Endocrine Drugs Flashcards
Indications of Insulin
1) Type 1 DM, or Type 2 DM when control of blood glucose is inadequate with oral hypoglycaemic treatment
2) Diabetic emergencies –> give IV
3) Hyperkalaemia –> give with glucose and calcium gluconate
How does insulin work
Functions similar to endogenous insulin
Stimulates glucose uptake from circulation into tissues
Increases use of glucose as an energy source
How does insulin treat hyperkalaemia
Drives potassium into cells (however only short term)
Once insulin is stopped potassium leaks back out hence need to start other treatment
What are the adverse effects of insulin
Hypoglycaemia –> can lead to coma/death
What are the warnings of using insulin
Renal impairment - insulin clearance is reduced hence higher risk of hypoglycaemia
Interactinos of insulin
1) Other hypoglycaemics
2) Systemic corticosteroids –> corticosteroids increase glucose in blood sugar
How often should you check HbA1c?
At least annually
Name bisphosphonates
Alendronic Acid
Disodium pamidronate
Zoledronic acid
What is disodium pamidronate
A bisphosphonate
Indications for bisphosphonates
1) Osteoporotic fragility fracture risk - 1st line
2) Severe hypercalcaemia of malignancy - use pamedronate and zoledronic
3) Myeloma + breast cancer with bone metastases
4) Paget’s disease - 1st line treatment if metabolically active
What should we treat severe hypercalcaemia of malginancy with
Pamedronate and coledronic acid
What should we treat myeloma and breast cancer with metastases with
Pamidronate and zoledronic acid
How do bisphosphonates work?
Inhibits the action of osteoclasts (osteoclasts break down bone) –> hence bone turnover is decreased
Bisphopshonates have a similar structure to natural pyrophosphate –> they are readily incorporated into bone –> when bone is resorbed the bisphosphonates accumulate in the osteoclasts –> these inhibit their activity and promote apoptosis
What is the net effect of bisphosphoantes
Reduction in bone loss
Improvement in bone mass
Adverse effects of bisphosphonates
1) Oesophagitis (if taken orally)
2) Hypophosphataemia
3) Jaw osteonecrosis (rare and mroe likely if given high dose IV)
4) Atypical femoral fracture - rare but important
Contraindications of bisphosphonates
1) Severe renal impairment - they are renally excreted
2) Hypocalcaemia
3) Oral administration in upper GI disorders
What is the effect of osteoclasts
They break down bone
Release calcium from bone to blood
Who should we take caution in using bisphosphonates in
1) Smokers
2) Major dental disease
BOTH OF THESE INCREASE JAW NECROSIS
Interactions of bisphosphoantes
Calcium salts, antacids and Iron
Bisphosphonates bind calcium so these all decrease its absorption
When do the calcium lowering effects of bisphosphonates become most apparent
3-4 days post administration their effect becomes apparent
Max effect at 7-10 days
How should you take alendronic acid
Take tablet whole 30 minutes before breakfast or other meals
Take with plenty of water
Sit upright for 30 minutes after to reduce the risk of oesophagitis
What monitoring should we do for bisphosphonates in osteoporosis
Check and replace calcium and vitamin D before starting treatment
Do a DEXA every 1-2 years
Monitor hypercalcaemia and sympytoms/bone complications in myeloma and Paget’s
Name some calcium and vitamin D supplements
Calcium carbonate
Calcium gluconate
Colecalciferol
Alfacalcidol
Indications of the use of calcium and vitamin D
1) Osteoporosis
2) CKD –> helps to treat and prevent secondary hyperparathyroidism and renal osteodystrophy
3) Hypocalcaemia that is symptomatic
4) Vitamin D deficiency –> treat and privent rickets and osteomalacia
5) Severe hyperkalaemia
What are the symptoms of hypocalcaemia
Paraesthesia
Tetany
Seizures
How do the kidneys influence calcium/vitamin D
Kidneys activate vitamin D
Vitamin D is needed to abrorb calcium
What goes wrong with calcium, vitamin D and phosphate in CKD
1) Kidneys dont activate vitamin D - calcium isnt absorbed
2) Kidneys dont filter out phosphate so phosphate levels rise
3) PTH is produced in large quantities –> this can cause renal osteodystrophy
What does calcitonin do
It decreases serum calcium levels
What happens in osteoporisis
Loss of bone mass - causing an increased risk of fragility fractures
What do bloods look like in CKD
Raised phosphate
Low calcium
This stimulates renal osteodystrophy
How should we treat CKD
Oral calcim supplements to bind phosphate in teh gut
Alfacalcidol to provide vitamin D that doesn’t need renal activation
How does hypercalcaemia affect the heart
High calcium raises the myocardial threshold potential
Makes arrhythmias more likely
Do calcium and vitamin D supplements have an effect if potassium levels
No
What are the adverse effects of oral calcium
Dyspepsia
Constipation
IV - if given for hyperkalaemia then can cause cardiovascular collapse if given too fast and local tissue damage if accidentally given into SC tissue
Interactions of oral calcium
Oral calcium decreases the absorption of many other drugs: iron, bisphophonates, tetracyclines and levothyroxine
IV Calcium MUSTNT mix with sodium bicarbonate –> risk of precipitation
How should we administer calcium gluconate
Slow IV injection over 5-10 minutes into a large vein
How much should time should we seperate calcium gluconate and sodium bicarbonate by
4 hours
What symptoms should we warn patients taking oral calcium or vitamin D to look out for
Abdominal or limb pain –> this may be a sign of hypercalcaemia
How should we take oral calcium
Chewed then swallowed
Indications of thyroid hormones
1) Primary hypothyroidism
2) Hypothyroidism secondary to hypopituitarism
Action of thyroid hormones
T4 is normally produced by thyroid –> converted to T3 (the active form)
What is levothyroxine
Synthetic T4 - most common for long term replacement
What is liothyroxine
Synthetic T3 - shorter T-half life than levothyroxine, quicker onset (few hours) and offset (24-48 hours)
Often reserved for treatment of sever or acute hypothyroidism
Adverse of effect of thyroid hormones
Usually due to excessive doses –> similar to hyperthyroid effects
DnV, Weight Loss
Palpitations, angina, arrhytmias
Tremor, restlessness, insomnia
Warnings of using thyroid hormones
Coronary artery disease
Thyroid hormones can increase heart rate and metabolism –> this can precipitate cardiac ischaemia. Start cautiously at low dosease and monitor
2) Hypopituatarism –> MUST START CORTICOSTEROIDS BEFORE THYROID HORMONES –> otherwise may precipirate an addisonian crisis
Interactions of thyroid hormones
1) Antacids, Iron, Calcium and Iron salts –> all decrease the GI absorption of levothyroxine
2) CP450 Inducers (phenytoin, carbamazepine) –> need to increase levothyroxine dose
3) Diabetes mellitus - can increase hypoglycaemic requirements due to changes in metabolism
4) Enhances warfarin effects
Do we need to monitor thyroid hormones
Initially change dose according to symptoms
Do TFTs after 3 months
What should you do if a patient experiences hyperthyroid symptoms after starting thyroid homrones
Lower dose and review in 1-2 weeks
Look for re-emergence of hypothyroidism
TFTs are unhelpful in this situation
Name a sulphnyurea
Glicazide
Indications for sulphonylureas
1) Type 2 DM - as single agent or a combination
Action of sulphonylureas
Stimulates pancreatic insulin secretion
Blocks ATP dependednt K+ channels in pancreatic B-cell membranes –> causes depolarisation –> Calcium channels open –> increases intracellular calcium –> causes insulin secretino
Is insulin anabolic or catabolic
Anabolic –> hence increased insulin causes weight gain
This weight gain can worsen DM over time
Adverse effects of sulphonylureasa
GI Upset
Hypoglycaemia
Rare hypersensitivity reactoins
What are the rare hypersensitivity reactions of sulphonylureas
1) Haeamatological abnormalities - agranulocytosis
2) Hepatic toxicity - cholestatic jaundice
3) Drug hypersensitivity syndrome (rash, fever, internal organ involvement)
Warnings of using sulphonylureas
1) Hepatic impairment - dose reduction
2) Renal impairment - monitor carefully
3) Increased risk of hypoglycaemia –> e.g. those with hepatic impairment (reduced gluconeogenesis), adrenal or pituitary insufficiency (as there is a lack of counter-regulatory hormones)
Interactions of sulphonyureas
1) Increased risk of hypoglycaemia with other antidiabetic drugs
2) Decreased efficacy by drugs that increase blood glucose e.g. steroids, thiazide and loop diuretics
Symptoms of hypoglycaemic attacks
Dizziness, nausea, sweating and confusion
HbA1c target for those on sulphonylureas
Less than 58
Name a biguanide
Metformin
Does metformin cause weight gain
NO - this is because it doesnt stimulate insulin secretion, it just increases the receptors sensitivity to insulin
Indications of metformin
1) Type 2 DM
Action of metformin
Increase the response (sensitivity) to insulin
Suppresses hepatic gluconeogenesis and glycogenolysis
It also increases glucose uptake and utilization by skeletal muscle
Suppresses intestinal glucose absorption
Adverse efects of metformin
GI upset - common
Lactic acidosis - rare. This occurs if precipitated by a intercurrent illnesss that cause metformin accumulation e.g. decrease renal function or increased lactate production (sepsis, hypoxia, cardiac failure) or decrease lactate metaboism (e.g. liver failure)
Symptoms of lactic acidosis
Vominting Stomach aches/cramps Muscle cramps Difficulty breathing Severe tiredness
Contraindications of metformin
Severe renal impairment (decreased dose if moderate impairment)
When should we acutely withhold metformin
AKI e.g. sepsis, shock, dehydration
Severe tissue hypoxia e.g. cardiac/respiratory fialure, MI
Acute acohol intoxication - may precipitate lactate acidosis
Caution of using metformin in
Hepatic impairment - lactate clearnce is impaired
Chronic alcohol overuse - risk of hypo
Interactins of metformin
1) IV contrast media - withold metformin before and 48 hours after as increased risk of renal impairment and metformin accumulation
2) Drugs affecting renal function e.g. ACEi, NSAIDs and diuretics
3) Prednisolone, thiazide and loop diuretics –> these all elevate blood glucose hence oppose action and reduce efficacy of metformin
Name a synthetic mineralcorticoid
Fludrocortisone
Indications of fludrocortisone
1) Replace aldosterone in forms of adrenal insufficiency
2) Orthostatic intolerance and postural orthostatic tachycardiac syndrome
3) Treats severe hypotension
4) Confirms conns syndrome - as you do a fludrocortisone suppression test
What is conns syndrome
An aldosterone producing adenoma
Name some forms of adrenal insufficiency
Addisons Salt wasting (21-hydroxylase deficiency) a form of CAH
Action of fludrocrotisone
Binds to mineraolcorticoid recepot and mimics the action of aldosterone
Acts on deistal nephron - promotes Na/K exchange
Sodium retention and urinary loss of K/H
Cl- is reabsorbed in conjunction with Na+
Water is alco reabsorbed
Adverse effects of fludrocortisone
Causes features of Conn’s syndrome
Oedema Nocturia Hypokalaemia Hypertension Weakness Tetany
Contraindications of fludrocortisone
Systemic fungal infection
Interactions of fludrocortisone
1) Amphotericin B/K+ depeleting diuretics –> enhances hypokalaemia
2) Oral anticoagulants - decreased prothrombin time
3) Aspirin - increaed ulcerogenic effect
4) Antidiabetic drugs –> diminished antidiabetic effect
5) Oestrogen –> oestrogen increases the amount of corticosteroid binding gloculin (inarivates the drug) but balanced by decreased metablism of corticosteroids hence may need a reduce drug dose
Indications for carbimazole
1) Treates hyperthyroidism
Action of carbimazole
Acts via its active metabolite METHIMAZOLE
Substrate inhibitor of peroxidase, which itself is iodinated and degraded within the thyroid
This divert oxidized iodine from thyroglocbulin hence decreasing hormone biosynthesis
ALSO HAS AN IMMUNOSUPPRESSANT ACTION WITHIN THE THYROID –> interferes with the generation fo oxygen free radicals in macrophages and hecne antigen presentation
Adverse effects of carbimazole
Pruritis and rashes Neutropenia Nausea Hair loss Drug fever Leukopenia Arthralgia
Use of carbimazole in pregnancy
Causes aplasia cutis in newborn (this is the absence of a portion of skin)
Contraindications of carbimazole
Hypersentivit
Severe hepatic insufficiency
Warnings of carbimazole
Stop whilst on radio-iodine treatment
Interactions of carbimazole
1) Warfarin - as carbimazole is a vitamin K antagonist –> hence enhances anticoagulant effect
2) Theophylline toxicity - serum levels increae if concurrent use
3) Prednisolone –> concurrent therapy increases prednisolone clearnce
4) Increased clearance of beta-blockers
