Pharmacy notes lesson, Summaries of Pharmacology

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ANTIDIABETIC DRUGS

REAGAN KABUKA (Bpharm, MPH)

DIABETES MELITUS

DM is a metabolic disorder characterized by chronic Hyperglycaemia due to absolute or relative lack of insulin or due to insufficient insulin activity

CAUSES OF DM

• Primary DM; IDDM; destruction of beta cells (autoimmune) NIDDM; Insulin resistance or insufficient insulin release
• Secondary DM;  due to either pancreatic, Hormonal disease (e.g. Cushing syndrome, acromegaly, Pheochromocytoma, Gestation (pregnancy induced) or drug induced

PATHOGENESIS

IDDM

• Auto immune antibodies are formed against the islets of Langerhans cells causing destruction of B-cells, thereby resulting into loss of insulin production.
• Drugs that suppress the immunity like cyclosporine may preserve the beta cells.
• This type is usually common in young people <30 years.

SIGNS AND SYMPTOMS

Tiredness Hyperglycaemia Frequent urination Increased thirst Blurred vision Weight loss Dehydration

MANAGEMENT OF DM

• TREATMENT GOALS FOR DM

To achieve near normal glycaemia. Minimise the occurrence of hyperglycaemia and hypoglycemia To reduce the risk for microvascular and macrovascular disease complications To improve symptoms, reduce mortality, and to improve quality of life.

INSULIN

• Insulin is secreted from the B-cells in the islets of langerhans of the pancrease
• Insulin is usually injected into the upper arms, thighs, buttocks, or abdomen
• Generally as subcutaneous insulin injections
• Fat hypertrophy occurs with this ROA, however, occur but can be minimised by using different injection sites in rotation
• Local allergic reactions are rare

Mechanism of insulin

• Insulin binds to a specific receptor consisting of two alpha and two beta subunits.
• The alpha subunits are extracellular and carry the insulin-binding site.
• The beta subunits span the cell membrane, its intracellular end has tyrosine kinase.
• Binding of insulin results in autophosphorylation of the tyrosine kinase. This causes activation of intracellular protein kinase affecting different metabolic enzymes e.g. phosphorylase, lipase
• The number of insulin receptors is increased by exercise and loss of weight
• The number of insulin receptors is decreased by excess insulin (down regulation), obesity and growth hormone
• The affinity of insulin to its receptors is decreased by glucocorticoid and oral contraceptives

INTERMEDIATE ACTING INSULIN;

• Onset 2 hours, duration 12 hours
• E.g. Natural protamine Hagedorn (NHP) LONG ACTING INSULIN
• Onset 3hours, duration 14-36hours
• E.g. Glargine, Detemir

INSULIN DOSING AND REGIMENS

• **Total Daily Insulin requirement (TDI) =0.55units/ kg

1. ONCE DAILY REGIMEN**

• Intermediate acting insulin with or without short acting insulin – once a day at breakfast

Indication

• IDDM

• DKA

• NIDDM after failure of diet control and full doses of sulphonylureas
• DM during pregnancy and lactation
• Treatment of hyperkalaemia
• Patients with severe renal or hepatic disease

Side effects

• Hypoglycaemia
• Insulin Allergy
• Redness, swelling and itching at the site of injection

Signs and Symptoms

• Polyuria
• Vomiting
• Abdominal pain
• Dehydration
• Hyperventilation
• Coma

Treatment of DKA

• Adequate Fluid replacement (3-5L) isotonic saline
• 5% glucose if the BG drops to 14mmol/L to avoid brain damage
• Insulin therapy continuous IV infusion 0.15units/kg/hour. Reduce to half when the blood glucose levels reduce to 14mmol/L
• Potassium replacement , if normal potassium levels, give 20mmol/L, if there is hypokalaemia give 40mmol/L
• Bicarbonate therapy is indicated in severe acidosis (pH< 7.1) and should be stopped when pH reaches 7.2.