Cardiovascular therapeutics Flashcards
Describe the action of beta-blockers and name their uses
They are the first choice for prevention of angina and treat CHF/AF/MI/hypertension
They block beta-adrenoceptors ;
Negative inotropic and chronotropic effects - weaken the heart’s contractions and slow the heart rate
Coronary blood flow only occurs during diastole ;
beta-blockers slow down the heart , increasing the diastolic period so more time for coronary blood flow
Also anti-arrhythmic effects
Calcium channel blockers When are they used What is they mode of action
treat hypertensions/angina ; All cause vasodilatation and improve coronary blood flow
Some are rate limiting agents - decreases force of hearts contraction and slows down HR
Verapamil also is anti-arrhythmic; most end in -dipine
K+ channel activators
Targets ATP-sensitive K+-channel (KATP)
they promote potassium efflux, hyperpolarize the cell membrane, thus preventing influx of calcium through the voltage-dependent calcium channels = vasodilation via relaxation of smooth muscle
treats hypertension and angina
Statins
Describe their use and mode of action
Inhibit cholesterol synthesis in liver
this leads to increased LDL uptake
reduces cardiovascular risk and reduces high cholesterol
Statin interactions
Macrolides (type of antibiotic e.g erythromycin and clarithromycin)
grapefruit juice
calcium channel blockers
Beta blockers + rate limiting Ca2+ blocker =
Fatal (dihydropyradine is the only exception)
ACEIs should be given to treat …
Hypertension
type 2 diabetes and diabetic nephropathy
non-black patients with <55years of age that pose a significant cardiovascular risk or secondary prevention post MI CHF
CCI(calcium channel inhibitors) are used to treat…
Patients that are >55years or black with significant cardiovascular risk
diagnosis of angina
History
ECG - ST segment depression
angiography of coronary arteries (x-ray of blood vessels)
Treatment of angina
Coronary artery bypass grafting
angioplasty + stenting
nitrates to cause veno/coronarydilation ; glyceryl trinitrate, or GTN. It comes as a mouth spray or tablets that dissolve under your tongue. beta-blockers and CCI are used to prevent angina
What is a CABG (coronary artery bypass graft)?
involves taking a blood vessel from another part of the body (usually the chest, leg or arm) and attaching it to the coronary artery above and below the narrowed area or blockage.
Describe how angioplasty and stenting work
Catheter with balloon and stent on the end inserted into the coronary arteries via a vessel in the arm
ballon is inflated to insert the stent then removed leaving the stent behind
Treatment given post MI
Beta-blocker
ACEI
statin
antiplatelet drugs
what is cardiomegaly?
enlarged heart
how is cardiomegaly detected on a chest X-ray?
cardiothoracic ratio (CTR) >0.5 ; ratio of max heart diameter to max thoracic diameter
histological consequences of hypertensive arteriosclerosis
Hypertrophy of media (middle layer)
Firboelastic thickening of intima
Elastic lamina reduplication
Reduction in size of lumen
Consequences of hypertensive vascular changes
Reduction in lumen = reduced flow - ischaemia
Increased rigidity of vessel wall = loss of elasticity and contractikuyt - unresponsive to vasodilators/constrictors
Atheroma occur in
High pressure systems (large and medium arteries)
What is an ulcer ?
A local loss of epithelium and sometimes deeper tissue in skin or mucous membrane
Describe the possible complications of atheroma symptoms:
Expansion of intima = reduction of lumen size = ischaemia
Ulceration of atheromatous intima = predisposition ot thrombus formation = vessel occlusion
Plaque fissure formation and haemorrhage
Replacement of muscle and elastic fibres in media = loss of elasticity = thinning and stretching = aneurysm
Ischaemia of coronary arteries causes
Angina (chest pain)
Ischaemia in the leg arteries can cause
Intermittent claudication (leg pain)
Ischaemia in the mesenteric arteries results in
Ischaemic colitis (inflammation of large intestine
Describe the formation of aneurysm
Aneuryms = abnormal permant focal dilation of an artery
Enlarging intimate atheroma plaque leads to atrophy of media
Muscle and elastic fibres in media replaced by collagen
Collagen strong but neither contractile nor capable of elastic recoil = with each heart beat the wal stretches and thins
Most common in abdominal aortas
What are the 3 common aneurysm*
Atheromatous aortic aneurysm (most likely to occur in abdominal area) Aortic dissection (when there is a tear in the innermost layer wall of the aorta) Cerebral berry
Common treatments for chronic heart failure
ACEIs
Diuretics
Beta blockers or CCIs
Digoxin
Treatment for hypertension
ACEIs
Ca2+ channel inhibitors (used instead of beta-blockers for asthmatics )
How is stable angina represented on an ECG
ST-segment depression
Management of stable angina
Lifestyle changes
Coronary artery bypass grafting
Balloon angioplasty and stenting
Describe percutaneous transluminal coronary angioplasty (PTCA)
Balloon inflated at site of plaque and inserts stent
Drug in stent prevent regrowth of blood vessel
Pharmacological management of stable angina
Nitrate such as glyceryl trinitrate (GTN)
Results in release of NO which leads to venodilatation (decreased preload anf reduction in cardiac work) ; coronary vasodilation also occurs (but minor effect)
Nitrate tolerance can occur upon prolonged exposure
Chronic heart failure (aka congestive heart failure) What is it?
Due to failure of heart muscle or failure of the heart valves
failure can occur in LV or RV or both
Chronic or acute (post MI)
Often secondary : most commonly (ischaemic heart disease), hypertension, cardiomyopathies (alcohol/viral)
CHF is precipitated (made worse) by …
Pregnancy
Anaemia
Hyper/hypothyroidism
Fluid retaining drugs (glucocorticoids and NSAIDs)
explain the neurohormonal adaptation of the body in CHF
Neurohormonal adaptation to compensate for circulatory failure
- activation of SNS, RAAS + release of ADH, ANP(atrial natriuretic peptide)
- Release of ANP is the only good effect ;
- the other the effects causes afterload/preload/resistance(from vasoconstriction) to increase and blood pressure to decrease (in the short term cardiac output increases but long-term heart failure is exacerbated due to cardiac remodelling)
- vicious cycle occurs; impaired renal function=more water/salt retention=further activation of RAAS(also due to decreased BP due to action of SNS/ADH)
Effect of ANP
Acts on kidneys causing increased K+ excretion this results in:
reduction of extracellular fluid (ECF) volume,
improved cardiac ejection fraction with resultant improved organ perfusion, decreased blood pressure,
Describe left-sided failure
Often secondary to hypertension
poor output of LV = increase in left atrial/pulmonary venous pressure and pulmonary oedema (breathlessness)
Signs and symptoms of CHF
Fatigue
Poor exercise tolerance (determines grade)
Cold peripheries
Low blood pressure
Reduced urine flow
Weight loss
Echocardiogram - ejection fraction <45%
BNP levels abnormal
chest X-ray to check for cardiomegaly
Signs and symptoms of LV failure
Pulmonary oedema
Breathlessness – sensation of drowning. ‘Cardiac asthma’
wet cough
Orthopnoea – breathless on lying which is relieved by sitting up. Nocturnal problem(paxosysmal nocturnal dyspnoea)
Inspiratory crepitations
Signs and symptoms of RV failure
Raised venous pressure
Increased JVP - jugular venous pressure
Enlarged liver
Oedema – ankles; if lying down rises to thighs/abdomen
Describe RV failure
RV output fails
causes:
- often due to lung disease such as COPD (cor pulmonale)
- pulmonary hypertension as an adaptation to prolonged hypoxia = increased preload = increase pressure on RHS of heart
- pulmonary valvular stenosis
- due to congenital or rheumatic heart disease
- secondary to left sided heart failure
- increased pressure in pulmonary vasculature due to backward flow of blood from dysfunctional LV/LA
Biventricular failure
When both chambers fail
can be secondary to LVF due to pulmonary congestion or due to disease that affects both ventricles (such as ischaemic heart disease)
What are the 2 most important drugs for treating CHF?
ACE inhibitors (they have -pril at the end) and beta-blockers (vasoprilol and very low dose)
Side effects of ACEIs
Hyperkalaemia
May cause severe hypotension ; treatment withdrawn for a few days
cause deterioration of renal function in pre-existing renal disease
cough
Explain the mechanism of action for ACEIs
describe how counselling for them would work
ACE inhibitors prevent an enzyme in the body from producing angiotensin II, a substance that narrows blood vessels
This reduces afterload/preload
reduce salt/water retention
inhibits RAAS
also used to treat hypertension
start low go slow ; monitor eGFR and K+ before and during treatment
when should ACEIs be contraindicated ?
stenosis of renal arteries ;
reduced blood flow to kidneys = xs renin secreted = renal function dependant on RAAS ; as ACEIs block this compensatory method they can cause renal failure in these patients
Effect of ACEIs on K+ levels
Aldosterone is a sodium retaining K+ losing enzyme
ACEIs cause K+ retention so plasma [K+] increase
Describe the alternative drugs to ACEIs
AT1 Receptor antagonists - block the action of AII ; inhibits vasoconstriction ; less likely to cause cough so can be given to people who experience severe coughing with ACEIs
uses of beta-blockers
Often used in COPD treatment
reduce sympathetic stimulation/heart rate/O2 consumption/anti-arrhythmic/oppose neurohormonal activation during CHF (especially ischaemic heart failure)
start with low dose for CHF ; symptoms may get worse at first
describe the mechanism of action of diuretics
Loop diuretics used to treat CHF such as furosemide
reduce circulating volume/pre-load/oedema
some may cause hypokalaemia
Describe the action of digoxin
+ve inotrope - increases force of heart contraction ; inhibits Na+/K+ ATPase = accumulation of Na+ in myocyte which is exchanged with Ca2+ = more intracellular [Ca2+]
What is the major use of digoxin
To treat AF/CHF in elderly patients
positive ionotropic (increased contractility but slowed down SAN conduction = slower HR); while also inhibiting SNS and RAAS
rarely used now - reserved for HF with AF or when ACEIs/diuretics fails
its effects are enhances by ACEIs
What are the negative effects of cardiac remodelling
Myocyte apoptosis
changed expression of contractile proteins
remodelling of matrix
dilatation
Pulmonary oedema histology
Alveolar walls are congested by fluid
Right ventricular failure results in ….
Raised end diastolic pressure
raised atrial and JVP
raised central venous pressure
liver distension(abdominal discomfort) and peripheral oedema
Why does CHF cause oedema
Heart failure diminishes blood flow and in response, your body tends to retain fluid in an effort to maintain adequate blood volume. But a failing heart is unable to accommodate this extra fluid, so it is transferred out of your blood vessels and into your tissues – usually in those body parts that are lower than others.
also increased venous pressure opposes re absorption of fluid
Why are creatinine levels monitored?
Abnormal creatinine levels indicate impaired renal function
If there is a problem with your kidneys, creatinine can build up in the blood and less will be released in urine
Why are NSAIDs/glucocorticoids contraindicated with CHF?
They are fluid retaining so can exacerbate CHF?
Counselling for furosemide
Take in morning to prevent sleep disturbance
may cause falls due to dizziness side effect - be careful
omit dose when patient has diarrhoea or vomiting
furosemide dosing is interrupted as few days before administering beta-blockers
Does CHF cause renal impairment ?
Yes;
When the heart is no longer pumping efficiently it becomes congested with blood, causing pressure to build up in the main vein connected to the kidneys and leading to congestion of blood in the kidneys, too. The kidneys also suffer from the reduced supply of oxygenated blood.
How does heart failure cause elevated BNP ?
Symptom of failing ventricles ; BNP primarily is secreted by the ventricles in the heart as a response to left ventricular stretching or wall tension ; only released after prolonged volume overload
Counselling for ACEIs
Purpose - to treat heart failure
expect blood presssure to go lower
take at night to reduce the effects of low blood pressure
Effects of ACEIs and Furosemide on [K+]
ACEI can cause hyperkalaemia because aldosterone causes K+ excretion so reduced aldosterone release = increased K+ retention
Furosemide can cause hypokalemia as its a diuretic (loss of all electrolytes in blood)
When are DOACs contraindicated?
in patients with mechanical heart valve replacements
Why is cardiac hypertrophy problematic ?
It increases the work of the heart whilst also lessening the ejection fraction
Congested liver histology
Dark areas - centrolobular congestion
pale areas - periportal fatty change
Causes of RVHF
lung disease
thromboemboli
Pulmonary valve stenosis
How does lung disease cause RVF
emphysema destroys alveolar walls and capillaries
hypoxia constricts pulmonary arteries
pulmonary hypertension
what is a normal creatinine clearance?
100 mL/min
Most common cause of haemorrhagic stroke
most caused by ontracerebral haemorrhage
some caused by subarachnoid haemorrhage
Define infarct and describe the types
Area of ischaemic necrosis due to abrupt cessation of arterial supply (arterial infarction) OR venous drainage (venous Infarction)
arterial infarction is the most common
pale or white infarct occur in solid organs such as the heart and spleen (due to lack of blood flow)
red or haemorrhagic infarcts occur in loose spongy tissue rich in blood supply or has dual blood supply (ischemia results in vessels bursting)
causes - septic (due to vegetation of sub acute bacterial endocarditis )
factors affecting the development of an infarction
Vascular occlusion - degree of obstruction
rate of development of occlusion - is it abrupt or gradual
nature of vascular supply - is there dual blood supply or just one artery to that organ/tissue
type of tissue - neurones can only survive minutes without oxygen, myocardium can survive 20-40 mins, fibroblasts can survive many hours
Describe the cellular morphology of iscaemic coagulative necrosis
Wedge shapes infarct - apex at occluded artery
occurs in all organs except the brain
inflammatory response (tissue turns red from pale) followed by reparative response and scar tissue formation
What are the cardiac muscle injury markers ?
Troponin, myoglobin CK MB
Describe the appearance of myocardium 12-24 post MI
Coagulative necrosis occurring
nuclei are breaking down and streaks in muscle (mottling)
Describe the appearance of myocardium 3-14 days post MI
Macrophagic removal of debris and vascular granulation tissue formation
area of necrosis is pale and still soft
hyperaemic(excess blood) border around area of necrosis
Morphological changes in myocardium 3 week + post MI
fibrous granulation tissue becomes tough scar tissue
Describe the early and late complication of MI
Early :
sudden death due to dysrhythmia,
rupture of myocardium during healing stage = heart fills with blood (haemopericardium) and cardiac tamponade,
rupture of papillary muscle = acute valve failure = LVF,
mural thrombus (blood clot form on wall on heart/vessel where the infarct has occurred ) = embolism elsewhere
fibrinous pericarditis = pericardium becomes rough, granular, and has many fibrous adhesions
late :
CHF
ventricular aneurysm - loss of flexibility of ventricular wall
Describe renal infarcts
Usually caused by emboli from the L side of heart
wedge shaped
pale area with surrounding hyperaemia
heals by scar formation
Describe cerbral infarcts (aka ischaemic stroke)
Liquedative necrosis due to the lack of CT in the brain; Brain cells have a large amount of digestive enzymes (hydrolases). These enzymes cause the neural tissue to become soft and liquefy.
results in hypoperfusion and microembolism
heals by astrocytic gliosis (perforation of glial cells) - loss of cells
describe gangrene
Arterial infarction in extremities or bowel
Complication of necrosis caused by ischaemia following Injury or infection
common in diabetics
tissue becomes black (bacteria break down dead tissue to form black iron sulfate) and smells bad
dry gangrene occurs when the arterial blood supply is occluded but the venous drainage is intact
wet gangrene occurs when the venous drainage is occluded plus putrefaction; can also be caused by bacterial infection (without the need of ischaemia)
Describe venous infarctions and give some common examples
Occur when venous drainage from an organ or tissue is and remains completely obstructed
tissues become congested with blood and capillaries/venules may rupture ; arterial blood cannot enter as venous pressure>arterial pressure = hypoxia
bowel infarction - volvulus(bowel twists on itself), hernial strangulation
torsion in testes and ovaries
pros and cons of LMWH
usually administered subcutaneously so unpleasant for patient; unsuitable for renal failure; short acting and good intial treatment
pros and cons of vit K antagonists
pros - only needs to be take once daily ; several reversal agents ; cheaper cons; requires close INR monitoring, many drug/food interactions, variable dosing
pros and cons of DOACs
pros - no monitoring required; lower risk of haemorrhage; cons - reversible agents less available; may need to be taken twice a day, more expensive
A patient appears to be hypertensive and their blood pressure continue to increase, which three tests should you order and why
eGFR - to guide which medication to give ; long term hypertension can also cause a decline in eGFR
glucose later haemoglobin (HbA1c) to test for diabetes (hypertensive diabetics have higher risk of stroke and MI) or hypertension can be a symptom of diabetes
plasma potassium levels - low potassium can be a cause of hypertension (symptom of overactivation of the RAAS)
NICE guidlines for antihypertensive drugs : what are the first line antihypertensive choices for a) type 2 diabetic hypertensive patients b) >55 or black at any age c)<55 and non-black
a) ACEIs or ARB (AT1 Receptor Blockers) b) CCI c) CCI (you start adding one drug at a time if hypertension persists)
NSAIDs can exacerbate hypertension
true or false
True
Main differences between right sided and left sided heart failure
How do ischaemic and haemorrhagic stroke arise?
Ischaemic stroke - when a thrombus or embolus gets stuck in the cerebral vessels → necrosis of neurons → release of hydrolyses → inflammation
haemorrhagic stroke : stress up brain tissue → vessel rupture → infarction
2 types : intracerebral (bleeding inside brain) due to hypertension or XS use of anticoagulants/thrombolytics and subarachnoid due to head injury or cerebral aneurysm
