Endocrine drugs Flashcards
What is fludrocortisone
A synthetic mineralcorticoid
Uses of fludrocortisone
1) Replace aldosterone in forms of adrenal insufficiency
2) Orthostatic intoleance and postual orthostatic tachycardia syndrome (POTS) –> 1st line to increase Na+ levels
3) Hypotension treatment (if severe)
4) Confirms Conn’s syndrome
What is Conns syndrome
An aldosterone producing adenoma
What usually secretes aldosterone
The zona glomerulosa of the adrenal cortex
Action of fludrocortisone
Binds to mineralcorticoid receptors and mimics the action of aldosteroine
Acts on the distal nephron, promotes Na/K exchange
Sodium retention and urinary loss of K and H+
CL- is absorbed in conjuction with Na –> water follows
Adverse effects of fludrocortisone
FEATURES OF CONNS Sodium/water retention --> nocturia Hypokalaemia Hypertension Weakness Nocturia Tetany
Warnings of fludrocortisone
Contraindicated in patients with systemic fungal infections
Steroids can cause immunosuppression
Interactions of fludrocortisone
1) Amphotericin B/K+ Depleteing diruiteics –> enhance hypokalaemia
2) oral anticoagulants –> decrease prothrombin time
3) Aspirin –> Increased ulcerogenic effect
4) Antidiabetic drugs –> diminished antidiabetic effect
5) Oestrogen –> oestrogen increases the amoutn of corticosteroid binding globulin (inactivates the drug) BUT balanced by decreased metabolism of corticosteroid hence may need a reduced drug dose.
Name a biguanide
Metformin
Metformin indications
1) Type 2 DM –> First choice to control it –> use alone or in combo with other oral hypoglycaemiacs or insulin
Action of biguanides
NOT A REPLACEMENT FOR LIFESTYLE CHANGES
Increases the response (sensitivity) to glucose
Suppresses hepatic gluconeogenesis and glycogenolysis
Also increases glucose uptae and utilization by skeletal muscle
Suppresses intestinal glucose absoprtion
Overall decreaes blood glucose
What effect do biguanides have on insulin secretion
NO EFFECT –> as it doesnt stimulate pancreas insulin secretions, it only makes cells more sensitive to insulin
Hence there is no risk of hypoglycaemic episodes
What effect do biguanides have on weight
It reduces weight gain and can induce weight loss (as it doesnt increase insulin secretion)
This prevenet the worsening of insulin resistance and the slow deteorioration of diabetes
Adverse effects of metformin
1) GI Upset - common
2) Lactic acidosis - can be fatal. Onlyl occurs if precipitated by illness that causes metformin accumulation (e.g. renal function decreased), or lactate production increased (sepsis, hypoxia, cardiac failure), or decreased lactate metabolism (liver failure)
Contraindications of metformin
1) severe renal impairment –> need to significnalty reduce
When should we acutely withhold metformin
AKI e.g. sepsis, shock, dehydration
Severe tissue hypoxia e.g. MI, cardiac/resp failure
Withhold in actue alcohol intoxictaion –> may precipiate lactic acidosis
Caution of metformin in
1) Hepatic impairment –> decreased lactate clearance
2) Chronic Alcohol overuse –> risk of hypoglycaemia
Interactions of metformin
1) IV contrast media –> increased risk of renal impairment
2) Drugs affecting renal function e.g. NSAIDs, ACEi, diuretics
3) Prednisolone, thiazide and loop diuretics –> these elevate blood glucose hence oppose the action and reduce its efficacy
HbA1c target with metformin
<58
Also test renal function before and annually
How is metformin excreted
Unchanged by the kidneys
Symtpoms of lactic acidosis
Vomiting Stomach ache/pain Muscle cramps Difficutly breathing Severe tiredness
Link between insulin and weight gain
Insulin is an anabolic hormone
This means drugs that increase insulin secretion cause WEIGHT GAIN hence worsening DM over time
Name a sulphnoylurea
Glicazide
Indications for sulphonylureas
1) Type 2 DM –> a signel agent where metformin CI or not tolerated
2) DM –> in combo with metformin or other agents if BM not adequately controlled
How should you take sulphonylureas
Orally with meals, start low dose and increase gradually
How do sulphonylureas work
Stimulate pancreatic insulin secretion
They block ATP dependent K+ channels in pancreatic B cell membranes –> this causes depolarisation and opening of voltage gated Ca2+ channels –> the rise in intracellular calcrium causes insulin secretion
Adverse effects of sulphonylureas
Weight gain –> as insulin is anabolic
GI Upset
Hypogylcaemia –> more likely with increased doses
Rare hyperesensetitivity reactions e.g.
a) Haematological abnormalities (agranulocytosis)
b) Hepatic toxicity (cholestatic jaundice)
c) Drug hypersensitivity syndrome (rash, fever, internal organ involvement)
What happens to insulin resistance in acute illness
Increased insulin resistace
Also impairs hepatic and renal function
Oral hypoglycaemic become less effective
Insulin may be needed temporarily
Warnings of using sulphonylureas
1) Hepatic and renal impairment
2) High risk of hypoglycaemia e.g. those with hepatic impairment (reduced gluconeogenesis), malnutrition, adrenal or pituitary insufficiency (lack of counter regulatory hormones) and the elderly
Interactions of Sulphonylureas
1) Antidiabetic drugs –> risk of hypoglycaemia
2) efficacy reduced by drugs that increase blood glucose e.g. steroids, loop and thiazide diuretics
What are the syptoms of hypoglycaemia
Dizziness, nausea, sweating, confusoin
Take something sugary and then something starchy
How are sulphonylureas excreted
Excreted unchanged in the urine
Name thyroid hormone repolacement
Levothyroxine
Liothyroxine
Indications for thyroid hormones
Hypothyroidism
Action of thyroid homrones
Thyroid hormones regulate emtabolism and growth
What is levothyroxine
Synthetic T4 - the inactive from –> most common for long term replacement
What is liothyroxine
Synthetic T3 –> shorter half life, quicker onset and offset, hence usually reserved for emergency treatment of severe or acute hypothyroidism
Adverse affects of thyroid homrones
Usually related to overdose –> GI upset, neurological (tremors, restlessness, insomnia), Cardiac (palpitations, angina, arryhythmia)
Warnings of thyroid hormones
1) Coronary artery disease –> can increase heart rate and metabolism
2) Hypopituatism –> must start corticosteroids before thyoird homrones, otherwise may precipitate an addisonian crisis
Interactions of thyroid hormones
1) Antacids, Ca2+ or Fe2+ salts reduce the GI absorption of levothyroxine
2) CP450 inducers (phenytoin, carbamazepine) increase speed of elimination
3) DM –> can increase insulin or oral hypoglycaemic requirement due to changes in metabolism
4) Enhances warfarins effect
Name calcium and vitamin D replacements
Calcium carbonate, calcium gluconate, colecalciferol, alfacalcidol
Indications for calcium and vitamin D
1) Osteoporosis
2) CKD –> treat and prevent secondary hyperparathyroidism and renal osteodystrophy
3) Hypocalcaemia that is symptomatic
4) Vit D deficiency –> Prevents rickets and osteomalacia
5) Severe hyperkalaemia
Symptoms of hypocalcaemia
Paraesthesia
Tetany Seizures
Action of calcium and vitamin D
Need Ca for normal muscle/bone/nerve function –> controlled by Vit D and PTH
Calciutonin decreases serum Ca levels
Why do we need calcium and vitamin D in CKD
Impaired phosphate excretion and decreased activation of itamin D cause high phosphate and low potassium –> this stimulates secondary hyperparathyroidism –> leads to osteodystrophy
Give oral calcium supplements to bind phopshate in the gut
Give alfacalcidol to provide vitamin D that doesn’t require renal activation
How does calcium treat hyperkalemia
Increaes the myocardial threshold potential, reducing the risk of arryhtmias
It has no effect on serum K+ levels
Adverse effects of Calcium
Oral - dypspesia and constipation
IV - if given for hyperkalaemia can cause CV collapse or local tissue damage if given too quickly
Interactions of calcum
1) Oral Ca –> decreases absorption of many drugs e.g. iron, bisphosphonates, tetracyclines, levothyroxine
2) IV –> MUST MIX WITH SODIUM BICARBONATE –> risk of precipitations
What foods should you wait 2 hours with after taking calcium
Spinach
Banana
Whole cereals
Name some bisphosphonates
Alendronic Acids
Disodium pamidronate
Zoledronix acid
Indicatinos of bisphosphonates
1) Osteoporotis fragility fractures risk
2) Severe hypoermcalcaemi of maligancy
3) MYeloma and breast cancer with bone metastases
4) Pagets disease - first line treatment to reduce bone turnover and pain
Action of bisphosphonates
Inhibit action of osteoclasts –> decreses bone turnover
Similar sturcture to natural pyrophosphate hence incorporated into bone, when bone is resorbed they accumulate in osteoclasts –> inhibit their activity and promote apoptosis
NET EFFECT IS REDUCTION IN ONE LESS AND IMPROVEMENT IN BONE MASS
Adverse effect of bisphosphonates
1) Osteophagitis - if taken orally
2) hypophosphataemia
3) Jaw osteonecrosis (rare, more likley if high-dose IV)
4) atypical femoral fracture
Contraindications of bisphophantes
1) Severe renal impairment - as renally excreted
2) Hypocalcaemia
3) Oral administration in upper GI disorders
Caution of bisphosphonates in
Smokers
Major Dental disease
This is because of the higher risk of jaw osteonecrosis
Interactinos of bisphosphonates
1) Calcium salts, antacids and FE –> bind calcium and reduce its absorption
How should you take bisphosphonates
Take 30 mins before breakfast –> take with plenty of water –> sit upright for 30 mins after taking it to reduce the risk of oesophagitis
Indications of insulin use
1) Type 1 - DM insulin replacement, Type 2 DM –> if oral hypoglycaemics not working/tolerated
2) Diabetic emergencies –> give IV e.g. diabetic ketoacidosis, hyperglycaemic hyperosmolar syndrome and peri-operative hyperglycaemic control
3) Hyperkalaemia –> give with glucose
Action of insulin
Stimulates glucose uptake from circulation into tissues
Stimulates glycogen, lipid and protein synthesis
Inhitis gluconeogenesis and ketogenesis
Also drives K+ into cells –> only for short term though
Rapid insulin
Insulin apart e.g. novarapid
Short insulin
Actrapid
Adverse effects of insulin
Hypoglycaemia –> can lead to coma/death
Lipohypertrophy –> if given SC repeatedly at the same site
Warning of insulin
Renal impairment –> insulin clearance is reduced hence increased risk of hypo
Interactions of insulin
1) other hypoglycaemics
2) Systemic corticosteroids –> icnreases insulin requirements and steroids increase glcuose
When to use carbimazole
Treats hyperthyroidism
How does carbimazole work
Acts via its active metabolist methimazole
Substrate inhibitor of peroxidase –> which itself is iodinated and degraded within the thyroid –> this diverst oxidized iodine from thyroglobulin hence decreasing thyroid hormone biosynthesis
It also has an mmunosuppressant action within the thyroid and interferes with generation of oxygen free radicals in macrophages (and hence antigen presentation)
Adverse effects of carbimazole
Usually well tolerated BUT;
1) Pruritis and rashes
2) Neutropenia –> rare
3) Nausea, hair loss, fever, leukopneia, arthralgia
Use of carbimazole in pregnancy
Causes aplasia cutis in newborn (absence of portion of the skin)
Contraindicatinos of carbimazole
1) hypersensitivity
2) Severe hepatic insufficiency
Warnings of carbimazole
Stop during whil undergoing radio-iodine treatment to acoid a thyroid crisis
Interactions of carbimazole
1) Warfarin –> carbimazole is a vitmain K antagonist hence increases anticoagulation
2) Theophylline toxicity –> serum levels can increse if concurrent use without decreases dose of theophylline
3) Prednisolone –> concurrent therapy increases prednisolone clearance
4) Beta-adrenergic blockers –> increases their clearance
