Cardiovascular Pharmacology Flashcards
What is the half life of esmolol?
10mins
How is esmolol metabolised?
Rapidly metabolised by red-cell esterases
Is esmolol a selective or non-selective beta blocker?
Non selective
(although mainly blocks B1 receptors, only blocks B2 at high doses)
In selective phosphodiesterase inhibitors, inhibition of which isoenzyme family causes a positive inotropic action?
Isoenzyme family no III
In selective phosphodiesterase inhibitors, does inhibition of isoenzyme family no III cause clinically important bronchodilation?
No. It does cause slight bronchodilatation but not to a clinically significant degree.
How do selective phosphodiesterase inhibitors affect myocardial oxygen consumption?
There is unchanged or even slightly reduced myocardial oxygen consumption as systemic vasodilation reduces left ventricular systolic wall tension.
Do selective phosphodiesterase inhibitors cause a reflex tachycardia?
Yes
What effect do selective phosphodiesterase inhibitors have on BP?
Hypotension is often seen as a result of reduced systemic vascular resistance due to smooth muscle relaxation.
What is milrinone?
Is one of the bipridine derivative group of phosphodiesterase inhibitors.
What are enoximone and piroximone?
Enoximone and piroximone are imidazolone derivatives.
Is milrinone structurally related to amrinone?
No
What is the terminal half life of milrinone?
2.5hrs
Can milrinone be given as an infusion?
Yes but a loading dose is required. Half life is 2.5hrs.
How should you alter the dose of milrinone in renal failure?
Reduce the dose when creatinine clearance < 30ml/min.
80% is excreted unchanged via the kidneys.
Which drug should not be given with milrinone in the same cannula due to incompatibility?
Furosemide
What is clonidine?
A selective partial agonist for the alpha-2 adrenoceptor with a ratio of approximately 200:1 (alpha2 : alpha1)
What is the effect of clonidine when given as a premedication?
It’s rapidly absorbed when given orally.
It reduces the MAC, but not by as much as 50% (only highly selective drugs like dexmedetomidine can lower MAC this much)
What can occur on discontinuation of clonidine after long term use?
Rebound hypertension
Does clonidine cause diuresis?
Yes, it inhibits ADH
Why is ephedrine not a catecholamine?
It does not have a hydroxyl substitution of the benzene ring, and therefore cannot be called a catecholamine
Which receptor does ephedrine act on?
Stimulation of both alpha and beta adrenoceptors
What isomeric forms of ephedrine are there?
It can exist in four isomeric forms but the only active one is the l-form. Ephedrine is supplied as the racaemic mixture or simply in the l-form
What are the indications for use of ACE inhibitors?
- essential hypertension
- following acute MI
- chronic heart failure
Is digoxin well-absorbed orally?
Yes
How protein bound is digoxin?
An insignificant amount
How is digoxin excreted?
Largely unchanged in the urine
Can potassium levels affect digoxin levels?
Hypokalaemia can cause increased digoxin levels
What kind of heart block can digoxin toxicity result in?
All types of heart block including Mobitz Type II
What drugs can prolong the QT interval out of the following?
(sotalol, quinidine, verapamil, flecainide, disopyramide)
Sotalol, quinidine, disopyramide.
Sotalol posesses class III activity, and both quinidine and disopyramide have class 1A actions with mild class III activity prolonging the cardiac action potential and hence QT interval.
Which drugs have a potassium sparing effect?
Enalapril (ACEi have an anti aldostrone effect and act as weak potassium sparing diuretics)
Triamterene
Spironolactone
What does sodium nitroprusside do?
- stimulates release of nitric oxide in vascular tissue
- does not dilate arterioles
- is associated with a baroreceptor mediated rise in HR
- decomposes slowly in response to light (50% active after 2 days light exposure)
- broken down in RBCs with production of cyanomethaemoglobin
What are recognised complications of amiodarone?
- peripheral neuropathy
- prolongation of the QT interval
- hyper/hypothyroidism
- pulmonary fibrosis
- corneal microdeposits
Which beta blockers are metabolised predominantly in the liver? Which ones are metabolised by the kidney?
- labetalol
- propranolol
- metoprolol
Atenolol and sotalol are water soluble and therefore predominantly metabolised by the kidney.
What receptors does labetolol work on?
It has more affinity for beta receptors
Beta: alpha 3:1 (oral)
Beta: alpha 7:1 (IV)
How can labetolol cause retrograde ejaculation?
Secondary to it’s alpha action
Does labetolol have significant intrinsic sympathomimetic activity?
Yes
Can labetolol cause postural hypotension?
Yes
What are the natural precursors of adrenaline?
Dihydroxyphenylalanine and dopamine
The synthetic pathway is as follows:
Tyrosine-DOPA-Dopamine-Noradrenaline-Adrenaline.
What is dopexamine?
It’s an analogue of dopamine which acts mainly at beta2 and DA-1/DA-2 receptors.
No alpha activity.
Does not require a loading dose and is a weak positive inotrope but powerful splachnic vasodilator reducing afterload.
Which receptors does isoprenaline work on?
Beta1 and 2 only.
How does isoprenaline affect peripheral vascular resistance?
Causes a fall due to it’s beta2 effects
Can isoprenaline decrease MAP?
Yes
How are the effects of isoprenaline mediated?
Via adenylate cyclase
What does hydralazine do?
An arteriolar dilator
What is the 1st pass metabolism of hydralazine dependent on?
The acetylator status of the patient
How does hydralazine affect cerebral blood flow?
It increases it
What syndrome can hydralazine cause?
A lupus-like syndrome
Where is nitric oxide produced?
Vascular endothelium
Macrophages
Thrombocytes
What is nitric oxide synthesised from?
L-arginine
How much higher affinity does Hb have for NO than CO?
The haemoglobin molecule has an affinity 1500 times higher to NO than to CO. Nitrosyl haemoglobin is produced, which in the presence of oxygen, is oxidised to methaemoglobin.
What is nitric oxide metabolised to?
Nitrate which is excreted by the kidneys
What drugs exhibit tachyphylaxis?
GTN
Ephedrine
Trimetaphan
What is verapamil?
Synthetic papaverine derivative
Is verapamil absorbed orally?
It is well absorbed following oral administration, but undergoes extensive first pass metabolism with a bioavailability of 10-20%
How protein bound is verapamil?
~ 90%
How is verapamil excreted?
70% of metabolites are excreted by the kidney
How does trimetaphan work?
Induces hypotension by blocking sympathetic ganglia but also exhibits some direct vasodilatation.
It dilates both arterioles and veins.
It’s inactivated by plasma cholinesterase.
What are the SEs of trimetaphan?
- histamine release
- mydriasis
- potentiation of suxamethonium
- urinary retention
- impotence
- due to non-selective ganglion blockade
What is the plasma half life of trimetaphan?
Half life of 2 mins
What is phenoxybenzamine?
Non-selective alpha blocker
Where does phenoxybenzamine act?
Predominantly on post-synaptic alpha1 receptors
Which routes can phenoxybenzamine be given?
Orally or IV
What limits increasing the dose of phenoxybenzamine?
Nasal stuffiness and postural hypotension
What is phenoxybenzamine used for?
Treatment of phaeochromocytomas
What are the SEs of thiazide diuretics?
- hyperuricaemia
- hyponatraemia
- hypercalcaemia
- hyperglycaemia
- hypokalaemia
- hyperchloaremia
- result in hypokalaemic, hypochloraemic metabolic alkalosis
Ephedrine is unlikely to be effective in reversing hypotension in patient’s taking what medicines?
Indirectly acting sympathomimetics like ephedrine are unlikely to increase BP in patients taking drugs which alter neuronal storage, uptake, metabolism or release of neurotransmitters
- Reserpine- depletes neuronal granules of noradrenaline
- alpha-methyl dopa - acts as a false transmitter
- phenoxybenzamine
- propranolol
- both block peripheral receptors and industrial doses of directly acting sympathomimetics may be required to overcome their blockade
How do ACEi affect the onset of chronic renal disease secondary to hypertension?
They slow the onset
What does angiotension II do to the glomerular arterioles?
Angiotensin II causes glomerular arteriolar vasoconstriction (in the efferent arterioles to a greater extent than the afferent)
Does the fetus have high renin and angiotensin II levels?
Renin levels are high
Angiotensin II levels are low due to limited pulmonary blood flow
Does angiotensin II stimulate the release of aldosterone?
Yes. Angiotensin II stimulates the release of aldosterone from the adrenal cortex.
Do all ACE inhibitors have similar antihypertensive efficacy at equipotent doses?
What drugs would you give to control ventricular rate in AF?
- atenolol
- amiodarone
- digoxin
What is quinidine used for?
Can be used in atrial arrhythmias but it has a slight vagolytic effect so can accelerate the ventricular rate in AF unless digoxin is given at the same time.
Can disopyramide be given in AF?
It has class Ia and III activity and an anticholinergic effect.
It should not be given for AF by itself.
What does enoximone do in cardiogenic shock?
Reduces afterload (ie LVEDP) due to vasodilating effects
How does adrenaline affect SVR?
- acts on both alpha and beta receptors
- at low doses beta effects predominate (tachycardia, increased CO, lower SVR)
- at higher doses alpha effects take over with peripheral vasoconstriction
How does noradrenaline affect CO?
It increases SVR and hence reduces CO. It is mainly an alpha-agonist.
What does isoprenaline do in cardiogenic shock?
It produces a tachycardia via it’s beta agonist effect- increasing myocardial consumption
What effect does dobutamine have on SVR?
It decreases SVR by vasodilation through Beta2 adrenergic agonism.
What is dantrolene and how does it affect calcium actions on smooth muscle?
It’s a direct acting skeletal muscle relaxant.
It has no action on smooth muscle.
What drugs will have calcium antagonistic actions on smooth muscle?
- diltiazem
- nircardipine
Which rhythms is adenosine effective in treating?
Adenosine is effective in SVTs, depressing the SA node activity and blocking AV node conduction. Although ineffective in VTs, it can serve to distinguish SVT with associated bundle branch block from VT in a patient with broad complex tachycardia.
What is the half life of adenosine?
30 seconds
What SE can adenosine cause?
Wheeze
Coronary vasodilation -therefore coronary steal in susceptible patients
