1. Cardio pharmacology Angina

2. 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

3. decrease cardiovascular risk factors BP Cholesterol Smoking LVH

4. Decrease metabolic demands of the heart 1. Decrease HR 2. Decrease arterial pressure 3. Decrease ventricular dimensions

5. 1. Decrease HR Beta adrenoreceptor blockers Decrease sympathetic response Not for HF B1 Atenolol B2 Propranolol

6. 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 —   O 2 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

7. 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?

8. Details 2. 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

9. 3. Decrease ventricular size Nitrovasodilators GTN & isosorbide mononitrate/ dinitrate Active in 1-2 mins Lasts for 15-20 Metabolised to NO Increase venous capacitance

10. Details 3. 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)

11. 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

12. GTN ----> NO GTN is a prodrug for NO NO activates GC GC converts GTP ----> cGMP cGMP leads to smooth muscle relaxation......by decrease Ca

13. Potassium channel openers Nicorandil Vasodilator due to hyperpolarising of cells Ivabradine Acts selectively on SA node to slow HR

14. Details Potassium 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

15. 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