Cardiac Pharmacology Flashcards
Pre-load
Volume of blood in the ventricles before they contract
After-load
The force against which the heart has to push the blood.
Ischemia
- warning that the blood supply to the myocardium is insufficient.
- Normally due to a narrowed (artherosclerosed) coronary artery.
- This narrowing may get completely blocked off, leading to no blood supply to the myocardium (infarction, heart attack)
Aims of drug therapy in ischemic heart disease and heart failure
- reduce pre-load
- reduce afterload
- reduce myo-proliferative stimulus
Beta 2 receptors
Vascular smooth muscle relaxation causes Vasodilation
Alpha 1 receptors
Vascular smooth Muscle contraction
vasoconstriction
beta blockers
Reduce contractility
Reduce HR
Reduce O2 consumption in the heart
Increase myocardial viability
beta blocker 1
Decrease heart rate
Decrease contractility
Decrease arterial constriction
This decreases 02 demand
Beta blockers II
decrease contractility
decrease cardiac output
increase pre load
increase o2 demand
beta blocker II - beta blocker I = reduced o2 demand
this increases myocardial viability
myocardial viability
ability of heart muscle that has been damaged or weakened due to reduced blood flow to recover function if blood flow is restored.
non selective beta 1 + 2 blockers
Propanolol (first generation), Nodolol and Sotalol
beta 1 blockers meds
Atenolol, metoprolol, acebutolol,bisoprolol,
3rd generation beta blockers
are a class of beta-blockers that not only block beta-adrenergic receptors but also possess additional beneficial effects, such as vasodilation
common 3rd gen beta blockers :
Carvedilol:
Blocks beta-1 and beta-2 receptors (non-selective).
Has alpha-1 blocking activity, causing vasodilation.
Antioxidant and anti-inflammatory properties.
Commonly used in heart failure, hypertension, and after a heart attack.
common 3rd gen beta blockers :
Nebivolol
Selective for beta-1 receptors (cardioselective).
Stimulates nitric oxide (NO) release, causing vasodilation.
Reduces arterial stiffness and improves endothelial function.
Often prescribed for hypertension and chronic heart failure.
Choice of beta blockers
ardiac Selective
Bisoproplol
Mixed Effect cardiac selective
Carvidolol, Nebivolol
Beta 1 blockade + peripheral vasodilation
Beta blockers adverse effects
Bradycardia
AV conduction blocks
Sinus rhythm problems
Rebound tachycardia, angina & possibly MI
Changes in Blood glucose levels Carvedilol<metoprolol.
Erectile dysfunction (not nebivolol)
Sleep disturbances
Renin - Angiotensin system
A drop in BP causes the Kidney to secrete renin.
Renin then converts angiotensinogen into angiotensin I –> converted to angiotensin II in the lungs
this increases vasoconstriction and stimulates aldosterone which retains sodium and water which increases blood volume.
effect of ACE inhibitors
Vasodilatation
(without effecting Cardiac Output)
Reduce Sodium reabsorption
(via aldosterone secretion)
Reduce thirst
Clinical effect
Reduce Blood Pressure
Adverse and side effects of ACE inhibitors
Adverse effects:
Cough
Rash
Renal impairment
Headache
Side effects:
Hypotension
Hyperkalemia Too much Potassium in the blood (due to aldosterone inhibition)
Clinical management of Pt on ACE inhibitors
BP
Renal function (output and urea and electrolytes)
Liver function
* Some ACE inhibitors are prodrugs (depend upon the liver to convert them into their active form e.g. enalapril).
Postural stability
Angiotensin II receptor inhibitors
This inhibition reduces the effects of angiotensin II, which include vasoconstriction, sodium retention, and aldosterone release.
Common drug is called Candesartan
Adverse effects and side effects of Angiotensin II receptor antagonist
Adverse Effects:
Back pain
Fatigue
Poor kidney function: Increased plasma creatinine levels
Side Effects:
Hyperkaleamia (increased potassium) in DB II with renal disease
Dizziness
Headache
Organic nitrates
Relax arterial and venous smooth muscles via liberation of nitric oxide
Nitrates used in angina
Nitrates are converted to Nitric Oxide (NO) which causes peripheral dilation.
Preload is reduced –> decreased Cardiac workload and reduces O2 consumption
Nitrates: hemodynamic effects
- Venous dilation
Decreased preload, decreased ventricular size, vent wall stress and O2 demand - Coronary vasodilation
Increased myocardial perfusion, redistributes blood flow.
3.Arterial vasodilation
Decreased afterload so increased cardiac output and decreased BP
Adverse effects of nitrates
Vascular headache
Orthostatic hypotension
Syncope
Rash
Tolerance
What is nitrate tolerance
decrease in the effect of a drug
Develops with all nitrates
Is dose-dependent
Disappears in 24 h. after stopping the drug
Nitrate tolerance mechanisms
Increase Symp NT,
Increased intravascular volume,
Increased Vasopressin release
Avoidance of tolerance
- Intermittent administration
- Use the lowest possible dose
- Intersperse a nitrate-free interval
Calcium channel blockers
medications that primarily affect the movement of calcium ions through calcium channels in the muscle cells of the heart and blood vessels. Calcium is essential for muscle contraction, and by blocking its entry into these cells, CCBs help to relax and dilate blood vessels and reduce the force of heart contractions.
Effect of Ca++ channel blockers on the CVS
CHeck power point slide 44
Adverse affects
- Hypotension
- Headaches
- Peripheral oedema
- Constipation
- A-V block
Dihydropyridine Pharmacokinetics
(Amlodopine)
Amlodipine:
Bioavailability: 64-90%
Plasma protein binding: 93%
Metabolism: Phase 1 mainly CYP 3A4
Half life: (30-50 hours)
Excretion: Renal
Dihydropyridine Pharmacokinetics
lercanidipine
Lercanidipine:
Bioavailability: ~10% (high first pass effect)
Plasma protein binding: >98%
Metabolism: Phase 1 mainly CYP 3A4
Half life: (8-10 hours)
Excretion: 50% Renal
