•
– 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

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.

•
– Release nitric oxide (NO)
– NO dilates venules and coronary arteries
– Increases venous capacitance
– Decreases preload
– Decreases contractility (Frank-Starling mechanism)

• 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.

Drug Fast GTN Slow GTN Isosorbide dinitrate
Isosorbide mononitrate
Route Sublingual Transdermal Oral/sublingual Oral
500 mcg prn 10mg daily 10mg q.i.d
60mg daily Example
Dose
Trade name
Nitrolingual,
Lycinate,
Anginine
Minitran,
Nitro-dur
Sorbidin, Isordil 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.

GIT availability
Route
Glyceryl trinitrate
Onset poor sublingual (tablet, spray) <5 minutes patch
IV infusion
Isosorbide dinitrate
30–60 minutes
<10 minutes oral tablet
20–25% sublingual tablet
Isosorbide mononitrate
15–40 minutes
<10 minutes
100% controlled release tablet 1–2 hours
Australian Medicines Handbook
Duration
<1 hour prolonged
4–6 hours
1–2 hours prolonged

•
•
•
•
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

• 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

Drug
Metoprolol
Propanolol
Atenolol
Oxyprenolol
Pindalol
Receptors beta
1
Elimination Daily doses hepatic 1–2
Trade name hepatic 2–3
Betaloc, Lopressor,
Metohexal, Minax,
Metrol
Deralin, Inderal beta
1
, beta
2 beta
1 renal beta
1
, beta
2
, symp Hepatic beta
1
, beta
2
, symp Renal
1
2-3
2-3
Noten, Tensig, Tenormin
Corbiton
Barbloc, Visken
Australian Medicines Handbook

•
– Strong vasodilation (arterial)
– Decreases afterload
•
– Verapamil
– (less) Vasodilation and (more) cardiac depression
– Decreases afterload, heart rate, and contractility
•
– Diltiazem
– (more) Vasodilation and (less) cardiac depression
– Decreases afterload, heart rate, and contractility

• 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

Duration Drug
Verapamil
Diltiazem
Amlodipine
Felodipine
Nifedipine
Lercandipine
Long
Short
Short
Long
Example dose Trade name
80mg bid
30mg tid
180mg daily LA
5mg daily
Anpec, Isoptin, Cordilox,
Veracps
Cardizem, Coras, Dilzem,
Vasocardol, Diltahexal
Amlo, Nordip, Norvapine,
Norvasc
5mg daily (LA) Felodur, Felodil, Plendil
20mg bid Adalat, Adefin, Nifexal
10mg daily Zanidip
Australian Medicines Handbook
Nimodipine is a CCB indicated for subarachnoid hemorrhage management

Australian Medicines Handbook
Mechanism
Adverse effects
Unclear. Calcium channel blocker?
Carnitine palmitoyltransferase 1 inhibitor?
Peripheral neuropathy
Hepatotoxicity
Precautions
CYP2D6 saturable metabolism.
- Identify slow metabolizers
- Monitor plasma levels
- Titrate dose when changing other drugs
Trade name Pexsig

• 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

Australian Public Assessment Report for Ivabradine
Australian Medicines Handbook
Mechanism
Inhibits I f
(not so funny now)
Lowers heart rate
Side effects
Prolongs QT interval
“Luminous phenomena” (Retinal I h current)
Trade name Coralan
PBS Not subsidised