Cardio L28 Drug theraoy 4 Heart Failure Flashcards Preview

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Flashcards in Cardio L28 Drug theraoy 4 Heart Failure Deck (53):
1

→ Chronic heart failure is a syndrome characterised:



• By progressive cardiac dysfunction
• Breathlessness
• Tiredness
• Neuro-hormonal disturbances
• Oedema
• Sudden death

2

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.

3

HF Causes

Volume overload
Pressure overload
Loss of muscle
Restricted filling

4

Volume overload

Valve regurgitation

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Pressure overload

Systemic hypertension
Outflow obstruction

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Loss of muscle

Post MI: Chronic ischemia
Connective tissue disease
Infection, Poisons (drugs?)

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Restricted filling

Pericardial diseases
Restrictive cardiomyopathy
Tachyarrhythmia

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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

9

Increased RAA
Favourable effect
Undesired effect

Salt and water retention and increased VR

Vasoconstriction and increased after load

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Increased Vasopressin (ADH)
Favourable effect
Undesired effect

Salt and water retention and increased VR

Vasoconstriction and increased after load

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Increased interleukins and TNFalpha
Favourable effect
Undesired effect

May have roles in myocyte hypertrophy

Apoptosis

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Increased endothlin
Favourable effect
Undesired effect

Vasoconstriction and increase VR Increased
Afterload

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Heart Failure:

1. Heart failure is the condition where the heart fails to provide sufficient CO.
2. Can be the result of genetic predisposition, infection, infarction, valve problems or physical injury
3. With decreasing contractility the heart will dilate as atrial (R and/ or L) pressures increase…

14

Physiological adaptation: description and achieved by

1. With reduced CO arterial pressure is maintained by increasing TPR (BP = CO x TPR).
a. Achieved by: increasing sympathetic tone (further increasing cardiac work).
2. R-A-A vasopressin systems is activated to raise blood volume and filling pressure.
a. Peripheral and pulmonary oedema will appear.

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Heart Failure:

1. The rise in RAP serves to dilate the heart which via Frank-Starling should increase CO.
2. The failing heart does not respond well to stretch so dilates (increasing wall stress) and the patient develops oedema.
3. Further demands may increase RAP further which can decrease CO
4. Vicious CYCLE → increasing dilation → decreasing contraction strength.

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Problems

Inadequate tissue perfusion
Volume overload

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Cardiac remodelling

Enlarged ventricles
Spherical shape
Reduced efficiency

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To improve symptoms

1. Diuretics
2. Digoxin
3. ACE inhibitors

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To improve survival

1. ACE inhibitors
2. Beta blockers
3. Spironolacetone

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Drugs for Heart failure:

1. Diuretics
2. Vasodilators
a. Nitrates mono/dinitrate
3. ACE inhibitors
a. Catopril, enalopril
4. Angiotensin II receptors antagonists
a. Iosartan
5. Positive inotropic drugs
a. Cardiac glycosides such as Digoxin
b. Sympathomimetics such as Dobutamine
c. (Phosphodisterase inhibitors)

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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.

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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.

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Site of action and action

Na/K ATPase
• Act by inhibiting the action of the Na+/k+ pump

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Mechanism of action

Na/K pump inhibition leads to:
1. [Na[I and some depolarization
2. [Na]I and [Ca]I via Na/ca exchngae
3. [Ca]I SR Ca content via SR pump
4. SR Ca content SR release via CLCR
5. Contraction strength

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Actions

Increase force
Increase excitability
Increase AV conduction
Reduced rate

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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

27

Transduction Sympathomimetics:
examples
action

1. Milrinone and Amrinone
2. Increase activity of CAMP by inhibiting cAMP phosphodiesterase. This increases protein kinase A activity – hence ‘transduction sympathomimetic.
3. Used when other therapies fail.

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Nirtates: examples

GTN (Glycerol trinitrate) see Angina notes

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Nirtates: action

Rapidly metabolized to release NO

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Nirtates: function

Causes relaxation of vascular smooth muscle – arteriolar and venous.
Decrease pre- and after-load.

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Nirtates:allows

VR curve to move down to increase CO when decompensated. Also ease angina.

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Nirtates: administration

Sub-lingual or injection. Only useful in acute cases as adaptation.

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Nirtates: side effects

Headache
Dizzyness

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Loop agents

Furosemide (powerful removal of NA)

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Thiazide

Hydroclorothiazide (mild diuretic)

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K sparing

Amiloride, Spironolacetone (weak)

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Osmotic

Not useful in heart failure due to pulmonary oedema

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Thiazide effect

Mild diuretic effect (<10% filtered Na)

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Thiazide action site

Mainly acts at distal tubule

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Thiazide action

Direct vasodilator action on smooth muscle

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Thiazide limited because

Limited diuresis indicates limited use but potentially good for hypertensives

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Thiazide side effect

K loss
Hypotension

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loop agents: effect

Powerful up to 30% filtered Na

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Loop agents: useful for

Pulmonary and refractory oedema
Kidney failure

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Loop agents: side effects

Ototoxicity
Hypovoleamia
Hypokalemia
Hypomagnesia

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K sparing agents:
Effect

Weak diuresis (<5% filtered Na)

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K sparing agents:
Useful for

Controlling K loss

48

K sparing agents:
Side effects

Hyperkalemia
Spironolactone has oestrogen-like effects

49

ACE inhibitors: Example

Captopril
Analpril

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ACE inhibitors: Function

Inhibit production of AII:
1. Inhibit aldosterone production
2. Vasodilate (inhibits bradykinin breakdown)

51

ACE inhibitors: Useful for

Controlling K loss
Hypertension

52

ACE inhibitors: side effects

Cough
Hypotension
Hyperkalemia

53

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

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