eLFH - Drugs used to treat Diabetes Mellitus Flashcards
Definition of diabetes mellitus
Chronic multisystem disease with dysregulation of plasma glucose control resulting in macrovascular and microvascular complications
Classification of diabetes mellitus
Type 1 - absolute insulin deficiency
Type 2 - insulin deficiency or resistance
Type 3 - drug induced
Type 4 - gestational diabetes
Diagnosis of diabetes
Insulin administration
SC or IV
Short, medium or long acting preparations
Functions increased by insulin
Glucose uptake into muscle and fat
Glycogen synthesis
Fat synthesis
Protein synthesis
K+ uptake by cells
Functions decreased by insulin
Fat breakdown
Ketone body synthesis
Glycogen breakdown
Gluconeogenesis
Protein breakdown
Sulphonylurea mechanism of action
Increases insulin release - displaces insulin bound to beta cells
Decreases peripheral insulin resistance
Decreases glucagon secretion
Decreases hepatic insulinase activity
Sulphonylurea use
Oral hypoglycaemic
Primarily used on T2DM
Sulphonylurea examples
Gliclazide
Glibenclamide
Sulphonylurea pharmacokinetics
80% oral bioavailability
Bound to albumin
Liver metabolism
Renal excretion
Half life 8 - 12 hours
Side effect of sulphonylureas
Hypoglycaemia
Drugs which inhibit effect of sulphonylureas
Thiazides
Corticosteroids
Phenothiazines (e.g. prochlorperazine, promethazine)
Biguanide structure
2 guanide rings
Biguanide mechanism of action
Decreases gluconeogenesis in liver
Increases peripheral insulin utilisation in skeletal muscle
Delays glucose uptake from gut
Biguanide example
Metformin
Biguanide use
Oral hypoglycaemic - doesn’t cause hypos
T2DM
Biguanide pharmacokinetics
60% oral bioavailability
Unbound
Excreted in urine unchanged - caution in renal failure
Side effect of biguanides
Lactic acidosis
Doesn’t cause hypoglycaemia alone as doesn’t increase insulin release
Thiazolidinedione example
Rosiglitazone
Thiazolidinedione mechanism of action
Regulates genes involved in glucose and lipid metabolism
Improves insulin sensitivity
Acarbose mechanism of action
Delays intestinal glucose absorption
Reduces post-prandial hyperglycaemia
SGLT2 (sodium glucose cotransporter 2) inhibitor example
Dapagliflozin
SGLT2 inhibitor mechanism of action
Inhibits glucose reabsorption in kidney
Side effects of SGLT2 inhibitors
Hypoglycaemia
Negative cardiac chronotropy and inotropy
Glycosuria leading to UTIs
DPP4 inhibitor examples
Sitagliptin
DPP4 inhibitor mechanism of action
Prevents breakdown of GIP and GLP1
Gastric inhibitory polypeptide
Glucagon like peptide 1
Action of GLP1
Endogenous hormone which:
- Decreases gastric emptying
- Improves insulin sensitivity
- Decreases inflammation
Action of GIP
Endogenous hormone which:
- Stimulates insulin secretion
- Promotes bone formation.
- Facilitates fat deposition
- Reduces inflammation
GLP1 receptor agonist examples
Dulaglutide
Exenatide
Semaglutide - aka Ozempic
Side effects of GLP1 receptor agonists
Delayed gastric emptying - nausea and vomiting
Weight loss
Anaesthetic precautions with GLP1 receptor agonists
Injectable once weekly examples have long half life so would need to be stopped a long time before surgery to reduce aspiration risk
HbA1c level cut off required for diabetic patients attending for purely elective surgery, above which surgery should be delayed
HbA1c must be < 69
Patient insulin pumps mechanism
Continuous short acting insulin infusion with feedback loop to sensor
Perioperative blood glucose target
6 - 10 aim
Slight buffer to avoid hypoglycaemia
Anaesthetic issue with diabetic patients
Higher aspiration risk due to autonomic dysfunction leading to delayed gastric emptying
Generally avoid using supraglottic airway
