Pharmacology Flashcards
List the drugs which are dependent on insulin?
Increase insulin secretion
sulfonylureas
Incretin analogues
Glinides
DPP-4 inhibitors
List the drugs which are dependent on insulin?
Decrease insulin resistance
Biuanide
(Glitazones) Thiazolinediomes
List the drugs which are independent of insulin?
Slow Glucose absorption
alpha glucoside inhibitors
List the drugs which are independent of insulin?
Enhance glucose excretion
Sodium Glucose Transporter Type 2 Inhibitor
SGLT2 inhibitor
Name some sulfonylureas
Tolbutamide
Glibenclamide
Gliclazide
Glipizide
How do sulfonylureas function?
Bind to SUR1 subunit
Close KATP channels
Increase Ca2+ entry
Increase Insulin secretion
What is the issue with sulfonylureas?
Require functional B cells in order to work
Only type II
Short Acting Sulfonylureas
Tolbutamide ( large dosage is required)
Gliclazide
Long Acting sulfonylureas
Glibenclamide
Gliplizide
Positives of sulfonylureas
Well absorbed orally
Reduce microvascular damage
Negatives of sulfonylureas
Risk of hypoglycaemia
Unwanted weight gain
Increased appetite
When should sulfonyureas never be used?
Renal impairment
Pregnancy - crosses placenta
Breastfeeding
Elderly
When are sulfonylureas 1st line?
If intolerant to metformin
If patient has lost weight
Can sulfonylureas be used in combination?
Used with metformin second line
Glinides mode of action
Similar to sulfonylureas
Close KATP channels
Increase Ca2+ levels
Secreting insulin
Name some glinides
Repaglinide
Nateglinide
Benefits of glinides over sulfonylureas
Less likely to cause hypoglycaemia
Active orally
Safer for use in renal impairment as mainly subject to hepatic metabolism.
Negatives of glinide use
Active time is much shorter so must take more frequently
When should glinides not be used?
In hepatic impairment
Pregnancy
Breast feeding
What cells release GLP-1 and GIP?
Enteroendocrine cells in small intestine
L in ileum
K in duodenum
Effect of GLP-1 and GIP
Enhance insulin secretion and delay gastric emptying
Enhance glucose uptake by skeletal muscles
What does GLP-1 also do?
Decrease glucagon release from alpha cells
What triggers the release of GLP-1 and GIP?
Ingestion of food
Which molecule terminates GLP-1 and GIP?
DPP-4
Stops reduction in blood sugar levels
What is the function of DPP-4 inhibitors?
By inhibiting DPP-4 they maintain the incretin response and lower blood glucose levels and increase plasma insulin levels.
Name some DPP-4 inhibitors?
Sitagliptin
Saxagliptin
Alogliptin
Benefits of DPP-4 inhibitors
Can be used as a mono therapy
generally well tolerated
No hypoglycaemia
Orally active
What are the side effects of DPP-4 inhibitors?
Nausea
Incretin analogues
Mimic GLP-1 and GIP, acts as agonists at the receptors increasing intracellular cAMP
What do incretin analogues do?
Suppress glucagon release
Suppress gastric emptying
Decrease appetite
Increase glucose uptake by skeletal muscle
How are incretin analogues administered?
Subcutaneously
Some side effects of incretin analogues
Nausea
May rarely cause pancreatitis
Benefits of incretin analogues
Modest weight loss
No risk of hypoglycaemia
When are alpha glucosidase inhibitors used?
When lifestyles modification isn’t adequate
Rarely used
Function of alpha glucosidase inhibitors
Inhibit brush border enzyme that breaks down starch
Glucose isn’t absorbed
Side effects of alpha glucosidase inhibitors
GI flatulence nausea vomiting diarrhoea
When is metformin used?
First line irrespective of obesity
Function of metformin
Reduce hepatic gluconeogenesis
Stimulate AMP activated protein kinase
-GIP-1 is secreted
Increase glucose uptake by muscle
Benefits of metformin
Reduce microvascular changes Orally active Prevent hypoglycaemia Causes weight loss Can be used in combination
Side affects of metformin
GI upsets diarrhoea nausea anorexia
Can cause lactic acidosis - excessive alcohol can increase risk
When should metformin not be used?
Significant renal or hepatic disease
Glitazones (Thiazolidinediones) function
Promote transcription factor production which increases insulin secretion and signalling
Glitazones (Thiazolidinediones) mode of action
Promote fatty acid uptake an storage
Reduce hepatic glucose output
Enhance peripheral glucose uptake
Do Glitazones (Thiazolidinediones) increase risk of hypoglycaemia ?
No
Side affects of Glitazones (Thiazolidinediones)
Weight gain
Fluid retention
Risk of serious hepatotoxicity
Increase bone fractures
Sodium Glucose Cotransporter 2 inhibitor
Dagaglifozin
Empaglifozin
Sodium Glucose Cotransporter 2 inhibitor mode of action
Selectively blocks reabsorption of glucose from proximal tubule, more glucose is excreted into the urine.
Benefits of a Sodium Glucose Cotransporter 2 inhibitor
Reduced blood glucose with little hypoglycaemia risk
Calorific loss and water loss means weight loss
Which drugs have been shown to reduce CDV death?
GLP-I analogues
SGLT2i
Which GLP-I analogue has reduced CDV deaths swell as renal disease progression?
Liraglutide
Which SGLT2i has reduced CDV deaths as well as renal disease progression?
Empagliflozin
Which drug has been heavily criticised as it increased incidences of death on all accounts?
Rosiglitazon
Glitazones (Thiazolidinediones)
Cause maturation of adipose cells and shift weight away to the extremities.
SGLT2i what are 5-10% affected by?
Recurrent thrush and/or UTI
If a diabetic comes in with high blood pressure what is the medication of choice?
ACE or ARB
What should be given to anyone over 40 with diabetes?
Statin
Atorvastatin is
issues with metformin in renal failure?
Metformin doesn’t damage but does accumulate.
At what EGFR should metformin be removed?
30
Is Atorvastatin or simvastatin more potent?
Atorvastatin
SGLT2i in type I diabetes
There is no evidence to supports its use, it increases the risk of diabetic ketoacidosis so generally avoided.
Rapid acting insulin
Humalog
Novarapid
Apidra
Short acting insulin
Humulin B
Actrapid
Intermediate acting insulin
Isophane
Insulatard
Long acting insulin
Lantus Levemir
What isa rapid acting analogue intermediate mixture?
Basal bolus 2x daily
Humalog Mix 25/50 or Novomix 3
In order to use a basal bolus routine what is required?
A fixed routine of exercise at the same time each day and eating similar foods at similar times.
How does an insulin pump work>
Continuous subcutaneous administration of short acting insulin. Basal
Manually administer a bolus when calculated carbohydrate content of food.
What is the HbA1c of a non diabetic?
48mmol/ml
What is the ideal HbA1c target range of a long term diabetic?
53-58 mmol/ml
7-7.5 %
Name some factors which affect absorption of insulin
Temperature. Warmer = Faster
Injection site
Exercise
Adipose tissue. More = Slower
What should you check for at the injection site?
Lipohypertrophy
Why should injection sites be rotated?
As lipohypertrophy slows the rate of absorption down
