Cardio L28 Drug theraoy 4 Heart Failure

Question 1

→ Chronic heart failure is a syndrome characterised:

Answer 1

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

Question 2

Chronic Heart Failure

Answer 2

• 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.

Question 3

HF Causes

Answer 3

Volume overload
Pressure overload
Loss of muscle
Restricted filling

Question 4

Volume overload

Answer 4

Valve regurgitation

Question 5

Pressure overload

Answer 5

Systemic hypertension

Outflow obstruction

Question 6

Loss of muscle

Answer 6

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

Question 7

Restricted filling

Answer 7

Pericardial diseases
Restrictive cardiomyopathy
Tachyarrhythmia

Question 8

Increased Sympathetic activity

Favourable effect
Undesired effect

Answer 8

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

Question 9

Increased RAA
Favourable effect
Undesired effect

Answer 9

Salt and water retention and increased VR

Vasoconstriction and increased after load

Question 10

Increased Vasopressin (ADH)
Favourable effect
Undesired effect

Answer 10

Salt and water retention and increased VR

Vasoconstriction and increased after load

Question 11

Increased interleukins and TNFalpha
Favourable effect
Undesired effect

Answer 11

May have roles in myocyte hypertrophy

Apoptosis

Question 12

Increased endothlin
Favourable effect
Undesired effect

Answer 12

Vasoconstriction and increase VR Increased

Afterload

Question 13

Heart Failure:

Answer 13

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…

Question 14

Physiological adaptation: description and achieved by

Answer 14

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.

Question 15

Heart Failure:

Answer 15

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.

Question 16

Problems

Answer 16

Inadequate tissue perfusion

Volume overload

Question 17

Cardiac remodelling

Answer 17

Enlarged ventricles
Spherical shape
Reduced efficiency

Question 18

To improve symptoms

Answer 18

1. Diuretics
2. Digoxin
3. ACE inhibitors

Question 19

To improve survival

Answer 19

1. ACE inhibitors
2. Beta blockers
3. Spironolacetone

Question 20

Drugs for Heart failure:

Answer 20

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)

Question 21

Structure and profile of most important digoxins:

slow

Answer 21

• Digitoxin long duration and slow onset (half-life 5-7 days)
• Lipophilic, good absorption, strong binding and serum proteins.

Question 22

Structure and profile of most important digoxins:

Answer 22

• Digoxin, rapid onset of action and low oral activity (half-life 1-2 dyas)
• Hydrophilic, low affinity for serum proteins.

Question 23

Site of action and action

Answer 23

Na/K ATPase

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

Question 24

Mechanism of action

Answer 24

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

Question 25

Actions

Answer 25

Increase force
Increase excitability
Increase AV conduction
Reduced rate

Question 26

Side effects

Answer 26

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

Question 27

Transduction Sympathomimetics:
examples
action

Answer 27

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.

Question 28

Nirtates: examples

Answer 28

GTN (Glycerol trinitrate) see Angina notes

Question 29

Nirtates: action

Answer 29

Rapidly metabolized to release NO

Question 30

Nirtates: function

Answer 30

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

Question 31

Nirtates:allows

Answer 31

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

Question 32

Nirtates: administration

Answer 32

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

Question 33

Nirtates: side effects

Answer 33

Headache

Dizzyness

Question 34

Loop agents

Answer 34

Furosemide (powerful removal of NA)

Question 35

Thiazide

Answer 35

Hydroclorothiazide (mild diuretic)

Question 36

K sparing

Answer 36

Amiloride, Spironolacetone (weak)

Question 37

Osmotic

Answer 37

Not useful in heart failure due to pulmonary oedema

Question 38

Thiazide effect

Answer 38

Mild diuretic effect (<10% filtered Na)

Question 39

Thiazide action site

Answer 39

Mainly acts at distal tubule

Question 40

Thiazide action

Answer 40

Direct vasodilator action on smooth muscle

Question 41

Thiazide limited because

Answer 41

Limited diuresis indicates limited use but potentially good for hypertensives

Question 42

Thiazide side effect

Answer 42

K loss

Hypotension

Question 43

loop agents: effect

Answer 43

Powerful up to 30% filtered Na

Question 44

Loop agents: useful for

Answer 44

Pulmonary and refractory oedema

Kidney failure

Question 45

Loop agents: side effects

Answer 45

Ototoxicity
Hypovoleamia
Hypokalemia
Hypomagnesia

Question 46

K sparing agents:

Effect

Answer 46

Weak diuresis (<5% filtered Na)

Question 47

K sparing agents:

Useful for

Answer 47

Controlling K loss

Question 48

K sparing agents:

Side effects

Answer 48

Hyperkalemia

Spironolactone has oestrogen-like effects

Question 49

ACE inhibitors: Example

Answer 49

Captopril

Analpril

Question 50

ACE inhibitors: Function

Answer 50

Inhibit production of AII:

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

Question 51

ACE inhibitors: Useful for

Answer 51

Controlling K loss

Hypertension

Question 52

ACE inhibitors: side effects

Answer 52

Cough
Hypotension
Hyperkalemia

Question 53

Receptor blockers:

Answer 53

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