A Drugs: Angiotensin Receptor Blockers (ARBs)

Angiotensin Receptor Blockers (ARBs)

Overview

  • Several angiotensin receptor blockers (ARB or ‘sartans’) are in clinical use, including:

    • Losartan

    • Candesartan

    • Irbesartan

    • Valsartan

Usage

  • Pharmacological Distinction: Sartans are pharmacologically distinct from ACE inhibitors (ACEIs) but clinically similar in their efficacy for lowering blood pressure (hypotensive efficacy).

  • Adverse Effects: One key difference from ACEIs is that ARBs do not commonly cause the adverse effect of a dry cough.

  • Long-acting Options: Long-acting ARBs, such as candesartan, form a stable complex with the angiotensin II subtype 1 (AT1) receptor, providing good 24-hour blood pressure control.

Indications

  • Heart Failure and Myocardial Infarction:

    • ARBs are beneficial for patients suffering from heart failure or those who have experienced a myocardial infarction.

    • They are often recommended alongside ACEIs in hypertensive patients with these complications.

  • Diabetic Patients:

    • In diabetic patients, ARBs or ACEIs are preferred over other antihypertensive medications due to their ability to slow the progression of diabetic nephropathy.

  • Efficacy:

    • A head-to-head comparison of losartan versus atenolol in treating hypertension (the LIFE study) demonstrated a favorable outcome for losartan.

Safety and Tolerability

  • Tolerability: ARBs are known for excellent tolerability, making them the first-choice antihypertensive "A" drugs for many healthcare providers, although they are typically more expensive than ACEIs.

  • First-Dose Hypotension: Similar to ACEIs, ARBs may cause first-dose hypotension; thus, it is advised to initiate treatment at night and avoid starting in patients who are volume-depleted.

Mechanism of Action

  • Receptor Interaction: Most effects of angiotensin II, such as vasoconstriction and aldosterone release, occur via the angiotensin II subtype 1 (AT1) receptor.

  • Bradykinin: Unlike ACEIs, sartans do not inhibit the degradation of bradykinin, which likely accounts for the absence of cough associated with their use.

Adverse Effects

  • Renal Function: ARBs can adversely affect renal function in patients with bilateral renal artery stenosis, similar to ACEIs.

  • Electrolyte Imbalance: Hyperkalemia and fetal renal toxicity are also potential risks.

  • Angioedema: While angioedema is less frequent with ARBs compared to ACEIs, it can still occur.

Pharmacokinetics

  • Absorption: Sartans are well-absorbed following oral administration, with losartan having an active metabolite (E-3174).

  • Dosing Frequency: The half-lives of most marketed ARBs are sufficient to allow for once-daily dosing, enhancing patient adherence to treatment regimens.

Drug Interactions

  • Combination Therapy:

    • There is a rationale for using a sartan alongside an ACEI since not all angiotensin II originates from the action of ACE and some useful effects of ACEI could be kinin-mediated, allowing for some potential synergy.

    • However, clinical data suggest minimal additional benefits in hypertensive patients.

    • The usage of this combination in patients with heart failure is discussed in more detail in clinical literature, particularly in Chapter 31.