Cardio pharmacology Angina. angina Causes Atheroma Others: Aortic stenosis, aberrant coronary...

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Cardio pharmacology Angina

Transcript of Cardio pharmacology Angina. angina Causes Atheroma Others: Aortic stenosis, aberrant coronary...

Page 1: Cardio pharmacology Angina. angina Causes Atheroma Others: Aortic stenosis, aberrant coronary circulation, severe anaemia, arteritis Prevention Decrease.

Cardio pharmacologyAngina

Page 2: Cardio pharmacology Angina. angina Causes Atheroma Others: Aortic stenosis, aberrant coronary circulation, severe anaemia, arteritis Prevention Decrease.

angina

Causes

Atheroma

Others: Aortic stenosis, aberrant coronary circulation, severe anaemia, arteritis

Prevention

Decrease metabolic demands of the heart

Increase coronary blood flow

Decrease cardiovascular risk factors

Page 3: Cardio pharmacology Angina. angina Causes Atheroma Others: Aortic stenosis, aberrant coronary circulation, severe anaemia, arteritis Prevention Decrease.

decrease cardiovascular risk factors

BP

Cholesterol

Smoking

LVH

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Decrease metabolic demands of the heart

1. Decrease HR

2. Decrease arterial pressure

3. Decrease ventricular dimensions

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1. Decrease HR

Beta adrenoreceptor blockers

Decrease sympathetic response

Not for HF

B1

Atenolol

B2

Propranolol

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Detail 1. Drugs that ⇓ HR:

§ β-adrenoreceptor blockers – atenolol (β1) - , propranolol (β2). Block β receptors ∴ attenuate the sympathetic response of the heart → slow heart rate & improve capacity for exercise. Good if cardiac function is preserved, not for HF

§ Mode of action:

— ⇓ HR ⇑ with exercise etc.

— ⇓ contractility & arterial P

— ∴ ⇓ O2 demands of myocardium during exercise

§ Side effects:

— ⇑ LV dimensions∴ ⇑ LV work offsetting benefits

— Slow HR

— Heart failure

— Cold peripheries - Raynaud’s

§ Alternatives = Ca channel blockers – verapamil & diltiazem also slow HR due to effect on calcium channels in cardiac pacemaker cells

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2. decrease arterial pressure

Calcium channel blockers

Dihydropyridines

Nifedipine

Non-dihydropyridines

Diltiazem, verapamil

Mainly relax resistance arteries BP falls

Some effect on heart with...

...Diltiazem and Verapamil?

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Details2. Drugs that ⇓ Arterial Pressure

§ Ca channels blockers – verapamil, diltiazem & nifedipine (short acting)

§ Mode of action:

— Diltiazem (small effects) / Verapamil (large effects) - ⇓ Ca entry into cardiac pacemaker cells → HR ⇓. ⇓ Ca entry into myocytes ∴ ⇓ force of contraction

— Side effects: bradycardia & heart failure (oedema)

— All - ⇓ Ca influx thru L-type voltage-gated Ca channels in peripheral vasculature ∴⇓ peripheral resistance

— All - ⇓ Ca entry into vascular myocytes → relex at arteries, TPR ⇓, BP ⇓

Side effects:

§ reflex tachycardia (Nifedipine only) in response to peripheral vasodil

§ Flushing

§ Headaches

§ Ankle swelling

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3. Decrease ventricular size

Nitrovasodilators

GTN & isosorbide mononitrate/ dinitrate

Active in 1-2 mins

Lasts for 15-20

Metabolised to NO

Increase venous capacitance

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Details3. Drugs that ⇓ Ventricular Dimensions:

§ Nitrovasodilators – glyceryl trinitrate (GTN), isosorbide mononitrate, dinitrate relax vascular & other types of smooth muscle with preferential effect on veins

— ⇑ venous capacitance (& small ⇓ in arterial resistance) ⇓ central venous P → ⇓ in ventricular dimensions & CO. The ⇓ in cardiac size & small ⇓ in TPR = ⇓ in LV work. They also dilate coronary arteries → relief from angina

§ Mode of action: – nirtovasodilators metabolised to NO → activates vsmc guanylate cyclase in vascular smooth muscle → ⇑ in cGMP → ⇓ in IC free Ca → vascular relaxation

§ GTN – when swallowed is inactive until metabilsed in liver. If sucked under tongue absorbed rapidly, works within 1-2 mins & effects last for 15-20 mins

§ Isosorbide dinitrate ISDN– converted to ISMN in liver ∴ long acting orally active form of GTN (prophylactic)

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Details cont.§ Side effects:

— development of tolerance, resistance of vsm:· In withdrawal constriction of coronary arteries may

develop· Blood vessels may become insensitive to NO· Stable NO metabolite pool may become depleted Solution = give intermittently — Headaches due to dilation of muscular intracranial

arteries— Reflex ⇑ in HR— Limited potential for dilating sites of atheroma,

risk of steal syndrome – if one artery stenosed dilation of other = they take all the blood & leave that artery further depleted

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GTN ----> NO

GTN is a prodrug for NO

NO activates GC

GC converts GTP ----> cGMP

cGMP leads to smooth muscle relaxation...

...by decrease Ca

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Potassium channel openers

Nicorandil

Vasodilator due to hyperpolarising of cells

Ivabradine

Acts selectively on SA node to slow HR

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DetailsPotassium channel Openers

· Nicorandil – ⇓ ICK+ ∴ cells become hyperpolarised - vasodilator

§ Side effects:

— Severe headache

— Flushing

— Dizziness & low BP

· Ivabradine:

§ Selective action on SA node → slows HR

§ Protects endothelium dependant relaxation → relax coronary arteries

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Combinations

Increase in heart size caused by B-blockers can be offset by...

...nitrovasodilators

Tachycardia of nitrovasodilators or nifedipine can be prevented by giving...

...B-blockers

Aspirin good for stopping platelets sticking

Given to everyone unless...

...they are bleeding