Metformin - Indication
Type 2 diabetes
Metformin - MOA
Metformin decreases hepatic production of glucose
it also increases uptake and utilisation of glucose by skeletal muscle via AMP kinase
Thus lowering circulating levels of glucose
- Metformin (a biguanide) lowers blood glucose primarily by reducing hepatic glucose output (glycogenolysis and gluconeogenesis)
- And, to a lesser extent, increasing glucose uptake and utilisation by skeletal muscle.
- The cellular mechanisms are complex, involving activation of adenosine monophosphate-activated protein kinase (AMP kinase).
- This is a cellular metabolic sensor, activation of which has diverse effects on cell functions. - Its effects on glucose metabolism can be accompanied by other metabolic changes, notably modest weight loss, which can be a desirable side effect.
Metformin - Adverse effects
- GI upset : nausea & vomiting, taste disturbance, anorexia & diarrhoea
- Lactic Acidosis
Metformin - Contraindications
- Acute kidney injury
- Sever tissue hypoxia
- Withheld in acute alcohol intoxication
Metformin - Caution
Renal impairment:
- dose reduction: if eGFR is < 45mL/min per 1.73 m2
- Drug stopped: if if eGFR is < 30mL/min per 1.73 m2
Hepatic impairment
Chronic alcohol abuse
Metformin - Key interactions
- Withheld before and 48 hours after injection of IV contrast media in increased renal impairment
- ACEi, NSAIDs, diuretics
Metformin - Monitoring
- Assess HbA1c : target with single agent is < 48 mmol/mol
- Assess renal function before starting treatment
Metformin - Patient Education
- Long-term treatment to control blood sugar and reduce complications
- Advice on lifestyle measure
Insulin - Indications
1) T1DM / T2DM
2) Diabetic emergencies (e.g. DKA)
3) Hyperkalaemia
Insulin - MOA
In DM:
- Acts like endogenous insulin
- so increases the uptake of glucose from circulation into skeletal muscle and fat.
- thus lowering the circulating levels of glucose.
- It also inhibits gluconeogenesis.
In Hyperkalaemia:
- it drives the K+ into cells lowering the circulating levels of serum K+
Insulin - Adverse effects
- hypoglycaemia
- if recurrently injected at the same site can cause irritation or overgrowth
Insulin - Caution
- avoid in renal impairment
- use with other anti-diabetic drugs (increased risk of hypoglycaemia)
Thyroxine - Example
levothyroxine
Thyroxine - Indication
1) Primary hypothyroidism
2) hypothyroidism secondary to pituitary disorder
Thyroxine - MOA
- Long-term synthetic replacement of thyroid hormones.
Thyroxine - Adverse Effects
- Similar to hyperthyroidism = palpitations, arrhythmias, angina, tremor, insomnia
- GI = diarrhoea, weight loss
Thyroxine - Interaction
- Cytochrome P450 inducer
- Insuline
- Decreased GI absoprtion by antacids, calcium + iron
Thyroxine - Interaction
- Cytochrome P450 inducer
- Insuline
- Decreased GI absoprtion by antacids, calcium + iron
Carbimazole and Propylthiouracil - Indications
Hyperthyroidism
Carbimazole - MOA
Propylthiouracil - MOA
- It is an anti-thyroid agent acting on the thyroid peroxidase.
- This lowers the uptake of inorganic iodine hence preventing the synthesis of thyroid hormones
- inhibits the conversion of iodide to iodine
Carbimazole and Propylthiouracil - Adverse Effects
- neutropenia/agranulocytosis
- -> main side effect - check WCC
- may present with sore throat
haemolytic anaemia & thrombocytopenia, pancreatitis are more rare
Carbimazole and Propylthiouracil - Contraindication
- Severe blood disorders
Carbimazole and Propylthiouracil - Caution
- pregnancy/breastfeeding
- hepatic impairment
if there is any signs of acute pancreatitis after carbimazole and propylthiouracil use what should you do?
discontinue immediately
