1. Antidiabetic drugs

Question 1

definition: diabetes

Answer 1

chronic metabolic disorder characterised by high blood glucose concentration caused by: deficient secretion of insulin and/or insulin resistance.

Question 2

Type 1 diabetes

Answer 2

Autoimmune disorder (coxsackie virus trigger) where autoantibodies against Beta cells are produced. Insulin dependent (insulin producing cells destroyed).

Question 3

Type 2 diabetes

Answer 3

unknown cause. Insulin resistance or deficient secretion. Non insulin dependent. includes gestational diabetes and maturity onset diabetes of youth (MODY) in obese adolescents/children.

Question 4

How diet affects glucose

Answer 4

Foods we eat are broken down in the GIT to glucose. After a meal blood glucose levels rise and B cells in the pancreas start to secrete insulin. Insulin is a peptide hormone and stimulates the uptake of glucose, breaks it down and produces ATP to fuel the body.
When blood glucose levels drop, the pancreas releases glucagon causing breakdown of stored glycogen in the liver into glucose which is then released into the blood stream.

Question 5

insulin resistance characteristics (4)

Answer 5

abnormal insulin
mutation on insulin receptor
decreased number of receptors
decreased binding of insulin

Question 6

Diabetes symptoms (6)

Answer 6

hyperglycaemia (high blood sugar)
glycosuria (glucose in urine) 
polyuria (lots of urine)
polydipsia (excessive thirst)
polyphagia (excessive hunger) 
ketoacidosis

Question 7

Ketoacidosis

Answer 7

without insulin glucose cant enter a cell. Instead, energy is provided by the breakdown of fat and protein producing ketone bodies.
Loss of electrolytes (Na, K, Cl) through the urine.
Coma, depression

Question 8

MICROvascular complications of diabetes

Answer 8

• Eye: high blood glucose and bp damage blood vessels causing retinopathy, cataracts, glaucoma.
• kidney: high bp damages small blood vessels and excess blood glucose overworks kidneys–> nephropathy
• Neuropathy: hyperglycaemia damages nerves in PNS–> pain, numbness, foot wounds etc.

Question 9

MACROvascular complications of diabetes

Answer 9

• brain: increased risk of stroke, cerebrovascular disease, ischemic attack.
• heart: high bp and insulin resistances increases risk of coronary heart disease.
• extremities: narrowing of blood vessels, reduced blood flow in legs. feet wounds heal slowly.

Question 10

Pathology and treatment

Answer 10

Type 1: pathology: destruction of B cells and lack of insulin production. Treatment: insulin analogues.
Type 2: pathology: insulin resistance and impaired secretion. Treatment: diet intervention, oral& subcutaneous drug injections, 1/3 require insulin.

Question 11

Insulin analogues

Answer 11

obtained by recombinant DNA technology.
Given by injection as GIT will destroy it.
Treats type 1 diabetes and gestational diabetes.
A.E: hypoglycaemia, weight gain, allergic reactions, lipodystrophy.

Question 12

Sulfonylureas

Answer 12

GLI-IDE (glibenclamide, glipizide)
oral. type 2
M.O.A: block ATP sensitive K channels on B cell membrane accelerating depolarisation. Depolarisation activates Ca channels stimulating exocytosis of insulin increasing basal and food stimulated insulin release.
Requires functional B cells.
Active metabolite excreted in urine (action increased in elderly and renal disease). Strongly binds to plasma albumin competing with NSAIDS for binding sites.
A.E: hypoglycaemia, weight gain, X pregnancy/breastfeeding.

Question 13

Biguanides

Answer 13

Metformin (oral)
Type 2 and PCOS
M.O.A: inhibits genes important for gluconeogenesis, increases glucose uptake and utilisation in skeletal muscle reducing insulin resistance. Reduces carb absorption and LDL and VLDL levels.
Doesn’t cause hypoglycaemia and doesn’t bind to plasma proteins. Undergoes renal excretion.
A.E: Gastrointestinal: metallic taste, mild anorexia, nausea, abdo discomfort, diarrhea. VitB12 deficiency, rare lactic acidosis.

Question 14

Thiazolidinediones

Answer 14

GLITAZONES
M.O.A: increases insulin sensitivity by binding to PPARy (ligand activated transcription factor involved in expression of genes affecting metabolic processes e.g. lipid and glucose homeostasis).
Increases glucose uptake and utilisation in skeletal muscle and reduces hepatic glucose production.

Question 15

Importance of glitazones

Answer 15

action is mediated by PPARY involving redistribution of surplus fatty acid to peripheral fat reducing fatty acid availability in circulation, liver and muscle improving insulin sensitivity.
Adipocyte differentiation and proliferation (rapid increase)in peripheral fat mass.
Results in weight gain, edema, increased fracture risk.

Question 16

incretin hormones

Answer 16

secreted from gut in response to food ingestion and stimulate pancreas to produce more insulin. 
* GLP-1 
* GIP
Stimulate glucose dependent insulin release 
supress glucagon release 
enhance b cell proliferation/survival 
delay gastric emptying 
cleared by DPP4

Question 17

Liraglutide & Exenatide

Answer 17

GLP -1 AGONISTS 
mimics effects of GLP1 
resistant to DPP4 inactivation 
increase insulin secretion, suppress glucagon secretion, delay gastric emptying reducing food intake. 
Injection.Treats diabetes and obesity.

Question 18

Gliptins

Answer 18

DPP4 inhibitors.
extend production of GLP-1 and GIP.
weight neutral, no hypoglycaemia
A.E: upper respiratory infection, pancreatitis.

Question 19

SGLT2 Sodium glucose co transporter 2 inhibitors

Answer 19

PAGLIFOZIN
inhibit SGLT2 reducing glucose reabsorption in kidney and increasing its excretion in urine.
A.E: low hypoglycaemia monotheraphy. Increased hypoglycaemia with insulin theraphy.
Genital and urinary tract infections as bacteria feed on glucose. dehydration