Pharmacology Flashcards
Do you get a better response in resolution of signs with the use of diuretics in cardiogenic or noncardiogenic pulmonary edema?
Cardiogenic
What are the 5 classifications of diuretics?
Carbonic anhydrase inhibitors, osmotic diuretics, loop diuretics, thiazide diuretics, and potassium-sparing diuretics/aldosterone antagonists)
What are the two carbonic anhydrase inhibitor diuretics?
Dorzolamide and acetazolamide
Carbonic anhydrase inhibitors are not often used for treatment of cardiac diseases, what are they used to treat?
Glaucome, hyperkalemic periodic paralysis in horsies, and alkalosis
What type of diuretic are mannitol, urea, glycerol, hypertonic saline, DMSO, and isosorbide?
Osmotic diuretics
(T/F) Osmotic diuretics are contraindicated in treatment of cardiopulmonary disease.
True
What does it mean when loop diuretics are referred to as ‘high ceiling’ diuretics?
You can give high doses and get more diuretic effect as you give higher doses many times over
What is the loop diuretic drug used in veterinary species?
Furosemide, lasix is brand name
What occurs as a result of the decreased sodium and chloride reabsorption caused by loop diuretics?
Loss of water
How do loop diuretics induce the loss of magnesium and calcium?
By decreasing potassium recycling
What do loop diuretics enhance the secretion of?
Renin
What two minor effects do loop diuretics have on the heart?
Increased venous compliance and decrease peripheral vascular resistance
Where are loop diuretics excreted?
Kidneys
Why does proteinuria decrease the effectiveness of furosemide?
Furosemide is highly bound to proteins, will bind to any protein in the tubules of the kidneys and that will less its effect
Why does furosemide decrease in effectiveness as renal disease advances?
As renal disease advances, the kidneys have fewer organic acid transporters to bring furosemide into the tubular space → decreased effectiveness
In combination with what practice is furosemide used for the prevention or attenuation of exercise induced pulmonary hemorrhage in racehorses?
Decreased water intake prior to races/exercise
What can acute administration of large doses of furosemide lead to?
Dehydration and acute intravascular volume reduction → worsening of cardiac output and hypotension, may precipitate acute renal failure
Of the potential electrolyte abnormalities furosemide can cause (hypo- natremia, kalemia, chloremia, calcemia, and magnesemia) which affects cats more commonly?
Hypokalemia
Do you need to worry about administering furosemide to an animal already on digoxin or digitoxin if they are eating normally?
No
What two ways do NSAIDs decrease the effectiveness of furosemide?
One of furosemide mechs of action is PG-controlled natriuresis, NSAIDs reduce PGEs; NSAIDs compete for the organic acid transporters that transport furosemide into the renal tubules
Why isn’t hydrochlorothiazide (a thiazide diuretic) not used as frequently as furosemide?
Not as potent
What effects of hydrochlorothiazide are different from furosemide?
Does not block calcium transport, may actually enhance calcium reabsorption; decreases renal blood flow
When are thiazide diuretics combined with loop or potassium sparing diuretics?
When a patient has refractory fluid retention
What type of diuretic is spironolactone?
Potassium sparing diuretics
What is spironolactones mechanism of action?
Competitive antagonist of aldosterone
(T/F) Spironolactone is only effective in the presence of aldosterone so it is primarily used for animals with congestive heart failure
True
Why does spironolactone have beneficial effects on acute and chronic cardiac damage/remodeling?
Collagen deposition and fibrosis in cardiac tissue is mediated by increased aldosterone in heart failure patients → spironolactone competes with aldosterone
What drug is spironolactone often combined with for use in dogs with heart failure?
Ace inhibitors
In which species can spironolactone cause facial dermatitis several months after starting?
Cats
What do ace inhibitors block the conversion of?
Block conversion of angiotensin I to angiotensin II
What does it mean that ace inhibitors are balanced vasodilators?
Act on both veins and arteries
Why are ace inhibitors not used as a monotherapy treatment in patients with severe systemic hypertension?
Arterial effect is minor compared to venous, systemic hypertension is more of an arterial problem so would reach for a drug with more of an arterial effect than ACE inhibitors
What are the two most effective ace inhibitors used in veterinary medicine?
Benazepril and enalapril
(T/F) All ACE inhibitors are prodrugs
True
For which ace inhibitors, benazepril or enalapril, do you need to lower the administered dose in a renal disease patient?
Enalapril
For which ace inhibitors, benazepril and enalapril, which can be used in horses?
Benazepril
(T/F) Ace inhibitors can delay the onset of congestive heart failure in asymptomatic animals.
F, no proof of this
What should be done to monitor your patient, who is on an ace inhibitor, for azotemia (which may develop)?
Monitoring of BUN and creatinine
What can develop with concurrent use of other vasodilators or diuretics and ACE inhibitors?
Hypotension
What phosphodiesterase inhibitor is found in viagra?
Sildenafil
Where does sildenafil inhibit phosphodiesterase 5 (PDE5)?
Small arterioles of the lungs
What direct arterial vasodilator is very potent and whose effects persist after the drug is cleared from the plasma due to its binding to smooth muscle cells?
Hydralazine
What is an inotrope?
A drug/chemical that alters the force of cardiac muscle contraction
What is a chronotrope?
A drug/chemical that alters the heart rate
What is a lusitrope?
A drug/chemical that alters the rate of myocardial relaxation
What is a vasopressor?
A drug that elevates arterial blood pressure via vasoconstriction
What effect does digoxin have on the heart?
Positive inotrope and negative chronotrope
Is absorption of digoxin decreased or increased with food?
Decreased, should not be administered with food
What is the issue with giving digoxin to an animal with ascites?
Ascitic fluid gives patient extra weight, digoxin is dosed based on weight, digoxin does not distribute to the fluid so will overdose the patient if there is significant enough ascites
With what disease may digoxin dose adjustments be necessary?
Renal insufficiency
Does digoxin have a narrow or wide therapeutic index?
Narrow
What species is digoxin primarily used in?
Horses
What are the two clinical uses of digoxin?
Adjunctive tx of supraventricular arrhythmias such as atrial fibrillation or flutter and management of chronic, advanced, refractory congestive heart failure
What does it mean that pimobendan is an inodilator?
It is a positive inotrope, negative chronotrope, and a balanced systemic arterial and venous dilator
What characteristic of pimobendan allows it to be a positive inotrope?
Calcium sensitizer
How does pimobendan cause vasodilation?
Inhibits PDE
Where is pimobendan extensively metabolized?
Liver
Which of the effects of pimobendan (positive inotrope, negative chronotrope, and vasodilator) is blunted in feline patients?
Vasodilatory effects
Does pimobendan use prolong the time it takes an asymptomatic mitral valve disease or dilated cardiomyopathy dog to develop congestive heart failure?
Yes
What is the main advantage that pimobendan has over digoxin?
Safety, it’s much safer
What two drug types can attenuate the inotropic effects of pimobendan?
Calcium channel blockers and beta-blockers
What is triple therapy in terms of combo therapy for treatment of congestive heart failure?
Use of furosemide, enalapril, and pimobendan together
Of the adrenergic receptors (alpha1, beta1, beta2) which do epinephrine act on?
All of them
Why is epinephrine detrimental to a failing heart, result in reduced cardiac efficiency and cause ventricular arrhythmias?
Causes an increase in energy usage and myocardial oxygen demand
Epinephrine can be given in all routes except one, which one?
Orally
What receptors do dopamine work at?
Beta1 and dopamine receptors
What effects does dopamine have based on the receptor activity it has?
Beta1 - positive inotrope; dopamine receptors - vasodilation
Why can dopamine also have alpha1 and beta2 receptor mediate actions as well once in the body?
Dopamine is metabolized into norepinephrine and epinephrine in the body
What occurs at the 2-5 microgram/kg/min dose of dopamine?
Renal vasodilation
What dose range should you aim to be in to get ONLY the beta1 effects → positive inotropy and increased cardiac output? (Dopamine)
5-10 microgram/kg/min
What receptor activity is induced at doses >10 microgram/kg/min (domapine)?
Mixed alpha and beta receptor activity → vasopressor effects
What receptor does dobutamine work at?
Beta1
What is the effect of dobutamine based on the receptor activity it induces?
Positive inotrope
At typical doses, vasopressin promotes the renal absorption of solute-free water in the distal convoluted tubules and collecting duct but at higher doses, can cause what?
Constrictions of capillaries and small arterioles → decreases blood flow to several body systems
Listed below are the different vaughan-williams classes of antiarrhythmic drugs, give the phase of the action potential that they work at:
- Class I
- Class II
- Class III
- Class IV
- Class V
- Class I (Phase 0)
- Class II (Phase 4)
- Class III (Phase 3)
- Class IV (Phase 2)
- Class V (Other)
Listed below are the different vaughan-williams classes of antiarrhythmic drugs, give the mechanism of action of each class:
- Class I
- Class II
- Class III
- Class IV
- Class V
- Class I (Sodium channel blockers)
- Class II (Beta blockers)
- Class III (Potassium channel blockers)
- Class IV (Calcium channel blockers)
- Class V (Other)
Listed below are the different vaughan-williams classes of antiarrhythmic drugs, give the important drugs in each class:
- Class I
- Class II
- Class III
- Class IV
- Class V
- Class I (Quinidine, lidocaine)
- Class II (Atenolol, sotalol)
- Class III (Amiodarone, sotalol)
- Class IV (Diltiazem)
- Class V (Digoxin, magnesium sulfate)
Which of the following is not an effect class Ia drugs have on action potentials?
a) Slow rate of rise of phase 0
b) Increase refractory period
c) Prolong action potential and repolarization
d) Increase the electrical value for depolarization to -50mV
D
What effect do class Ia drugs have on an ECG wave?
Prolong PR and QRS
What effect do class Ia drugs have on sodium channels?
Block open sodium channels
What is the most common use of quinidine?
In tx of atrial fibrillation and flutter in horses
What cardiovascular adverse effects does quinidine have?
Alpha adrenergic blocker → hypotension and vasodilation; antivagal/‘anticholinergic’ effect → supraventricular tachycardia
Why is quinidine given via an NG tube?
Oral administration causes oral ulcerations
What drug would you co-administer with quinidine in the following cases…
- Decreased fractional shortening
- Increased resting heart rate
- Previous hx of sustained tachycardia during prior conversion
- Sustained tachycardia during therapy
Animals with refractory dz
Digoxin
Why do you have to be careful when coadministering quinidine and digoxin?
Quinidine inhibits digoxin excretion and can result in a doubling of serum digoxin concentrations
What advantage does procainamide have over quinidine?
Fewer antivagal effects → safer
What type of tissue do class Ib drugs work in only?
Ischemic or damaged tissue
Do class Ib drugs shorten or lengthen an action potential’s duration and repolarization?
Shorten
What effect do class Ib drugs have on sodium channels?
Block open and non-conducting sodium channels
Class Ib drugs are indicated in the treatment of what two things?
Acute ventricular arrhythmias and ventricular arrhythmias caused by digitalis intoxication
What are the two more commonly used class Ib drugs?
Lidocaine and mexiletine
What effect do class Ic drugs have on action potential duration?
None
Class II drugs reduce the effects of sympathetic or parasympathetic stimulation?
Sympathetic
Do class II drugs have a direct myocardial effect?
No
Class II drugs have a negative/positive inotropy and chronotropy.
Negative
Which adrenergic receptors does propranolol work at?
Beta 1 and 2
Animals with which disease should not be prescribed propranolol?
Asthma
Which adrenergic receptor is atenolol selective for?
Beta 1
What adrenergic receptors does carvedilol work at?
Beta 1 and 2, alpha 1
What are the possible cardiovascular adverse effects of class II drugs? Two answers.
Bradyarrhythmias and hypotension
What do class III drugs cause the prolongation of?
Cardiac action potential and its refractory period
What is the clinical use for sotalol?
Long term tx for hemodynamically significant ventricular arrhythmias
What are the possible cardiovascular adverse effects of sotalol? Three answers.
Negative inotropy, bradyarrhythmias, proarrhythmic
What vaughan-william classes do the drug amiodarone fit into?
Class I, II, III, and IV
What is the clinical use of amiodarone?
Life threatening ventricular arrhythmias and atrial fibrillation
Of the class IV drugs, diltiazem and amlodipine, which targets cardiac calcium channels and is therefore used in tx of heart diseases?
Diltiazem
Diltiazem blocks entry of calcium into cardiomyocytes during an action potential and blocks calcium channels in the conduction tissue in the heart which means diltiazem is:
___________ inotrope
___________ lusitrope
___________ chronotrope
inotrope (Negative)
lusitrope (Positive)
chronotrope (Negative)
(T/F) Diltiazem is used for a-fib and other supraventricular arrhythmias but has no effect on ventricular arrhythmias.
True
What nerve does atropine block the effect of on the SA node?
Vagus nerve
Atropine is a negative/positive chronotrope.
Positive
