Pharmacology of hormones

1. DIABETES MELLITUS

2. DEFINITION
• Diabetes is defined as a group of metabolic disorders as a result of the pancreas’
inability to produce insulin.
• Insulin is produced by the beta cells in the Islet of Langerhans in the pancreas.
• It is a hormone that’s used to metabolize glucose to be utilized by the different
organs in the body.
• It therefore results in high blood sugar (high blood glucose).

3. CLASSIFICATION
• Diabetes mellitus (DM) is classified into groups:
1) Type 1/ Insulin Dependent Diabetes Mellitus (IDDM)- This is an auto-immune
disease whereby the beta cells are destroyed by antibodies resulting in no insulin
production. Also known us Juvenile Onset Diabetes Mellitus. It is known as
juvenile for it mostly affects young people. These patients need insulin (IV or SC)
all their life.

4. CLASSIFICATION
2) Type 2/Non Insulin Dependent Diabetes Mellitus (NIDDM)
• This is whereby the beta cells become resistant to glucose presence in the body
resulting in little or inadequate insulin production.
• Also known as Adult Onset Diabetes Mellitus.
• It is mostly characterized by obesity in most patients, also risk factors include:
sedentary lifestyle, bad nutrition, alcoholism, smoking.
• Some patients require insulin, while others use different drugs including
secretagogues and insulin sensitizers.

5. CLASSIFICATION
3) Gestational Diabetes
• A condition by which a pregnant woman who was not previously diabetic is
diagnosed with diabetes, especially in the third trisemester. More often than not, the
gestational diabetes usually resolves after giving birth.

6. CARDINAL CLINICAL PRESENTAIONS
• Also known 3P’s :
1) Polyuria- Excessive urination.
2) Polydipsia- Excessive thirst and wanting to drink fluids
3) Polyphagia- Excessive eating.

7. SIGNS AND SYMPTOMS
1. Sweet smelling urine- Glucose is excreted in urine.
2. Weight gain.
3. Blurred vision
4. At times, diabetic coma.
5. Fatigue
6. Slow healing of wounds

8. RISK FACTORS
• Genetic disposition (Family History)
• Obesity
• Alcoholism
• Smoking
• Sedentary lifestyle

9. BLOOD GLUCOSE PARAMETERS

10. BLOOD SUGAR PARAMETERS

11. LAB INVESTIGATIONS
1. Fasting Blood Sugar (FBS)- Sugar levels are tested approximately 8 hours after a
meal, for by this time someone is hungry. Normal parameters : 4-5mmol/L
2. Random Blood Sugar (RBS)- Sugar levels are tested there and then and they are
expected to be within the normal parameters. Normal parameters:2.2-7.8 mmol/L
Oral Glucose Tolerance Test (OGTT)- A standard dose of glucose is administered
orally then blood glucose is measured 2 hours later. 7.8 mmol/L and below.
3. Glycated Haemoglobin (HbA1c)- Percentage of glucose found on haemoglobin.
Normal parameters: less than 6%

12. MANAGEMENT
1) NON-PHARMACOLOGICAL MANAGEMENT.
1.1 Patient Education
• This is the most important step. This includes:
 Drug compliance
 Clinic visits
 Diet and Nutrition
 Smoking cessation
 Alcohol Cessation
 Exercise

17. MANAGEMENT
2) PHARMACOLOGICAL MANAGEMENT
2.1 Insulin
• Used in all diabetic classes, but mostly with Type 1 and gestational diabetics. It has the
common side effects:
• hypoglycaemia
• weight gain because of its anabolic activity.
• Cause local reactions at site of injection- Patient advised to rotate sites of injection
• There are currently 3 types of insulin depending on their onset of action:
2.1.1 Rapid acting- Regular insulin, Insulin Lispro
2.1.2 Intermediate acting- Insulin zinc, Neutral Protamine Hagedorn (NPH)
2.1.3 Long acting– Insulin determir, Insulin glargine

18. INSULIN
• All patients require insulin and it’s administered either intravenously or
subcutaneously.
• The usual dosing is approximately 0.6 units/kg/day.
• Range lies between 0.5-1.0units/kg/day.
• For twice daily dosing it’s divided as 2/3 of total dose in the morning and 1/3 of total
dose in the evening.
• Advise patients on hypoglycaemia.

19. INSULIN COMBINATIONS
• In ways to make insulin more effective, different types of insulin are combined in an
attempt to mimic the pancreatic response upon introduction of glucose in the
bloodstream.
• Examples include:
• Insulin lispro protamine + insulin lispro= Humalog Mix 75/25®
• Human insulin NPH + Human insulin = Humulin 70/30®
• Insulin aspart protamine+ Insulin aspart= NovoMix Flexpen 70/30®
• Insulin Glargin- Lantus Solostar®
• Insulin Aspart - Flexpen®

20. MANAGEMENT
2.2 Insulin sensitizers
• Commonly used in Type 2 DM for they deal with insulin resistance.
2.2.1 Biguanides
• Prototype: Metformin (Glucophage®)
• First line in Type 2 DM.
• Prevents hepatic gluconeogenesis and promotes glucose uptake in the periphery and skeletal muscles.
• Side Effects:
• lactic acidosis.
• GI disturbances(nausea,vomiting,flatulence)
• Vitamin B12 defeciency
• NB: Off-label use for infertility for it induces ovulation.
• Dosage: 500mg-1gm BD
• Maximum dose- 3gm BD
• Maximum toelarble dose is 2gm BD

21. METFORMIN
• Drug-Drug Indications
1. H2-receptor antagonists- Cimetidine,Ranitidine
• Contraindications
1. Renal failure
2. Congestive Heart Failure

22. MANAGEMENT
2.2.2 Thiazolidinediones
• Prototype: Pioglitazone, Rosiglitazone
• They bind to Peroxisome Proliferated Activated Receptor-𝛾 and reduce glucose and
fatty acid blood concentrations.
• Side effects:
• Hepatotoxicity,
• bone fractures,
• weight gain.

23. MANAGEMENT
2.3 Secretagogues
• They increase insulin output from the pancreas.
2.3.1 Sulfonylureas (SURs)
• They bind to the Sulfonylurea Receptors(SURs) on the beta cells of the pancreas,
causing depolarization due to closure of the ATP sensitive K+ channels leading to an
increase in voltage results in voltage-gated Ca++ channels to open, promoting Ca++
influx resulting in insulin being released form the granules via exocytosis.

24. SULFONYLUREAS
• They are categorized in 3 generations:
1. 1st Generation- Chlorpropaminde, Tolbutamide
2. 2nd Generation-Glibenclamide, Gliclazide,
3. 3rd Generation- Glimepiride
• The 1st generation drugs were phased out due to lack of potency and short duration of
action.
• Glibenclamide (Nogluc®) usual dose is 5mg OD, but can be adjusted between 2.5 mg-
10mg OD.
• Glmepiride (Amaryl®) starting dose is between 1-2 mg OD maximum dose is 4mg OD

25. SULFONYLUREAS
• Side Effects
1. Hypoglycaemia
2. Weight gain
3. Hypersensitivity Reactions(sulfur)
4. Disulfiram-like reactions( alcohol)
5. Hepatotoxicity

26. SULFONYLUREAS
• Drug-Drug Interactions
1. Drugs that potentiate hypoglycaemic effect- alcohol,fluoroquinolones,
sympatholytics,lithium.
2. Drugs that potentiate hyperglycaemic effect- oral
contraceptives,thiazides,corticosteroids.
3. Drugs that decrease SUR efficacy- rifampicin,H2 antagonists

27. SECRETAGOGUES
2.3.2 Meglitinides
• They are non-SURs that have the same Mechanism of Action as SURs. They
promote release of insulin from the pancreatic beta cells by binding to the Sulfonyl
urea receptors.
• Unlike SURs, they have a rapid onset of action ,though short duration of action.
• Examples: repaglinide(NovoNorm®),nateglinide.

28. MEGLITINIDES
• Side Effects
1. Weight gain
2. Hypoglycaemia
• Contraindications
1. Azole antifungals
2. Clarithromycin
3. Gemifibrozil

29. MANAGEMENT
2.4 Incretinomimetics
• Incretins are gastric hormones produced by the small intestine in response to food.
• Promotes insulin secretion. In diabetics there is reduced incretin secretion.
• The intrinsic incretin is Glucagon like Peptide 1,which is metabolized by Dipeptidyl
peptidase 4 enzyme and has a short half life of about 10 minutes.

30. INCRETINOMIMETICS
• There are two types of incretinomimetics:
2.4.1 Glucagon Like Peptide 1(GLP1) analogs- Examples: exenatide,liraglutide.
• Resistant to DPP4.
• Has a long half life of approx. 10 hours.
• Administered twice a day subcutaneously.
• Decreses gastric motility and emptying.
• Inhibits apoptosis of beta cells.

31. MOA OF INCRETINOMIMETICS

32. INCRETINOMIMETICS
• Side effects
1. Causes pruritis at injection site
2. Causes nausea and vomiting
3. Causes hyperhidrosis
4. Severe anorexia
5. Dizziness and headache
• Contraindications
• Patients on insulin

33. INCRETINOMIMETICS
2.4.2 Dipeptidyl Peptidase 4 Inhibitors
• They inhibit the enzymes that degrade the incretins and their analogs.
• Examples: vitaligliptin,saxagliptin,sitaligliptin.
• Have become quite popular in the market because:
1. Associated with a lower risk of hypoglycaemia
2. Increases generation of beta cells
• Side effects:
1. Increased rates of infection.
2. Hypersensitivity reactions.

34. SODIUM GLUCOSE CO-TRANSPORTER 2
INHIBITORS
• Inhibition of SGLT2 results in excretion of both sodium and glucose from the body.
• Examples: Dapaglifozin, Canagliflozin, Empagliflozin.
• Doesn’t cause hypoglycaemia for it’s mechanism of action is insulin independent.
• Side effects:
• Hypotension
• Stroke-canagliflozin
• Glycosuria

35. MOA OF SGLT 2 INHIBITORS

36. ALPHA GLUCOSIDASE INHIBITORS
• Two drugs in this group: acarbose and miglitol.
• They are not so considered due to their notorious side effects: flatulence and
bloating.
• Also not so effective in achieving hyperglycaemia on their own.

37. COMPLICATIONS
• If diabetes is not managed appropriately the following can take place:
1. Diabetic Ketoacidosis
• A dangerous metabolic compensation by the liver in the event of low insulin levels,
to convert fatty acid to ketone bodies and if prolonged leads to a change in pH
causing Diabetic Ketoacidosis, quite expected in Type 1 DM and in non-compliant
Type 2 DM patients.
• Management: Rehydrate with 6L of Normal saline in 24 hours, then Potassium
Chloride (KCL).

38. COMPLICATIONS
2) Hypoglycaemia
• As a result of the diabetic medications. Oral dextrose is to be administered
immediately.
3) Hyperosmolar Non Ketotic State (HONK)
• Due to high glucose concentration in the blood stream, water is drawn out of the
cells due to osmosis. This leads to dehydration and electrolyte imbalances.
Rehydration orally or intravenously should be done immediately.

39. COMPLICATIONS
4) Microangiopathy
4.1 Diabetic retinopathy – Accumulation of glucose in the eye blood vessels leads to blurry
to complete loss of vision.
4.2 Diabetic neuropathy-The nerves taken excess glucose causing abnormally thicker
basement membranes and walls of nerves, resulting in loss of sensitivity, which more often
than not will result in diabetic foot (gangrenous foot) because of wounds that won’t heal
and loss of sensation in the feet.
4.3 Erectile dysfunction- The blood vessels in the penile area get damaged and loose
elasticity resulting in erectile dysfunction.
4.4 diabetic nephropathy- The kidneys also get glomerular damage resulting in glycosuria
and proteinuria. The patients need dialysis to assist the kidney in doing its job.

40. COMPLICATIONS
5. Macroangiopathy
5.1 Coronary Artery Disease
5.2 Gangerenous foot(Diabetic foot)
5.3 Stroke
5.4 Female infertility

41. THANK YOU!!