Cardiac pharmacology Flashcards
1
Q
List five causes of heart failure
A
- sustained pressure overload
- sustained volume overload
- depressed or altered contractility, or loss of, myofibres
- reduced ventricular compliance (diastolic dysfunction)
- abnormal heart rate or rhythm
2
Q
List three primary causes of reduction of myocardial contractility
A
- dilated cardiomyopathy
- taurine deficiency
- chronic myocarditis (rare)
3
Q
List two causes of pressure overload in the heart
A
- sub/aortic or pulmonary stenosis
- pulmonary hypertension
4
Q
List four causes of volume overloading
A
- chronic degenerative valve disease
- mitral or tricuspid dysplasia
- aortic or pulmonary insufficiency
- congenital L>R shunts (e.g. patent ductus arteriosis, ventricular septal defects)
5
Q
List two causes of diastolic mechanical inhibition
A
Pericardial disorders (pericarditis, neoplasia)
Ventricular myocardial disorders (feline hypertrophic and restrictive cardiomyopathies)
6
Q
List a cause of dysrhythimia
A
Altered electrical function
7
Q
Which ions are important in cardiac muscle contraction?
A
Ca++, Na+, K+
8
Q
List two endogenous compensatory mechanism in congestive heart failure
A
Intrinsic cardiac compensatory mechanisms
Systemic compensatory mechanisms
9
Q
What are the issues with the compensatory mechanisms in congestive heart failure?
A
Compensatory mechanisms are temporary and aimed at increasing O2 to meet metabolic demands
10
Q
List two intrinsic compensatory mechanisms for CHF
A
hypertrophy
dilation
11
Q
List two systemic compensatory mechanisms for response to inadequate cardiac function
A
- activation of sympathetic nervous system (+ inotrope and chronotrope: increased HR, contractility, vasoconstriction, BP)
- Activation of RAAS system
12
Q
What is the effect of the sympathetic response on alpha 1 receptors on the blood vessels
A
Constriction of smooth muscle (espeically at periphery): increased BP
13
Q
What is the effect of sympathetic stimulation on Beta2 receptors in blood vessels?
A
Dilation of smooth muscle (especially skeletal muscle): decreased BP
14
Q
What is the effect of adrenaline on blood vessels?
A
Alpha and Beta agonist: combination of vasodilation (sk. m) and vasoconstriction (periphery)
15
Q
What is the effect of noradrenaline on blood vessels?
A
Predominantly alpha agonist: vasoconstriction (esp periphery), increased systolic and diastolic BP, reflex bradycardia (decreased HR)
16
Q
What is the effect of isoprenaline on the cardiac system?
A
Predominately Beta agonist: vasodilation, increased cardiac force and rate, fall in mean arterial pressure
17
Q
Briefly describe the RAAS system
A
Liver: releases angiotensinogen
Kidney: releases renin
Renin: angiotensinogen -> angiotensin 1
Lung: releases angtiotensin-converting enzyme (ACE)
ACE: angiotensin 1 -> angiotensin 2
Angitotensin 2: Increases release of aldosterone from adrenal cortex
18
Q
What are the functions of angiotensin II?
A
+ vasopressin: + reabsorption by kidney tubules
+ thirst: increased fluid intake
+ arteriolar vasoconstriction
+ aldosterone: + Na+ reabsorption by kidney tubules
= conservation of Na+, H20
overall - NaCl, ECF fluid volume, arterial blood pressure
19
Q
What are four main treatment principles in cardiac disease?
A
- Reduce excessive compensatory mechanisms
- Promote perfusion of tissue
- Control ECF volume (- oedema)
- Correct any arrhythmias
20
Q
Name 5 general methods that might be considered in combination for treating CHF
A
- diuretics
- vasodilators
- digoxin
- beta blockers
- dietary modification (-salt, -obesity)
21
Q
What is the overall outcome of using diuretics?
A
decrease Na retention
increase water loss
= reduce preload
22
Q
What are the three main clases of diuretic used in CHF?
A
Loop
Thiazides
Potassium sparing
23
Q
Name a loop diuretic
A
Frusemide (or furosemide)
24
Q
What is the mechanism of action of frusemide (furosemide)
A
Inhibit Na, Cl, K reabsoprtion in thick ascending loop
Increase PGE2 = vasodilation
25
What is an alternative use of furosemide besides as a loop diuretic?
Bronchidlator in humans, horses, guinea pigs
26
What are some considerations when using furosemide?
Blocked by NSAIDs
Beware otoxicty and digitalis
May result in hypokalaemia, hyponatremia, dehydration \> can affect heart function
Use minimal dose to relieve clinical signs
27
What are the indications for use of furosemide?
Acute heart failure with pulmonary oedema
28
What are the indications for thiazide diuretics?
Resistance developed to loop diuretics ('rescue dieuretic)
29
What is the mechanism of action for thiazide diuretics
Prevent reabsorption of Na, Cl, K
30
Name three thiazide diuretics
Chlorothizide, hydrochlorthiazide, spironolactone
31
Name two potassium sparing diuretics
Triamterene, amiloride
32
What is the mechanism of action of triamterene, amiloride?
Inhibits reabsorption of Na and Cl in distal tubular cells and collecting duts by inhibiting Na/K ATPase pump
| (Spares K+)
33
What are the indications of using traimeterene, amiloride?
Weak efficacy, so used in conjunction with loop diuretics or thiazides in CHF.
34
What is the mechanism of action of spironolactone?
Aldosterone antagonist + weak Ca++ channel blocker
35
What is the purpose of using vasodilators in CHF?
To reduce pre and/or afterload
36
Name three arterial dilators
Hydralazine
Amlodipine
Nitroglycerin
37
Name four balanced dilators
Prazosin
Enalapril, Benazepril (ACE inhibitors
Nitroprusside
Pimobendan
38
Name one venodilator
Nitroglycerine
39
What are two potential problems with the overuse of vasodilators in CHF therapy?
Hypotension
Reflex tachycardia
40
Name two ACE inhibitors
Enalapril, enazepril
41
What is the mechanism of action of enalapril, benazepril?
Activated by liver -\> Angiotensin converting enzyme inhibitors -\> reduce angiotensin II
42
What are the outcomes of therapy with enalapril, benazepril?
Reduction in vasoconstriction
Reduction in sodium and water retention
Improved baroreceptor response
Reduced sympathetic tone
43
What are some side effects of ACE inhibitors?
Reduced BP
GIT upset
Increased potassium
Effect on GFR
44
Which ACE inhibitor is a better choice in the case of renal dysfunction?
Benazepril
45
Which is considered the best drug of choice for hypertension in cats?
Amlodipine
46
What is the mechanism of action of Amlodipine
Ca++ channel antagonist
47
What is the mechanism of action of pimobendin?
Sensitizes contractile proteins to Ca (positive inotrope)
Inhibition of phosphodiesterase III&V (balanced vasodilator)
Cytokine modulation, antiplatelet, positive lusitrope (cardiac relaxation)
48
What is an indication for pimobendin?
Valve insufficiency
49
What is the mechanism of action of digoxin?
Inhibition of Na/K ATP pumps in myocardium -\> increased intracellular Na -\> decreased extracellular Na / Ca++ exchange -\> Increased Ca++ available during contraction (positive inotrope: beats slower, stronger)
50
What are the other effects of digoxin?
Increases sensitivity of baroreceptors -\> increased vagal tone, decreased symathetic tone, decreased renin levels
Slow AV nodal conduction and prolong refractory periods (slow HR)
51
What are the indications for digoxin?
Arrhythmia e.g. supraventricular tachycardia, atrial fibrillation
52
What are the side effects of digoxin
LOW margin of safety
Toxicity = vomiting, diarrhoea, depression, cardac arrhythmia
53
What is the mechanism of action of propranalol?
Non-selective beta blocker (beta 1 &2)
54
What is the mechanism of action of atenolol?
Selective Beta 1 blocker
55
What is the use for Beta blockers in heart failure?
Arrhythmias, hypertension
56
Name three beta blockers
Propranalol
Atenolol
Carvedilol
57
What are the potential side effects of Beta blockers in CHF?
Slow the heart - should be used with caution
May remove the sypathetic compensation keeping the animal alive
58
Name three calcium channel blockers
Verapamil, nifedipine, diltiazem
59
What is the mechanism of action of verapamil?
Ca++ channel blocker in vascular and cardiac muscle
60
What is the mechanism of action of nifedipine?
Ca++ channel blocker in vascular and cardiac muscle
61
What is the mechanism of action of diltiazem?
Calcium channel blocker in smooth and cardiac muscle
62
What are the indications for Ca channel blockers?
Hypertension, arrhythmias
63
What are some important dietary considerations in CHF
Weight loss (reduce load on heart and reduce blood volume)
Reduce Na content
Ensure adequate energy intake
Ensure adequate vitamin intake
Taurine in cats
64
Which ion is involved in the first step of cardiac depolarisation in non-nodal tissue?
Na+
65
Which ion is involved in the first step of depolarisation in nodal cardiac tissue?
Ca++
66
What effect do drugs that decrease intracellular Na have on the heart?
Useful in treating arrhythmias
67
What effects do drugs that increase intracellular Ca++ have on the heart?
Useful in treating arrhythmia, but will also
- decrease HR
- decrease AV conduction
- decrease myocardial contractility
68
Name and describe the ion movement of phase 4
Resting potential (equilibrium)
69
Name and describe the ion movement of phase 0
Rapid depolarization, Na+ in
70
Name and describe the ion movement of phase 1
Partial repolarization, K+ out
71
Name and describe the ion movement of phase 2
Plateau; Ca++ in and K+ out (balanced)
72
Name and describe the ion movement of phase 3
Repolarization. K+ out
73
Name two places where arrhythmias originate
Supraventricular
Ventricular
74
Name two ways in which arrhythmias may arise
Ectopic foci with spontaneous activity
Abnormal propagation of impulses
75
What changes might you expect on an ECG of a FLUTD cat?
Hyperkalaemia =
Suppression of P waves
Widened QRS
Narrowing and peaking of T waves
Bradycardia
76
How do cardiac arrhythias impact heart function
Reduce CO:
- asynchronous atrial/ventricular contraction
- inefective premature contractions (low SV)
Decreased cardiac efficiency
- High heart rate (decreased CO)
- short diastolic period
i.e. increased cardiac oxygen demand, but decreased cardiac output
77
What is the mechanism of action of Class I antiarrhythmic drugs?
Block voltage gated Na+ channels
78
What is the mechanism of action of Class II antiarrhythmic drugs
Block Beta 1 receptors
79
What is the mechanism of action of Class III antiarrhythmic drugs
Block K+ channels
80
What is the mechanism of action of Class IV drugs
Block voltage gated Ca++ channels
81
List three class Ia antiarrhythmics
Discopyramide
Procainamide
Quinidine
82
What are the effects of Class Ia antiarrhythmics?
Block vgNa+ channels:
Decreased rate of depolarization
Decreased AV conduction
Decreased contractility
Increased action potential duration
Increased effective refractory period
83
What are the effects of class Ib antiarrhythmics?
Block vgNa+ channels:
Decreased rate of depolarization
Decreased AP duration
Increased effective refractory period
84
What are the effects of Class Ic antiarrhythmics?
Block vgNa+ channels:
Decreased rate of depolarization
Decreased AV conduction
Decreased contractility
85
Name two class Ib antiarrhythmics
Lignocaine
Mexiletine
86
Name one Class Ic antiarrhythmic
Flecainide
87
What are the effects of Class II antiarrhythmics
Beta blockers
Decreased AV conduction
Decreased contractility
Decreased heart rate
88
Name 2 class III antiarrhythmics
Amiodarone
Sotalone
89
What are the effects of Class III antiarrhythmics?
Block K+ channels
Increased action potential duration
Increased effective refractory period
Decreased AV conduction
Decreased contractility (sotalol)
90
Name two Class IV antiarrhythmics
Verapamil
Diltiazem
91
What are the effects of class IV antiarrhythmics
Block vgCa++ channels:
Decreased action potential duration
Decreased AV conduction
Decreased contractility
92
What are the uses of Class I antiarrhythmics
Ventricular tachycardia
Ventricular premature contractility
Procainamide for re-entrant supraventricular tachycardia
93
Briefly describe the re-entry phenomenon in cardiac muscle
Normal: Two pathways continue in the same direction
Re-entry: Damaged tissue causes slow propagation in one pathway; Refractory period blocks next depolarisation
Fast pathway depolarises damaged tissue, depol occurs in wrong direction
94
What are the uses of Class II antiarrhythmics
Ventricular tachycardia,
Supraventricular tachycardia
Hypertrophic cardiomyopathy in cats
Hypertension
Used with Class I for VT in dogs
95
What are the considerations/cautions with class II antiarrhythmics
Chronic use results in up-regulation of receptors: withdraw treatment slowly
Illegal in horse racing
96
What are the uses for Class III antiarrhythmics?
Anti-fibrillatory
97
What are the cautions with Class III antiarrhythmics?
Side effects poorly documented in animals
Amiodarone: several drug intreactions, particularly with heart medications (e.g. digoxin, quinidine, procainamide)
Sotalol: sudden withdrawal
98
What is the main difference between verapamil and diltiazem?
Verapamil: relatively selective for Ca++ channels in cardiac muscle
Diltiazem: Blocks Ca++ channels in cardiac and vascular smooth muscle (fewer cardiac effects, decreased peripheral resistance)
99
What are the uses for Class IV antiarrhythmics?
Supraventraicular tachycardia
Hypertrophic cardiomyopathy
Atrial flutter/fibrillation?
Reduce afterload (vasodilate)
100
What are the cautions with Class IV antiarrhythmias
Bradycardia, circulatory collapse
Esp in combination with Beta blockers (both slow heart rate)
Verapamil with high first pass effect
101
How is digoxin used as an antiarrhythmic?
Supraventricular arrhythmias (atrial fibrillation)
102
Name three other drug classes that might be useful in treating arrhythmias?
Anticholinergics
Sympathomimetics
Anticoagulants
103
Name two anticholinergic drugs that might be useful in treating arrhythmias
Atropine, glycopyrrolate
104
What are the effects of anticholinergics in treating arrhythmias?
Increase sinus rate in AV conduction in bradycardia/bradyarrhythmias, heart block
105
Name a sympathomimetic that might be useful in treating arrhythmias
Isoprenaline
106
What are the effects of isoprenaline in treating arrhythmias?
Beta selective: increases sinus node rate, AV conduction
107
Name four anticoagulants
Warfarin, heparine, aspirin, clopidogrel
108
Why are anticoagulants useful in treating cardiomyopathies?
Used for prevention of thromboembolism in cats with HCM and other cardiomyopathies
109
When should treatment of arrhythmias be considered?
Treat if haemodynamically signficant: most antiarrhythmics can induce arrhythmias as well as suppress them
- to restore CVS function
- to prevent sudden death
TREAT UNDERLYING CAUSE FIRST
110
What three questions should you ask when considering treatment of arrhythmias?
1. Is the arrhythmia compromising the circulovascular system?
2. Is the arrhythmia a sign of a more life threatening rhythm disturbance?
3. Is the arrhythmia indicative of underlying cardiac or systemic disease?
111
What treatment would you consider for atrial fibrilation?
E.g. in dogs with DCM or MV insufficency
- Digoxin or diltiazem
Treat enlarged atria/CHF: diuretics, ACE inhibitor, pimobenden, anticoagulant
112
Which treatments might you consider for rate control of the heart?
Diltiazem +/- digoxin
Beta blockers
113
What treatment might you consider for rhythm control?
Electrical cardioversion
Pharmacological cardioversion with amiodarone
Treat enlarged atria/CHF: Diuretics, ACE inhibitor, Pimobenden, anticoagulant
114
What treatment might you consider for re-entrant supraventricular tachycardia?
Procainamide
115
What treatment would you consider for ventricular tachycardia?
If significant, treat or correct underlying disease
Beta blockers for cats
Lignocain or sotalol for dogs
