16.1 Cardiovascular disease and drugs Flashcards
What is the difference between pharmacokinetic variability and pharmacodynamic variability?
- Pharmacokinetic variability: what the body does to the drug
- Pharmacodynamic variability: what the drug does to the body
What are the 2 main types of adverse drug reaction?
- Type A: dose dependent, predictable from the known pharmacology of the drug
- Tybe B: bizarre/idiosyncratic, dose-independent, rare, unpredictable
What are the 3 common cardiac drug types?
- Drugs which affect the blood vessels: the endothelium or tunica media
- Drugs which affect the autonomic nervous system
- Drugs which affect the renin-angiotensin-aldosterone process e.g. ACE inhibtors
Explain the renin-angiotensin-aldosterone system.
- Drop in blood pressure causes renin release from kidneys
- Renin converts angiotensinogen to angiotensin I
- ACE (angiotensin converting enzyme) secreted (mostly from the lungs)
- ACE converts angiotensin I to angiotensin II
- Angiotensin II is a potent vasoconstrictor, increases blood pressure
- Angiotensin II also increases aldosterone synthesis, increasing BP
What 3 drugs are most commonly used to treat hypertension?
- ACE inhibitors
- Calcium channel blockers
- Thiazide-like diuretics
What BP is classed as hypertension?
140/90
High risk = 130/80
How is blood pressure determined?
Cardiac output x total peripheral resistance
Examples of factors which affect BP
What is the relationship between blood pressure and age?
- As we age, systolic BP tends to increase (top number)
- Diastolic tends to increase until around 60 and then decreases
What is the order of drug choice for treatment of hypertension?
Majority of people with hypertension require 2 agents
What is the first line therapy for hypertension in a non-black patient under 55?
ACE inhibitor
Name ACE inhibitors.
- Ramipril
- Lisinopril
- Captopril
Different ACE inhibitors have different half lives. Ramipril is the most common.
When are ACE inhibitors used?
- Hypertension
- Heart failure
When are ACE inhibitors contraindicated?
Pregnancy, affects foetal development.
Other than ACE inhibitors, what other drug targets the renin-angiotensin-aldosterone system?
Angiotensin II receptor blockers
Used to treat hypertension and heart failure.
Blocking receptors decreases aldosterone synthesis and reduces vasoconstriction thus reducing BP.
Name angiotensin II receptor blockers.
- Losartan
- Candesartan
- Irbesartan
What are the possible adverse effects of ACE inhibitors and angiotensin II receptor blockers?
- Hyperkalaemia (high potassium)
- Acute kidney injury
What are the 3 groups of calcium channel blockers?
- Dihydropyridines e.g. amlodipine, nifedipine. Suitable for most patients.
- Benzothiazepines e.g. diltiazem
- Phenylalkylamines e.g. verapamil. Not suitable in majority of cases.
What type of drug are calcium channel blockers?
- Antagnosists
- L-type calcium channel blockers
Describe the action of calcium channel blockers.
- Act on smooth muscle cells and cardiac myocytes to cause vasodilation
- Reduces blood pressure
Also used to treat angina.
What cautions are there for calcium channel blocker use?
- They are metabolised by CYP3A4 enzymes so patients may have interacting drugs
- Patients must avoid grapefruit
What are thiazide diuretics?
- Drug used to treat hypertension and mild heart failure
- Sulphonamide derivatives
- Side effects: hyponatremia (low sodium), hypokalaemia, erectile dysfunction
What are alpha blockers?
- Cause vasodilation
- Treats hypertension and benign prosthetic hypertrophy
- Side effects: mild postural hypotension
- E.g. Doxazosin
Which alpha blocker is rarely used nowadays?
Clonidine
- Large range of side effects including bradycardia, dry eyes, sedation, withdrawal syndrome
Which drugs are used for patients with resistant hypertension?
Aldosterone antagonists
- Act in the nephron
- Block the action of aldosterone to reduce BP
Name 2 aldosterone antagonists.
- Spironolactone
- Eplerenone
What are the causes of resistant hypertension?
- Sub-optimal drug regimes
- Non-adherence
- Secondary hypertension: an underlying cause of high BP e.g. other medication, target organ damage, Conn’s disease, Cushing’s
What is ischaemic heart disease?
Aka. coronary heart disease
- Where the myocardial demand for oxygen exceeds the supply of oxygen to the heart by the coronary arteries
- Reduced blood flow to the heart
Describe the blood flow to the heart.
- The coronary arteries arise from the base of the aorta via the coronary sinuses
The 3 principle epicardial arteries are:
- Right coronary artery
- Left anterior descending artery
- Circumflex artery
What factors cause decreased oxygen supply?
-Extreme anaemia, reduced Hb thus reducing oxygen
- Atherosclerosis (blockages)
- Coronary artery spasm, caused by inflammation, temporary constriction
- Hypoxia
- Hypovolaemia
- Tachydysrhythmia
What factors cause increased oxygen demand?
- Beriberi disease
- Left ventricular hypertrophy
- Paget’s
- Tachydysrhythmia
What is atherosclerosis?
- Cholesterol plaques building up in the arteries
- Can cause unstable angina (angina when resting)- central chest pain
- Plaque rupture can lead to an acute coronary syndrome
- If pt is in pain GTN spray is used, if it lasts for 30 minutes or more it is advised that the pt visits hospital
What is the difference between ischaemia and infarction?
- Reduced blood flow = ischaemia
- No blood flow = infarction
How is stable angina managed?
- Beta blockers or calcium channel blockers
- If this is unsuccessful, they should be used in combination
- Next option: addition of a long acting nitrate
What are the range of acute coronary syndromes?
- NSTEMI = partial blockage of blood supply to heart
- STEMI = complete blockage
Diagnosed through elevated troponins.
Both are heart attacks. Unstable angina is not but can lead to heart attack.
What is the emergency management for an acute coronary syndrome?
- Morphine
- Oxygen
- Nitrates (e.g. GTN spray)
- Aspirin, 300mg
- Antiplatelet, clopidogrel
- Anticoagulant, rivaroxaban
Which drugs are used post MI?
- ACE inhibitors
- Beta blockers
- Statins
When are beta blockers used?
- Post MI (not if pt has cardiogenic shock or asthma)
- Left ventricular failure
- Tachyarrhythmia
- Portal hypertension
Side effects: bradycardia, erectile dysfunction
What is ivabradine?
A relatively new drug used to treat stable angina and heart failure.
Targets the SA node to reduce heart rate.
- Risk of bradycardia, contraindicated if heart rate is less than 60bpm
Heart disease can be managed through the modification of risk factors, what are these?
- Smoking
- Hypertension
- Hyperlipidaemia (raised triglycerides, cholesterol)
- Diabetes Mellitus
- Family history
- Inflammatory conditions
How does chronic inflammatory disease increase ischameic heart disease risk?
Diseases like COPD and rheumatoid arthritis are associated with increased risk.
