carcinoma
• It is contraindicated in pregnancy and lactation as it affects
thyroid gland in the fetus and the infant.
• Its important toxicity is hypothyroidism.
Role of β- adrenergic blocker
Propranolol
• This is an important drug which controls the peripheral
manifestations of hyperthyroidism (tachycardia, tremor).
• It also decreases the peripheral conversion of T4 to T3.
Drugs for Contraction
of the Uterus
Oxytocin
• Known as the love hormone, is activated by touch, intimacy and
sex and promotes a deeper sense of bonding between couples.
• It's also the hormone that bonds a mother to her newborn baby and
has anti-inflammatory and calming effects.
Mechanism of action:
• Stimulates the uterus and cause physiologic type of contraction.
• Causes ejection of milk through contraction of the myo-epithelial
cells around the alveoli of the mammary gland.
Pharmacokinetics
• Inactivated orally & absorbed rapidly after IM administration.
• It can also be absorbed from the nasal and buccal membranes.
• Administered intravenously for initiation and augmentation of labor.
• It also can be administered IM for control of postpartum bleeding.
Therapeutic Uses
• Induction of labor in women with uterine inertia;
• Relief of breast engorgement during lactation (few minutes
before breast feeding) as nasal spray; and postpartum
hemorrhage
Side Effects
• Oxytocin may cause over stimulation and leads to rupture of the
uterus in the presence of cephalo-pelvic disproportion
• Therefore it’s contraindicated in woman with a uterine scar
• High concentrations can cause excessive fluid retention, or water
intoxication, leading to hypernatremia, heart failure, seizures, and
death.
Prostaglandins
• They induce labor at anytime during pregnancy but are most effective
at the third trimester.
In female reproductive system:
• Prostaglandin E & F are found in ovaries, endometrium and menstrual
fluid which are responsible for initiating and maintaining the normal
birth process.
• PGF, PGF2ά, PGE stimulate both the tone and amplitude of the uterine
contraction.
Adverse Reactions
• Nausea; vomiting; headache; diarrhea and, fever etc.
• PGs should be used cautiously in the presence of
hypo/hypertension, angina, and diabetes
• They are contraindicated in the presence of cardiac, renal,
pulmonary or hepatic disease
Ergometrine
• It is one of the ergot alkaloids which has the ability to cause
contraction of the uterine smooth muscle.
• It causes sustained uterine contraction.
• It is completely absorbed after subcutaneous and intravenous
administration.
• It is metabolized in the liver and eliminated in the urine.
• Liver damage enhances the toxicity of ergot alkaloid.
Therapeutic Use:
• After delivery of placenta if bleeding is severe
• Prevent postpartum bleeding
Adverse effects:
• Nausea and vomiting - but serious toxic effects are rare
Contraindications:
• Pregnancy, and a history of a cerebrovascular accident or
hypertension.
Thank
You!
Any Questions?
beyene.dereje@ddu.edu.et
