Angina pharmacology - Ipswich-Year2-Med-PBL-Gp-2

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Angina pharmacology

Summary

Drugs

Stable angina management: reduce heart O

2

Nitrates (reduce venous return)

Beta blockers (reduce sympathetic drive)

Calcium channel blockers (reduce inotropic state) demand

Refractory stable angina options

Perhexiline, Ivabradine

Preventative agents

Thrombosis prophylaxis

( Aspirin , clopidigrel, dipyrimadole, heparins)

Statins

ACE inhibitors

Diuretics

Triple Whammy

ACE Inhibitor, diuretic, and NSAID: a dangerous combination

(TGA.gov.au, Australian Adverse Drug Reactions Bulletin 2003)

NSAID + Diuretic + ACE inhibitor

Correlation with Renal failure

ADRAC wishes to remind prescribers that the combination of ACE inhibitors (or angiotensin receptor antagonists), diuretics and

NSAIDs (including COX-2 inhibitors) should be avoided if possible, and great care should be taken with ACE inhibitors and NSAIDs in patients with renal impairment.

Nitrates

Mechanism

Release nitric oxide (NO)

NO dilates venules and coronary arteries

Increases venous capacitance

Decreases preload

Decreases contractility (Frank-Starling mechanism)

Nitrates

Adverse effects

Headaches, hypotension, flushing, palpitations, orthostatic hypotension, fainting, peripheral oedema, contact dermatitis

Contraindications

Hypovolemia or hypotension

Raised intracranial pressure

Significant anemia

G6PD deficiency (risk of hemolytic anemia)

Recent (1-5 days) use of PDE5 inhibitors (excacerbates hypotension)

– hypertrophic obstructive cardiomyopathy

– cardiac tamponade

Aortic stenosis, mitral stenosis, cor pulmonale.

Precautions

Tolerance. 10-12 hour nitrate free interval recommended each day.

Withdrawal. Reduce dose gradually.

Nitrates

Drug

Route

Example

Dose

Trade name

Fast GTN

Sublingual

Slow GTN

500 mcg prn 10mg daily

Isosorbide dinitrate

Transdermal Oral/sublingual

10mg q.i.d

Nitrolingual,

Lycinate,

Anginine

Minitran,

Nitro-dur

Sorbidin, Isordil

Isosorbide mononitrate

Oral

60mg daily

Imtrate, Duride,

Imdur, Monodur

Nicorandil

Oral

10mg b.i.d

Ikorel

Nicorandil

Also opens KATP channels in smooth muscle, dilating arterial as well as venous vessels.

Can cause ulcers, often in the mouth.

Nitrates

GIT availability

Route

Glyceryl trinitrate

poor sublingual (tablet, spray) patch

IV infusion

Isosorbide dinitrate

oral tablet

20–25% sublingual tablet

Isosorbide mononitrate

100% controlled release tablet

Onset

<5 minutes

30–60 minutes

<10 minutes

15–40 minutes

<10 minutes

1–2 hours

Australian Medicines Handbook

Duration

<1 hour prolonged

4–6 hours

1–2 hours prolonged

β-blockers

Competitively antagonise beta adrenergic receptors

Blunt sympathetic stimulation

Reduce contractility and rate

No reflex rise in peripheral resistance

β-1 receptors

mainly in heart muscle

β-2 receptors

mainly in lungs and peripheral vessels

β-3 receptors

mainly in heart and adipose tissue

β-blockers

Contraindications

Reversible airway disease

Cardiogenic and hypovolemic shock

Prinzmetal (vasospasm) angina

Bradycardia, 2 nd and 3 rd degree Heart block, Sick sinus

Adverse effects

– nausea, diarrhoea, bronchospasm, dyspnoea, cold extremities, exacerbation of

Raynaud's syndrome, bradycardia, hypotension, orthostatic hypotension (carvedilol, labetalol), heart failure, heart block, fatigue, dizziness, abnormal vision, decreased concentration, hallucinations, insomnia, nightmares, depression, alteration of glucose and lipid metabolism, oedema (carvedilol)

Precautions

Diabetes: hypoglycemia sign can be masked

Hyperthyroidism: signs masked

Anaphylaxis risk: Reduces epipen effect

Phaeochromocytoma: aggravates hypertension

Myasthenic symptoms: aggravated

Peripheral vascular disease or Raynaud’s phenomenon: aggravated

Renal or hepatic impairment: Choose drug with appropriate elimination route

β-blockers for angina

Drug

Metoprolol

Propanolol

Atenolol

Oxyprenolol

Pindalol

Receptors

beta

1 beta

1

, beta

2 beta

1 beta

1

, beta

2

, symp beta

1

, beta

2

, symp

Elimination

hepatic

Daily doses

1–2 hepatic 2–3

Trade name

Betaloc, Lopressor,

Metohexal, Minax,

Metrol

Deralin, Inderal renal

Hepatic

Renal

1

2-3

2-3

Noten, Tensig, Tenormin

Corbiton

Barbloc, Visken

Australian Medicines Handbook

L-type Calcium channel blockers

Dihydropyridines

Strong vasodilation (arterial)

Decreases afterload

Phenylalkylamine

Verapamil

(less) Vasodilation and (more) cardiac depression

Decreases afterload, heart rate, and contractility

Benzothiazepine

Diltiazem

(more) Vasodilation and (less) cardiac depression

Decreases afterload, heart rate, and contractility

L-type Calcium channel blockers

Contraindications

Cardiogenic shock, Heart failure, Aortic stenosis

Adverse effects

Transient worsening of angina symptoms

Reflex tachycardia (short acting dihydropyridines)

Bradycardia (Diltiazem, Verapamil)

Headache, flushing, peripheral oedema (especially dihydropyridines)

Gingival hyperplasia

Constipation (Verapamil)

Rash, fatigue, dizziness, nausea, abdominal pain

Precautions

Myasthenia-like disease – exacerbated symptoms

Avoid β blockers with Verapamil

Use β blocker with dihydropyridines? (Murtagh)

CCB related oedema may not respond to diuretics

L-type Calcium channel blockers

Duration Drug

Verapamil

Diltiazem

Amlodipine

Felodipine

Nifedipine

Lercandipine

Long

Short

Short

Long

Example dose

80mg bid

30mg tid

180mg daily LA

5mg daily

5mg daily (LA)

20mg bid

10mg daily

Trade name

Anpec, Isoptin, Cordilox,

Veracps

Cardizem, Coras, Dilzem,

Vasocardol, Diltahexal

Amlo, Nordip, Norvapine,

Norvasc

Felodur, Felodil, Plendil

Adalat, Adefin, Nifexal

Zanidip

Australian Medicines Handbook

Nimodipine is a CCB indicated for subarachnoid hemorrhage management

Refractory stable angina options

Perhexiline

Australian Medicines Handbook

Mechanism

Adverse effects

Precautions

Trade name

Unclear. Calcium channel blocker?

Carnitine palmitoyltransferase 1 inhibitor?

Peripheral neuropathy

Hepatotoxicity

CYP2D6 saturable metabolism.

- Identify slow metabolizers

- Monitor plasma levels

- Titrate dose when changing other drugs

Pexsig

Saturable hepatic metabolism

Australian Medicines Handbook – Drugs and CYP enzymes

Cytochrome P450 enzyme family

CYP1A2

CYP2B6

CYP2C8

CYP2C9

CYP2C19

CYP2D6

CYP3A4/5

Interactions

Grapefruit, Starfruit , St John’s Wort, Nicotine, Watercress

Pharmaceuticals

Refractory stable angina options

Ivabradine

Australian Public Assessment Report for Ivabradine

Australian Medicines Handbook

Mechanism

Side effects

Trade name

PBS

Inhibits I f

(not so funny now)

Lowers heart rate

Prolongs QT interval

“Luminous phenomena” (Retinal I h current)

Coralan

Not subsidised

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