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Antihypertensive Agents
Physiology
- MAP = CO × SVR
CO depends on preload, heart rate and contractility; SVR is set by arteriolar tone, circulating/renal volume and neuro-humoral modifiers (SNS, RAAS, vasopressin, natriuretic peptides). Modern drug therapy therefore targets:
| Target | Representative drug classes |
|---|---|
| RAAS blockade | ACE-Is, ARBs, renin inhibitors, MR-antagonists |
| Sympatholysis | β-blockers, α1-blockers, central α2-agonists |
| Vascular smooth-muscle Ca²⁺ influx | Dihydropyridine (DHP) & non-DHP CCBs |
| Sodium & fluid balance | Thiazide/loop diuretics, K⁺-sparing agents |
| Direct vasodilatation | Hydralazine, minoxidil, nitrates, nitroprusside (acute) |
Evidence-based First-line Therapy
- Both the 2023 ESC/ESH and 2024 NICE-NG136 updates recommend starting with one of four major classes (ACE-I/ARB, thiazide-like diuretic, CCB, or β-blocker in selected younger patients) and early step-up to dual or triple fixed-dose combinations if BP remains >140/90 mmHg.
- Low-renin phenotypes (age > 55 y or of African/Caribbean ancestry) respond best to a DHP-CCB or thiazide-like diuretic first.
Drug Classes in Clinical Practice
Renin–angiotensin–aldosterone System (RAAS) Blockers
| Class | Key points | Anaesthetic considerations |
|---|---|---|
| ACE inhibitors (enalapril, perindopril) | ↓ Ang II & ↑ bradykinin → arteriolar & venous dilation; renal & CV protection | Cough, angio-oedema, hyperkalaemia; intra-op vasoplegia possible—individualised continuation/withholding (see §5) |
| ARBs (losartan, candesartan) | AT1 receptor blockade without bradykinin accumulation | Less cough/angio-oedema; similar peri-op haemodynamic profile to ACE-Is |
| Direct renin inhibitor (aliskiren) | Reduces Ang I formation; niche use | Limited data, but profound refractory hypotension reported |
| ARNI (sacubitril/valsartan) | Inhibits neprilysin & blocks AT1 | Mainly for HFrEF; marked vasodilatation—treat like ACE-I peri-op |
Sympatholytics
| Agent | Main effects | Typical indications | Peri-op pearl |
|---|---|---|---|
| β-blockers (bisoprolol, atenolol, labetalol) | ↓ HR, contractility, renin release | Post-MI, AF, thyrotoxicosis, pregnancy (labetalol) | Continue long-term therapy; initiate only in high-risk pts ≥ 1 week pre-op with titration |
| α1-blockers (doxazosin) | Arteriolar & venous dilation | Resistant HTN, BPH | Risk of first-dose syncope—avoid new starts pre-op |
| Central α2-agonists (clonidine, methyldopa) | ↓ SNS outflow | Pregnancy (methyldopa), adjunct HTN | Abrupt cessation → rebound HTN; continue peri-op |
Calcium-channel Blockers (CCBs)
| Sub-class | Vascular selectivity | Typical uses | Key adverse effects |
|---|---|---|---|
| DHP (amlodipine, nifedipine) | High | First-line in low-renin HTN, pregnancy | Ankle oedema, reflex tachycardia |
| Non-DHP (diltiazem, verapamil) | Cardiac > vascular | Rate control in SVT/AF, angina | Bradycardia, AV block, LV dysfunction |
Diuretics
| Class | Site of action | BP effect | Peri-op caution |
|---|---|---|---|
| Thiazide-like (indapamide) | DCT NCC blockade | ↓ SVR via chronic natriuresis & vasodilatation | Morning dose; monitor Na⁺/K⁺ |
| Loop (furosemide) | NKCC2 TAL | Acute preload off-load | Volume depletion, ototoxicity |
| K⁺-sparing / MRA (spironolactone) | Collecting duct ENaC / MR | Adjunct in resistant HTN, HFpEF | Hyperkalaemia, gynaecomastia |
Direct Vasodilators
Hydralazine (selective arteriolar) & minoxidil (K_ATP opener) are reserved for resistant HTN or pregnancy-related acute control; tachyphylaxis and reflex tachycardia demand concurrent β-blocker. Sodium nitroprusside & GTN are titratable options for intra-operative HTN crises.
Special Topics for the Anaesthetist
Peri-operative Management of Chronic Antihypertensives
| Drug class | 2024 ACC/AHA peri-op guidance ¹ | Practical approach |
|---|---|---|
| β-blocker | Continue (Class I) | Check HR/BP; hold only for severe brady-hypotension |
| ACE-I / ARB / ARNI | Individualise (Class IIb)–may stop morning of surgery to mitigate vasoplegia | Stop-or-Not RCT 2024: no difference in 28-day MACE; continuation ↑ intra-op hypotension acc.org |
| CCB | Continue | Watch for potentiated negative inotropy when combined with β-blockers |
| Diuretics | Consider withholding morning dose in major surgery to avoid hypovolaemia | Replace electrolytes early |
| Central α2-agonist | Continue to avoid rebound | Have phenylephrine ready for brady-hypotension |
Statins & Vascular Protection
High-intensity statins reduce peri-operative myocardial injury and post-CABG AF; continue therapy and start ≥ 7 days pre-vascular/cardiac surgery when feasible.
Fast Reference Table (doses & On-table rescue)
| Scenario | First-choice IV agent | Bolus / infusion | Notes |
|---|---|---|---|
| Hypertensive crisis on table | Nicardipine | 5 mg h⁻¹, ↑2.5 mg h⁻¹ q5 min | Preferred over sodium nitroprusside (cyanide risk) |
| ACE-I/ARB vasoplegia post-induction | Vasopressin | 0.5–1 units bolus, then 0.03 U min⁻¹ | Consider methylene blue 1–2 mg kg⁻¹ if refractory |
| Severe reflex tachycardia after hydralazine | Esmolol | 500 µg kg⁻¹ bolus → 50–200 µg kg⁻¹ min⁻¹ | Short t½ allows rapid titration |
Links
References:
- Williams B, Mancia G, Spiering W, et al. 2023 ESH guidelines for the management of arterial hypertension. J Hypertens. 2023;41:1874-2071.
- National Institute for Health and Care Excellence. Hypertension in adults: diagnosis and management (NG136). Updated Nov 2024.
- Legrand M, Stop-or-Not Investigators. Continuation vs discontinuation of RAAS inhibitors before major surgery: a randomised trial. JAMA. 2024;332:1121-1131.
- American Heart Association/American College of Cardiology. 2024 Guideline for peri-operative cardiovascular evaluation and management of non-cardiac surgery. Circulation. 2025;151:e255-e388.
- Rifai R, Hasan A, et al. Peri-operative ACE-I/ARB continuation versus withdrawal: systematic review and meta-analysis. Br J Anaesth. 2025;134:1024-1035.
- Chen J, Huang P, et al. High-intensity statins and postoperative atrial fibrillation after CABG: meta-analysis. Intensive Care Med. 2024;50:212-222.
- The Calgary Guide to Understanding Disease. (2024). Retrieved June 5, 2024, from https://calgaryguide.ucalgary.ca/
- Greenstein, B. & Wood, D. (2017). “Antihypertensive Drugs,” BJA Education, 15(6), 280-287. doi:10.1016/j.bja.2017.04.002.](https://linkinghub.elsevier.com/retrieve/pii/S2058534917301221)
- Beta blockers and statins. University of Cape Town refresher 2009. Dr D Kirsch
- FRCA Mind Maps. (2024). Retrieved June 5, 2024, from https://www.frcamindmaps.org/
- Anesthesia Considerations. (2024). Retrieved June 5, 2024, from https://www.anesthesiaconsiderations.com/
- ICU One Pager. (2024). Retrieved June 5, 2024, from https://onepagericu.com/
Summaries:
Beta-blocker
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© 2025 Francois Uys. All Rights Reserved.
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