The heart and vascular systems

The heart and vascular systems drugs

You should be aware of cardiac physiology as part of your course. Normal function of the heart depends on the rate, rhythm, contractility, blood supply and autonomic control. Drugs acting on the heart fall into three main groups:

direct action on myocardial cells (anti-dysrhythmic drugs, inotropes, etc.);

indirect cardiac function (diuretics, angiotensin converting enzyme (ACE) inhibitors, etc.);

calcium antagonists.

Anti-dysrhythmic drugs are typically applied during emergency cardiac events in adjunct to, or in place of, physical treatments, such as electrical cardioversion (e.g. defibrillator). They include drugs that block voltage-sensitive sodium channels thus inhibiting the action potential, for example lidocaine (a local anaesthetic) will associate and dissociate within the time frame of a normal heartbeat, thus normalising the rate. It essentially pauses all electrical activity in order to allow normality to resume. It is delivered i.v. as it has a very low bioavailability (see above). It is metabolised rapidly, giving a short half-life, thus allowin rapid alteration of plasma concentration to avoid the central side effects of drowsiness and convulsions. Another action is that of β-adrenoceptor antagonism which effectively reduces sympathetic expression on the heart by increasing the refractory period of the atrioventricular (AV) node (i.e. slowing the heart’s pacemaker). These drugs, such as propanolol and atenolol, have the unfortunate side effect of bronchospasm, fatigue and bradycardia, but in the absence of lung disease the risk is relatively low.

Increasing cardiac contraction may require poison. The extract of the foxglove (genus Digitalis) is used as a cardiac glycoside (e.g. digoxin). The effects are reduction of conduction, increased force of contraction and disturbance of rhythm. They enhance vagal activity and inhibit the Na+/K+ pump, thus increasing the twitch tension in cardiac muscle. It is given orally (i.v. in emergencies) but unfortunately the clinical risk of such drugs is the fine line between effectiveness and toxicity. It is excreted via the kidneys

which poses a problem in patients with less effective renal function in terms of maintaining plasma concentrations at a safe level.

Angina is an important symptom which indicates insufficient oxygen supply for cardiac activity. It is controlled by either increasing perfusion or reducing demand (or both). Two important drugs that you may encounter are glyceryl trinitrate (GTN) and isosorbide mononitrate. These organic nitrates are metabolised into nitric oxide which initiates a cascade of effects resulting in relaxation of vascular muscles and therefore reduced central venous pressure (and thus preload and afterload of the heart), reducing stroke volume and metabolic demand. The relaxation of coronary arteries will enhance the oxygen delivery to the myocardium. GTN is given orally by spray or sublingual tablet (owing to extensive first-pass metabolism it

is ineffective if swallowed). It acts within minutes and is rapidly metabolised by the liver and effectively eliminated in half an hour, hence its usefulness in acute situations. Isosorbide is similar, but is taken as a tablet and lasts

longer in the system which makes it a useful prophylaxis for angina.

Calcium antagonists block entry of Ca2+ to the cell by acting on voltage gated channels. Drugs such as verapamil and diltiazem are used occasionally for their antidysrhythmia action, but this group of drugs is more commonly used for hypertension (e.g. amlodipine and nifedipine). The action on the heart is generally a complicated balancing act but the effects of the arterial and arteriolar smooth muscle is relaxation, thus reducing peripheral resistance (and hence blood pressure). They are well-absorbed and thus taken orally, for example amlodipine is taken once daily because of its long

half-life.

The renin-angiotensin system is of significant importance in terms of fluid volume and vascular tone. Renin is released by the kidneys and converts angiotensinogen into angiotensin I (AT1) which is converted by ACE into the

potent vasoconstrictor angiotensin II (AT2). The ACE is a epithelial membrane-bound enzyme particularly abundant in the lungs and is the site of action for the antihypertensive ACE inhibitors (e.g. ramipril and captopril)

whose action is simply to block the active site of the enzyme, thus preventing the formation of AT2.

Statins help reduce the levels of low-density lipoprotein cholesterol (LDL-C) which adhere to damaged blood vessel walls as part of the athrogenesis chain reaction which ultimately results in significant vessel damage. The action is rather complex and involves an understanding of the mechanism of cholesterol transport and lipoprotein metabolism that exceeds the scope of this chapter. Suffice to say, they reduce circulatory HDL levels (see Chapter 20 of Rang and Dale’s Pharmacology for more detail). Examples of common statins are simvastatin, atorvastatin and pravastatin. As a physiotherapist, it is worth remembering that statins commonly cause muscle pain, so additional medical history may be required relating to how long they have been taking statins: does the pain correspond? Usually, by alerting the prescriber, the problem may be resolved by reducing the dose or changing the drug.

Diuretics increase NaCl excretion and thus water excretion. They are used to reduce oedema and decrease the load of the circulatory system on the heart. The most potent of these drugs are loop diuretics (e.g. furosemide), which inhibit transit of Na+, K+ and 2Cl− ions in the loop of Henle. They are typically given orally or i.v. in acute pulmonary oedema. Another example is the thiazides (e.g. bendroflumethiazide), which are more often used to treat

simple hypertension. They act on the distal tubule binding to, and inhibiting, the Na+/Cl− transport system which increases the loss of NaCl. A caution with these diuretics is the loss of K+ ions which is important to monitor in

patients who also have cardiac conditions requiring digoxin. An unwanted side effect of thiazides is erectile dysfunction. Potassium-sparing diuretics, such as spironolactone, are weak diuretics but they inhibit the secretion of

K+. These are particularly important to monitor as hyperkalaemia (too much potassium) can quickly become fatal.

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