CV pharma

Starting info :

Whaat can we change to alter heart rate / rhythm?

AP conduction

refractory period length

Starting info : what can we alter to change contractility of cardiac muscle

intracellular Ca2+

Starting info : what two factors affect preload

circulting volume + vscular resistance

Starting info : what affects afterload?

vascular resistance

Starting info: what affects perfusion ?

compensatory vasoconstriction of organs

Starting info : what can effect arterial pressure?

baroreceptors

What is an inotrope

a drug tht alters the strength of muscular contractions

What is a lusitrope?

a drug effecting myocardial relaxtion

What is a chronotrope?

a drug effecting the heart rate

Describe the control of heart rate and rhythm.

ANS and CV centre in medulla oblongata regulate rate + rhythm.

AP conduction is essential

• Na+, K+, Ca++ channels

• ion levels

• correct function of intercalated disks

What is a tachyarhythmia and why are these a problem?

Very fast heart rate!

decreased diastolic filling time → reduced EDVV → reduced SV → reduced CO!

can cause myocardial hypertrophy

What is the name of the classification system for antidysrhythmics?

Name and describe the classes

vaughan - williams

1. drugs that block na channels

2. beta blockkers

3. drugs that prolong AP by blocking some K channels

4. drugs that block Ca channels

5. miscellaneous

Describe class 1 (Vaughan-Williams) antidysrhythmics

Bind to and block FAST NA CHANNELS

• this slows AP, and therefore HR.

They only affect tachyarthymias, not normal HR. Why?

• use dependent Na channel blockade - more channels = faster HR = drug binds to those

Describe class 1 (Vaughan-Williams) antidysrhythmics, classes 1a, 1b and 1c giving examples.

a) old drugs. immediatly dissociate from Na channels.

• Quinidine (horses). Oral drug.

b) bind during phase 0, dissociate for next AP, so prevents premature beats.

• Lidocane. Parenteral.

c) bind and dissociate slowly and reach a steady state.

• flecainide

Describe class 2 (Vaughan-Williams) antidysrhythmics. Give an example

Beta blockers! (B1)

• selective (not at higher doses tho)

• if hit b2 can causse vasoconstriction

Slow pacemakercell potential by slowing Ca influx, slows conduction through AV bunde.

Causes negative inotropy and negative lucitropy.

Atenolol.

Describe class 3 (Vaughan-Williams) antidysrhythmics. Give an example

Multiple MOAs, prolong cardiac AP and block K+ channels.

Sotalol, non-slective betablocker AND inhibits K channels, has adverse ffects of bradycardia and hypotension

Describe class 4 (Vaughan-Williams) antidysrhythmics. Give an example

Block Ca++ channels in cardiomyocytes, nodal tissue and vasculr smooth muscle.

• slower conduction in SA and AV nodes.

  • basically an AV block

Negative inotrope, positive lusiotrope, vasodialator.

Diltiazem.

• coronary + systemic vasodialator

• can cause myocrdial depression, hypotension, AV block

Describe digoxin (antidysrhythmic)

Negative chronotrope, increases vagal outflow.

slows concuction through AV node

What is a bradyarythmia?

slow heart beat

Why are bradyarythmis hard to treat?

usually cuases by a break in the bodys normal pathways to increase HR. require pacemakers instead.

Give some autonomic drugs tht can treat bradyarhythmias

Sympthomimetics

• B1 agonists eg dobutamine

• B2 agonists eg terbutline

Anticholinergics

• Atropine, muscarinic antagonist.

What other types of drug can treat bradyarythmias? give examples.

Methylxanthines

• non-selctive PDE inhibition - theophylline

PDE III inhibitors

• pimobendan

In general, how do postivite inotropes increase strength of muscular contraction?

Endogenous - symapthetic NS

Pharmacologically - symptic stim, increase Ca++ intracellularly,

How do PDE III inhibitors work?

inhibits pde3 enzyme from degrading intracellular cAMP → incresed cAMP causes ^ activate ProKinA → more Ca++ phosphotlytion → more Ca++ into cardiac myocyte.

What are the other effects of PDEIII inhibitors?

vasodialation, tachycardia.

Give an example of a PDE3 inhibitor and how it works

Pimobendan

• calcium sensitiser, positive inotrope, vasodialator

• adverse effects : inappetence, lethargy, dyspnoea, azotaemia

Give an example of a cardiac glycoside and how this works.

Digoxin

• + inotrope, - chronotrope

inhibits Na/K pump to decrese intracellular Na

reduces Ca extrusion from cell

What MOAs can negative inotrope have?

sympathetic antagnonists

• b blockers

cholinergics

• antagonises sympathetic M2 receptors on cariomyocytes

calcium channel blockers

• redcues ca influc into cell

List some direct vasodilators

nitrates, ca channel blocker, pde3 inhibitors, hydralazine

How do nitrates (drug) cause vasodilation, give examples

Nitric oxide action

cGMP → inactivates K channels → inhibits Ca entry + activates PK-G → activates MLCP. ( relaxed bvs )

• Sodium nitroprusside

• Nitroglycerine

  • venodiltor

What is the action of Ca++ channel blockers and give an example.

antidysrhythmics + vasodilators

Almodipine

What is hydralazine used for

arteriodilator, decreases afterload,

What are PDEIII and V inhibitors used for? give an exam-le of a pde5 inhibitor

3- CHF

5- arteriodialtion

• sildenafil (viagra) inhibt breakdown of cGMP

What body systems can we activate to trigger indirect vasodilation?

Symapthetic NS

RAAS

list some sympathetic antagonist that can act as idirect vasodilators

a1 adrenoreceptor blockade

• prazosin

• phenooxybenzamide

What three classes of drugs effect the RAAS and can be used as indirect vasodilators

ACE inhibitors

AII receptor agonists

Aldersterone agonists

Give examples of ace inhibitors,what is their MOA

enalapril remairil, benzapril

• vasodilation, reduced circulating volume

give an example of a A II inhibitor and its MOA

telmisartan

• inhibit A II to stop vasoconstriction

Give examples of aldersterone antagonists adn their MOA

spironolactone

cardalis

• reduce Na + H2O retention

• reduce cardiac remodelling

• potassiu sparing diuretic