Anti-arrhythmic drugs (Vaughan Williams classification)
Class I: sodium channel blockers …
Ia - Disopyramide
Ib - Ligocaine
Ic - Flecainide
Sodium channel blockers have ‘loose dependence’ - I can bind to na+ channel in a certain state in its cycle e.g inactivated
Resting channels are unaffected
Anti-arrhythmic drugs (Vaughan Williams classification)
Class II: Beta adrenoreceptor antagonsists …
(non-selective) - Propranolol
(b1 Selective) - Bisoprolol, Metaprolol
Anti-arrhythmic drugs (Vaughan Williams classification)
Class III: Prolong the Action potential
Act to prolong the refractory period (therefore the heart isn’t susceptible to incoming AP’s)
Amiodarone, Sotalol
Anti-arrhythmic drugs (Vaughan Williams classification)
Class IV: Calcium channel blockers
- Verapamil
- Diltiazem
Anti-arrhythmic drug that doesnt fall into this classification …
Digoxin
- comes from a group of drugs called cardiac glycosides
- inhitis na+/k+ ATPase = decrease in na+ gradient = decrese na+/ca2+ pump activity= increase [ca2+]i (because it cant be pumped out) = INCREASE IN FORCE OF CONTRACTION
Another arrhythmic drug used in A-fib
(has narrow therapeutic window) and is commonly used for Severe HF
Digoxin
- causes bradycardia (increased vagal tone)
- causes slowing of av conduction
however too high dose = ectopic activy (pro-arrhythmi) and force of contraction = all due to increase ca2+
therefore narrow therapeutic range
very effective anti-arrhythmic drug that increased Q-T interval but has many side effects and risk of polymorphic ventricular tachycardia from increasing Q-T interval too much
Amiodarone
what would you treat a patient with HF with so ensure their LVEDP isnt too high and their CO isnt too low
- Diuretic e.g furosemide, to shift them left (.e decrease LVEDP
- ACE inhibtior (e.g captopril, enalopril) to therefore vasodilation = decrease afterload for same EDP therfore increase in CO
-digoxin may be used to increase contractility to therefore increase CO
-
ACE inhibitors
-Captopril. enalopril
humoral control of coronary blood flow, heart also secreted them in response to HF
Cardiac Natriuretic peptides
- atrial natriuretic peptide (ANP)
- Brain natriuretic peptide (BNP)
both released by stretching of the atrial and ventricular muscle cells of the heart caused by:
- increase in atrial or ventricular pressure
- volume overload
What metabolises cardiac natriuretic peptides
Neutral endopeptidase (NEP) e.g Neprilysin
What is entrestro and why is it used for HF
combination of both:
- Sacubitril (Neprilysin inhibitor= therefore increase in Cardiac natriuretic peptides)
- Valsartan (ANGII blocker = prevents angII from contributing to HF through vasocontriction etc)
4 classes of diuretics
- Thaizides (bendroflumethiazide)
- Loop Diuretics ( furosemide, bumetanide)-
- K+ sparing diuretics ( Spironolactone)
- Aldosterone antagonists (Spironolactone- inhibits RAAS)
Personalised medicine examples
- Warfarin dosage via genetic testins of VKOR and CYP29 genes
- Isosorbide Dintatres as part of vasodilator therapy in HF - more effective in afro-caribbean patients
- Stent size shape length etc for in Percutaneous coronory intervention for STEMI patients
- Specific coagulation factors for hameophillia patietns
2 drugs that make up ‘vasoldilator therapy’ in HF
- Hydralazine (arterial dilator) = decrease afterload
- Isosorbide dinitrate (venous dilator) = decreased pre-load by increasing the storage capacity of veins
Overall Treatment options for HF
- ACE inhibtiors
- Digoxin
- Vasodilator therapy
- Diuretics
- Cardiac natriueritc peptides (naturally released from heart)
- Entresto (sacubitril, valsartan)
- Ivabradine (used in angina and HF in patients with HR over 70 that cant have b-blocker - show significant benefit to HF patients)
Treatments to inhibti RAAS/symp.NS system that acts to exaccerbate HF
- B-blockers
- ACE inhibtior (ramipril)
- AngII antagonist blocker (ARB)
- Vasodilator
- Aldosterone antagonist
- Diuretic
Immediate treatment for acute heart failure
- Oxygen
- Diamorphine
- Nitrates (isosorbide dinitrate - venous dilator used in vasodilator therapy for Chronic HF)
- Loop diuretics e.g furosemide
- Inotropes (adrenergic agonists, PDEIII inhibtiors-increase cAMP)
Different types of adrenergic receptors and their action
a1- in periphery and cause vasoconstriction
b1- in heart and cause posiive inotropic effects (increase F.O.C)
b2 - mainly in skeletal muscle and cause vasodilation
inocontrictors (norepinephrine) and inodilators (isoproterenol) are the two main groups of adrenergic agoists
- ino = because act on b1 ionotropic receptors
- constrictors = act on a1
- dilators = act on b2
both Given I.V
What is the mainstay treatment of HF
Triple therapy
- ACE inhibitor (ramipril)
- Beta-adrenoreceptor blocker (bisoprolol - b1 specific, propranolol - on selective)
- Aldosterone antagonist (Spironolactone) = diuretic
Name the different types of NO donor therapies
- Nitroglycerine (treat angina)
- Sodium nitroprusside (treat emergency hypertension in A+E)
- Inhaled NO - (treats severe pulmonary hypertension)
Name the different prostanoid therapies
- Iloprost (PGI2 stable analogue, activates PGI2 causing vasoidlation) - treats pulmonary hypertension, raynauds
- Epoprostenol (IP-R agonist, causing vasodilation) - treats pulmonary hypertension
- Corticosteroids (acts on cox1/2 to supress formation of prostanoids) =prevents shock (hypotension)
Endothelin therapies
- Bosentan (ETA/B antagonist) = vasodilation =treats pulmnary hypertension
- ECE inhibitor - phosporamidon
AngiotensinII /ACE therapies
ACE inhibtiors
AT1- receptor antagonists (Sartans e.g valsartan)
