SBI242 Week 9 - Pharmacology of the Endocrine System

What are the exocrine functions of the pancreas?

Production of digestive enzymes and bicarbonate

What are the endocrine functions of the pancreas?

Production of insulin and glucagon

How is insulin synthesized?

As a preprohormone that is converted to proinsulin and then insulin

How is insulin released?

From the beta cells of the pancreas in response to increased blood glucose levels

What stimulates insulin secretion?

High blood glucose levels, amino acids, and gastrointestinal hormones like GLP-1

What inhibits insulin release?

Low blood glucose levels, fasting, somatostatin, adrenaline (via α2-receptors), and thiazide diuretics

Why must insulin be administered parenterally?

Because it is a protein that would be digested in the gastrointestinal tract if taken orally

How does insulin work?

Binding to receptors on muscle and adipose cells, stimulating glucose uptake

How is insulin's action inhibited?

Physiologically inhibited by the catabolic hormones – adrenocorticotrophic hormone (ACTH), glucocorticoids, adrenaline, growth hormone (GH) and thyroxine

What is glucagon?

A hormone produced by the pancreas that raises blood glucose levels

What are incretins?

Hormones released from the gut in response to food intake that enhance insulin secretion

What is diabetes mellitus?

A group of metabolic disorders characterized by high blood glucose levels

What is Type 1 diabetes?

An autoimmune disease causing insulin deficiency due to pancreatic beta-cell destruction

What is Type 2 diabetes?

A condition characterized by insulin resistance and impaired insulin secretion

What is glycosuria?

Excess glucose secreted by the kidneys

What are some signs and symptoms of diabetes?

Polyuria, polydipsia, polyphagia, weight loss

How is diabetes diagnosed?

By signs and symptoms; measurement of high BGL (casual >11.1 mmol/L, fasting >7.0 mmol/L), by glucose tolerance testing after overnight fasting; and/or by glycated haemoglobin levels

What are the early symptoms of hypoglycaemia?

Shakiness, sweating, hunger, dizziness, palpitations, and confusion

What is ketoacidosis?

In T1DM, high breakdown of proteins and fats causes ketone bodies to accumulate, resulting in ketosis and acidosis

How do untreated diabetes progress?

Developing complications such as cardiovascular disease, nephropathy, neuropathy, and retinopathy

What is metabolic syndrome?

A cluster of conditions including central obesity, hypertension, dyslipidemia, and insulin resistance

What are the general aims of diabetes treatment?

Controlling blood glucose levels, preventing complications, and improving quality of life

What is Metformin?

A biguanide oral medication used to treat type 2 diabetes indicated for the treatment of uncomplicated type 2 diabetes when diabetes is not controlled by diet and exercise

How do sulfonylureas work?

Bind to receptors and block ATP-sensitive potassium channels (K-ATP), blocking potassium efflux and causing cell depolarisation, calcium entry and insulin secretion from pancreatic beta cells

How do thiazolidinediones (glitazones) work?

Activating peroxisome proliferator-activated receptor gamma (PPAR-γ), that regulates gene transcription especially in adipocytes, reducing insulin resistance

How do incretin-mimetics (GLP-1 analogues) work?

Mimicking the action of glucagon-like peptide-1 (GLP-1), stimulating insulin release

How do incretin-enhancers (DPP-4 inhibitors, gliptins) work?

Inhibiting dipeptidyl peptidase-4 (DPP-4) enzyme, the enzyme that inactivates GLP-1 and GIP; thus, enhancing release of insulin

How does acarbose act?

Inhibiting alpha-glucosidases in the intestine, delaying digestion and absorption of carbohydrates in the small intestine, reducing glucose load

How do SGLT-2 inhibitors act?

Inhibiting glucose reabsorption in the kidneys

What are some glucocorticoid drugs?

Prednisolone, hydrocortisone, betamethasone, dexamethasone

What are the anti-inflammatory actions of glucocorticoids?

Glucocorticoids act by binding to intracellular receptors which then act to modulate gene transcription in target tissues. They stabilise lysosomal membranes and prevent movement of neutrophils and release of proteolytic enzymes during inflammation

What are the therapeutic uses of glucocorticoids?

Replacement therapy (physiological doses) for Addison’s disease (adrenal insufficiency), and in non-endocrine disorders (pharmacological doses) for excessive or inappropriate inflammatory or immune response, severe allergy, asthma, graft rejection, gout, and rheumatoid arthritis

What are potential adverse effects of glucocorticoids?

All of the above

What are some thyroid disorders?

All of the above

What is produced by parafollicular (C) cells in the thyroid?

Calcitonin

What are T4 and T3 essential for?

Regulating metabolism and energy production

How do thyroid hormones affect Thyroid-Stimulating Hormone (TSH) levels?

C) Both A and B

What are stable formulations for synthetic thyroid hormones?

A) Levothyroxine (T4) tablets and liothyronine (T3) tablets

What are some examples of thioureylenes?

Carbimazole and propylthiouracil

How can amiodarone lead to thyroid dysfunction?

D) Both A and B

Which cells in the pancreas produce insulin?

Beta cells

Which of the following inhibits the release of insulin:

Somatostatin

Which of the following is NOT a sign and symptom of diabetes?

Reduced appetite

Complications of diabetes include all of the following EXCEPT:

Asthma

Which of the following drugs can cause hypoglycaemia?

ACE inhibitors

Which of the following is a sign/symptom of hypoglycaemia:

Cold sweats and confusion

Which of the following is NOT a component of ‘metabolic syndrome’:

High high-density lipoprotein cholesterol level

Metformin is a biguanide oral hypoglycaemic agent. Which of the following is NOT one of its functions?

Reduce the number of insulin receptors

What is the mechanism of action sulfonylureas in the treatment of type 2 diabetes?

Block ATP-sensitive potassium channels (K-ATP), causing increased insulin secretion
from pancreatic beta cells

Which of the following is NOT a typical adverse reaction of Thiazolidinediones?

Weight loss

Dapagliflozin is a selective, reversible inhibitor of the sodium-glucose co-transporter 2 (SGLT2) which reabsorbs glucose in the renal tubules. Thus, it increases the renal excretion of glucose. One of its consequential adverse effects is:

Hypovolaemia

Many adverse reactions are associated with overuse of corticosteroids. Which of the following adverse reactions is NOT associated with corticosteroids?

Improved wound healing

What is one of the main functions of the thyroid hormone?

Regulates carbohydrate, lipid and protein metabolism

High levels of circulating TSH in the blood indicate:

Underproduction of thyroid hormone

Clinical signs and symptoms of hyperthyroidism include:

Swelling/fullness in the neck (goitre)

The main indication for the thyroid medication Thyroxine is to treat:

Hypothyroidism

A patient is taking both insulin (type 1 diabetic) and an ACE inhibitor for high blood pressure. What would be a concern?

Risk of hypoglycaemia

Which of the following drugs can cause hyperglycaemia?

Glucocorticosteroids

Why is carvedilol contraindicated for patients with severe asthma?

Beta blockers inhibit beta 2 receptors in the bronchiole causing bronchoconstriction

A 35-year-old female presents to her doctor with lethargy, lack of energy, excessive sleeping patterns and extreme chronic tiredness. Her doctor orders a full blood examination and notices that she had high levels of circulating TSH in the blood. High levels of TSH indicate:

Underproduction of thyroid hormone

A 55-year-old male patient is currently being treated for several medical conditions and is taking several different medications. He recently experienced an episode of hypoglycaemia. Which of the following drugs can cause hypoglycaemia?

ACE Inhibitors

A 50-year-old female patient is currently taking an oral hypoglycaemic medication for her diabetes. She is also taking a corticosteroid medication at the same time for a different medical condition. What would the doctor need to consider in regards to the dose of the oral hypoglycaemic agent?

Increase the dose

Where are corticosteroids produced?

Adrenal cortex

ACTH (adrenocorticotropic hormone):

Stimulates secretion of hormones by adrenal cortex

CRH (corticotropin releasing hormone):

Stimulates release of ACTH

Corticosteroids:

A group of hormones, including cortisol, released by the adrenal glands at times of stress

Mineralcorticoids (aldosterone):

Promote sodium retention and potassium excretion

Glucocorticoids (cortisol):

Have potent anti-inflammatory and immunosuppressive effects

Aldosterone:

Regulates electrolyte balance and fluid status

Insulin:

Lowers blood glucose levels

Glucagon:

Raises blood glucose levels

TRH (Thyrotropin releasing hormone):

Stimulates the anterior pituitary gland to release TSH

TSH (Thyroid-stimulating hormone):

Stimulates the thyroid gland to produce thyroid hormones (T3 and T4)

T4 (Thyroxine):

Consists of two tyrosine molecules with four bound iodine atoms and Is converted to T3 in peripheral tissues

T3 (Triiodothyronine):

Consists of one tyrosine molecule with three bound iodine atoms and is the more active form of thyroid hormone, regulating BMR

Calcitonin:

Lowers blood calcium levels

Amylase:

Is an enzyme that breaks down carbohydrates

Proteases:

Break down proteins into amino acids

Lipases:

Break down fats into fatty acids and glycerol

Somatostatin:

Inhibits the release of growth hormone and other hormones

Disulfide bridges:

Are covalent bonds between amino acids in a protein

Polypeptide chains:

Long sequences of amino acids linked by peptide bonds that form proteins

Glycerols:

Three-carbon molecules that serve as the backbone for triglycerides and phospholipids

Incretins:

Hormones produced in the GIT that stimulate insulin secretion

Addison’s disease:

Is characterized by insufficient production of cortisol and aldosterone

Gout:

Is a type of arthritis caused by increased uric acid levels

Cushing syndrome:

Is caused by an excess of cortisol

What is the hypothalamus-pituitary-adrenal (HPA) axis?

A sequence of hormone sectretions starting in the hypothalamus

Thyroxine:

Increases systemic metabolism and produced by follicle glands in the thyroid

Thioureylenes:

A class of anti-hyperthyroid drugs that inhibit the production of thyroid hormones by blocking the incorporation of iodine

Radioiodine:

An oral anti-hyperthyroid drug that gradually shrinks the thyroid