Review of Pharmacology - 9E (2015)

Endocrinology
I 131 can be used for the treatment of hyperthyroidism but response is slow (maximum response
may take 3 months). Thyroid peroxidase inhibitors are administered to make the patient
euthyroid. After a gap of 5 days (after stopping anti-thyroid drugs), radioactive iodine
is given and thyroid peroxidase inhibitor treatment is resumed till the effect of I 131 starts.
Radioactive iodine therapy is primarily indicated for patients older than 35 years, those with
heart disease and in the presence of other contra-indications of surgery. These drugs are
not suitable for young children and in the pregnancy. Another disadvantage of radioactive
iodine is that if hypothyroidism develops, it is permanent (requiring life long T 4
therapy).
Coexisting ophthalmopathy is a relative contra-indication.
5. Drugs inhibiting the peripheral conversion of T 4
to T 3
Propanolol and propylthiouracil inhibits the generation of more active T 3
from T 4
by inhibiting
5’-deiodinase. These drugs therefore, can be used in the treatment of hyperthyroidism.
Amiodarone also inhibit this enzyme and thus can result in hypothyroidism.
6. Adjuvant Drugs
• β-blockers (propanolol, esmolol, atenolol) antagonize the sympathetic effects of
thyrotoxicosis like tremors, tachycardia, palpitations and anxiety.
• Calcium channel blockers like diltiazem can also be used for this purpose.
• Steroids (i.v. methylprednisolone) are used for Graves’s opthalmopathy. Latter can
be aggravated by I 131 and thiazolidinediones (like pioglitazone and rosiglitazone).
INSULIN AND ORAL HYPOGLYCEMIC AGENTS
Diabetes mellitus (DM) is diagnosed when fasting blood glucose exceeds 126 mg/dl
(or postprandial > 200 mg/dl or HbA 1c
> 6.5g%). Type I DM (IDDM) is treated only by
insulin whereas in the treatment of type II DM (NIDDM), orally active drugs are tried first
in uncomplicated cases. Insulin is used in all the patients of type I diabetes mellitus and
in the patients of type II diabetes who are not controlled with oral hypoglycemic agents
(OHA), in pregnancy, to tide over stressful situations (like surgery) and in complications (like
ketoacidosis and hyperosmolar coma).
Insulin
It was discovered by Banting and Best in 1921. It consists of 51 amino acids arranged in two
chains; A (21 amino acids) and B (30 amino acids). Pork insulin differs from human insulin
by one amino acid only whereas beef insulin has a difference of three amino acids. Half
life of insulin in plasma is about 5-6 minutes. Glucose is the main stimulus for the release of
insulin from the β cells of pancreas. Glucose stimulates GLUT-2 and inhibits ATP sensitive K +
channels; factors that are responsible for the depolarization of β cells and release of insulin. α 2
receptor stimulation inhibits insulin secretion whereas β 2
agonists and vagal stimulation
enhances insulin release. Somatostatin inhibits whereas glucagon stimulates the release of insulin.
Adrenergic system regulates insulin release via α 2
(decreases) and β 2
(increases) receptors.
Actions
α 2
receptor stimulation inhibits
insulin secretion whereas β 2
agonists and vagal stimulation
enhances insulin release.
General Endocrinology Pharmacology
1. It decreases blood glucose by
• Stimulating the entry of glucose in muscle and fat (by increasing the synthesis
of GLUT 4).
• Inhibiting glycogenolysis (by inhibiting phosphorylase) and gluconeogenesis
(by inhibiting phosphoenol pyruvate carboxykinase). These processes are
inhibited at lower concentration of insulin.
• Increasing glycolysis (by stimulation of glucokinase) and glycogenesis (by
stimulating glycogen synthase). These require more concentration of insulin.
2. It inhibits lipolysis and thus favors triglyceride deposition.
3. It increases the synthesis and inhibits the breakdown of proteins.
Advantage of rapid acting
insulins (lispro etc) is that
their duration of action remain
constant (~ 4 hours) irrespective
of dose. This contrasts with all
other insulins (including regular)
where duration of action is
prolonged with increase in dose
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