Cardiovascular Pharmacology Flashcards by Patrick Enion

Do do positive and negative inotropes do, what are positive inotroped used to treat?

Positive inotropes- increase contractility
Used for dilated cardiomyopathy
Negative inotropes- decrease contractility

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What do lusiotropes, positive and negative chronotropes do and what are they used to treat?

Lusiotropes- relax ventricles- used for hypertrophic and restrictive cardiomyopathy

Positive chronotropes increase HR- used for AV block
Negative chronotropes decrease HR- used for atrial fibrillation

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What is heart rate determined and altered by?

CV centre in medulla oblongata

Autonomic nervous system

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What is the conduction of the action potential of the heart dependent on?

Normal activity of Na, K, Ca2+ channels
Normal intracellular and extracellular concs of ions
Correct function off intercalated disks

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Why can control of HR go wrong?

Ectopic pacemakers
Damage to conducting tissue
Depression of CV centre

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Why are tachycardias a problem?

Reduced diastolic filling time
Lower end diastolic ventricular volume
Lower stroke volume= lower cardiac output
Increased cardiac work= hypertrophy

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What is the name of the classes of antidysrhythmics and what are the different classes?

Vaughan-Williams classification

Classes- I, II, III, IV, mis (V)

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What does each class (I ,II, III, IV) do?

I- sodium channel blockers
II- Beta blockers
III- Drugs which prolong AP by blocking some K channels
IV- calcium channel blockers

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What do class I drugs bind to and what do they cause?

Bind to and block fast sodium channels- use dependent Na channel blockade (open over resting)
Cause reduced heart rate in tacyarrhythmias while not significantly affecting normal heart rates

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What does the efficacy of class I sodium channel blockers depend on?

Normal concentration of extracellular K
Hypokalaemia reduces their function
Hyperkalaemia increases their function

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What are the three sub-classes of Class I sodium channel blockers and how do their actions differ?

Ia- old, intermediate rate of dissociation
Ib- bind during phase 0, begin to dissociate for the next AP, prevents premature beats
Ic- bind and dissociate slowly, reach steady state and reduce His-purkinje system

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Name an example of each sub-class of sodium channel blockers?

Ia- quinidine- increase effective refractory period
Ib- lidocaine - decrease effective refractory period
Ic- flecainide- doesn’t affect effective refractory period

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How is quinidine (class Ia) administered and what are its adverse effects?

Oral or parenteral- not IV
Adverse- Various rhythm disturbances as blockage persists, negative inotropy and vasidilation, GI signs, nervousness, depression

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How is lidocaine administered and what are its adverse effects:

Parenteral (slow IV) as almost complete first pass hepatic metabolism
Adverse- CNS- excitation, disorientation, seizures, nausea

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What is the effect of class II antidyshrthmics?

B2 blockade- some vasoconstriction
Slow pacemaker potential by slowing calcium influx
Slow conduction through AV bundle- increase refractory period
Negative isotropy and reduced myocardial relaxation

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What are class II antidysrythmics used for?

Supraventricular or ventricular tachycardias

Hypertension

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What is an example of class II and what are its adverse effects?

Atenolol- beta 1 selective

Adverse effects limited to CNS

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What are the 2 modes of actions of class III?

Prolong cardiac AP

Block K+ channels- slows repolarisation, increases refractor period

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Name an example of class III antidysrhythmics and what is it made up of and what are its adverse effects?

Sotalol
Racemic mixture of isomers I and D
I- non-selective beta blocker
D- inhibits K channels 
Adverse- hypotension, bradycardia, GI signs

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What is the mode of action of class IV and therefore their effect?

Block ca channels of cardiomyocytes, nodal tissue, vascular and smooth muscle
Effect- shorten plateau phase, slow conduction in SAN and AVN
Negative inotropes and positive lusiotropes

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Name an example of class IV, how is it administered?

Diltiazem
Oral and parenteral administration
Toxicity- myocardial depression, hypotension, AV block

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Name an example of Class ‘V’, what is its mode of action, how is it administered, what are its adverse effects?

Digoxin
MOA- chronotropic effects without negative inotropy
Oral admin
Adverse- myocardial toxicity, GI toxicity

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How are bradyarrythmias treated?

Most require pacemaker if causing clinical signs
Sympathomimetics
Anticholinergics
Methylxanthines 
PDE III inhibitors

What are examples of categories of sympathomimetics and anticholinergics and what do they do?

Beta 1 agonists- dobutamine- inotropic
Beta 2 agonists- terbutaline- +ve chronotropy
Muscarinic antagonists- atropine- +ve chronotropy

Name an example of methylxanthines/PDE III inhibitors?

Methylxanthines- theophylline | PDE III inhibitor- Pimobendan

What are the endogenous mechanisms of positive inotropes?

Endogenous increase of contractility | Sympathetic stimulation/stretch increases Ca and increases EDVV

What drug groups are used for positive inotropy?

``` PDE III inhibitors Sympathomimetics Cardiac glycosides Anticholinergics Glucafon ```

When would positive inotropes not be used?

If there is is aortic/pulmonary stenosis

What is the mode of action of PDE III?

Increases intracellular cAMP by inhibiting phosphodiesterase which degrades it cAMP activates protein kinase A, which phosphorylates a site on ca channels making them more likely to open, increased ca release- stronger contraction

What are the side effects of PDE III and why?

Vasodilation- cAMP activates a kinase which phosphorylates myosin light chain kinase, this prevents phosphorylation of myosin- relaxation Tachycardia- faster Ca flow= faster depolarisation

What is an example of a PDE III inhibitor and what are its adverse effects?

Pimobendan oral or parenteral Adverse- inappetence, lethargy, dyspnoea, azotaemia

What cardiac glycoside is used in practice and what is its 'supposed' mode of action?

Digoxin MOA- inhibit Na/K pump in cardiac myocyte- increased intracellular NA, reduced Ca extrusion via Na/Ca exchanger, therefore more Ca into SR for AP

What is the mode of action of sympathomimetics, predict its side effects, and what is their other use?

B1 receptors on cardiac myocytes- agonist action increases contractility Side effects- tachycardia, increased risk of automaticity used for anaesthesia

What are the three types of negative inotropes?

Sympathetic antagonists- beta blockers Cholinergics- antagonises sympathetic action on cardiomyocytes via M2 receptor Calcium channel blockers- reduced calcium influx

How can drugs affect vessel diameter and blood volume?

Affect preload Affect afterload Affect perfusion Affect arterial pressure

How can preload, after load, perfusion, systemic arterial pressure be changed?

Preload- alter venous/atrial volume, venous diameter Afterload- alter TPR Perfusion- CO, vascular diameter, circulating volume Systemic arterial pressure- CO, TPR

How can venodilators act?

Direct- smooth muscle (faster) | Indirect- affect another system

Name types of drugs which are direct vasodilators?

``` Nitrates Dopamine Ca channel blockers PDE III inhibitors Hydralazine K channel activators ```

What is the mode of action of nitrates?

Peripheral vasodilation | cGMP activates K channels, inhibits Ca2+ entry into cell and activates PK-G which activates MLCP- causes relaxation

What two nitrate drugs are used in practice?

Nitroprusside- given parenterally, causes mixed arterial and venodilation- can lead to cyanide poisoning Nitroglycerine- venodilator- causes hypotension

What class of antidysrythmics are Ca++ blockers and what drug is used as a vasodilator?

Class IV | Amlodipine- hypotension, taccycardia

What does hydralazine cause and where, predict its adverse effects?

Arteriodilator- coronary, cerebral, renal, splanchnic Reflex tacycardia Adverse effects- hypotension

What PDE V inhibitor is used for vasodilation, what is its mode of action?

Sildenafil MOA-inhibits breakdown of cGMP- activates proteins kinase G- MLCP activates- dephosphorylates MLC- relaxation Arteriodilator

What two extrinisic mechanisms do indirect vasodilator act on?

Sympathetic | RAAS

What are two examples of alpha 1 adrenoreceptor sympathetic antagonists?

Prazosin- adverse- hypotension, tachycardia | Phenoxybenzamine

What parts of RAAS causes vasoconstriction?

AngII | Stimulated ADH release

Other than Ang II and stimulated ADH release what of the RAAS affects blood pressure and preload?

Retained water and Na+ increases blood pressure and preload

What conditions would benefit from RAAS blockade?

Congestive heart failure Hypertension Chronic renal failure

What types of drugs affect RAAS?

``` Renin inhibitors ACE inhibitors AII receptor antagonists Aldosterone antagonists ADH blockers ```

What is the effect of ACE inhibitors and adverse effects, when are they contraindicated?

Cause vasodilation and reduced circulating volume- improved tissue perfusion, reduced preload and systemic arterial pressure Adverse- uncommon- Hypotension Contraindicates it renal artery stenosis is present

What are the names of the ACE inhibitor drugs used in. practice, where are they activated and excreted?

Enalapril, Ramipril, Benzapril, Catopril, Imidapril Activated in liver Excreted in kidneys (except benazepril)

What AII receptor agonists are used in practice and where is it excreted?

Telmisartan | Bile and urine

What is the action of aldosterone agonists?

Reduce retention of sodium and water

What aldosterone agonists are used in practice?

Sprionolactone | Cardalis

What other drugs can reduce preload?

Diruretics- loop, thiazide, potassium sparring, osmotic