Clinical Pharmacology Flashcards
What is the mechanism of action of metformin?
- Lowers blood glucose by increasing the response (sensitivity) to insulin
- Suppresses hepatic glucose production (glycogenolysis and gluconeogenesis),
- Increases glucose uptake and utilisation by skeletal muscle
- Suppresses intestinal glucose absorption.
- It reduces weight gain and can induce weight loss, which can prevent worsening of insulin resistance and slow deterioration of diabetes mellitus.
Why does metformin cause lactic acidosis?
Inhibits lactic acid uptake by liver
What are contraindications to metformin use?
- General anaesthesia - should be withheld on the day of surgery
- Intra-venous contrast x-rays - should be withheld for at least 2 days
- AKI/eGFR < 36
- Illness
What are adverse effects of metformin use?
- GI upset - diarrhoea, vomiting, abdo pain
- Lactic acidosis
- B12 malabsorption
When would you consider not giving someone metformin?
eGFR < 36 ml/min - risk of lactic acidosis
What is the mechanism of action of sulphonylureas?
Sulfonylureas act by increasing insulin secretion from pancreatic islet cells. In order for them to be effective, there must be some residual insulin secretion.
What are the contraindications (absolute and relative) for sulphonyurea use?
- Acute porphyria
- Renal impairment
- Hepatic impairment
- Pregnancy and breast feeding
- Elderly (avoid long acting sulfonylureas)
What are the main side effects of sulphonylureas?
- Hypoglycaemia
- Weight gain
- Gastro-intestinal upset
- Hepatic impairment
- Hypersensitivity reaction (rash, liver disease)
- Rarely haematological abnormalities - agranulocytosis
When (during the course of a day) should sulphonylureas be given?
Before meals - Absorption may be postponed by eating
What is the mechanism of action of DPP-4 inhibitors?
Inhibition of DPP-4 activity causes an increase in incretin hormones GLP-1 (glucagon-like peptide 1) and GIP (glucose-dependent insulinotropic polypeptide). This increases glucose dependent insulin secretion and reduces glucagon secretion.
What are examples of sulphonylureas?
- Gliclazide
- Glimepiride
- Glipizide
What are example of DPP-4 inhibitors?
- Sitagliptin
- Vildagliptin
What are contraindications (absolute and relative) to DPP-4 inhibitors?
- Pregnancy / breast feeding
- Elderly
- Renal impairment
- Hepatic impairment
What are adverse reactions to DPP-4 inhibitors?
- Gastrointestinal upset
- Oedema
- Hepatic toxicity (vildagliptin)
- Pancreatitis
- Upper respiratory tract infection / nasopharyngitis
- Stevens-Johnson syndrome
Can cause hypoglycaemia.
What is the mechanism of action of GLP-1 agonists?
GLP-1 agonists act by mimicking the action of GLP-1, which causes increased insulin secretion, reduced glucagon secretion and slows gastric emptying.
What is the mechanism of action of SGLT-2 antagonists?
SGLT-2 is primarily responsible for mediating glucose reabsorption in the kidneys, and is expressed in on the epithelial cells lining the first segment of the proximal convoluted tubule. It promotes approximately 90% of the kidney’s glucose reabsorption.
By inhibiting SGLT-2, the kidneys’ reuptake of glucose from the glomerular filtrate is reduced and subsequently lower the glucose level in the blood and promote the excretion of glucose in the urine (glucosuria)
