Cardio pharmacology Angina. angina Causes Atheroma Others: Aortic stenosis, aberrant coronary...
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Transcript of Cardio pharmacology Angina. angina Causes Atheroma Others: Aortic stenosis, aberrant coronary...
Cardio pharmacologyAngina
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
decrease cardiovascular risk factors
BP
Cholesterol
Smoking
LVH
Decrease metabolic demands of the heart
1. Decrease HR
2. Decrease arterial pressure
3. Decrease ventricular dimensions
1. Decrease HR
Beta adrenoreceptor blockers
Decrease sympathetic response
Not for HF
B1
Atenolol
B2
Propranolol
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
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?
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
3. Decrease ventricular size
Nitrovasodilators
GTN & isosorbide mononitrate/ dinitrate
Active in 1-2 mins
Lasts for 15-20
Metabolised to NO
Increase venous capacitance
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)
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
GTN ----> NO
GTN is a prodrug for NO
NO activates GC
GC converts GTP ----> cGMP
cGMP leads to smooth muscle relaxation...
...by decrease Ca
Potassium channel openers
Nicorandil
Vasodilator due to hyperpolarising of cells
Ivabradine
Acts selectively on SA node to slow HR
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
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