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# Direct renin inhibitors

Antihypertensives that block renin itself, the first step of the renin-angiotensin-aldosterone system.

Updated Nov 1, 2026

## What they are

Oral drugs that inhibit renin. Aliskiren is the only one in use; it lowers blood pressure about as much as other RAAS blockers but has no outcome advantage, so it is a second-line choice.

## Mechanism of action

Table 1**Drugs that act on the RAAS**

| Drug class | Blocks | Examples | Key effects | Pregnancy |
| --- | --- | --- | --- | --- |
| [ACE inhibitors](https://durgical.com/en/pharmacology/classes/ace-inhibitors/) | Angiotensin-converting enzyme (ACE) | [Enalapril](https://durgical.com/en/pharmacology/enalapril/) · [Captopril](https://durgical.com/en/pharmacology/captopril/) | Dry cough · angioedema · hyperkalaemia | Contraindicated |
| [ARBs](https://durgical.com/en/pharmacology/classes/angiotensin-ii-receptor-blockers/) | Angiotensin II AT1 receptor | [Losartan](https://durgical.com/en/pharmacology/losartan/) · [Valsartan](https://durgical.com/en/pharmacology/valsartan/) | Hyperkalaemia · cough is rare | Contraindicated |
| Renin inhibitor | Renin (first step of the axis) | [Aliskiren](https://durgical.com/en/pharmacology/aliskiren/) | Diarrhoea · hyperkalaemia | Contraindicated |
| [ARNI](https://durgical.com/en/pharmacology/classes/angiotensin-receptor-neprilysin-inhibitors/) | AT1 receptor and neprilysin | [Sacubitril/ valsartan](https://durgical.com/en/pharmacology/sacubitril-valsartan/) | Hypotension · angioedema · never with an ACE inhibitor | Contraindicated |
| [Mineralo­corticoid antagonist](https://durgical.com/en/pharmacology/classes/potassium-sparing-diuretics/) | Aldosterone receptor | [Spironolactone](https://durgical.com/en/pharmacology/spironolactone/) · [Eplerenone](https://durgical.com/en/pharmacology/eplerenone/) · [Finerenone](https://durgical.com/en/pharmacology/finerenone/) | Hyperkalaemia · gynecomastia (spironolactone) | Limited data; spironolactone is usually avoided |

Swipe to see more columns →

Five classes slow the same axis at different points, and all share the risk of hyperkalaemia. Source: Durgical, CC BY 4.0 Table comparing five classes that act on the renin-angiotensin-aldosterone system: what each blocks, examples, key effects and pregnancy risk level. ACE inhibitors, ARBs, renin inhibitors and ARNIs are contraindicated in pregnancy; mineralocorticoid antagonists have limited data.

Renin cuts angiotensinogen into angiotensin I. Aliskiren occupies the active site of renin, so angiotensin I, angiotensin II and aldosterone all fall. Plasma renin concentration rises because feedback is lost, but its activity stays blocked.

Target: Renin (active site)

## Key points

- Blocks the RAAS at its first, rate-limiting step.
- Not combined with an ACE inhibitor or ARB in diabetes (contraindicated): more kidney injury, hyperkalaemia and hypotension without benefit.
- Contraindicated in pregnancy, like every RAAS blocker (fetal toxicity).
- Very low oral bioavailability; high-fat meals reduce absorption.
- Diarrhoea is the commonest adverse effect; cough is much less frequent than with ACE inhibitors.

## Drugs in this class

- [**Aliskiren** The only direct renin inhibitor: lowers blood pressure by blocking the first step of the renin-angiotensin system. A… Renin](https://durgical.com/en/pharmacology/aliskiren/)

## Test yourself

Think of the answer, then tap the question to see it.

## What does aliskiren do to plasma renin activity and plasma renin concentration?

Renin activity falls because the enzyme is blocked, while renin concentration rises because angiotensin II no longer feeds back.

## In which patients is aliskiren contraindicated together with an ACE inhibitor or ARB?

In patients with diabetes, because of kidney injury, hyperkalaemia and hypotension.

## Why is aliskiren stopped when pregnancy is detected?

Drugs acting on the renin-angiotensin system injure the developing fetus, especially in the second and third trimesters.

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Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.

Sources: [Aliskiren: MedlinePlus Drug Information](https://medlineplus.gov/druginfo/meds/a607039.html) (MedlinePlus (U.S. National Library of Medicine), 2023); [DailyMed - ALISKIREN tablet, film coated](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f3fd2503-25ef-4660-a29a-f62c491e28fb) (DailyMed (U.S. National Library of Medicine), 2026).

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Representative model, for educational purposes only.

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Source: https://durgical.com/en/pharmacology/classes/direct-renin-inhibitors/
License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/pharmacology/classes/direct-renin-inhibitors/