Cardiovascular Pharmacology Flashcards
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
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
What is heart rate determined and altered by?
CV centre in medulla oblongata
Autonomic nervous system
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
Why can control of HR go wrong?
Ectopic pacemakers
Damage to conducting tissue
Depression of CV centre
Why are tachycardias a problem?
Reduced diastolic filling time
Lower end diastolic ventricular volume
Lower stroke volume= lower cardiac output
Increased cardiac work= hypertrophy
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)
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
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
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
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
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
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
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
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
What are class II antidysrythmics used for?
Supraventricular or ventricular tachycardias
Hypertension
What is an example of class II and what are its adverse effects?
Atenolol- beta 1 selective
Adverse effects limited to CNS
What are the 2 modes of actions of class III?
Prolong cardiac AP
Block K+ channels- slows repolarisation, increases refractor period
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
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
Name an example of class IV, how is it administered?
Diltiazem
Oral and parenteral administration
Toxicity- myocardial depression, hypotension, AV block
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
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
