chapter
Beta-blockers
Pages 16

Hypokalaemia, a side-effect of these diuretics, predisposes to arrhythmias during sotalol therapy

Normalize potassium levels before starting sotalol in patients already taking these diuretics. When starting these diuretics in patients already taking sotalol, monitor potassium levels every 4-6 weeks until stable

BETA-BLOCKERS – SOTALOL

IVABRADINE Risk of arrhythmias Additive effect; ivabradine slows the sinus node

Monitor ECG closely

BETA-BLOCKERS

BETA-BLOCKERS ALCOHOL Acute alcohol ingestion may ≠ hypotensive effect. Chronic moderate/heavy drinking ↓ hypotensive effect

Additive hypotensive effect. Mechanism of opposite effect with chronic intake is uncertain

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

BETA-BLOCKERS ANAESTHETICS – GENERAL Risk of severe hypotensive episodes during induction of anaesthesia (including patients using timolol eye drops)

Most general anaesthetics are myocardial depressants and vasodilators, so additive ↓ BP may occur

Monitor BP closely, especially during induction of anaesthesia

BETA-BLOCKERS ANAESTHETICS – LOCAL

Remember that ≠ BP can occur when epinephrine-containing local anaesthetics are used with patients on beta-blockers ➣ Sympathomimetics, below BETA-BLOCKERS BUPIVACAINE Risk of bupivacaine toxicity Beta-blockers, particularly

propranolol, inhibit hepatic microsomal metabolism of bupivacaine

Watch for bupivacaine toxicity – monitor ECG and BP

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↓ intravenous lidocaine 2. Risk of lidocaine toxicity due to ≠ plasma concentrations of lidocaine, particularly with propranolol and nadolol 3. ≠ plasma concentrations of propranolol and possibly some other beta-blockers

1. Additive negative inotropic and chronotropic effects 2. Uncertain, but possibly a combination of beta-blocker-induced reduction in hepatic blood flow (due to ↓ cardiac output) and inhibition of metabolism of lidocaine 3. Attributed to inhibition of metabolism by lidocaine

1. Monitor PR, BP and ECG closely; watch for development of heart failure when intravenous lidocaine is administered to patients on betablockers 2. Watch for lidocaine toxicity 3. Be aware. Regional anaesthetics should be used cautiously in patients with bradycardia. Betablockers could cause dangerous hypertension due to stimulation of alpha-receptors if epinephrine is used with local anaesthetic

BETA-BLOCKERS ANALGESICS

BETA-BLOCKERS NSAIDS – INDOMETACIN, PIROXICAM, POSSIBLY IBUPROFEN, NAPROXEN

↓ hypotensive efficacy of betablockers. There does not seem to be this effect with other NSAIDs

Additive toxic effects on kidney, and sodium and water, retention by NSAIDs. NSAIDs can raise BP by inhibiting renal synthesis of vasodilating prostaglandins. It is uncertain why this effect is specific to these NSAIDs

Watch for ↓ response to betablockers

METOPROLOL VALDECOXIB Risk of ≠ hypotensive efficacy of metoprolol

Metoprolol is metabolized by CYP2D6, which is inhibited by valdecoxib

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

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CARDIOVASCULAR DRUGS BETA-BLOCKERS Other beta-blockers

of timolol eye drops 2. ≠ plasma concentrations of esmolol when morphine is added 3. ≠ plasma concentrations of metoprolol and propranolol when dextropropoxyphene is added

1. Methadone inhibits CYP2D6, which metabolizes these betablockers 2. Unknown 3. ↓ hepatic clearance of metoprolol and propanolol

1. Monitor BP at least weekly until stable 2. Monitor BP closely 3. Monitor BP at least weekly until stable. Warn patients to report symptoms of hypotension (lightheadedness, dizziness on standing, etc.)

BETA-BLOCKERS ANTACIDS CONTAINING MAGNESIUM AND ALUMINIUM

≠ bioavailability of metoprolol and ↓ bioavailability of atenolol, which may produce mild variation in the response to metoprolol and atenolol

Variations in absorption of the respective beta-blockers

Clinical significance may be minimal but be aware; monitor BP at least weekly until stable when initiating antacid therapy. Warn patients to report symptoms of hypotension (light-headedness, dizziness on standing, etc.)

BETA-BLOCKERS ANTIARRHYTHMICS – AMIODARONE, DISOPYRAMIDE, FLECAINIDE, MEXILETINE, PROCAINAMIDE, PROPAFENONE

Risk of bradycardia (occasionally severe), ↓ BP and heart failure. A single case report has described bradycardia when timolol eye drops were given to a patient on flecainide. Also, ≠ plasma levels of propranolol and metoprolol

Additive negative inotropic and chronotropic effects. In addition, high-dose amiodarone is associated with ≠ plasma levels of metoprolol due to inhibition of CYP2D. Also, mexiletine is known to inhibit CYP1A2-mediated metabolism of propanolol. Lastly, propafenone is extensively metabolized by CYP2D6 enzymes and interferes with the metabolism of propranolol and metoprolol

Monitor PR, BP and ECG closely, especially when loading patients on beta-blockers with antiarrhythmics; watch for the development of heart failure. ↓ doses of beta-blocker accordingly, especially when coadministering propafenone with metoprolol or propanolol

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Mechanism Precautions

are halved by 1 g doses of ampicillin (but not smaller doses)

Uncertain Monitor BP closely during initiation of therapy with ampicillin

BETA-BLOCKERS RIFAMPICIN ↓ plasma concentrations and efficacy of bisoprolol, carvedilol, celiprolol, metoprolol and propanolol

Rifampicin induces hepatic enzymes (e.g. CYP2C19), which ≠ metabolism of the beta-blockers; in addition, it may also ≠ P-gp expression

Monitor PR and BP; watch for poor response to beta-blockers

BETA-BLOCKERS ANTICANCER AND IMMUNOMODULATING DRUGS

BETA-BLOCKERS CYTOTOXICS Imatinib may cause an ≠ in plasma concentrations of metoprolol, propanolol and timolol, with a risk of toxic effects

Imatinib is a potent inhibitor of CYP2D6 isoenzymes, which metabolize beta-blockers

Monitor for clinical efficacy and toxicity of beta-adrenergic blockers

ACEBUTOLOL, ATENOLOL, BETAXOLOL, BISOPROLOL, METOPROLOL, PROPANOLOL

CICLOSPORIN ≠ risk of hyperkalaemia Beta-blockers cause an efflux of potassium from cells, and sideeffect has been observed during ciclosporin therapy

CARVEDILOL CICLOSPORIN Possible ≠ in plasma concentrations of ciclosporin

Carvedilol is metabolized primarily by CYP2D6 and CYP2D9, with a minor contribution from CYP3A4

Usually a dose reduction (20%) of ciclosporin is required

BETA-BLOCKERS CORTICOSTEROIDS ↓ efficacy of beta-blockers Mineralocorticoids cause ≠ BP as a result of sodium and water retention

Watch for poor response to beta-blockers

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CARDIOVASCULAR DRUGS BETA-BLOCKERS Other beta-blockers

Additive hypotensive effect. Aldesleukin causes ↓ vascular resistance and ≠ capillary permeability

Monitor BP at least weekly until stable

BETA-BLOCKERS ANTIDEPRESSANTS

BETA-BLOCKERS LITHIUM Report of episode of ≠ lithium levels in elderly patient after starting low-dose propanolol. However, propanolol is often used to treat lithium-induced tremor without problems

Mechanism uncertain at present, but propanolol seems to ↓ lithium clearance

Monitor lithium levels when starting propanolol therapy in elderly people

BETA-BLOCKERS MAOIs ≠ hypotensive effect Additive hypotensive effect. Postural ↓ BP is a common side-effect of MAOIs

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

METOPROLOL SSRIs ≠ plasma concentrations of metoprolol

SSRIs inhibit metabolism of metoprolol (paroxetine, fluoxetine, sertraline, fluvoxamine via CYP2D6, and (es)citalopram via mechanism uncertain at present)

Monitor PR and BP at least weekly; watch for metoprolol toxicity, in particular loss of its cardioselectivity

PROPANOLOL, TIMOLOL SSRIs ≠ plasma concentrations and efficacy of propranolol and timolol

Fluvoxamine inhibits CYP1A2-, CYP2C19-and CYP2D6-mediated metabolism of propranolol. Fluoxetine inhibits CYP2C19-and CYP2D6-mediated metabolism of propanolol and timolol. Paroxetine and sertraline inhibit CYP2D6mediated metabolism of propanolol and timolol and can impair conduction through the AV node

Monitor PR and BP at least weekly. Warn patients to report symptoms of hypotension (light-headedness, dizziness on standing, etc.). Watch for propanolol toxicity

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Mechanism Precautions

CLOMIPRAMINE

with amitriptyline and clomipramine

These TCAs inhibit CYP2D6mediated metabolism of betablockers

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

LABETALOL, PROPANOLOL

IMIPRAMINE ≠ imipramine levels with labetalol and propanolol

Uncertain at present. Postulated that imipramine metabolism ↓ by competition at CYP2D6 and CYP2C8

Monitor plasma levels of imipramine when initiating beta-blocker therapy

PROPANOLOL MAPROTILINE Cases of ≠ plasma levels of maprotiline with propanolol

Uncertain at present. Postulated that maprotiline metabolism ↓ by alterations in hepatic blood flow

Monitor plasma levels of maprotiline when initiating beta-blocker therapy

BETA-BLOCKERS VENLAFAXINE ≠ plasma concentrations and efficacy of metoprolol, propranolol and timolol

Venlafaxine inhibits CYP2D6mediated metabolism of metoprolol, propanolol and timolol

Monitor PR and BP at least weekly; watch for metoprolol toxicity (in particular, loss of its cardioselectivity) and propanolol toxicity

BETA-BLOCKERS ANTIDIABETIC DRUGS

BETA-BLOCKERS ANTIDIABETIC DRUGS Beta-blockers may mask the symptoms and signs of hypoglycaemia. They also ↓ insulin sensitivity; however, beta-blockers that also have vasodilating properties (carvedilol, celiprolol, labetalol, nebivolol) seem to ≠ sensitivity to insulin

↓ glucose tolerance and interfere with the metabolic and autonomic responses to hypoglycaemia

Warn patients about masking of signs of hypoglycaemia. Vasodilating beta-blockers are preferred in patients with diabetes, and all betablockers should be avoided in those having frequent hypoglycaemic attacks. Monitor capillary blood glucose levels closely, especially during initiation of therapy ➣ For signs and symptoms of hypoglycaemia, see Clinical Features of Some Adverse Drug Interactions, Hypoglycaemia

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CARDIOVASCULAR DRUGS BETA-BLOCKERS Other beta-blockers

propanolol or timolol eye drops

These beta-blockers inhibit the rebound in blood glucose that occurs as a response to a fall in blood glucose levels

Cardio-selective beta-blockers are preferred, and all beta-blockers should be avoided in those having frequent hypoglycaemic attacks. Monitor capillary blood glucose levels closely, especially during initiation of therapy ➣ For signs and symptoms of hypoglycaemia, see Clinical Features of Some Adverse Drug Interactions, Hypoglycaemia

BETA-BLOCKERS ANTIDIARRHOEALS – KAOLIN

Possibly ↓ levels of atenolol, propanolol and sotalol

↓ absorption Separate doses by at least 2 hours

BETA-BLOCKERS ANTIEPILEPTICS

BETA-BLOCKERS BARBITURATES Regular barbiturate use may ≠ elimination of those beta-blockers metabolized by the liver (metoprolol, propanolol, timolol)

Barbiturates induce CYP1A2-, CYP2C9-and CYP2C19-mediated metabolism of propanolol

Monitor BP at least weekly until stable and watch for ≠ BP

BETA-BLOCKERS PHENYTOIN Phenytoin may ↓ propanolol levels Phenytoin induces CYP1A2-and CYP2C19-mediated metabolism of propanolol

Monitor BP at least weekly until stable and watch for ≠ BP

BETA-BLOCKERS ANTIGOUT DRUGS – SULFINPYRAZONE

Antihypertensive effects of oxprenolol ↓ by sulfinpyrazone

Unknown Monitor PR and BP closely; consider starting an alternative beta-blocker

BETA-BLOCKERS ANTIHYPERTENSIVES AND HEART FAILURE DRUGS

BETA-BLOCKERS ACE INHIBITORS, ADRENERGIC NEURONE BLOCKERS, ANGIOTENSIN II RECEPTOR ANTAGONISTS

≠ hypotensive effect Additive hypotensive effect; may be used therapeutically

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

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prazosin and terazosin

Additive hypotensive effect; may be used therapeutically. Betablockers prevent the ability to mount a tachycardia in response to ↓ BP; this ≠ the risk of firstdose ↓ BP when starting alphablockers in patients already on beta-blockers

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

BETA-BLOCKERS CENTRALLY ACTING ANTIHYPERTENSIVES

Risk of withdrawal ≠ BP (rebound ≠ BP) with clonidine and possibly moxonidine

Withdrawal of clonidine, and possibly moxonidine, is associated with ≠ circulating catecholamines; beta-blockers, especially noncardioselective ones, allow the catecholamines to exert an unopposed alpha-receptor action (vasoconstriction)

Do not withdraw clonidine or moxonidine while a patient is taking beta-blockers. Withdraw betablockers several days before slowly withdrawing clonidine and moxonidine

BETA-BLOCKERS VASODILATOR ANTIHYPERTENSIVES

≠ hypotensive effect Additive hypotensive effect with diazoxide, hydralazine, minoxidil and sodium nitroprusside. In addition, hydralazine may ≠ the bioavailability of beta-blockers with a high first-pass metabolism (e.g. propanolol and metoprolol), possibly due to alterations in hepatic blood flow or inhibited hepatic metabolism

Monitor BP closely

BETA-BLOCKERS ANTIMALARIALS

METOPROLOL ARTEMETHER/ LUMEFANTRINE

≠ risk of toxicity Uncertain Avoid co-administration

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CARDIOVASCULAR DRUGS BETA-BLOCKERS Other beta-blockers

Mefloquine can cause cardiac conduction disorders, e.g. bradycardia. Additive bradycardic effect. Single case report of cardiac arrest with co-administration of mefloquine and propanolol, possibly caused by Q-T prolongation

Monitor PR closely

BETA-BLOCKERS QUININE Risk of ≠ plasma concentrations and effects of labetalol, metoprolol and propranolol; ≠ systemic effects of timolol eye drops

Quinine inhibits CYP2D6, which metabolizes these beta-blockers

Monitor BP at least weekly until stable

BETA-BLOCKERS ANTIPARKINSON’S DRUGS – LEVODOPA

≠ hypotensive effect Additive hypotensive effect; however, overall, adding betablockers to levodopa can be beneficial (e.g. by reducing the risk of dopamine-mediated risk of arrhythmias)

Monitor BP at least weekly until stable

BETA-BLOCKERS ANTIPSYCHOTICS

BETA-BLOCKERS ANTIPSYCHOTICS ≠ hypotensive effect Dose-related ↓ BP (due to vasodilatation) is a side-effect of most antipsychotics, particularly the phenothiazines

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

PROPANOLOL, TIMOLOL CHLORPROMAZINE, HALOPERIDOL

≠ plasma concentrations and efficacy of both chlorpromazine and propranolol during co-administration

Propanolol and chlorpromazine mutually inhibit each other’s hepatic metabolism. Haloperidol inhibits CYP2D6-mediated metabolism of propanolol and timolol

Watch for toxic effects of chlorpromazine and propranolol; ↓ doses accordingly

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metoprolol, propanolol and timolol

Inhibition of CYP2D6-mediated metabolism of these beta-blockers and CYP2C19-mediated metabolism of propanolol

Use an alternative beta-blocker if possible; if not, monitor closely

BETA-BLOCKERS ANXIOLYTICS AND HYPNOTICS

BETA-BLOCKERS ANXIOLYTICS AND HYPNOTICS

≠ hypotensive effect Additive hypotensive effect; anxiolytics and hypnotics can cause postural ↓ BP

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

BETA-BLOCKERS DIAZEPAM May occasionally cause ≠ sedation during metoprolol and propranolol therapy

Propranolol and metoprolol inhibit the metabolism of diazepam

Warn patients about ≠ sedation

BETA-BLOCKERS BRONCHODILATORS

BETA-BLOCKERS BETA-2 AGONISTS Non-selective beta-blockers (e.g. propanolol) ↓ or prevents the bronchodilator effect of beta-2 agonists

Non-selective beta-blockers antagonize the effect of beta-2 agonists on bronchial smooth muscle

Avoid co-administration

BETA-BLOCKERS THEOPHYLLINE ≠ plasma levels of theophylline with propranolol

Propranolol exerts a dosedependent inhibitory effect on the metabolism of theophylline

Monitor theophylline levels during propranolol co-administration

BETA-BLOCKERS CALCIUM CHANNEL BLOCKERS

BETA-BLOCKERS CALCIUM CHANNEL BLOCKERS

≠ hypotensive effect, bradycardia, conduction defects and heart failure

Additive hypotensive effect; may be used therapeutically

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

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CARDIOVASCULAR DRUGS BETA-BLOCKERS Other beta-blockers

beta-blockers

It is uncertain why this severe effect occurs

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

BETA-BLOCKERS DILTIAZEM ≠ hypotensive and bradycardic effects: cases of severe bradycardia and AV block when both drugs are administered concurrently in the presence of pre-existing heart failure or conduction abnormalities

Additive effects on conduction; diltiazem causes bradycardia, sinoatrial block and AV block. Also, diltiazem inhibits CYP1A2mediated metabolism of propanolol

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

BETA-BLOCKERS VERAPAMIL 1. Risk of cardiac arrest when parenteral verapamil is given to patients on beta-blockers 2. Risk of bradycardias when both are given orally

Additive effect. Also, verapamil inhibits CYP1A2-mediated metabolism of propanolol

1. Do not administer intravenous verapamil to patients taking betablockers 2. Monitor ECG and BP carefully when both are given orally

BETA-BLOCKERS CARDIAC GLYCOSIDES

BETA-BLOCKERS DIGOXIN Risk of bradycardia and AV block Additive bradycardia Monitor PR, BP and ECG closely

CARVEDILOL DIGOXIN Carvedilol may ≠ digoxin plasma concentrations, particularly in children

↓ P-gp-mediated renal clearance of digoxin

↓ the dose of digoxin by 25%; watch for signs of digoxin toxicity and monitor digoxin levels

BETA-BLOCKERS COCAINE Risk of hypertensive crisis Cocaine produces both alpha-and beta-adrenergic agonist effects; selective beta-blockade leads to unopposed alpha-agonism (vasoconstriction)

Avoid concurrent use

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Modafinil is a reversible inhibitor

of CYP2C19 when used in therapeutic doses, and a moderate inducer of CYP1A2 in a concentration-dependent manner

Be aware

BETA-BLOCKERS DRUG DEPENDENCE THERAPIES – BUPROPION

≠ plasma concentrations of metoprolol, propranolol and timolol, with risk of toxic effects

Bupropion and its metabolite hydroxybupropion inhibit CYP2D6

Initiate therapy of these drugs at the lowest effective dose

BETA-BLOCKERS DIURETICS ≠ hypotensive effect Additive hypotensive effect; may be used therapeutically

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

BETA-BLOCKERS ERGOT DERIVATIVES Three reported cases of arterial vasoconstriction and one of ≠ BP occurred when ergotamine or methysergide was added to propanolol or oxprenolol

Ergotamine can cause peripheral vasospasm, and absence of betaadrenergic activity can ≠ the risk of vasoconstriction

Ergot derivatives and beta-blockers are often co-administered without trouble; however, monitor BP at least weekly until stable (watch for ≠ BP) and warn patients to stop the ergot derivative and seek medical attention if they develop cold, painful feet

PROPANOLOL 5-HT1 AGONISTS – RIZATRIPTAN

Plasma levels of rizatriptan almost doubled during propranolol therapy

Propanolol inhibits the metabolism of rizatriptan

Initiate therapy with 5 mg rizatriptan and do not exceed 10 mg in 24 hours. The manufacturers recommend separating doses by 2 hours, although this has not been borne out by the studies

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CARDIOVASCULAR DRUGS BETA-BLOCKERS Other beta-blockers

propranolol; ≠ systemic effects of timolol eye drops

Cimetidine inhibits CYP2D6, which metabolizes these beta-blockers, and inhibits CYP1A2-and CYP2E1mediated metabolism of propanolol. Ranitidine is a weaker inhibitor of CYP2D6

Monitor BP at least weekly until stable

BETA-BLOCKERS NIZATIDINE ≠ bradycardia when nizatidine is added to atenolol. Other betablockers have not been studied

Uncertain Monitor PR when administering nizatidine to patients on betablockers

BETA-BLOCKERS MUSCLE RELAXANTS

BETA-BLOCKERS NON-DEPOLARIZING 1. Modest ≠ in efficacy of muscle relaxants, particularly with propanolol 2. Risk of ↓ BP with atracurium and alcuronium

1 and 2. Uncertain 1. Watch for prolonged muscular paralysis after muscle relaxants 2. Monitor BP at least weekly until stable

BETA-BLOCKERS SKELETAL – BACLOFEN, TIZANIDINE

≠ hypotensive effect with baclofen or tizanidine. Risk of bradycardia with tizanidine

Additive hypotensive effect. Tizanidine has a negative inotropic and chronotropic effect

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

BETA-BLOCKERS NITRATES ≠ hypotensive effect Additive hypotensive effect; may be used therapeutically

Monitor BP at least weekly until stable

BETA-BLOCKERS OESTROGENS ↓ hypotensive effect Oestrogens cause sodium and fluid retention

Monitor BP at least weekly until stable; routine prescription of oestrogens in patients with ≠ BP is not advisable

BETA-BLOCKERS ORLISTAT Case report of severe ≠ BP when orlistat started on a patient on atenolol

Uncertain at present Monitor BP at least weekly until stable

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PYRIDOSTIGMINE

when neostigmine or physostigmine was given to reverse anaesthesia 2. ↓ effectiveness of neostigmine and pyridostigmine in myasthenia gravis

1. Neostigmine and pyridostigmine cause accumulation of ACh, which may cause additive bradycardia and ↓ BP 2. Beta-blockers are thought to have a depressant effect on the neuromuscular junction and thereby ≠ weakness

1. Monitor PR and BP closely when giving anticholinesterases to reverse anaesthesia to patients on betablockers 2. Monitor the response to neostigmine and pyridostigmine when starting beta-blockers

BETA-BLOCKERS PILOCARPINE ≠ risk of arrhythmias Pilocarpine is a parasympathomimetic and can cause additive bradycardia

Monitor PR and ECG closely

BETA-BLOCKERS PERIPHERAL VASODILATORS – MOXISYLYTE (THYMOXAMINE)

≠ hypotensive effect Additive hypotensive effect Monitor BP at least weekly until stable

BETA-BLOCKERS POTASSIUM CHANNEL ACTIVATORS

≠ hypotensive effect Additive effect Monitor BP at least weekly until stable

BETA-BLOCKERS PROSTAGLANDINS – ALPROSTADIL

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

BETA-BLOCKERS PROTON PUMP INHIBITORS Risk of ≠ plasma concentrations and effects of propranolol

Omeprazole inhibits CYP2D6-and CYP2C19-mediated metabolism of propanolol

Monitor BP at least weekly until stable

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CARDIOVASCULAR DRUGS BETA-BLOCKERS Other beta-blockers

The hypertensive effect of sympathomimetics opposes the hypotensive actions of betablockers

Monitor BP at least weekly until stable; watch for poor response to beta-blockers

BETA-BLOCKERS SYMPATHOMIMETICS – DIRECT

1. Severe ≠ BP and bradycardia with non-cardioselective betablockers (including reports of severe ≠ BP in patients given infiltrations of local anaesthetics containing epinephrine, and one case of a fatal reaction with phenylephrine eye drops) 2. Patients on beta-blockers may respond poorly to epinephrine when given to treat anaphylaxis

1. Unopposed alpha stimulation causes vasoconstriction, which results in a rise in BP. Beta-2 receptors, when stimulated, cause vasodilatation, which counteracts any alpha action; non-selective beta-blockers antagonize beta-2 receptors

1. Monitor BP at least weekly until stable. When using local anaesthetics with epinephrine, use small volumes of low concentrations (such as 1 in 200 000 epinephrine); avoid high concentrations (e.g. 1 in 1000 mixtures) 2. Look for failure of epinephrine therapy and consider using salbutamol or isoprenaline

BETA-BLOCKERS X-RAY CONTRAST SOLUTIONS

Beta-blockers are associated with ≠ risk of anaphylactoid reactions to iodinated X-ray contrast materials

Uncertain, but postulated that beta-receptors have a role in suppressing the release of mediators of anaphylaxis

Consider using low-osmolality contrast media and pretreating with antihistamines and corticosteroids. Stopping beta-blockers a few days before the X-ray is associated with a risk of withdrawal ≠ BP and tachycardia; a risk-benefit assessment must therefore be made