Cardiovascular Drugs

Pharmacology quiz 2 Midterm 1-7

Sodium Channel Blocker Antiarrhythmic Drugs

-Reverse arrhythmias by blocking the fast sodium channels that allow Na+ influx into the cell (depolarization)

-Slowed sodium influx prolongs Phase 0, prolonging the refractory period (stabilizes the cell and prevents it from being depolarized again quickly)

-Decreases spontaneous depolarization of ectopic foci cells

The SA node is usually unaffected by these drugs at the doses used to control arrhythmias

• if the SA node is depolarizing quicker than the ectopic focus source of the arrhythmia, the SA node will “recapture” control over the heart and reestablish normal rhythm

Lidocaine, Mexiletine, Procainamide, Quinidine

Sodium Channel Blocker-Antiarrhythmic Drug

-Low dose: sedation, ataxia, drowsiness (suppression of excitatory neurons in the brain)

-High dose: excitement and seizures (suppression of inhibitory neurons)

IV, if PO has strong first pass effect, often given as a CRI to maintain arrhythmia control

-Cats are more sensitive and require lower doses

Lidocaine

Sodium Channel Blocker-Antiarrhythmic Drug

ONLY used for local anesthesia

-Epinephrine causes vasoconstriction of local arterioles, reducing tissue perfusion and delaying absorption from the local site

-if given to an animal with an arrhythmia, the stimulatory effect of the epinephrine on the heart could make the arrhythmia worse

Lidocaine plus epinephrine

Sodium Channel Blocker-Antiarrhythmic Drug

PO -same class as lidocaine

-Minimal first-pass effect, Long-Minimal Term antiarrhythmic drug

-May still reduce GI and CNS side effects at higher doses, but minimal at therapeutic doses

-Generic compounded drug used with lidocaine-responsive arrhythmias in dogs

Mexiletine

Sodium Channel Blocker Antiarrhythmic Drugs

Same as lidocaine BUT can control ventricular foci AND atrial Fibrillation/flutter

use: small animals

Procainamide

Sodium Channel Blocker Antiarrhythmic Drugs

Same as lidocaine, BUT can control ventricular foci AND atrial Fibrillation/flutter

use: horse atrial fibrillation or flutter

-When used in horses to suppress atrial flutter/fib, the HR increases (it should decrease because the bombardment of the AV node by atrial depolarization waves should decrease)

-has an anti-vagal or vagolytic effect: BLOCKS acetylcholine at the AV node, so blocks the slowing effect of PSNS → HR increases

Quinidine

Beta-Blocker Antiarrhythmics

Beta 1 (B1) antagonists

-blocks B1 receptor; they prevent norepinephrine from reaching the site and increases HR and force

Sympathetic stim. makes the heart electrically unstable→ more prone to arrhythmias

Blocking sympathetic stim. makes heart more electrically stable→ decreases ectopic foci activity

ALLOW:

-SA node effect: decreased HR

-AV node effect: decreased conduction and possible AV block

-Allows force of contraction to return to base line (doesn’t decrease force)

Propranolol, Atenolol, Esmolol, Metoprolol

Beta Blocker AV block effect - What degree is this?

-prolonged PR segment (between end of P wave and the beginning of QRS complex)- reflects delay of wave getting through AV node

1st degree AV block

Beta Blocker AV block effect - What degree is this?

-dropping of occasional QRS complex- reflects such long delay getting through AV node the wave dies out, never emerges on other side- see P wave w/o corresponding QRS, then normal P-QRS-T pattern

2nd degree AV Block

Beta Blocker AV block effect - What degree is this?

-no wave gets through the AV node- ventricles depolarize according to timing set by bundle branches - P waves are independent of QRS

3rd degree AV Block

what is PSNS dominance on AV node slows depolarization wave- takes longer for the wave to get through the AV node to the ventricles

Beta Blocker AV block effect

Beta-blocker — old

-blocks B1, but also blocks B2 receptors to some degree (bronchodilation effect)

-Has more side effects than newer drugs because it stimulates more receptors than newer drugs because it stimulates more receptors and is less specific

Propranolol

Beta-Blocker —Newer

-more selective for only B1 receptors and do not bind and block B2

-Has less side effects because it stimulates less receptors and is more specific

Esmolol, metoprolol, atenolol

Other Antiarrhythmics -Old drug used as a positive inotropic agent (it increased the cardiac muscle force of contraction)

-Side Effect: increases parasympathetic like effect on the AV node→ slowed impulses going like effect on the AV node→ slowed impulses going from atria to ventricles (AV block)

-pts w/ A Fib- have hundreds of uncoordinated depolarization waves hitting the AV node every minute → can increase Ventricular rate very high (tachycardia) →increases work ventricles are doing!

-V Tach- can be controlled using this to reduces the number of depolarizarion waves that get thorugh from the atria→ slows ventricular rate

Digoxin

Positive Inotropic Drugs and Inodilators

Catecholamines, Pimobendan, Digoxin

Catecholamines

epinephrine, norepinephrine, dobutamine

Positive Inotropic Drugs and Inodilators

-Also called Adrenergic drugs

Used for: short-term boost to the heart’s force of contraction; NOT for long-term use

-Similar in chemical nature to epi/norepi, dobutamine, and dopamine

-Simulate SNS receptor (B1, A1. etc.)

-Increase force of contraction through B1 stim. →causes a greater release of Ca++ from intracellular storage site→ increases force

Problems: cells quickly downregulate to this “over stim.“ and retract B1 receptors from the cardiac muscle cell surface → become less responsive

Catecholamines

Inodilator - Vetmedin: largely replaced older digoxin for most commonly used positive inotropic drug

-Increases the binding

Use: advanced heart failure associated with dilated cardiomyopathy or severe valvular disease in CA/FE

Should NOT be used in hypertrophic cardiomyopathy because the thickened ventricles obstruct the outflow tracts when they are strongly stim to contract → contraction impedes the ejection of blood by the ventricles

Pimobendan

Long-term positive inotrope largely replaced by Pimobendan

Site of Action: Sodium-Potassium-ATPase pump on cell membrane

-Impaired pump allows more Na+ than normal to sneak into the cell → increased Na+ displaces Ca++ from intracellular storage

-More Ca++ available to the contractile elements → increased force of contraction → positive inotropic effect

-A cardiac glycoside and a natural poison found in foxglove plants

-Later tox signs reflect ____ PS effect: bradycardia, AV block

Excreted: Kidneys- old animals with poor kidneys more at risk for toxicity

Digoxin

Vasodilator Drugs (categories)

Arterial vasodilators, Venous vasodilators, Mixed vasodilators

Arterial Vasodilators

Amlodipine, Hydralazine

Venous Vasodilators (Venodilators)

Nitroglycerin

Arterial Vasodilator -Calcium channel blocker drug

-reduces the amount of calcium entering the smooth muscle surrounding the arterioles- decreases the calcium available for contraction- contraction decreases (vasodilation)

Used: CA/FE Hypertension- especially cats with hypertension secondary to CKD, hyperthyroidism, or diabetes mellitus

-Not used for antiarrhythmic purposes in vet med

Amlodipine

Arterial Vasodilator - direct arteriolar smooth muscle relaxant

Mechanism: not completely understood (probably still related to decreased availability or binding Ca with smooth muscle contractile elements)

Used: to relieve left-sided heart failure signs from bad AV valve where blood from the ventricles regurgitates back to the atria. Used with mixed arterial/venous vasodilators as an additional drug

-Drops arterial blood pressure enough that more blood is ejected into the aorta than goes back through the damaged AV valve into the atria

Problem: they do not inhibit the renin-angiotensin-aldosterone mechanism → can still cause vasoconstriction and increased workload on the heart

Hydralazine

Pacemaker- depolarizes spontaneously (has automaticity) more frequently than any other spontaneously depolarizing cell in the heart.

-Depolarization spreads thoughout atria causing contraction (P wave on ECG)

-Atria and Ventricles are insulated from each other

-Only way the depolarization wave can get to the ventricles is through the AV node

SA node

-delays depolarization wave long enought for blood to be physically moved from the atria (by atrial contraction) into the ventricles

-w/o this delay, the whole heart would contract at once

-shows up on ECG as a flat PR segment

-this passes the depolarization wave to the ventricles, producing a large QRS complex

AV node

Before stim: the heart is Negative on the inside and positive on the outside

When stimulated:

1. Sodium (Na+) rushes INTO the cell

2. The inside becomes more positive

3. The cell has now depolarized

4. This causes the heart muscle to contract

Heart after:

Inside: positive

Outside: negative

Depolarization

After the cell fires, it needs to get back to its normal resting state

Inside: positive

Outside: negative

1. Sodium channels close

2. Potassium (K+) moves OUT of the cell

3. The inside becomes negative again

4. The cell is repolarized

5. Now it is ready to fire again

Return to normal

outside: positive

inside: negative

Repolarization

atrial depolarization →atria contract

P wave

ventricular depolarization→ ventricles contract

QRS complex

ventricular repolarization → ventricles reset

T wave

Fixes depolarization by moving the ions to the correct side of the heart

Moves:

-Na+ OUT of the cell

-K+ IN to the cell

ATPase pump

After depolarization

As K+ leaves:

-Positive charge leaves with it

-The inside becomes negative again

-The cell returns toward its resting state

As K+ OUT = Cell becomes negative = Repolarization

Potassium channel

Cardiac Muscle Cell Phases

What happens in Phase 0?

Rapid Na+ influx (depolarization)

Cardiac Muscle Cell Phases

What happens in Phase 1?

K+ efflux begins

Cardiac Muscle Cell Phases

What happens in Phase 2?

Ca++ influx → plateau

Cardiac Muscle Cell Phases

What happens in Phase 3?

Ca++ channel close; K+ efflux continues → repolarization

Cardiac Muscle Cell Phases

What happens in Phase 4?

Resting baseline

Conducting cells (SA,AV)

What is automaticity

ability to depolarize spontaneously

Conducting cells (SA,AV)

Why is the SA node the pacemaker?

It is the leakiest to Na+ and reaches threshold fastest

Conducting cells (SA,AV)

Which cells have slower automaticity?

AV node, bundle branches

Refractory Periods

What is the absolute refractory period

Cell cannot depolarize regardless of stimulus.

Refractory Periods

What is the relative refractory period?

Cell may depolarize if stimulus is strong.

Refractory Periods

Why is the refractory period important?

Prevents chaotic depolarization and fibrillation.

What neurotransmitters does the SNS use?

Norepinephrine and epinephrine.

SNS effects on the heart?

↑ HR, ↑ AV conduction, ↑ force of contraction.

SNS effects on vasculature?

Vasoconstriction of skin, GI, kidneys

What neurotransmitter does the PSNS use?

Acetylcholine

PSNS effects on the heart?

↓ HR, ↓ AV conduction

PSNS effects on cardiac muscle or vasculature?

none

What does Beta‑1 stimulation do?

↑ HR and ↑ force of contraction

What does Beta‑2 stimulation do?

Bronchodilation and vasodilation in skeletal muscle

What does Alpha‑1 stimulation do?

Vasoconstriction of arterioles → ↑ resistance

What does Alpha‑2 stimulation do?

Shuts down norepinephrine release → sedation

What happens when B1 receptors are blocked?

HR decreases

What happens when acetylcholine receptors are blocked?

HR increases

What happens when drugs mimic acetylcholine?

HR decreases

What happens when drugs stimulate B1 receptors?

HR increases

Fast heart rate

tachycardia

fast irregular heart rate

Tachyarrhythmia

slow heart rate

Bradycardia

slow irregular heart rate

bradyarrhymia

What is an ectopic focus

Damaged myocardial cell firing early

What is PVC?

Premature ventricular contraction

What is Paroxysm

Short burst of PVCs

What is flutter

Long series of PVCs with some organization

What is fibrillation?

No organization; chaotic electrical activity

What arrhythmias does lidocaine treat?

PVCs and ventricular arrhythmias

Does lidocaine work for atrial fibrillation/flutter

no

How does lidocaine work

Blocks Phase 4 automaticity in ectopic cells

Why is lidocaine given IV

String first-pass effect removes oral drug

Why is lidocaine often given as a CRI

Rapid metabolism

WHy must cats get lower doses

They are more sensitive to side effects

What are lidocaine CNS toxicity signs?

Low dose: sedation, ataxia High dose: excitement, seizures

Why must lidocaine + epinephrine NEVER be used for arrhythmia?

Epinephrine worsens arrhymias

What is mexiletine used for?

Long‑term control of lidocaine‑responsive arrhythmias

Why is mexiletine effective orally?

Minimal first‑pass effect

What side effects may occur?

GI and CNS signs at high doses

What arrhythmias does procainamide treat?

Ventricular foci AND atrial fibrillation/flutter

Why is procainamide less available?

Human use has declined

What species is quinidine used in?

horses

What arrhythmias does quinidine treat?

Atrial fibrillation/flutter

Why does quinidine increase HR

Anti‑vagal (vagolytic) effect → blocks acetylcholine at AV node

What do beta blockers block?

B 1 receptors

What happens when B1 receptors are blocked

↓ HR, ↓ conduction, ↓ ectopic activity

Why do beta blockers stabilize the heart?

They reduce sympathetic stimulation

Why does propranolol have more side effects?

It blocks both B1 and B2 receptors

Why are newer beta blockers safer?

They selectively block B1 receptors.

What is special about esmolol?

Very short‑acting

Why must beta blockers be used cautiously in CHF?

Blocking SNS may remove the only mechanism maintaining cardiac output.

What happens when B1 receptors are blocked long‑term?

Cells sprout more receptors

What happens if beta blockers are stopped suddenly?

Massive NE response → severe arrhythmias → death

What must be done when stopping beta blockers?

withdraw slowly

What was digoxin historically used for?

Positive inotrope

What effect does digoxin have on the AV node?

Increases parasympathetic‑like effect → slows conduction

Why is digoxin useful in atrial fibrillation?

Reduces number of depolarization waves reaching ventricles → slows ventricular rate

What do catecholamines stimulate?

SNS receptors (B1, A1, etc.)

How do catecholamines increase force?

B1 stimulation → ↑ Ca++ release

Why are catecholamines short‑term only?

Cells downregulate B1 receptors

What type of drug is pimobendan?

Inodilator