Top 100 Drugs: Amiodarone, Doxazosin, Nitrates, Aldosterone antagonists

common indications with amiodarone?

-used in a wide range of tacharrhythmias

-generally used only if other treatments are ineffective or contraindicated.

what effects does amiodarone have on myocardial cells?

-blockage of sodium, calcium and potassium channels, and antagonism of a and b adrenergic receptors.

-these effects reduce spontaneous depolarisation, slows conduction velocity and increase resistance to depolarisation, including in the AV node.

important adverse effects with amiodarone?

-in acute use, amiodarone uses little myocardial depression

-can cause hypotension during IV infusion

-pneumonitis, brandycadia, AV block, hepatitis, photosensitivity

what effect does the iodine content of amiodarone have?

-may cause thyroid abnormalities, including hypo and hyperthyroidism

does amiodarone have a long or short half life?

long half life- may take months to be completely eliminated.

-25 to 100 days

-therefore interactions may still occur after stopping the drug

warnings with amiodarone?

-a potentially dangerous drug that should only be used when the risk-benefit balance justifies it

-should be avoided in severe hypotension, heart block, and active thyroid disease.

important interactions with amiodarone?

-interacts with MANY drugs

-increases plasma concentration of digoxin, diltiazem, and verapamil -this increases the risk of bradycardia, AV block, and heart failure

-doses of these drugs should be HALVED if amiodarone is started.

-grapefruit juice (by down regulating CYPP450 3A4 can increase exposure to amiodarone, so should be avoided.

common indications for doxazosin?

-as a first line option to treat lower urinary tract symptoms in benign prostatic enlargement

-as an add on treatment in resistant hypertension when other medications are insufficient.

MOA of doxazosin?

-an alpha-blocker, mainly found in smooth muscle, including blood vessels and urinary tract

-stimulation induces contraction, blockage induces relaxation

-therefore, inhibiting the A1-adrenoreceptor therefore causes vasodilation and a fall in blood pressure and reduces resistance to urine outflow from the bladder.

important adverse effects with doxazosin?

-postural hypotension, dizziness, syncope

-particularly prominent after the first dose.

warnings with doxazosin?

-avoid in people with existing postural hypotension

important interactions with doxazosin?

-if on 2 antihypertensives, could omit one dose on the first day doxazosin is started, due to the pronounced antihypertensive effects.

common indications of aldosterone antagonists?

1. ascites and oedema due to liver cirrhosis: spironolactone is the first-line diuretic in this indication

2. chronic heart failure: of at least moderate severity or arising within 1 month of a myocardial infarction, usually as an addition to a b-blocker and an ACEi/ARB

3. primary hyperaldosteronism - while awaiting surgery or if surgery is not an option.

MOA of aldosterone antagonists?

-aldosterone is a mineralocorticoid that is produced in the adrenal cortex.

-it acts on mineralocorticoid receptors in the distal tubules of the kidney to increase the activity of luminal epithelial sodium channels

-this increases reabsorption of sodium and water, elevating blood pressure, with a corresponding increase in potassium excretion

-aldosterone antagonists inhibit the effect of aldosterone by competitive inhibition at MRA receptors

-this increases sodium and water excretion and potassium retention.

-their effect is greatest when circulating aldosterone is highest, eg in cirrhosis or primary hyperaldosteronism.

important adverse effects with aldosterone antagonists?

-hyperkalemia - which can lead to muscle weakness, arrhythmias and cardiac arrest.

-spironolactone causes gynaemastia- enlargement of male breast tissue (has significant effect on adherence in men)

-epleronone is less likely to cause endocrine side effects

-can also cause liver impairment, jaundice

-spiro is a cause of stevens-johnsons syndrome

warnings with aldosterone antagonists

contraindicated in:

-severe renal impairment

-hyperkalemia

-adrenal insufficiency

-avoid in pregnancy/lactating women as they can cross placenta/appear in breast milk

important interactions with aldosterone antagonists?

-combination of aldosterone antagonists with other potassium-elevating drugs, including ACE inhibitors and ARBs, increases the risk of hyperkalaemia

-should not be combined with potassium supplements except in specialist practise

common indications of nitrates?

1. short-acting nitrates are used in acute angina and chest pain associated with ACS

2. long-acting nitrate are used for prophylaxis of angina where a B-blocker and/or a calcium channel blocker are insufficient or not tolerated

3. IV nitrate infusions are used in the treatment of ACS, pulmonary oedema and hypertensive emergencies.

MOA of nitrates

-nitrates are rapidly converted to NO after absorption.

-NO increases cyclic guanosine monophosphate synthesis and reduces intracellular Ca2+ in vascular smooth muscle cells, causing them to relax.

-this results in venous and arterial vasodilation

-this vasodilation causes reduces cardiac preload and left ventricular filling.

-these effects reduce cardiac work and myocardial oxygen demand, relieving angina and cardiac failure

important adverse effects with nitrates?

due to their vasodilator effects, they cause flushing, headaches, light-headedness, and hypotension

-regular use can lead to tolerance

nitrates warnings?

-contraindicated in severe aortic stenosis - where arterial constriction is necessary to maintain blood pressure in the face of relatively fixed cardiac output.

-avoid in hypotension

important interactions with nitrates?

-must not be taken concurrently with phosphodiesterase inhibitors (eg sildenafil) as it is responsible for metabolising cGMP and so PDE inhibitors enhance and prolong the hypotensive effects of nitrates.

-nitrates should also be used with caution in people taking antihypertensive medication - may lead to hypotension