Cardio L28 Drug theraoy 4 Heart Failure Flashcards
→ Chronic heart failure is a syndrome characterised:
- By progressive cardiac dysfunction
- Breathlessness
- Tiredness
- Neuro-hormonal disturbances
- Oedema
- Sudden death
Chronic Heart Failure
- 2-5% of population affected
- Increases with age
- Commonly due to coronary artery disease but can also reflect infection, physical injury and genetics.
- Has a poor prognosis with a 5 year mortality of 50% rising to 80% in a year for some patients.
HF Causes
Volume overload
Pressure overload
Loss of muscle
Restricted filling
Volume overload
Valve regurgitation
Pressure overload
Systemic hypertension
Outflow obstruction
Loss of muscle
Post MI: Chronic ischemia
Connective tissue disease
Infection, Poisons (drugs?)
Restricted filling
Pericardial diseases
Restrictive cardiomyopathy
Tachyarrhythmia
Increased Sympathetic activity
Favourable effect
Undesired effect
Increased Heart rate and Increased contractility.
Vasoconstriction leads to increased venous return and increased filling,
Arteriolar constriction leads to
After load and increased workload
Therefore increased oxygen consumption
Increased RAA
Favourable effect
Undesired effect
Salt and water retention and increased VR
Vasoconstriction and increased after load
Increased Vasopressin (ADH)
Favourable effect
Undesired effect
Salt and water retention and increased VR
Vasoconstriction and increased after load
Increased interleukins and TNFalpha
Favourable effect
Undesired effect
May have roles in myocyte hypertrophy
Apoptosis
Increased endothlin
Favourable effect
Undesired effect
Vasoconstriction and increase VR Increased
Afterload
Heart Failure:
- Heart failure is the condition where the heart fails to provide sufficient CO.
- Can be the result of genetic predisposition, infection, infarction, valve problems or physical injury
- With decreasing contractility the heart will dilate as atrial (R and/ or L) pressures increase…
Physiological adaptation: description and achieved by
- With reduced CO arterial pressure is maintained by increasing TPR (BP = CO x TPR).
a. Achieved by: increasing sympathetic tone (further increasing cardiac work). - R-A-A vasopressin systems is activated to raise blood volume and filling pressure.
a. Peripheral and pulmonary oedema will appear.
Heart Failure:
- The rise in RAP serves to dilate the heart which via Frank-Starling should increase CO.
- The failing heart does not respond well to stretch so dilates (increasing wall stress) and the patient develops oedema.
- Further demands may increase RAP further which can decrease CO
- Vicious CYCLE → increasing dilation → decreasing contraction strength.
Problems
Inadequate tissue perfusion
Volume overload
Cardiac remodelling
Enlarged ventricles
Spherical shape
Reduced efficiency
To improve symptoms
- Diuretics
- Digoxin
- ACE inhibitors
To improve survival
- ACE inhibitors
- Beta blockers
- Spironolacetone
Drugs for Heart failure:
- Diuretics
- Vasodilators
a. Nitrates mono/dinitrate - ACE inhibitors
a. Catopril, enalopril - Angiotensin II receptors antagonists
a. Iosartan - Positive inotropic drugs
a. Cardiac glycosides such as Digoxin
b. Sympathomimetics such as Dobutamine
c. (Phosphodisterase inhibitors)
Structure and profile of most important digoxins:
slow
- Digitoxin long duration and slow onset (half-life 5-7 days)
- Lipophilic, good absorption, strong binding and serum proteins.
Structure and profile of most important digoxins:
- Digoxin, rapid onset of action and low oral activity (half-life 1-2 dyas)
- Hydrophilic, low affinity for serum proteins.
Site of action and action
Na/K ATPase
• Act by inhibiting the action of the Na+/k+ pump
Mechanism of action
Na/K pump inhibition leads to:
- [Na[I and some depolarization
- [Na]I and [Ca]I via Na/ca exchngae
- [Ca]I SR Ca content via SR pump
- SR Ca content SR release via CLCR
- Contraction strength
Actions
Increase force
Increase excitability
Increase AV conduction
Reduced rate
Side effects
Effective range =1.0-2.5 ng/ml Toxic range >1.5 ng/ml GI: related to vagal effects 1. Anorexia 2. Abdominal pain 3. Vomiting 4. Diarrhoea Arrhythmias 1. PVCs 2. Atrial tachycardias AV dissociations
Transduction Sympathomimetics:
examples
action
- Milrinone and Amrinone
- Increase activity of CAMP by inhibiting cAMP phosphodiesterase. This increases protein kinase A activity – hence ‘transduction sympathomimetic.
- Used when other therapies fail.
Nirtates: examples
GTN (Glycerol trinitrate) see Angina notes
Nirtates: action
Rapidly metabolized to release NO
Nirtates: function
Causes relaxation of vascular smooth muscle – arteriolar and venous.
Decrease pre- and after-load.
Nirtates:allows
VR curve to move down to increase CO when decompensated. Also ease angina.
Nirtates: administration
Sub-lingual or injection. Only useful in acute cases as adaptation.
Nirtates: side effects
Headache
Dizzyness
Loop agents
Furosemide (powerful removal of NA)
Thiazide
Hydroclorothiazide (mild diuretic)
K sparing
Amiloride, Spironolacetone (weak)
Osmotic
Not useful in heart failure due to pulmonary oedema
Thiazide effect
Mild diuretic effect (<10% filtered Na)
Thiazide action site
Mainly acts at distal tubule
Thiazide action
Direct vasodilator action on smooth muscle
Thiazide limited because
Limited diuresis indicates limited use but potentially good for hypertensives
Thiazide side effect
K loss
Hypotension
loop agents: effect
Powerful up to 30% filtered Na
Loop agents: useful for
Pulmonary and refractory oedema
Kidney failure
Loop agents: side effects
Ototoxicity
Hypovoleamia
Hypokalemia
Hypomagnesia
K sparing agents:
Effect
Weak diuresis (<5% filtered Na)
K sparing agents:
Useful for
Controlling K loss
K sparing agents:
Side effects
Hyperkalemia
Spironolactone has oestrogen-like effects
ACE inhibitors: Example
Captopril
Analpril
ACE inhibitors: Function
Inhibit production of AII:
- Inhibit aldosterone production
- Vasodilate (inhibits bradykinin breakdown)
ACE inhibitors: Useful for
Controlling K loss
Hypertension
ACE inhibitors: side effects
Cough
Hypotension
Hyperkalemia
Receptor blockers:
Losartan blocks -> the AT1 receptor • Does not affect bradykinin (no cough) • Reduces BP • Better tolerated than ACE inhibitors • Side effects: o Less vasodilation than ACE inhibitors o Birth defects
