Cardiovascular Pharmacology Flashcards
Examples of class one antiarrhythmics
Effect on phase o slope ,ap, repolarisation
Ia quinadine, some, longer, longer
Ib lidocaine, little, shorter, shorter
Ic flecanide, marked slowing, none, none
What is the pharmacological difference between the vw 1a/b/c drugs
A - half way between b and c
B - shorter association with receptors than duration of cardiac cycle so blocks myofibrils from premature contractions. Bind preferentially to refractory channels so selective for ischaemic myocardium
C - longer association with receptors so blocks cycle to cycle generally reducing excitability effective for re-entry type rhythms
Which class 1 antiarrhythmics effect QT
A lengthens, b shortens
Which class 1 antiarrhythmics effect pr and qrs
Class c lengthens both significantly, class a to a small extent
What is the effect of beta blockade on cardiac cycle
Why
Slows and lengthens phase 4 depolarisation
Ap is shortened and refractory period prolonged
Mediated by blockage of Gs activated slow l type calcium channels
What is the effect of class III antiarrhythmics
Examples
Amiodarone, bretylium, sotalol
Prolong repolarisation and thus the action potential and increase the effective refractory period
Cautions for sotalol use
Hypokalaemia
When other qt prolonging agents used
As with other beta blockers asthma etc
What phase of the ap do class iV antiarrhythmics effect
Phases 2 and 3 (reduces)
Effects of adenosine receptor activation
A1 - inhibits av node, reduce heart rate, reduce atrial contractility, anti hypertensive, decreased cerebral excitability, renal vasoconstriction, bronchoconstriction,
A2a- vasodilation, inhibition of platelet aggregation
A2b - anti inflammatory
A3 - cardioprotection
How do a1 receptors result in cardiac slowing
Gs link to k channels (same as opened by m2 receptors)
Adenosine half life
10 seconds
Structure of a cardiac glycoside
Steroid nucleus,
lactose ring - pharmacologically active
carbohydrate unit - makes it soluble
Mechanism of action of cardiac glycosides
Reversible bind to cardiac NaKATPase
Results in more sodium and less k intracellular
Less naca pump activity thus more ca in the cell
Causes positive inotropy,
Direct slowing at av node and increased vagal tone also causing slowing
Elimination of cardiac glycosides
Slow! Highly bound to cardiac muscle
Most excreted unchanged in urine however digoxin metabolised hepatically
Side effects of cardiac glycosides
Exacerbated by k loss
Heart block
Arrhythmia
Fatigue
Nausea
Anorexia
Confusion
Neuralgia
Gynaecomastia
How is mg stored in the body
53% in bone
27% in muscle
0.3% in plasmaa
Physiological effects of magnesium
Cofactor in 300 enzyme systems
Neuronal activity
Neurotransmitter release
Adenylel cyclase and ip3 regulation
Uses of mg as a med
Replacement of deficit
Tx of eclampsia and pre eclampsia
Treatment of dysrhthmia
Inhibition of prem labour
Cardioplegia (arresting heart in cardiac surgery)
Prevention of hypertensive response to intubation
Treatment of asthma
Reduction of catecholamine release in phaeochromocytoma surgery
What type of calcium channel do ccbs work on
L type voltage gated
Groups of ccbs and examples with broad characteristics
Papaverines - verapamil - mainly effect cardiac muscle inhibiting ca entry in phase 2/3 of AP (with decreased contractility and slower av node conduction)
Benzothiapines - diltiazem - both cardiac and smooth muscle with moderate effect on vascular system (dilatation) and cardiac output.
Dihydropyridines - amlodipine, nifedipine - mainly act at smooth muscle effecting vascular tone
How do ccbs effect SVR and CO
Reduce it by causing vasodilatation (mainly arterial)
Slight negative inotropy
Combination of above mean lower preload and afterload so less myocardial work
What are selective phosphodiesterase inhibitors
Only inhibit pde3 which is in myocardial and vascular smooth muscle
General pde inhibitors inhibit all 5 isoenzymes (eg theophylline)
Sildenafil inhibits pde5
Classifications and Examples of selective pde3 inhibitor
Bipyridines - milrinone
Imidazolines - enoximone
How do selective pde3 inhibitors work
Inhibit pde3 which is responsible for cAMP breakdown
Increase in cAMP in myocardial and vascular smooth muscle
Phosphorylation of protein kinases in the cell
In heart Increased influx of calcium through slow calcium channels by increased number and duration of opening and increased reuptake of calcium
Increased ca and thus increased contraction and improved relaxation
In vasculature phosphorylation if myosin light chain kinase reducing affinity of calmodulin and dephosphorylates the myosin - causes relaxation and vasodilation
