The Hypertension Drug Report
Section 1: Introduction -- The Condition That Touches Every Prescription Pad
A 71-year-old man in Castries takes lisinopril 20 mg, hydrochlorothiazide 25 mg, amlodipine 10 mg, and aspirin 81 mg. He has controlled hypertension, mild CKD (eGFR 48), and occasional knee pain for which he purchases diclofenac over the counter.
His medication list contains four antihypertensives and one analgesic. The analgesic undermines the antihypertensives. The lisinopril and hydrochlorothiazide, combined with the diclofenac he has not disclosed, form the triple whammy documented in Report 2. His eGFR of 48 places him in the range where hydrochlorothiazide loses efficacy (thiazides are less effective below eGFR 30, and some evidence suggests reduced benefit below 45). His amlodipine is causing ankle swelling that he attributes to "old age" -- a prescribing cascade (Report 1) waiting to generate a furosemide prescription.
One in three Jamaican adults has hypertension. In Trinidad and Tobago, the prevalence is approximately 26%. Across the OECS states, the figures are comparable. Hypertension is the most common chronic condition managed in Caribbean primary care, and antihypertensives are the most commonly prescribed drug class in the region.
Every drug added to manage hypertension or its complications introduces interactions, organ function considerations, and cascade risks that compound with polypharmacy. This report brings together every hypertension-relevant interaction, safety flag, organ function adjustment, and deprescribing consideration from the ElesRx database into a single reference.
Section 2: The Antihypertensive Classes -- Interactions and Adjustments
Nine antihypertensive classes and their primary risk domains in Caribbean practice.
| Class | Triple whammy | K+ risk | Renal concern | Beers flagged | Pregnancy |
|---|---|---|---|---|---|
| ACE inhibitors | Yes (with NSAID + diuretic) | Hyperkalaemia | eGFR drop on initiation | -- | Contraindicated |
| ARBs | Yes | Hyperkalaemia | Same as ACE | -- | Contraindicated |
| Amlodipine | -- | -- | -- | -- | -- |
| Nifedipine IR | -- | -- | -- | Yes | MR form acceptable |
| Thiazides | Yes | Hypokalaemia | Less effective below eGFR 30 | -- | -- |
| Furosemide | Yes | Hypokalaemia | Monitor electrolytes | -- | -- |
| Beta-blockers | -- | -- | -- | ACB Score 1 | Labetalol acceptable |
| Spironolactone | -- | Hyperkalaemia | Avoid above 25 mg if eGFR below 30 | Yes (above 25 mg) | -- |
| Methyldopa | -- | -- | -- | Yes | First-line in pregnancy |
| Clonidine | -- | -- | -- | Yes | -- |
| Alpha-blockers | -- | -- | -- | Yes -- falls | -- |
2.1 ACE Inhibitors -- Lisinopril, Enalapril, Ramipril
The most prescribed antihypertensive class in the Caribbean. First-line for hypertension, heart failure, and diabetic nephropathy. Renoprotective.
Key interactions:
| Interacting drug/substance | Mechanism | Clinical consequence |
|---|---|---|
| NSAIDs (ibuprofen, diclofenac) | Reduced antihypertensive effect + reduced renal prostaglandins | Blood pressure elevation; acute kidney injury (triple whammy with diuretic) |
| Potassium-sparing diuretics (spironolactone, amiloride) | Additive potassium retention | Hyperkalaemia -- potentially fatal |
| Trimethoprim | ENaC blockade in collecting duct | Additive hyperkalaemia, particularly in CKD |
| Lithium | Reduced lithium excretion | Lithium toxicity |
| Aliskiren | Dual renin-angiotensin blockade | Hypotension, hyperkalaemia, renal impairment -- avoid combination |
Renal consideration (Report 2): ACE inhibitors reduce eGFR by 10-15% on initiation due to efferent arteriolar dilation. This is haemodynamic, not nephrotoxic, and is expected. A rise in creatinine of up to 30% is acceptable. Beyond 30%, reassess.
Pregnancy (Report 5): Contraindicated -- fetotoxic in second and third trimesters. Switch to methyldopa, labetalol, or nifedipine MR before conception or immediately on confirmation of pregnancy.
Cough: ACE inhibitor cough occurs in up to 20% of patients, more commonly in women and patients of African descent -- directly relevant to Caribbean demographics. The cough is mediated by bradykinin accumulation and does not respond to cough suppressants. Switch to an ARB. Do not add codeine (Report 1, Cascade 2).
Deprescribing (Report 4): ACE inhibitors are rarely deprescribing candidates. However, in the elderly patient on three or more antihypertensives with postural hypotension, reducing the total antihypertensive load -- potentially by removing the most recently added agent -- may be appropriate.
2.2 ARBs -- Losartan, Valsartan, Telmisartan
Same interaction profile as ACE inhibitors with the exception of cough (ARBs do not cause bradykinin-mediated cough). ARBs are the standard alternative when ACE inhibitor cough occurs.
Dual blockade: ACE inhibitor + ARB should not be prescribed concurrently. The ONTARGET trial demonstrated increased hypotension, hyperkalaemia, and renal impairment without meaningful benefit (Report 1, Section 6).
Pregnancy (Report 5): Same contraindication as ACE inhibitors -- fetotoxic.
2.3 Calcium Channel Blockers -- Amlodipine, Nifedipine
Amlodipine is the most commonly prescribed CCB in the Caribbean. It is effective, well-tolerated, and does not require renal dose adjustment.
Key interactions:
| Interacting drug/substance | Mechanism | Clinical consequence |
|---|---|---|
| CYP3A4 inhibitors (clarithromycin, itraconazole, grapefruit juice) | Reduced amlodipine metabolism | Increased amlodipine levels -- excessive hypotension |
| Simvastatin | CYP3A4 competition | Increased simvastatin levels -- myopathy risk. Simvastatin dose should not exceed 20 mg with amlodipine |
| Soursop leaf tea (Report 3) | Additive hypotensive effect | Postural hypotension, dizziness |
| Fever grass tea (Report 3) | Mild additive hypotensive effect | Clinically significant only with multiple antihypertensives or volume depletion |
The amlodipine oedema cascade (Report 1): Amlodipine causes dose-dependent peripheral oedema through arteriolar vasodilation. This is not fluid overload. It should not be treated with a diuretic. Reducing the dose or adding an ACE inhibitor (which causes venodilation) often resolves it.
Nifedipine immediate-release (Report 1): Beers-flagged. Associated with precipitous hypotension and reflex tachycardia. Risk of myocardial ischaemia in older adults. Modified-release formulations are appropriate; immediate-release capsules are not.
2.4 Thiazide and Thiazide-Like Diuretics -- Hydrochlorothiazide, Chlorthalidone, Indapamide
Key interactions:
| Interacting drug/substance | Mechanism | Clinical consequence |
|---|---|---|
| NSAIDs | Reduced diuretic and antihypertensive effect | Blood pressure elevation; fluid retention |
| Lithium | Reduced lithium excretion due to sodium depletion | Lithium toxicity |
| Digoxin | Thiazide-induced hypokalaemia potentiates digoxin toxicity | Cardiac arrhythmias |
| Corticosteroids | Additive hypokalaemia | Muscle weakness, cardiac risk |
Metabolic effects: Thiazides cause hypokalaemia, hyperuricaemia (gout -- Report 1, Cascade 5), hyperglycaemia (can worsen diabetic control), and hypercalcaemia. These are dose-dependent and more pronounced with higher doses.
Renal consideration: Thiazides lose diuretic efficacy below eGFR 30 (some evidence suggests below eGFR 45). In advanced CKD, loop diuretics (furosemide) are more effective.
Fixed-dose combinations (Report 2): Hydrochlorothiazide + amiloride and hydrochlorothiazide + triamterene combination tablets are widely available in Caribbean pharmacies. The potassium-sparing component (amiloride, triamterene) is contraindicated at CrCl below 30 -- a fact that may be obscured when the combination is dispensed by brand name.
2.5 Loop Diuretics -- Furosemide
Key interactions:
| Interacting drug/substance | Mechanism | Clinical consequence |
|---|---|---|
| ACE/ARB + NSAID | Triple whammy (Report 2) | Acute kidney injury |
| Digoxin | Furosemide-induced hypokalaemia | Digoxin toxicity |
| Aminoglycosides (gentamicin) | Additive ototoxicity and nephrotoxicity | Hearing loss; renal damage |
| Lithium | Reduced lithium excretion | Lithium toxicity |
Monitoring: Electrolytes (potassium, sodium, magnesium) should be checked within 1-2 weeks of starting and periodically thereafter. Hypokalaemia is common and clinically significant.
2.6 Beta-Blockers -- Atenolol, Metoprolol, Bisoprolol, Carvedilol
Key interactions:
| Interacting drug/substance | Mechanism | Clinical consequence |
|---|---|---|
| Non-dihydropyridine CCBs (verapamil, diltiazem) | Additive negative chronotropy and dromotropy | Severe bradycardia, heart block |
| Insulin and sulfonylureas | Mask hypoglycaemic symptoms (tremor, tachycardia) | Delayed recognition of hypoglycaemia |
| Clonidine | Rebound hypertensive crisis if clonidine stopped while on beta-blocker | Do not stop clonidine before beta-blocker |
Deprescribing (Report 4): Beta-blockers must not be stopped abruptly -- rebound tachycardia and hypertension can occur. Taper over 1-2 weeks.
Beers Criteria: Atenolol appears on the ElderWatch flag list with a Score 1 ACB rating. Non-selective beta-blockers carry higher interaction potential with insulin than cardioselective agents.
2.7 Central Alpha-Agonists -- Methyldopa, Clonidine
Methyldopa: First-line in pregnancy (Report 5). Beers-flagged for older adults due to sedation, depression, and orthostatic hypotension (Report 1). The deprescribing candidate is the post-partum patient still on methyldopa months after delivery (Report 4, Drug 9).
Clonidine: Beers-flagged. Risk of rebound hypertensive crisis if stopped abruptly. Must be tapered. Should not be combined with beta-blockers (rebound risk is magnified).
2.8 Alpha-Blockers -- Doxazosin, Prazosin, Terazosin
Beers-flagged (Report 1): High risk of orthostatic hypotension and falls in older adults when used for hypertension. Their role has shifted to benign prostatic hyperplasia rather than hypertension management.
2.9 Mineralocorticoid Receptor Antagonists -- Spironolactone
Indicated for: Resistant hypertension (fourth-line agent), heart failure, primary aldosteronism, ascites.
Key risk (Report 2): Hyperkalaemia, particularly when combined with ACE/ARB in patients with declining renal function. Doses above 25 mg/day in patients with eGFR below 30 are associated with significant hyperkalaemia risk.
Monitoring: Potassium within 1 week of starting, after any dose change, and every 3 months thereafter.
Section 3: The Interactions That Clinicians Miss
3.1 The triple whammy -- revisited
ACE/ARB + diuretic + NSAID. Documented in Report 2, Section 4. Included here because hypertension is the condition that places the ACE/ARB and diuretic on the medication list, and the NSAID is added by the patient or another prescriber for pain.
The clinical intervention is the same: ask about OTC NSAID use at every hypertension review.
3.2 Grapefruit juice and amlodipine
Grapefruit juice inhibits intestinal CYP3A4, increasing the bioavailability of amlodipine and other dihydropyridine CCBs. A single glass of grapefruit juice can increase amlodipine plasma levels by 15-20%. In a patient on the maximum dose (10 mg), this can produce excessive hypotension. In the Caribbean, grapefruit is commonly consumed as a breakfast fruit and as juice.
3.3 Liquorice and hypertension
Liquorice root (Glycyrrhiza glabra) contains glycyrrhizinic acid, which inhibits 11-beta-hydroxysteroid dehydrogenase, causing mineralocorticoid excess -- sodium retention, potassium loss, and blood pressure elevation. The effect is dose-dependent and can be clinically significant with regular consumption. Liquorice-flavoured confections and herbal teas containing liquorice root are available in the Caribbean.
In a patient with resistant hypertension on multiple antihypertensives, liquorice consumption should be specifically asked about.
3.4 Soursop leaf and antihypertensives
Documented in Report 3. Soursop leaf tea has antihypertensive activity through vasodilation. In patients on multiple antihypertensives, the additive effect can produce clinically significant hypotension. The three questions from Report 3 apply at every hypertension review.
Section 4: Blood Pressure Targets in Older Adults
Blood pressure targets in patients aged 80 and older are less aggressive than in younger adults. Treating to a systolic target of 130 mmHg with three or four antihypertensives in a frail 82-year-old carries risks -- orthostatic hypotension, falls, fractures, acute kidney injury -- that may outweigh the cardiovascular benefit.
Current evidence supports: - Systolic target below 150 mmHg in patients aged 80 and older (some guidelines permit below 140) - Individualised targets based on frailty, fall risk, and patient preference - Willingness to reduce the antihypertensive load if postural symptoms develop
The deprescribing framework from Report 4 applies: is the third or fourth antihypertensive still contributing more benefit than harm?
Section 5: The Monitoring Checklist -- Hypertension Edition
Print and use at every hypertension medication review.
| Drug | Check | Frequency | Act when |
|---|---|---|---|
| ACE inhibitor / ARB | K+, eGFR | At start; 1-2 weeks; then every 3-6 months | Hold if K+ above 5.5; reassess if eGFR drops more than 30% |
| Thiazide | K+, Na+, urate, glucose | At start; 4-6 weeks; then every 6-12 months | Supplement K+ if below 3.5; investigate gout if urate elevated |
| Furosemide | K+, Na+, Mg2+, eGFR | At start; 1-2 weeks; then every 3-6 months | Supplement electrolytes as needed; reassess dose if eGFR declining |
| Spironolactone | K+, eGFR | At start; within 1 week; then every 3 months | Hold if K+ above 5.5; avoid above 25 mg/day if eGFR below 30 |
| Amlodipine | Blood pressure; ankle oedema assessment | Every visit | Do not add diuretic for vasodilatory oedema; reduce dose or add ACE/ARB |
| Beta-blocker | Heart rate, blood pressure | Every visit | Do not stop abruptly; taper over 1-2 weeks if discontinuing |
| Methyldopa | Blood pressure; assess for sedation, depression | Every visit post-partum | Switch to alternative antihypertensive post-partum |
| Clonidine | Blood pressure | Every visit | Do not stop abruptly; taper; do not combine with beta-blocker |
| Alpha-blocker | Postural blood pressure | Every visit | Assess fall risk; consider alternative if postural symptoms present |
| All antihypertensives | OTC NSAID use inquiry | Every visit | Document; counsel on triple whammy risk |
| All antihypertensives | Herbal tea use inquiry | Every visit | Document soursop leaf, fever grass use; adjust doses if needed |
Section 6: About ElesRx
ElesRx flags the interactions described in this report when a clinician enters a hypertensive patient's medication list. The triple whammy, ACE/ARB + potassium-sparing diuretic hyperkalaemia risk, amlodipine oedema cascade, and herbal interactions with antihypertensives are all checked automatically.
The tool is available at elesrx.com. ElesRx is a product of PIPPS Smart Apps, a division of J.C. Epiphany Limited (Jamaica, est. 1998).
Section 7: Methodology and References
7.1 Data sources
Antihypertensive interaction and safety data is drawn from the ElesRx clinical database, verified against DailyMed, the European Medicines Agency, Health Canada, and published clinical guidelines. This report consolidates hypertension-relevant content from Reports 1-8 and supplements it with additional class-specific pharmacology.
7.2 Limitations
This report focuses on outpatient hypertension management as encountered in Caribbean primary care. Hypertensive emergencies, secondary hypertension workup, and specialist-level resistant hypertension management are beyond its scope.
7.3 Author and conflict of interest disclosure
This report was authored by Juliet Duncan, BPharm, founder of J.C. Epiphany Limited and developer of ElesRx. The author has a commercial interest in ElesRx. This report is published without an access gate as a contribution to Caribbean clinical education. No external funding was received.
7.4 Citation
Duncan J. The Hypertension Drug Report: Every Interaction, Flag, and Adjustment for the Most Prescribed Drug Class in the Caribbean. ElesRx Clinical Reports, Report 9. Published 2026 at elesrx.com/reports/hypertension-drug-report/. J.C. Epiphany Limited, Jamaica.
References
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ONTARGET Investigators; Yusuf S, Teo KK, Pogue J, et al. Telmisartan, ramipril, or both in patients at high risk for vascular events. N Engl J Med. 2008;358(15):1547-1559. doi:10.1056/NEJMoa0801317
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Lapi F, Azoulay L, Yin H, Nessim SJ, Suissa S. Concurrent use of diuretics, angiotensin converting enzyme inhibitors, and angiotensin receptor blockers with non-steroidal anti-inflammatory drugs and risk of acute kidney injury. BMJ. 2013;346:e8525. doi:10.1136/bmj.e8525
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Beckett NS, Peters R, Fletcher AE, et al. Treatment of hypertension in patients 80 years of age or older (HYVET). N Engl J Med. 2008;358(18):1887-1898. doi:10.1056/NEJMoa0801369
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Williams B, Mancia G, Spiering W, et al. 2018 ESC/ESH Guidelines for the management of arterial hypertension. Eur Heart J. 2018;39(33):3021-3104. doi:10.1093/eurheartj/ehy339
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American Geriatrics Society 2023 Updated AGS Beers Criteria for Potentially Inappropriate Medication Use in Older Adults. J Am Geriatr Soc. 2023;71(7):2052-2081. doi:10.1111/jgs.18372