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
Clinical effects of pde3 inhibitors
Improved heart contractility Without increasing oxygen utilisation
Reduced pre and after load
Reduced coronary vascular resistance
Some bronchodilation
How does milrinone present
Clinical administration and effects
Yellow solution of lactate salt
Loading dose then infusion
May cause hypotension because of vasodilation
Milirinone elimination
80% unchanged in urine thus renal failure can have large impact on effect (including renal effects of heart failure)
Issues with use of enoximone
Reduces refractoriness of atrium and av and ventricle so may cause ectopics and VT
Hypotension
Metabolism of enoximone
Hepatic
T1/2 4 hrs
Effects of angiotensin 2, what sort of molecule is it
Vasoconstriction
Release of aldosterone resulting in na and water conservation
An octopeptide
What type of molecule is ace
A carboxypeptidase
What dose ace do
Ang 1 to 2
Inactivates bradykinin
Types of angiotensin II receptor
What do ARBS block
AT1 - GRPC - triggers vasoconstriction and aldosterone secretion
AT2 - anti proliferation at endothelial cells
ARBS block AT1
How does furosemide work
Acts on thick ascending limb of loop
Interferes with sodium and chloride reabsorption
Thus more water excreted due to higher osmotic pressure
Also cause vasodilation - also increases renal blood flow without effecting gfr meaning distal tubule protein more dilute thus lower osmotic pressure
Overall decreased gradient so less waster reabsorption
How are the vascular effects of furosemide mediated I
Interference with prostaglandin e2 and i2 degradation
Why do loop diuretics cause hypokalaemia and alklalaemia
More filtrate and na to DCT so more na/k exchange pump action
Also more hydrogen ions secreted in exchange for k
How do loop diuretics enter tubules
Why
How are they excreted
Highly protein bound so not readily filtered at glomerulus
Actively secreted into pct
Excreted in urine
How do thiazide diuretics work?
Act on luminal membrane pumps of DCT inhibiting na Cl reabsorption
What secretion is increased with thiazides
Magnesium
Potassium
Sodium
What secretion is reduced with thiazides
Calcium and uric acid
Effect of thiazides on diabetics
Hyperglycaemia
How do potassium sparing diuretics work
Examples
Spironolactone, amiloride
Spironolactone inhibits nak exchange pump in DCT
Amiloride interferes with na channels o which effect of aldosterone is mediated
Efficacy of loop diuretics, thiazides and k sparing diuretics at causing na and water excretion
25, 10 and 5% respectively
Examples of osmotic diuretics
Mechanism
Mannitol, urea
Freely filtered but not reabosorbable in tubule
What is amiodarones structure
An iodinated benzofuran derivative
Bioavailability and protein binding of amiodarne
T1/2
22-86%
97%;protein bound
54 days
What visual changes result from amiodarone
Benign reversible corneal micro deposits
Side effects of amiodarone
Peripheral neuropathy
Nightmares
Tremor
Ataxia
Av block
Alveolitis
Pulmonary fibrosis
Thyroid issues
Effect of amiodarone on thyroid function
Blocks t2 to thyroid. Conversion thus may cause hyo or hyper thyroid is
Why is amiodarones half life so long
Highly lipid soluble and highly tissue bound
Bioavailability of digoxin
Protein binding
75%
25%
