Cardiovascular system Flashcards
What is the common indication for adenosine?
As a first-line diagnostic and therapeutic agent in supraventricular tachycardia (SVT).
What is the mechanism of action of adenosine in cardioversion (allowing the depolarisations from the SA node to resume normal control of the heart)?
Adenosine is an agonist of adenosine receptors on cell surfaces. In the heart, activation of these GPCRs induces a number of effects: reducing the frequency of spontaneous depolarisations (automaticity) and increaseing resistance to depolarisation (refractoriness). In turn, this transiently slows the sinus rate, conduction velocity, and increases atrioventricular node refractoriness.
Increasing the refractoriness in the AV node breaks the re-entry circuit, which allows normal depolarisations from the SA node to resume normal control of heart rate.
What is the mechanism of action of adenosine in atrial flutter?
Does not induce cardioversion, however by blocking conduction to the ventricles. It allows closer inspection of the atrial rhythm on the ECG. Which may reveal the diagnosis.
What are the important adverse effects of adenosine?
It interferes with the function of the SA and AV nodes so adenosine can induce bradycardia and even asytole (flat line).
Sinking feeling, impending doom, breathlessness.
What type of patients are especially sensitive to the effects of adenosine?
Those who have had a heart transplant.
Which patients should not be administered adenosine?
Those who cannot tolerate the transient bradycardic effects, hypotensive patients, those with coronary ischaemia or decompressed heart failure.
As adenosine may also induce bronchospasm it should be avoided in those such as people with asthma or copd or may be suceptible.
Why would we avoid adenosine in a COPD patient?
As adenosine may also induce bronchospasm it should be avoided in those such as people with asthma or copd or may be suceptible.
What is the interaction between adenosine and dipyridamole?
Dipyridamole (is a medication that inhibits blood clot formation when given chronically and causes blood vessel dilation when given at high doses over a short time) blocks cellular uptake of adenosine, which prolongs and potentiates the effects of adenosine.
The adenosine dose should be halved.
What is the interaction between adenosine and theophylline, aminophylline and caffeine?
Theophylline, aminophylline and caffeine are all competitive antagonists of adenosine receptors and may reduce its effect - may require higher doses.
How is adenosine given and at what doses? where would it be found on the drug chart?
IV, once-only section, 6mg IV or 12mg in selected cases.
What are the three main indications for Aldosterone antagonists?
- Ascities and oedema due to liver cirrhosis - spironolactone is the first - line diuretic.
- Chronic heart failure of at least moderate severity or arising within 1 month of a MI, usually as an addition to a B-blocker and an ACEI/ATRB.
- Primary hyperaldosteronism for patients awaiting surgery or for those who surgery is not an option.
What are the two common examples of aldosterone antagonists?
Spironolactone + epleronone
What is the first - line diuretic for ascities and oedema due to liver cirrhosis?
Spirinolactone
What is the place in the heart failure therapy of an aldosterone antagonist?
Moderate severity heart failure or heart failure within 1 month of a MI.
Used in addition to a B-blocker and an ACEi/ATRB
When are aldosterone antagonists used in the treatment of primary hyperaldosteronism?
While awaiting surgery or when surgery is not an option.
Where is aldosterone produced and what is its mechanism of action?
Mineralcorticoid produced in the adrenal cortex which acts on mineralcorticoid receptors in the distal tubules of the kidney to increase the activity of luminal epithelial sodium channels ENaC.
This increases the reabsorption of sodium and water (which elavates blood pressure and heartload) with the by-product of increased potassium excretion.
What is the by-product of the increased sodium and water retention caused by aldosterones? (electrolyte)
Increased potassium excretion = hypokaleamia
What is an important adverse effect of aldosterone antagonists?
Hyperkalaemia (aldosterone can cause hypokalaemia).
But also liver impairment, jaundice and Stevens-Johnson syndrome which is a T-cell mediated hypersensitivity reaction.
What are the symptoms of hyperkalaemia caused by aldosterone antagonists?
Muscle weakness, arrhythmias and even cadiac arrest.
What is the most common reason males stop taking spironolactone?
Gynaecomastia + impotence.
These are benign and reversible and may abate on dose reduction.
Aldosterone antagonists such as epleronone and spironolactone are contraindicated in which patient groups? [4]
- Severe renal impairment
- Hyperkalaemia
- Addisons disease (aldosterone deficient)
- Aldosterone antagonists can cross placenta and appear in breast milk so should be avoided in pregnant/breast feeding women when possible.
The combination of an aldosterone antagonist with ACE inhibitors and aniotensin receptor blockers increases the risks of what?
Hyperkaleamia.
Epleronone is an aldosterone antagonist which is only licensed for the treatment of
heart failure,
spironolactone: acities/oedema due to liver cirrhosis, primary hyperaldosteronism + heart failure.
What are the typical starting doses for spironolactone in the treatment of ascities and heart failure?
Ascities: 100mg daily
Heart failure: 25mg daily.
Which aldosterone antagonist is also available as a combined preparation with a thiazide or loop diuretic?
Spironolactone: Lasilactone 20mg/50mg capsules: furosemide (LD).
CO-FLUMACTONE: Hydroflumethiazide
When should spironolactone generally be taken?
With food.
What monitoring is needed for Aldosterone antagonists?
Efficacy: patient reporting and clinical findings i.e. reduction in ascities or blood pressure.
Safety: renal function and serum K+ concentration due to risk of renal impairment and hyperkalaemia.
Why should spironolactone be prescribed instead of epleronone?
A month of spironolactone = £1.50, epleronone = £40 as it is still protected by patent.
Why is spironolactone usually precribed alongside a loop or thiazide diuretic?
It is a relatively weak diuretic that takes several days to start having an effect.
In the treatment of ascities due to chronic liver failure, spironolactone and furosemide are generally used together in a ratio of what?
5:1 eg spironolactone 200mg, furosemide 40mg.
What are the common indications of alpha-blockers?
- First-line medical option to improve symptoms in benign prostatic hyperplasia, which lifestyle changes are insufficient.
[5alpha-reductase inhibitors may be added in selected cases, surgical treatment is also an option - especially if evidence of urinary tract damage]
- As an add-on treatment in resistant hypertension, when other medicines (eg CCB, ACEI, thiazide diuretics) are insufficient.
Why is the term alpha blocker not the most accurate when describing drugs such as doxazosin, tamsulosin and alfuzosin?
They are highly selective for the alpha-1 adrenoreceptor which are found mainly in smooth muscle, including blood vessels and the urinary tract. Stimulation induces contraction; blockade induces relaxation.
Alpha-blockers therefore cause vasodilation and a fall in blood pressure, and reduced resistance to bladder outflow.
What is the mechanism of action of doxazosin, tamsulosin and alfuzosin in the treatment of BPH and resistant hypertension?
They are highly selective for blocking the alpha-1 adrenoreceptor which is found mainly in smooth muscle, including blood vessels and the urinary tract. The blockade induces relaxation and a fall in blood pressure, and reduced resistance to bladder outflow.
What are the important adverse effects of alpha-blockers?
Predictably from their effects on vascular tone, alpha-blockers can cause postural hypotension, dizziness and syncope.
When are the adverse effects of alpha-blockers most prominent?
After the first dose - similar to ACE inhibitors and angiotensin receptor blockers.
In what patients should alpha blockers not be used in?
In those patients with existing postural hypotension.
What are the important interactions with regard to the use of alpha blockers?
What adjustments to a patients existing medicines regime may need to be made?
Combining anti-hypertensive drugs results in additive blood pressure lowering effects. In order to avoid pronounced first-dose hypotension, we may need to omit doses of one or more existing anti-hypertensive drugs on the day the alpha blocker is started.
This is particularly the case for B-blockers, which inhibit the reflex tachycardia that forms part of the compensatory response to vasodilation.
What is the main difference between the licensing for Doxazosin and Tamsulosin?
Doxazosin is licensed both for BPH and hypertension, tamsulosin is only licensed for BPH - this is because it has a less pronounced blood pressure lowering effect.
What is the typical starting dose for Doxazosin for both BPH and hypertension?
1mg daily and increased at 1-2 weeks intervals according to response.
When is the best time to take doxazosin, at least initially?
Because of the pronounced blood pressure lowering effect of doxazosin, it is best taken at bedtime, at least initially.
Why might we introduce an alpha blocker at an earlier stage in the hypertension treatment pathway for a man?
They may also have BPH and thus an alpha blocker could relieve symptoms of both with the use of a single drug.
Why would we use modified release forms of alpha blockers?
There is little convincing evidence that MR forms are any more effective than standard-release forms and since they are taken at the same frequency (daily) they do not improve convenience for patients.
As they are branded products they are more expensive for the NHS.
Long acting nitrates are used for what?
Isosorbide nitrate is used for the prophylaxis of angina where a beta blocker and/ or a ccb has been insufficient or not tolerated
What are intravenous nitrates used for?
IV nitrates are used in the treatment of pulmonary oedema usually in combination with furosemide and oxygen
What are short acting nitrates used for?
Treatment of acute angina and the chest pain associated with acute coronary syndrome
What is the mechanism of action of nitrates?
Nitrates are converted to nitric oxide (NO) which increases cGMP synthesis and reduces intracellular calcium in smooth muscle cells causing them to relax and a reduction in cardiac preload and ventricular filling.
What are the important adverse effects of nitrates?
They are vasodilator so can cause: flushing, headaches, lightheadedness and hypotension. Sustained nitrate use can cause tolerance thus a nitrate free period overnight needs to be adhered to: take morning and afternoon
In who should the use of nitrates be contraindicated?
Patients with severe aortic stenosis as can cause cardiovascular collapse.
Patients with haemodynamic instability such as hypotension.
What is an important prescribing issue when dealing with prescriptions for generic modified release isosorbide mononitrate?
It must be prescribed by brand are there are important differences between preparations.
What are the practical communication points regarding a prescription for nitrates?
Patient may develop headache when starting nitrates but normally passes.
Patient should use sublingual GTN before tasks that normally bring on their angina.
Due to the risks of postural hypotension, it is a good idea to advise them to sit down and rest before and for 5 minutes after taking sublingual GTN.
Due to the risk of tolerance, doses should be taken morning and afternoon with twice daily isosorbide mononitrate.
What are the major interactions to be aware of with nitrate drugs?
Contraindicated in patients using phosphodiesterase inhibitors such as sildenafil, as they enhance and prolong the hypotensive effect of nitrates.
Nitrates should also be used with care in patients on antihypertensive medication as they may precipitate hypotension.
What are the common indications for aspirin use?
- Treatment of ACS and acute ischaemic stroke - where the rapid inhibition of platelet aggregation can prevent or limit arterial thrombosis and reduce mortality.
- Secondary prevention of thrombotic arterial events in patients with cardiovascular, cerebrovascular and peripheral arterial disease.
- As an alternative to warfarin and novel anticoagulants to reduce the risk of intracranial thrombus and embolic stroke in AF
- Mild to moderate pain relief and fever.
What is the mechanism of action of aspirin?
Aspirin irreversibly inhibits COX to reduce the production of the pro-aggregatory factor thromboxane from arachidonic acid, reducing platelet aggregation and the risk of arterial occlusion.
The antiplatelet effect of aspirin occurs at low doses and lasts for the lifetime of the platelet as they do not have Nuclues and thus no ability to synthesis New COX.
What are the important adverse effects of aspirin?
GI upset but more serious include gastrointestinal ulceration, bronchospasm etc.
In regular high dose aspirin therapy tinnitus can occur.
ASPIRIN is life threatening in overdose: hyperventilating, metabolic acidosis, confusion followed by convulsions, cardiovascular collapse and respiratory arrest.
Why should aspirin not be given to people under the age of 16?
There is the risk of Reye’s syndrome, a rare but life threatening illness that principally affects the liver and brain.
Can aspirin be used by people with asthma?
Yes, but it should not be taken by people with aspirin hypersensitivity.
Can aspirin be used safely in pregnancy?
Aspirin should not be used in the third trimester or pregnancy because prostaglandin inhibition may lead to premature closure of the ductus arteriosus.
Can someone taking allopurinol use aspirin?
Aspirin should be avoided in people with gout as it can precipitate an attack.
