Endocrine Flashcards
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
Dipeptidylpeptidase-4 inhibitors - Examples
sitagliptin
linagliptin
saxagliptin
DDP4-inhibitors - Indications
T2DM - as single agent or combined
DPP4-inhibitors - MOA
- Incretins and GIPs are responsible for insulin secretion
- however DPP4 usually hydrolyses the Incretin molecules.
- Thus, inhibition of DDP4 allows insulin secretion and thus the lowering of glucose.
DDP4-inhibitors - Adverse Effects
- GI upset
- headaches
- peripheral oedema
- more seriously hypoglycaemia
DPP4-inhibitors - Contraindications
Do not give in hypersensitivity, T1DM or ketoacidosis, pregnancy/breastfeeding,
DDP4-inhibitors - Caution
renal impairment, pancreatitis and elderly (>80)
Sulphonylurea - Example
Glicazide
Sulphonylureas indications
T2DM = either as single agent or combined
Sulphonylureas - MOA
- Lowers blood glucose by stimulating pancreatic secretion of insulin.
- This is mainly by acting on the K+ channels on pancreatic β-cell.
- Resulting in depolarisation , causing an increase in calcium levels
- Increase in intracellular Ca2+ stimulates insulin secretion which subsequently lowers glucose levels
Sulphonylureas - Adverse Effects
GI upset: Nausea & vomiting, diarrhoea and constipation
more seriously = hypoglycaemia and hypersensitivity
Sulphonylureas - Caution
Hepatic/renal impairment
risk of hypoglycaemia or elderly
Sulphonylureas - Interactions
- Beta - blockers = may mask symptoms of hypoglycaemia
- Reduced efficacy by drugs that elevate blood glucose: prednisolone, thiazide and loop diuretics
Carbimazole - Interactions
Digoxin
