chapter
Antihypertensives and heart failure drugs
Pages 20

Monitor BP closely as unpredictable responses can occur. Advise patients to drink only in moderation and avoid large variations in the amount of alcohol drunk

ALPHA-BLOCKERS ALCOHOL ≠ levels of both alcohol and indoramin occurs with concurrent use

Uncertain Warn the patient about the risk of ≠ sedation

CENTRALLY ACTING ANTIHYPERTENSIVES

ALCOHOL Clonidine and moxonidine may exacerbate the sedative effects of alcohol, particularly during initiation of therapy

Uncertain Warn patients of this effect and advise them to avoid driving or operating machinery if they suffer from sedation

ANGIOTENSIN II RECEPTOR ANTAGONISTS

ALISKIREN Aliskiren levels possibly ↓ by irbesartan

Uncertain Monitor BP at least weekly until stable

ANTIHYPERTENSIVES AND HEART FAILURE DRUGS

ANAESTHETICS – GENERAL

Risk of severe hypotensive episodes during induction of anaesthesia

Most general anaesthetics are myocardial depressants and vasodilators. Additive hypotensive effect

Monitor BP closely, especially during induction of anaesthesia

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CARDIOVASCULAR DRUGS ANTIHYPERTENSIVES AND HEART FAILURE DRUGS ACE inhibitors and other drugs

epidural bupivacaine in patients on captopril

Additive hypotensive effect; epidural bupivacaine causes vasodilatation in the lower limbs

Monitor BP closely. Ensure that the patient is preloaded with fluids

ADRENERGIC NEURONE BLOCKERS – GUANETHIDINE

LOCAL ANAESTHETICS ↓ clinical efficacy of guanethidine when used in the treatment of complex regional pain syndrometype I

The local anaesthetic ↓ the reuptake of guanethidine

Be aware. Consider use of a local anaesthetic that minimally inhibits reuptake, e.g. lidocaine when possible

ANTIHYPERTENSIVES AND HEART FAILURE DRUGS

ANALGESICS

ANTIHYPERTENSIVES AND HEART FAILURE DRUGS

NSAIDs ↓ hypotensive effect, especially with indometacin. The effect is variable amongst different ACE inhibitors and NSAIDs, but is most notable between captopril and indometacin

NSAIDs cause sodium and water retention and raise BP by inhibiting vasodilating renal prostaglandins. ACE inhibitors metabolize tissue kinins (e.g. bradykinin) and this may be the basis for indometacin attenuating hypotensive effect of captopril

Monitor BP at least weekly until stable. Avoid co-administering indometacin with captopril

ACE INHIBITORS, ANGIOTENSIN II RECEPTOR ANTAGONISTS

NSAIDs 1. ≠ risk of renal impairment with NSAIDs and ACE inhibitors 2. ≠ risk of hyperkalaemia with ketorolac

1. Additive effect 2. Ketorolac causes hyperkalaemia, and ACE inhibitors can ↓ renal function

1. Monitor renal function and BP closely. Benefits often outweigh risks for short-term NSAID use 2. Ketorolac is only licensed for short-term control of perioperative pain. Monitor serum potassium daily

VASODILATOR ANTIHYPERTENSIVES

NSAIDs Etoricoxib may ≠ minoxidil levels Etoricoxib inhibits sulphotransferase activity

Monitor BP closely

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Mechanism Precautions

↓ absorption due to ≠ in gastric pH

Watch for poor response to ACE inhibitors

ACE INHIBITORS ANTIARRHYTHMICS – PROCAINAMIDE

Possible ≠ risk of leukopenia Uncertain at present Monitor FBC before starting treatment, 2-weekly for 3 months after initiation of therapy, then periodically thereafter

ANTIHYPERTENSIVES AND HEART FAILURE DRUGS

ANTIBIOTICS

ACE INHIBITORS RIFAMPICIN ↓ plasma concentrations and efficacy of imidapril and enalapril

Uncertain. ↓ production of active metabolites noted despite rifampicin being an enzyme inducer

Monitor BP at least weekly until stable

ACE INHIBITORS TETRACYCLINES ↓ plasma concentrations and efficacy of tetracyclines with quinapril. The absorption of tetracyclines may be reduced when taken concurrently with quinapril, due to the presence of magnesium carbonate as an excipient in quinapril’s pharmaceutical formulation

Magnesium carbonate (found in a formulation of quinapril) chelates with tetracyclines in the gut to form a less soluble substance that ↓ absorption of tetracycline

For short-term antibiotic use, consider stopping quinapril for duration of the course. For longterm use, consider an alternative ACE inhibitor

ACE INHIBITORS TRIMETHOPRIM Risk of hyperkalaemia when trimethoprim is co-administered with ACE inhibitors in the presence of renal failure

Uncertain at present Avoid concurrent use in the presence of severe renal failure

ANGIOTENSIN II RECEPTOR ANTAGONISTS – LOSARTAN

RIFAMPICIN ↓ antihypertensive effect of losartan

Rifampicin induces CYP2C9 Monitor BP at least weekly until stable

VASODILATOR ANTIHYPERTENSIVES

RIFAMPICIN ↓ bosentan levels Induction of metabolism Avoid co-administration

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CARDIOVASCULAR DRUGS ANTIHYPERTENSIVES AND HEART FAILURE DRUGS ACE inhibitors and other drugs

HEART FAILURE DRUGS

ACE INHIBITORS PORFIMER ≠ risk of photosensitivity reactions when porfimer is administered with enalapril

Attributed to additive effects Avoid exposure of skin and eyes to direct sunlight for 30 days after porfimer therapy

ANGIOTENSIN II RECEPTOR ANTAGONISTS

IMATINIB ≠ plasma concentrations of losartan, irbesartan and valsartan

Imatinib is a potent inhibitor of CYP2C9 isoenzymes, which metabolize these angiotensin II receptor blockers

Monitor for toxic effects of losartan, e.g. hypotension, hyperkalaemia, diarrhoea, cough, vertigo and liver toxicity

ACE INHIBITORS AZATHIOPRINE Risk of anaemia with captopril and enalapril and leukopenia with captopril

The exact mechanism is uncertain. Azathioprine-induced impairment of haematopoiesis and ACE inhibitor-induced ↓ in erythropoietin may cause additive effects. Enalapril has been used to treat post-renal transplant erythrocytosis

Monitor blood counts regularly

ACE INHIBITORS, ANGIOTENSIN II RECEPTOR ANTAGONISTS

CICLOSPORIN ≠ risk of hyperkalaemia and renal failure

Ciclosporin causes a dosedependent ≠ in serum creatinine, urea and potassium, especially in renal dysfunction

Monitor renal function and serum potassium weekly until stable, then at least every 3-6 months

VASODILATOR ANTIHYPERTENSIVES

CICLOSPORIN 1. Co-administration of bosentan and ciclosporin leads to ≠ bosentan and ↓ ciclosporin levels 2. Risk of hypertrichosis when minoxidil given with ciclosporin 3. ≠ sitaxentan levels

1. Additive effect; both drugs inhibit the bile sodium export pump, which is associated with hepatotoxicity 2. Additive effect 3. Uncertain

1. Avoid co-administration of bosentan and ciclosporin 2. Warn patients of the potential interaction 3. Avoid co-administration

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Mechanism Precautions

Corticosteroids cause sodium and water retention leading to ≠ BP

Monitor BP at least weekly until stable

VASODILATOR ANTIHYPERTENSIVES

CORTICOSTEROIDS Risk of hyperglycaemia when diazoxide is co-administered with corticosteroids

Additive effect; both drugs have a hyperglycaemic effect

Monitor blood glucose closely, particularly with diabetes

ANTIHYPERTENSIVES AND HEART FAILURE DRUGS

IL-2 (ALDESLEUKIN) ≠ hypotensive effect Additive hypotensive effect; may be used therapeutically. Aldesleukin causes ↓ vascular resistance and ≠ capillary permeability

Monitor BP at least weekly until stable. Warn patients to report symptoms of hypotension (light-headedness, dizziness on standing, etc.).