Drugs for cardio Flashcards
What class of drugs are nitrates
Venous dilators
Give two examples of nitrates
Sodium nitroprusside
Nitroglycerin
What does sodium nitroprusside do
Venous dilator
What does nitroglycerin do
Venous dilator
What is the mechanism of action for nitrates?
NO donors - Stimulate cGMP formation which inactivates phosphorylated myosin, causing relaxation
Nitrates most reduce preload or afterload?
Preload - by reducing venous return
Apart from reduced preload, what are two other effects of nitrates?
Reduced afterload
Increased coronary blood flow
Can you give nitrates orally?
No - they have poor bioavailability. Must be subcutaneous, IV
In what situation, in vet medicine, are nitrates most commonly used?
Acute tx of cardiogenic oedema (decompensated heart failure)
Example of an arterial dilator?
Hydralazine
What does hydralazine do?
Arteriolar dilator
Example of a clinical situation where you might choose hydralazine
Super hypertensive cat with pulmonary oedema due to mitral valve insufficiency
Which drug should always be used WITH hydralazine if used for any length of time?
Diuretics - as hypotension could activate RAAS and switch on water conservation in kidneys
Give three examples of calcium channel blockers.
Verapamil
Diltiazem
Amlodipine
What does verapamil do?
Calcium channel blocker - equally selective for myocardium and VSMC
What does diltiazem do?
Calcium channel blocker - more selective for VSMC than myocardium
What does amlodipine do?
Calcium channel blocker - significantly more selective for VSMC than myocardium
Give one situation where verapamil would be useful
For a supraventricular tachycardia
What is one major risk of verapamil use?
Severe hypotension
Short half life
Why could diltiazem be good for atrial fibrillation dogs?
Slows nodal rate so get fewer impulses sent to ventricles > slows HR
Reduces TPR and afterload
= could get overall better CO
Other than atrial fibrillation, when might you use diltiazem?
In feline hypertrophic cardiomyopathy
- slow HR
- dilate coronary circulation
- reduce afterload
- improve diastolic relaxation > better SV
Which calcium channel blocker are you likely to choose in a cat with hypertension secondary to renal disease?
Amlodipine
Example of an alpha1 antagonist?
Prazosin
Which pathway does prazosin act by to cause vasodilation?
The alpha1-IP3-DAG pathway
Why doesn’t prazosin cause much reflex tachycardia?
Because NA is still able to bind to the presynaptic inhibitory alpha2 receptors, so don’t get excessive NA release
What is an example of a nonselective beta blocker?
Propanolol
What might be two side effects of propanolol use?
Cold extremities
Fatigue
Bronchoconstricton
How does propanolol reduce BP?
By reducing CO (HR, and SV by reducing contractility) and inhibiting RAAS activation
Reduces overall workload of heart
How does propanolol reduce CO?
Reduce HR by inhibiting Ca2+ influx to nodal cells
Reduce contractility by inhibiting Ca2+ influx to myocytes, thence reducing SV
What are two examples of ACE inhibitors?
Enalapril
Benzalapril
What is enalapril?
ACE inhibitor
Which patients are enalapril and benzalapril frontline therapy?
CHF dogs
Hypertrophic cardiomyopathy cats
If your CHF patient only had 50% renal function, which ACE inhibitor would you recommend?
Benzalapril - 50% clearance via biliary system
What are the three types of indirect BP reducing drug classes?
Beta blockers
ACE inhibitors
Angiotensin II Receptor antagonists
What are the 4 types of positive inotrope drugs?
- Cardiac glycosides
- Beta-adrenoceptor agonists
- PDE inhibitors
- Ca2+ sensitisers
What sort of drug is digoxin?
A cardiac glycoside
Give an example of a cardiac glycoside.
Digoxin
What are the three important effects of digoxin?
Blocks Na/K ATPase which inhibits action of Ca/Na exchanger, keeping more Ca in the cell and increasing contractility
Increases vagal tone to reduce SA and AV firing rate and increase their refractory periods
Reduces SNS tone and catecholamine levels (and thence BP and venous return)
How long is the half life of digoxin? What is the major clearance route?
24 - 36h
Renal excretion
What is the nature of the interaction between hypokalaemia and digoxin?
K+ competes with digoxin for binding site on the Na/K ATPase pump
K+ acts as as a competitive inhibitor of digoxin
If you have low K+, the effect elicited by the same concentration of digoxin will increase
What two things should you always check before commencing digoxin?
K+ levels
Renal function
What are two examples of beta agonists other than adrenaline and noradrenaline?
Dobutamine (beta1 select)
Dopamine (low dose)
Under what circumstances would you use beta agonists ?
Severe acute heart failure and cardiogenic shock
Give IV
What is dobutamine?
A Beta1 agonist - provides increased contractility without increase in BP
Why use dobutamine over adrenaline?
While both increase heart contractility, adrenaline causes more tachycardia and arrhythmias
Would you use beta agonists long term?
No
They increase cardiac wok and may cause arrhythmias
Give two examples of PDE inhibitors
Caffeine
Amrinone
What does PDE do
Breaks down cAMP
Give an example of a Ca2+ sensitiser
Pimobendan
What is vetmedin?
= pimobendan
A ca2+ sensitiser
What are the three important effects of pimobendan?
- Inhibit PDE III to increase amount of Ca2+ in cell
- Sensitise troponin C to Ca2+ to increase contractility without increasing energy expenditure
- Vasodilation of arterioles and venules to reduce afterload
Name two conditions where pimobendan would be your included in your therapy
- DCM
2. Mitral valve disease
What are the two categories of negative inotropes?
Beta blockers
Ca2+ channel blockers
What are the three most important effects of beta blockers on a failing heart?
- Reduce demand for O2 and nutrients by reducing HR and contractilty
- Increase time spent in diastole so increase the amount of time for blood perfusion of myocardium through the coronary circulation (less compression by systole)
- Decreased RAAS activation
Name two beta blockers
Propanolol (general)
Atenolol (B1 specific)
What are three possible side effects of beta blockers
Bradycardia
Hypotension
Bronchospasm
Name three scenarios where you might use a Ca2+ channel blocker
- Supraventricular arrhythmia
- Hypertension
- feline HCM
What are the four broad classes of anti-arrhythmic drugs?
- Na+ channel blockers
- beta blockers
- K+ (outbound) channel blockers
- Ca2+ channel blockers
Which cells of the heart do Na+ channel blockers work best on?
Myocardial cells
Purkinje fibres
- as they block the ‘fast’ Na+ channels responsible for initial depolarisation
There are both hydrophilic and hydrophibic Na+ channel blockers. What implication does being hydrophobic have on their function?
A hydrophobic drug does not exhibit use-dependence; ie. it will target all cells regardless of whether the channel is active or not as it can pass through the membrane to bind.
Hydrophilic drugs require the channel to be open to pass through.
Name four Na+ channel blocker drugs
Lignocaine
Procainamide
Quinidine
Mexiletine
What would be a good drug class to use for an atrial tachycardia?
Beta blocker
Why shouldn’t you administer a beta blocker for the first time to a patient in chronic, end stage heart failure?
Because their CVS may be dependent on SNS tone to maintain CO and contractility, and administration of a beta blocker could be fatal
What is metoprolol?
A cardioselective beta blocker
What effects do beta blockers have on sinus rhythm and AV conduction?
Slow sinus rhythm
Slow AV conduction
How do K+ channel blockers slow HR?
By increasing the length of the AP, through extending the time taken to repolarise the cell
This leads to an increased refractory period and thence slower HR
Are K+ channel blockers used in veterinary medicine?
Not really
Which (myocardial or nodal) cells are dependent on Ca2+ flux for DEPOLARISATION?
Nodal tissue
Which cardiac tissue would a Ca2+ channel blocker have greatest effect on?
Nodal tissue, as it relies on slow Ca2+ channels to depolarise
L type Ca2+ channel blockers are front line therapy for which two conditions?
Atrial tachycardias
Nodal re-entry arrhythmias
Would you use verapamil to treat ventricular tachycardia?
No
If the patient had normal BP, but pathological tachycardia, would you choose verapamil or amlodipine?
Verapamil - amlodipine would cause significant vasodilation and the patient would become hypotensive.
If you had a patient with atrial tachycardia and hypertension, which drug would be your first line of treatment?
Amlodipine - reduce HR, contraction force and vasodilation
What kind of arrhythmia can an overdose of digoxin cause?
Ventricular arrhythmia
What kind of arrhythmias does mitral valve failure in dogs generally cause?
Atrial fibrillation or a supraventricular tachycardia
What kind of arrhythmias does hypertrophic cardiomyopathy in cats usually cause?
Atrial fibrillation or a supraventricular tachycardia
What drugs (drug names) could increase AV node refractory period?
Digoxin
Diltiazem
Verapamil
Propanolol
What are two drugs that could increase refractory period of atrial tissue?
Quinidine
Procainamide
Lignocaine
Match the Na+ channel blocker to the species it is most commonly used in - dog, cat or horse.
Lignocaine
Procainamide
Quinidine
Lignocaine - cats
Procainamide - dogs
Quinidine - horses
What class of drugs is first line therapy for ventricular tachycardia?
Na+ channel blockers
What sorts of diseases usually cause ventricular tachycardias?
Severe systemic disease caused by congestive heart failure or dilated cardiomyopathy
What is mexiletine?
An oral tablet Na+ channel blocker
What are the four considerations when developing a drug treatment plan for a heart failure patient?
- Is there congestion?
- relieve if necessary - Would the patient benefit from a reduced preload or afterload?
- venodilators such as betablockers
- ACE inhibitors
- nitrates in short term - Would the patient benefit from increased contractility?
- pimobendan - Does the patient have a cardiac arrhythmia that needs to be corrected?
Give an example of an injectible anti-coagulant
Heparin
LMW heparin
What might be one advantage of LMW heparin
Longer half life, so good for at-home patient use
What is the anticoagulant mechanism of heparin?
Exposes active site of antithrombin III to promote inactivation of factor 10a and 2a (thrombin)
Is heparin orally available?
No
Brodificoum and bromadiolone are examples of what sort of drug?
Procoagulants
Give one example of a therapeutic procoagulant
Warfarin
Are you likely to see the effects of first-generation rodenticide poisoning on the same day?
No - shortest coag factor half life is 72h; take at least 3 days to become deficient
Give an example of an ADP-receptor antagonist
Clopidogrel
What is the mechanism of action of clopidogrel? What class of drug?
Anti-platelet
Blocks ADP receptors which prevents externalisation of GpIIb/IIIa complex and platelet plug formation
What is an example of an inhibitor of thromboxane synthesis? What part of the coagulation process might this affect?
Aspirin
Prevents platelet release of TXA2 by inhibiting COX
TXA2 is a potent activator of more platelets
What is the mechanism of the drugs tirofiban and abciximab? What class of drug?
Anti-platelet
Block GpIIb/IIIa receptors and thence fibrin binding
What is the mechanism of action of dypyridamole? What class of drug?
Anti-platelet
Increases prostacyclin production, which is a potent inhibitor of platelet aggregation
What are the two major effects of aspirin on the cardiovascular system?
Inhibits platelet activation through inhibitng TXA2 synthesis and release
Causes vasodilation through inhibiting VSMC contraction
What common drug could you choose to reduce coagulability of the blood without causing vasodilation?
Aspirin
Give two examples of fibrinolytic drugs
Streptokinase
Alteplase
What is the function of streptokinase? What class of drug?
Fibrinolytic drug
Promotes plasminogen»_space; plasmin to promote fibrinolysis
What is one risk of streptokinase use?
Highly antigenic. Can only be used once in each patient without extreme risk of anaphylaxis/reaction
What fibrinolytic drug might you choose in a patient that has been treated with streptokinase in the past?
Alteplase - less antigenic. Though shorter half life - must have IV infusion.
Clot-selective.
