StudyLoop

CARDIOVASCULAR SYSTEM DRUGS-1

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CARDIOVASCULAR SYSTEM DRUGS

A-adrenoceptor antagonists (blockers) 

EXAMPLES 

Doxazosin, prazosin, tamsulosin, alfuzosin

MECHANISM OF ACTION 

Inhibits a1-adrenoceptors in arterioles, thereby reducing the tone of vascular smooth muscle and reducing total peripheral resistance. Inhibition of a1-adrenoceptors in periurethral prostatic stroma results in relaxation of the internal urethral sphincter and some relief of obstructive urinary symptoms in males.

INDICATIONS

  • Hypertension (i.e. doxazosin, particularly in resistant cases as part of polytherapy)
  • Benign prostatic hyperplasia

CAUTIONS AND CONTRA-INDICATIONS

Caution in patients with a susceptibility to heart failure

SIDE-EFFECTS

  • Postural hypotension.
  • Dizziness.
  • Weakness and fatigue.
  • Reflex tachycardia.
  • Headache.
  • Dry mouth.
  • Ejaculatory failure

METABOLISM AND HALF-LIFE 

Variable – e.g. doxazosin (t½ 22h) extensively metabolised by the liver; alfuzosin (t½ 3–5h) partially metabolised.

MONITORING 

May cause severe first-dose hypotension, therefore, need to start at a low dose and warn the patient of side-effects.

DRUG INTERACTIONS

Enhanced hypotensive effect with antihypertensives and alcohol

IMPORTANT POINTS

  • Centrally acting a2-adrenoceptor agonists (e.g. clonidine, methyldopa) also have an antihypertensive effect (mediated via suppression of the vasomotor centre in the brain).
  • These agents are rarely used due to infrequent but potentially severe adverse effects (methyldopa may cause hepatitis). Methyldopa continues to be used for hypertension in pregnancy

Adenosine 

MECHANISM OF ACTION 

Stimulates specific A1 receptors on the surface of cardiac cells thus influencing adenosine-sensitive Kþ channel and cAMP production. This leads to prolonged conduction through the AV node, often with a high degree AV block.

INDICATIONS

  • Rapid reversal of SVT to sinus rhythm. SVT with aberrant conduction (specialist use only).
  • Aiding diagnosis of narrow or broad complex tachycardias

CAUTIONS AND CONTRA-INDICATIONS 

  • Second and third-degree AV block. Sick sinus syndrome.
  • Prolonged QT syndrome.
  • Severe hypotension.
  • Decompensated heart failure. Asthma

SIDE-EFFECTS

  • Chest pain
  • Dyspnea
  • Bronchospasm
  • Nausea
  • Severe bradycardia
  • Choking sensation
  • Light-headedness

METABOLISM AND HALF-LIFE

t½ <2s. Metabolised by uptake into red blood cells and deaminated in plasma.

MONITORING 

Cardiac monitoring required.

DRUG INTERACTIONS. 

Effects of adenosine are potentiated by dipyridamole

IMPORTANT POINTS. 

  • Ensure the patient is linked to a cardiac monitor or defibrillator.
  • Attempt vasovagal manoeuvres prior to administration unless contra-indicated
  • If no response to the above, start with 6mg IV rapid bolus given through a large vein and flush with 20ml of normal saline.
  • Repeat with 12mg after 1–2 minutes if no response. A further 12mg can be given.
  • Early specialist cardiology advice is warranted if no response to 12mg of adenosine or if adverse signs are present at any stage e.g. heart failure.
  • Patients should be informed prior to adenosine administration of possible chest pain and the sensation of the heart ceasing to beat

Aldosterone antagonists 

EXAMPLES Spironolactone, eplerenone

MECHANISM OF ACTION 

Competitive antagonist at intracellular aldosterone receptors in renal tubules causing a reduced production of aldosterone-induced proteins. This indirectly reduces the activity of Naþ/Kþ ATPase in the collecting ducts, increasing excretion of Naþ and decreasing Kþ loss. Spironolactone, in particular, also acts on receptors in other tissues, including androgen receptors.

INDICATIONS

  • Congestive cardiac failure (spironolactone)
  • Oedema and ascites in liver disease (spironolactone)
  • Post-MI heart failure (eplerenone)
  • Nephrotic syndrome (spironolactone)
  • Primary hyperaldosteronism (including Conn’s syndrome) (spironolactone)

CAUTIONS AND CONTRA-INDICATIONS

  • Electrolyte disturbances (including hyperkalaemia and hyponatraemia)
  • Caution in renal impairment

SIDE-EFFECTS 

  • Hyperkalaemia (Kþ sparing effect)
  • GI disturbance
  • Anti-androgenic effects (spironolactone – menstrual irregularities in females, gynecomastia and hypogonadism in males)

METABOLISM AND HALF-LIFE 

Metabolised to active metabolites. t½ of drug is 60–90min but t½ of active metabolites is longer (up to 11h)

MONITORING 

Monitor plasma electrolytes for adverse effects as above.

DRUG INTERACTIONS

  • Enhanced hypotensive effect with other antihypertensives.
  • Increased risk of hyperkalaemia with ACEIs/ARBs and amiloride.
  • Increased risk of nephrotoxicity with NSAIDs

IMPORTANT POINTS

  • Eplerenoneismoreselectivethanspironolactoneandthereforecausesfewersexhormonerelated adverse effects.
  • Spironolactone may also be used in hypertension (unlicensed indication).

Amiodarone

MECHANISM OF ACTION InhibitsNaþ/KþATPasesinmyocardium.Prolongsactionpotential duration and refractory period slow AV conduction and SA node function.

INDICATIONS 

  • Paroxysmal SVT
  • Nodal and ventricular tachycardias
  • Atrial fibrillation and flutter
  • VF
  • Tachyarrhythmias associated with Wolff–Parkinson–White syndrome

CAUTIONS AND CONTRA-INDICATIONS 

  • Sinus bradycardia
  • SA node block
  • Thyroid dysfunction

SIDE-EFFECTS

  • Photosensitive rash
  • Slate-grey skin discolouration
  • Bradycardia
  • Hypothyroidism or hyperthyroidism
  • Corneal microdeposits (dazzling at night)
  • Pulmonary fibrosis/pneumonitis

METABOLISM AND HALF-LIFE 

Plasma t½ is long 50 days (ranges from 10–100 days)

MONITORING 

LFTs, TFTs and chest x-ray prior to commencing treatment. LFTs and TFTs every 6 months while on treatment.

DRUG INTERACTIONS

  • Increases plasma levels of warfarin, digoxin and phenytoin (reduce doses accordingly) leading to toxicity.
  • Drugs that prolong QT interval

IMPORTANT POINTS

  • Should only be initiated under specialist supervision .
  • ECG monitoring required when given intravenously.
  • Should be administered through a central line or large IV cannula.
  • Can cause torsades de pointes, particularly in individuals with prolonged QT interval (congenital or acquired)

Angiotensin-converting enzyme inhibitors (ACEIs)

EXAMPLES 

Ramipril, lisinopril, perindopril

MECHANISM OF ACTION 

Inhibit angiotensin-converting enzyme, preventing the conversion of angiotensin I to angiotensin ii. This prevents angiotensin-mediated effects(arteriolar constriction and aldosterone release) resulting in reduced afterload and reduced circulating volume, thereby reducing BP.

INDICATIONS

  • Hypertension
  • Heart failure (result in improved survival in LV dysfunction)
  • Prophylaxis of further cardiovascular events post-MI
  • Diabetic nephropathy (lisinopril – results in reduced progression of the disease) Patients at high cardiovascular risk (ramipril)

CAUTIONS AND CONTRA-INDICATIONS

  • Hypersensitivity to ACEIs.
  • Pregnancy
  • Renal artery stenosis (reversal of angiotensin II-mediated constriction of efferent arteriole results in reduced GFR)
  • Caution in peripheral vascular disease as this may be associated with undiagnosed renal artery stenosis

SIDE-EFFECTS

  • Persistent dry cough. Hypotension (may get severe first-dose hypotension)
  • Renal impairment
  • Hyperkalaemia
  • Angioedema (rare)

METABOLISMANDHALF

LIFE Variable–e.g.ramipril(t½13–17h)has an active metabolite; lisinopril (t½ 12h) does not undergo metabolism.

MONITORING 

  • Monitor U&Es for renal impairment prior to and 1–2 weeks after commencing treatment.OncestableontherapyU&Esmustbecheckedatleastannually.
  • Careful clinical monitoring is required when used in severe heart failure.

DRUG INTERACTIONS

  • Risk of profound first-dose hypotension with loop diuretics and enhanced hypotensive effect with other antihypertensive agents
  • Increased risk of renal impairment with NSAIDs