Endocrinology Drugs Flashcards
Insulin examples
Insulin aspart, insulin glargine, biphasic insulin, soluble insulin
Insulin indications
- Insulin replacement in TI DM
- Control of blood glucose in TII DM where oral hypoglycaemics inadequate / poorly tolerated
- IV in diabetic emergencies e.g. DKA, hyperglycaemic hyperosmolar syndrome
- Hyperkalaemia: alongside glucose while underlying cause investigated
Insulin MOA
Comes in rapid, short, intermediate, long acting and biphasic forms.
DM: works in similar way to endogenous insulin.
- Increases glucose uptake
- Increases use of glucose as energy
- Stimulates glycogen, lipid and protein synthesis
- Inhibits gluconeogenesis and ketogenesis
Hyperkalaemia: drives K+ into cells. Only short-term as leaks out again once stopped.
NB: biphasic insulin contains mixture of rapid and intermediate acting. Number in name indicates % short-acting
Insulin administration
SC: self-administered
IV in diabetic emergencies
Insulin contrainidactions
Higher risk of hypoglycaemia in renal failure as clearance reduced
Insulin side effects
Hypoglycaemia: coma and death
Lipid overgrowth at SC injection site
Insulin interactions
- Hypoglycaemic agents: increased risk hypoglycaemia
2. Corticosteroids: increases requirements
Gliclazide class
Sulphonylureas
Gliclazide indications
- TII DM: single agent to control blood glucose and reduce complications where metformin contraindicated or not tolerated
- TII DM in combination with metformin where glucose not adequately controlled
Gliclazide MOA
- Stimulates pancreatic insulin secretion
- Block ATP dependent K+ channels in beta-cell membranes
- Causes depolarisation of cell and opening of voltage gated Ca2+
- Increases intracellular Ca2+
- Stimulates insulin secretion
- Only useful in pts with residual pancreatic function.
- Insulin anabolic hormone - causes weight gain
- Weight gain increases insulin resistance, can worsen DM in long term
Gliclazide contraindications
- Hepatic / renal impairment: dose reduction
- Caution in those at risk of hypoglycaemia
Gliclazide side effects
Dose-related: Infrequent but include nausea, vomiting, diarrhoea and constipation.
Hypoglycaemia: caution in high doses / combination.
Hypersensitivity: rare but include hepatic toxicity, drug hypersensitivity syndrome, haematological abnormalities
Gliclazide interactions
- Other hypoglycaemic agents
- Efficacy reduced by drugs which elevate glucose: prednisolone, thiazide / loop diuretics
Gliclazide patient info
Take with meals
Metformin class
biguanides
Metformin MOA
- Lowers blood glucose by increasing sensitivity to insulin.
- Suppresses hepatic glucose production .- glycogenolysis and gluconeogenesis
- Increases glucose uptake and utilisation by skeletal muscle and suppresses intestinal glucose absorption
- Does not stimulate pancreatic insulin secretion and therefore does not cause hypoglycaemia
- Reduces weight gain and can induce weight loss - prevents worsening of insulin resistance
Metformin indications
TII DM: 1st line for controlling blood glucose. Alone or combination.
Metformin contraindications
- Severe renal impairment as excreted unchanged - dose reduce if moderate
- AKI / severe tissue hypoxia: withhold acutely
- Hepatic impairment: impaired clearance of excess lactcate
- Alcohol: acute intoxication - withhold as precipitates lactic acidosis. Chronic use risk of hypoglycaemia, use with caution.
Metformin side effects
- GI upset
- Lactic acidosis: rare but fatal - caused by: concurrent illness that causes metformin to accumulate (renal disease), increased lactate production (sepsis, hypoxia, cardiac failure) reduced lactate metabolism (liver failure)
Metformin interactions
- Contrast: withhold 48 hours before and after due to risk of metformin accumulation, renal impairment and lactic acidosis.
- Other drugs that risk renal impairment: ACEi, NSAIDs, diuretics - monitor renal function
- Drugs which elevate glucose: prednisolone, thiazide and loop diuretics: - reduce efficacy
Metformin patient information
Swallow with whole glass of water, with / after food. Aware of signs of lactic acidosis. Advise lifestyle being more permanent treatment.
Thyroxine examples
Levothyroxine, leiothyronine
Thyroxine indication
Primary or secondary hypothyroidism
Thyroxine MOA
- Thyroid produces T4 which is converted to more active T3 in target tissue
- Levothyroxine = synthetic T4.
- Liothyronine = synthetic T3 - shorter half-life, rapid action - reserved for emergency treatment of severe hypothyroid
Thyroxine contraindications
- Increase HR and metabolism: can precipitate ischaemia in coronary artery disease
- Hypopituitarism: corticosteroid therapy must be initiated before to avoid Addisonian crisis
Thyroxine side effects
Due to excessive doses, similar hyperthyroidism
Thyroxine interactions
- Antacids / calcium / iron salts: absorption reduced, so must separate by ~4h
- cP450 inducers: reduce efficacy
- Insulin: metabolism changes can increase insulin requirements
- Warfarin: metabolism can enhance effects
Carbimazole class
Imidazole anti-thyroid agent
Carbimazole indications
- Hyperthyroidism and thyrotoxicosis
2. Prepare patients for thyroidectomy
Carbimazole MOA
- Decreases uptake and concentration of inorganic iodine by thyroid
- Reduces formation of diiodotyrosine and thyroxine.
- Once converted to its active form, it prevents thyroid peroxidase enzyme from coupling and iodinating the tyrosine residues on thyroglobulin, which reduces production of T3 or T4.
Carbimazole contraindications
- Blood disorders
- Hepatic impairment
- Pregnancy / lactation
Carbimazole side effects
Common: arthralgia, fever, malaise, mild GI disturbance
Rare: agranulocytosis, alopecia, bone marrow suppression, jaundice, myopathy, pancytopenia
Carbimazole interactions
Warfarin: increases anti-coagulant effects
Bisphosphonates examples
Alendronic acid, disodium pamidronate, zoledronic acid
Bisphosphonates indications
- Alendronic acid: 1st line for patients at risk of osteoporotic fragility fractures
- Pamidronate and zoledronic acid: severe hypercalcaemia of malignancy after appropriate IV rehydration
- Myeloma and breast cancer with bone metastases: pamidronate and zoledronic acid reduce risk of pathological fractures, cord compression and need for radiotherapy / surgery
- Paget’s disease: 1st line in metabolically active - reduce bone turnover and pain
Bisphosphonates MOA
- Reduces bone turnover by inhibiting osteoclasts (responsible for bone resorption)
- Similar to naturally occuring pyrophosphate, so readily incorporated into bone
- Bone is resorbed: bisphosphonates accumulate in osteoclasts
- Inhibit activity and promote apoptosis
- Net effect: reduction in bone loss, improvement in bone mass
Bisphosphonates contraindications
- Renal impairment
- Hypocalcaemia
- Oral admin in upper GI disorders
- Smokers / major dental disease: risk of jaw osteonecrosis
Bisphosphonates side effects
- Oesophagitis (oral)
- Hypophosphataemia
- Jaw osteonecrosis: rare effect with high dose IV therapy
- Atypical femoral fracture if on long-term
Bisphosphonates interactions
- Calcium salts, antacids and iron salts: bisphosphonates binds
Bisphosphonates patient info
- Swallow whole at least 30 mins before breakfast with plenty of water
- Remain upright for 30 mins after taking to reduce oesophageal irritation
Calcium and Vitamin D indications
- Osteoporosis: ensure positive calcium balance when dietary intake ± sunlight exposure insufficient
- CKD: treat + prevent secondary hyperparathyroidism and renal osteodystrophy
- Severe hyperkalaemia: calcium gluconate used to prevent life-threatening arrhythmias
- Hypocalcaemia: Ca that is symptomatic or severe
- Vit D deficiency: Vit D used to prevent / treat including rickets and osteomalacia
Calcium and Vitamin D MOA
-Calcium: essential for normal function of muscle, nerves, bone and clotting.
Homeostasis controlled by parathyroid hormone and vitamin D, which increase serum calcium and bone mineralisation, and calcitonin, which reduces serum calcium levels.
Osteoporosis: loss of bone mass increases risk of fracture. Restoring positiv calcium balance may reduce rate of bone loss.
CKD: impaired phosphate excretion and reduced vit D activation cause hyperphosphatemia and hypocalcaemia. This stimulates secondary hyperparathyroidism which leads to a range of bone changes = renal osteodystrophy. Treatment = oral calcium to bind phosphate in gut, or alfacalcidol to provide vit D that does not depend on renal activation.
Hyperkalemia: calcium raises myocardial threshold potential, reducing excitability and risk of arrhythmias
Calcium and Vitamin D side effects
Oral ca: dyspepsia and constipation
Calcium gluconate: cardiovascular collapse if admin too fast, local tissue damage if accidentally given subcut
Calcium and Vitamin D interactions
Oral calcium reduces absorption of many drugs: iron, bisphosphonates, tetracyclines, levothyroxine
Sodium bicarbonate: calcium gluconate cannot mix due to risk of precipitation
