Cardiology COPY COPY Flashcards
What is the equation for Stroke volume?
EDV-ESV
What is the equation for cardiac output?
CO = HR X SV
What is the equation for Blood pressure?
CO X TPR
What is the equation for pule pressure?
Systolic - Diastolic
What is the equation for mean arterial pressure?
Diastolic pressure + 1/3(PP)
What is the equation for ejection fraction?
SV/EDV
What is Ohms Law?
Flow = pressure gradient / R
What is the equation for Poiseuille Law?
R = 8lu/pi x r^4
Define Preload
Volume of blood in ventricles immediately before contraction. The volume of blood that causes the degree of stretch on the heart muscle for contraction
Define Afterload?
Force against which the ventricles must contract to expel the blood out of the ventricles
Define Contractility?
Inherent strength and vigor of the hearts contraction during systole
Define Elasticity?
The ability of the heart to return to its normal shape after stretching by recoiling once the force has been removed
Define compliance?
How easily the heart chamber will stretch when it is filled with a volume of blood
Define Resistance?
The force that must be overcome to push blood through the circulatory system
What is atherosclerosis?
Inflammatory process characterised by hardened plaques within the intima of a vessel wall. Eventually, plaque will either occlude vessel lumen resulting in a restriction of blood flow (angina) or rupture (thrombus formation - death).
Where do atherosclerotic plaques often occur?
Peripheral and Coronary arteries!
How are atherosclerotic plaques distributed in these arteries?
Focally distributed - governed by haemodynamic factors. For example, changes in flow/ turbulence (e.g. bifurcations)
What is neointima?
As the intima grows (new intima)
Changes in blood flow altering the phenotype of endothelial cells.
Altered gene expression in key; endothelial cells, smooth muscle cells, macrophages and fibroblasts
What makes up the structure of an atherosclerotic plaque?
Lipid
Necrotic core
Connective tissue
Fibrous cap
Lymphocytes
What are the 5 main stages of atherosclerosis progression over the course of the condition?
Fatty Streak
Intermediate Lesions
Fibrous Plaques (advanced lesions)
Plaque Rupture
Plaque Erosion
What is the fatty streak stage of atherosclerosis?
Earliest lesion of atherosclerosis < 10 years:
- Scavenger receptors take up lipids in intima layer of vessel wall
- Aggregations of lipid-laden macrophages (Foam Cells) and T lymphocytes within the intima layer of the vessel wall.
What is the intermediate lesion stage of atherosclerosis?
Lesion progresses to comprise layers of;
Foam cells
Vascular smooth muscle cells
T lymphocytes
Adhesion and aggregation of platelets to vessel walls
Extracellular Lipid Pools
What is the fibrous plaque stage of atherosclerosis?
- Growth of the atheroma.
- Covered by dense fibrous caps made of ECM proteins including; collagen (strength), elastin (flexibility) - these are laid down by SMCs
- Impedes blood flow and prone to rupture
What is the plaque rupture stage of atherosclerosis?
Why might atherosclerotic plaques Rupture?
- Plaque is constantly growing and receding - fibrous cap has to be resorbed and redeposited in order to be maintained
- If balance shifted in favour inflammatory conditions (e.g. increased enzyme activity) the cap becomes weak and plaque ruptures.
- Exposure of basement membrane, collagen, necrotic tissue and haemorrhage of vessels within plaque causes thrombus formation and vessel occlusion
What is the plaque erosion stage of atherosclerosis?
- Small early lesions
- Fibrous cap does not disrupt
- Luminal surface underneath the clot may not have enough endothelium present but is smooth muscle rich
- Prominent lipid core
What are the stages of atherosclerotic plaque formation?
1️⃣ Initiation of inflammation and endothelial cell dysfunction
2️⃣ Stimulus for adhesion of leukocytes - release of chemo-attractants
3️⃣ Dysfunctional endothelial cells allow the transmigration of LDLs into the tunica intima
4️⃣ Accumulation of LDLs tunica intima cause dysfuntional endothelial cells to release ROS and metalloproteases which function to oxidised the LDL → activated oxLDL
5️⃣ The activation of oxLDLs causes endothelial cells to express adhesion receptors for leukcocytes on their surface, leading to uptake of LDLs and monocytes
6️⃣ Surface of macrophages contain a scavenger receptor which facilitates the uptake of oxidised LDLs to form a foam cells
7️⃣ Foam cells have multiple pathophysiological functions:
- Release chemokines to attract more macrophages
- Release IGF-1 into tunica media to promote migration of SMCs (from media to intima) that increase collagen synthesis leading to the hardening of the atherosclerotic plaque
8️⃣ During this process, foam cells will die → releasing lipid content. This drives the growth of the plaque
9️⃣ Death of foam cells also causes release of contents which causes increased inflammation
🔟 T-cells also facilitate inflammation
🔟+ Excessive growth of the plaque causes it to rupture, leading to accumulation of the RBC, platelets and clotting factors → thrombosis
What initiates inflammation and leads to endothelial cell dysfunction in atherosclerosis?
Cholesterol/ high LDLs in the blood damages the endothelial cells
ROS from inflammation.
What chemo attractant is released by the endothelium and what does this lead to?
Selectins cause leukocyte rolling and firm adhesion to the blood vessel walls.
What are the pathological functions of a foam cell?
Release chemokines and attract further macrophages to the tunica intima
Release IGF-1 into the tunica media to promote migration of Smooth muscle cells from the tunica media into the tunica intima which increases the collagen synthesis and leads to the hardening of the atherosclerotic plaque.
What is a foam cell?
A macrophage that has been up take into the tunica intima that expresses scavenger receptors that will uptake oxidised LDLs
This uptake forms a foam cell.
What is a foam cell?
A macrophage that has been up take into the tunica intima that expresses scavenger receptors that will uptake oxidised LDLs
This uptake forms a foam cell.
What does the death of the foam cell release in atherosclerosis?
DNA material that attracts neutrophils
Proinflammatory cytokines
ROS
These all lead to increased inflammation.
What inflammatory cytokines are found in atherosclerotic plaques?
- IL1, 6 and 8.
- IFN-γ - strong proinflammatory cytokine
- TGF-β - involves in wound healing
- Chemokines (e.g. Monocyte Chemoattractant Protein-1)
How can Atherosclerosis (Coronary Heart Disease) be treated?
Percutaneous Coronary Intervention
Drugs
What is Percutaneous Coronary Intervention?
Non-surgical procedure that uses a catheter to place a stent into a narrowed blood vessel
What is Re-stenosis?
The recurrence of abnormal narrowing of an artery or valve after corrective therapy
What drugs are used to reduce restenosis in patients who have undergone corrective surgery?
Taxol and Sirolimus - work by reducing SMC proliferation after placement of stent. The stent is washed (eluted) with these drugs
How does Aspirin help to treat CHD?
Irreversible inhibitor of platelet cyclo-oxygenase to prevent Thromboxane A2 production and further platelet aggregation
How does Clopidogrel/ Ticagrelor help to treat CHD?
Inhibitors of the stimulatory P2Y12 ADP receptor on platelets preventing platelet response amplification
How does Statins help to treat CHD?
Inhibit HMG CoA reductase - reduces cholesterol synthesis
What inflammation-causing cytokine is targeted using drugs alongside statin therapy?
IL-1
What drug therapy is used as an alternative to statins if ineffective or not tolerated?
PCSK9 inhibitors
Give 5 Modifiable risk factors for atherosclerosis.
- Smoking.
- High levels of LDL’s.
- Obesity.
- Low exercise
- Diabetes.
- Hypertension.
- Alcohol consumption
Which histological layer of the artery may be thinned by an atheromatous plaque?
Tunica Media
What is the precursor for atherosclerosis.
Fatty streaks.
What are the functions of chemoattractants?
Chemoattractants signal to leukocytes. Leukocytes accumulate and migrate into vessel walls -> cytokine release e.g. IL-1, IL-6 -> inflammation!
Describe the process of leukocyte recruitment.
- Capture.
- Rolling.
- Slow rolling.
- Adhesion.
- Trans-migration.
Define atherogenesis.
The development of an atherosclerotic plaque.
What is the key principle behind the pathogenesis of atherosclerosis?
It is an inflammatory process!
What are Acute Coronary Syndromes?
Spectrum of acute cardiac conditions ranging from unstable angina to varying degrees of MI
What is the most common causes of Acute Coronary Syndromes?
Atherosclerotic rupture and consequential arterial thrombosis!
What is the mainstay treatment for ACS? why is this?
Anti-platelet medications:
Aspirin
Clopidogrel
Ticagrelor
Since a thrombus formed in a fast flowing artery are mostly made up of platelets.
Name some less common causes of Acute Coronary Syndromes?
Coronary vasospasm without plaque rupture
Drug abuse (amphetamines, cocaine)
Spontaneous Coronary Artery Dissection
What drugs can cause ACS?
Amphetamines
Cocaine
What are the types of Acute Coronary Syndrome (ACS)?
Unstable Angina
ST Elevation Myocardial Infarction (STEMI)
Non-ST Elevation Myocardial Infarction (NSTEMI)
Explain how Spontaneous Coronary Artery Dissection can lead to Acute Coronary Syndrome?
tear in lining, lining comes away from the wall of the artery and blocks vessel.
Briefly describe the pathophysiology of ACS?
Atherosclerosis -> plaque rupture -> platelet aggregation -> thrombosis formation ->
ischaemia -> hypoxia of cells -> angina
infarction -> necrosis of cells -> permanent heart muscle damage and ACS.(MI)
How would you Diagnose someone presenting with ACS symptoms such as Chest pain?
ECG:
If there is ST elevation or new left bundle branch block the diagnosis is STEMI.
If there is no ST elevation then perform troponin blood tests:
If there are raised troponin levels and other ECG changes (ST depression or T wave inversion or pathological Q waves) the diagnosis is NSTEMI
If troponin levels are normal and the ECG does not show pathological changes the diagnosis is either:
unstable angina
Another cause such as musculoskeletal chest pain
What is Cardiac Troponin?
Protein complex functioning to regulate actin and myosin contraction
What would a rise in Troponin suggest?
Consistent with myocardial ischaemia as the proteins are released from the ischaemic muscle.
However they are non specific so a raised troponin does not automatically mean ACS
Why is Cardiac Troponin relevant in diagnosing ACS?
Highly sensitive marker for cardiac muscle injury - increased levels is very indicative of myocardial cause
What is important to remember about Cardiac Troponin when being used for diagnosis?
not specific for ACS → also increases in conditions that causes stress in myocardium (e.g. PE, gram negative sepsis, myocarditis)
Give some other potential causes of raised troponins?
Chronic renal failure
Sepsis
Myocarditis
Aortic dissection
Pulmonary Embolism
Define angina.
Angina is a type of Ischaemic Heart Disease (IHD) characterised by chest pain
It is an imbalance of O2 supply/demand mismatch to the heart due to reduced blood flow from a blockage
What is the most common cause of angina?
Narrowing of the coronary arteries due to atherosclerosis.
What are the different types of Angina Pectoris?
Stable
Unstable
Decubitus
Crescendo Angina
Prinzmetals’s Vasospastic
Microvascular Angina
What type of angina is associated with ACS?
Unstable Angina
What is Unstable angina?
An acute coronary syndrome (ACS) that is defined by the absence of biochemical evidence of myocardial damage but characterised by chest pain at rest/minimal exertion
Give 5 possible causes of angina.
- Narrowed coronary artery = impairment of blood flow e.g. atherosclerosis.
- Increased distal resistance = LV hypertrophy.
- Reduced O2 carrying capacity e.g. anaemia.
- Coronary artery spasm.
- Thrombosis.
Give 5 modifiable risk factors for angina.
- Smoking.
- Diabetes.
- High cholesterol (LDL).
- Obesity/sedentary lifestyle.
- Hypertension.
Give 3 non-modifiable risk factors for angina.
- Increasing age.
- Gender - Males
- Family history/genetics.
What are the symptoms associated with ACS?
Central, Crushing chest pain associated with:
Nausea and vomiting
Sweating and clamminess
Feeling of impending doom
Shortness of breath
Palpitations
Pain radiating to jaw or arms
Briefly describe the pathophysiology of angina that results from atherosclerosis.
On exertion there is increased O2 demand. Coronary blood flow is obstructed by an atherosclerotic plaque -> myocardial ischaemia -> angina.
Briefly describe the pathophysiology of angina that results from anaemia.
On exertion there is increased O2 demand. In someone with anaemia there is reduced O2 transport -> myocardial ischaemia -> angina.
How do blood vessels try and compensate for increased myocardial demand during exercise.
When myocardial demand increases e.g. during exercise, microvascular resistance drops and flow increases!
Why are blood vessels unable to compensate for increased myocardial demand in someone with CV disease?
In CV disease:
Epicardial resistance is high meaning microvascular resistance has to fall at rest to supply myocardial demand at rest.
When this person exercises, the microvascular resistance can’t drop anymore and flow can’t increase to meet metabolic demand = angina!
What percentage of stenosis is associated with stable angina?
70% occlusion of the artery.
This still allows enough blood flow through the artery at rest.
What is Stable angina?
Occlusion of an artery (70%) leading to ischaemia of the myocardial tissue resulting in chest pain.
At rest enough blood can still flow through the artery to meet the demands of the tissue.
Upon exercise or exertion, the tissue requires more oxygen and therefore a greater blood flow at which point the flow through the stenosed artery is not adequate enough and hence results in chest pain upon exertion.
what is the most common type of angina?
Stable angina
What is the most commonly affected region of the heart in stable angina?
Subendocardium.
The coronary arteries struggle to perfuse the deeper layers of the myocardium either due to coronary artery stenosis or LV hypertrophy resulting in ischaemia to this portion of the tissue.
What are the Symptoms of angina?
Central Crushing chest Pain on exertion/rest /emotion/cold/heavy meals.
May radiate to one or both arms, neck, jaws or teeth.
Worsens with time
Other Symptoms: Dyspnoea, nausea, sweatiness, faintness
What is the difference between symptoms of angina in Stable, unstable and decubitus types?
Stable angina occurs in periods of roughly 20 mins upon exertion or exercise.
Unstable angina can be continuously painful at rest or even minimal exertion.
Decubitus angina causes pain when lying down flat.
What is the difference pathophysiologically between stable and unstable angina?
Both are commonly caused by atherosclerotic plaque causing obstruction of a coronary artery.
In unstable angina, the plaque may rupture causing blood to leak out and a secondary thrombus to form which occludes the artery further creating an even narrower lumen for blood to flow through.
What is a key distinction between angina and MI?
Angina results in pain due to myocardial ischaemia where the heart tissue is starved of oxygen but is still alive.
MI is when the ischaemia has resulted in infarction that has led to the death of the heart tissue.
Angina is therefore reversible and MI is not.
What is Prinzmetals Vasospastic angina?
angina where patients may or may not have atherosclerosis of the coronary vessels.
instead ischaemia occurs due to vasospasms of the coronary arteries where they constrict so much they can cause ischaemia.
These can occur at any time not just on rest or on exertion.
What is the mechanism that causes prinzmetals angina?
Not clearly understood but likely due to vasoconstriction factors such as Thromboxane A2 release
What layers of the heart are affected in Prinzmetals angina?
Transmural Ischaemia
All layers of the heart wall supplied by the coronary arteries are affected.
What ECG reading would be shown on stable angina?
AT rest: Normal
On exertion:
ST segment depression due to subendocardium ischaemia.
What ECG reading would be shown in prinzmetals angina?
ST segment elevation due to transmural ischaemia.
How can symptoms of stable angina be relieved?
Relieved upon rest (after approx 5 mins)
OR
Symptoms relieved by GTN spray
What cardiac enzymes are used to aid the diagnosis of ACS?
Cardiac troponin (Troponin T and I):
Released into the blood when cardiac muscle is damaged.
Highly sensitive but not specific.
Creatine Kinase - MB (CK-MB):
Helpful to determine re-infarction as levels should drop back to normal 36-72 hours after.
What is the progression of cardiac troponins following an MI?
Rise within 3-12 hours
Peak at 24-48 hours
Return to baseline by 5-14 days
<14g/l normal = no MI, 14-30 ng/l = possible MI, >30ng/l = definite MI
Are troponin levels elevated in angina?
Often they are normal since the ischaemia has not killed the cells and thus the troponin have not been released
sometimes they may be elevated
Describe the primary prevention of angina.
- Risk factor modification.
- Low dose aspirin.
Describe the secondary prevention of angina.
- Risk factor modification.
- Pharmacological therapies for symptom relief and to reduce the risk of CV events.
- Interventional therapies e.g. PCI.
Name 3 symptom relieving pharmacological therapies that might be used in someone with angina.
- Beta blockers.
- Nitrates e.g. GTN spray.
- Calcium channel blockers.
Describe the action of beta blockers.
Beta blockers are beta 1 specific.
They antagonise sympathetic activation and so are negatively chronotropic and inotropic.
Myocardial work is reduced and so is myocardial demand = symptom relief.
Give 4 side effects of beta blockers.
- Bradycardia.
- Tiredness.
- Erectile dysfunction.
- Cold peripheries.
When might beta blockers be contraindicated?
They might be contraindicated in someone with asthma or in someone who is bradycardic.
Give an example of a cardio-specific beta blocker
Atenolol
Describe the action of nitrates in GTN spray
Nitrates e.g. GTN spray are venodilators. Venodilators -> reduced venous return -> reduced pre-load -> reduced myocardial work and myocardial demand.
Describe the action of Ca2+ channel blockers.
Ca2+ blockers are arterodilators and negative Chronotropic/ionotropic agents:
Reduced O2 demand -> reduced BP -> reduced afterload -> reduced myocardial demand.
Name 2 drugs that might be used in someone with angina or in someone at risk of angina to improve prognosis.
- Aspirin.
- Statins.
How does aspirin work?
Aspirin irreversibly inhibits COX. You get reduced TXA2 synthesis and so platelet aggregation is reduced.
Caution: Gastric ulcers!
What are statins used for?
They reduce the amount of LDL in the blood.
What ECG reading would be shown on unstable angina?
May be normal
May have some ST depression/T wave inversion/depression
What ECG reading would be shown on unstable angina?
May be normal
May have some ST depression/T wave inversion
What is the treatment for Stable angina?
Immediate Symptomatic Relief - GTN sublingual stray
Long Term Symptomatic Relief - Beta Blocker (Atenolol) or Calcium Channel Blocker (Amlodipine)
Secondary Prevention of CVD:
Aspirin
Atorvastatin
ACE inhibitor
Already on a beta blocker
What are the investigations for stable angina?
Clinical Hx of pain / relief
ECG :
Rest - normal
Exertion - ST depression/Flat T waves
CT Angiography - Stenosed atherosclerotic artery
What treatment should be considered for angina if pharmacology is unsuccessful?
Referral for revascularisation
Through PCI or CABG
What is revascularisation?
Revascularisation might be used in someone with angina. It restores the patent coronary artery and increases blood flow.
Name 2 types of revascularisation.
- PCI.
- CABG.
Give 2 advantages and 1 disadvantage of PCI.
- Less invasive.
- Convenient and acceptable.
- High risk of restenosis.
Give 1 advantage and 2 disadvantages of CABG.
- Good prognosis after surgery.
- Very invasive.
- Long recovery time.
How is unstable angina diagnosed?
History
ECG - may present as ST-segment depression, transient ST-segment elevation, or T-wave inversion
No elevation in troponin - unstable angina not associated with damage to the heart
What is the Clinical Classification of Unstable Angina?
- Cardiac chest pain at rest or during minimal exertion
- Severe and of new onset cardiac chest pain
- Cardiac chest pain with crescendo pattern (distinctly more severe, prolonged, or frequent than before)
Define Myocardial Infarction?
Necrosis of cardiac tissue due to prolonged myocardial ischaemia due to COMPLETE occlusion of an artery by thrombus.
What are the types of MI?
Non-ST Elevated Myocardial Infarction (NSTEMI)
ST Elevated Myocardial Infarction (STEMI)
Silent MI
What would the ECG for a STEMI look like?
ST elevation and tall T waves
Will produce pathological Q waves some tome after an MI
There may be a new LBBB in larger MIs (WiLLiaM)
V1 – W shape
V6 – M shape
What would the ECG for a NSTEMI look like?
ST depression
T wave inversion
Q waves may be present hours/days after infarct
(often a retrospective diagnosis)
What heart sound signs may be heard in an MI?
4th heart sound – due to forceful contraction of the atria to overcome a stiff or dysfunctional ventricle
Pansystolic murmur – due to papillary muscle dysfunction or rupture
What is the difference in an NSTEMI and STEMI when caused by atherosclerosis?
NSTEMI occurs after a partial occlusion of major Coronary artery
STEMI occurs after complete occlusion of a major Coronary artery.
What is the management plan for ACS that is not an STEMI?
Risk Factor modification:
Stop smoking
Lose weight
Healthy diet
Exercise
Anti-platelet therapy:
- Aspirin (300mg initially then 75mg daily)
- Dual therapy with P2Y12 receptor inhibitors - Clopidogrel (300 mg initially then 75mg for 12 months), ticagrelor (180 mg initially then 90 mg twice daily) or prasugrel
Platelet glycoprotein IIb/IIIa receptor inhibitor for high risk patients (Abciximab)
PCI (if risk assessment score (GRACE) is medium/high) and CABG
Anti-coagulants:
Heparin/LMWH e.g. enoxaparin has better efficacy than unfractionated heparin
Fondaparinux
Other Sx Control:
Nitrates – GTN spray or IV infusion
Beta blockers – bisoprolol
Statins
ACE inhibitors - Ramipril
Calcium channel blockers (if beta blocker contraindicated) – amlodipine
What are the complications of ACS?
DARTHVADER:
Death
Arrhythmias
Ruptured septum
Tamponade
HF
Valve disease
Aneurysm of ventricle
Dressler’s syndrome – pericarditis and pericardial effusion after 2-12 weeks
Embolism
Reoccurrence of ACS
What is the acute treatment for ACS (STEMI/NSTEMI)?
MONAC:
Morphine
Oxygen (if Sats < 94%)
Nitrates (GTN)
Aspirin (300mg)
Clopidogrel (dual antiplatelet)
What is the treatment for an NSTEMI following acute treatment of ACS?
GRACE score:
low risk - monitor
Med-High risk - angiogram / PCI
What is the treatment of choice for STEMI?
PCI
May also have thrombolysis (IV alteplase) or CABG
What is the long term treatment/Secondary prevention management following ACS?
6 As
Aspirin (75g once daily)
Another antiplatelet - Ticagrelor/Clopidogrel
Atorvastatin (80mg once dail)
ACE inhibitors (ramipril)
Atenolol (or another bB)
Aldosterone antagonist (spironolactone) in those with clinical heart failure
What is Dressler’s Syndrome?
Post myocardial infarction syndrome
Occurs around 2-6 weeks post MI
Localised immune response causing pericarditis.
What is the pathology of Dresslers Syndrome?
thought to be an autoimmune reaction against antigenic proteins formed as the myocardium recovers. It is characterised by a combination of fever, pleuritic pain, pericardial effusion and a raised ESR. It is treated with NSAIDs.
What are the complications of MI?
DREAD:
Death
Rupture of the heart septum/papillary muscles
Edema (causing heart failure)
Arrythmia and Aneurysm
Dressler’s Syndrome
What are the subsequent complications from rupture of the ventricular septum, LV wall or papillary muscles due to MI?
Ventricular Septum - Right HF
LV wall - Cardiac tamponade
Papillary Muscles - Mitral regurgitation/prolapse
What are the time periods of the consequences of an acute MI?
Immediate:
Ventricular Fibrillation (cardiac arrest) - most common cause of death post MI
<24hrs:
Cardiogenic shock
Bradyarrythmias
3-5 days:
Mitral regurgitation - papillary muscle rupture
Ventricular septal rupture
2-6 weeks:
Dressler syndrome
What are the differential diagnoses for an MI?
MI
Stable/unstable angina
Pericarditis
Aortic aneurysm
Endocarditis
Pulmonary Embolism
Pneumothorax
What heart area and ECG leads correspond to:
Left Coronary Artery
LAD
Circumflex
Right Coronary Artery
Left Coronary Artery:
Heart area - Anterolateral
ECG leads - I, aVL, V3-V6
LAD:
Heart area - Anterior
ECG leads - V1-4
Circumflex:
Heart area - Lateral
ECG leads - I aVL, V5-6
Right Coronary Artery:
Heart area - Inferior
ECG leads - II, III, aVF
What is the Epidemiology for an MI?
600/100,000 for men.
200/100,000 for women
Name some of the function of platelets during arterial thrombosis
- Procoagulant activity; release of thrombin
- Dense granule secretion; contributes to platelet activation
- Alpha granule secretion; contributes to coagulation and inflammation
- Platelet-fibrin clot; fibrin acts as glue that keeps the thrombus growing and allow it block of arteries to cause MI.
Give a brief overview of the process by which platelets cause the platelet plug?
(1) Shear flow
(2) Initial adhesion GPIb/VWF
(3) Rolling GPIb/VWF/α2β1/collagen
(4) Stable adhesion activation/aggregation GPVI, GPIIb/IIIa
(5) Platelets are activated by ADP (vai P2Y12R), causing them to change shape, aggregate and seal off the endothelial breach
What combined therapy is used to manage patients with ACS?
Aspirin, P2Y12 Inhibitors and GPIIb/IIIa antagonists
Give some examples of P2Y12 inhibitors?
Clopidogrel
Ticagrelor
Prasugrel
What is a major side effect of P2Y12 inhibitors?
Increases risk of bleeding!
Serious bleeding must subside prior to administration and risk of thrombosis vs. risk of bleeding must be monitored throughout use.
Why are GPIIb/IIIa Antagonists very useful in STEMI pateints undergoing PCI?
Cover for delayed absorption of oral P2Y12 Inhibitors occuring due to opiates delaying gastric emptying
What is the role of anticoagulants used in the treatment of ACS?
Targets formation and/or activity of thrombin; inhibiting both fibrin formation and platelet activation
What anticoagulant is commony used during Non-STEMI ACS?
Fondaparinux (a pentasaccharide) is used prior to coronary angiography
What anticoagulants are used during PCI?
Full Dose:
Heparin (unfractionated or LMWH)
Bivalirudin
What is a Silent MI?
When a diabetic patient may not experience typical chest pain during an acute coronary syndrome
What umbrella term does Stable Angina come under?
What umbrella Term does Unstable Angina come under?
Ischaemic Heart Disease (IHD)
Acute Coronary Syndrome (ACS)
What determines if Angina is stable?
Angina is stable if symptoms are always relieved by rest or GTN (glyceryl Trinitrate) spray.
What is the gold standard diagnostic investigation for Stable Angina?
CT Coronary Angiography
Name some causes of oxygen supply reduction associated with IHD?
- Common: anaemia and hypoxaemia
- Uncommon: polycythemia, hypothermia, hypovolaemia, hypervolaemia
Name some causes of oxygen demand increase associated with IHD?
- Common: hypertension, tachyarrhythmia, valvular heart disease
- Uncommon: hyperthyroidism, hypertrophic cardiomyopathy
Give some risk factors associated with IHD?
- Age
- Smoking
- Family history
- Diabetes mellitus
- Hyperlipidemia
- Hypertension
- Kidney disease
- Obesity
- Physical inactivity
- Stress
What are the three major physiological factors lending to oxygen mismatch associated with IHD?
- Impairment of blood flow by proximal arterial stenosis (e.g. atherosclerosis)
- Increased distal resistance (e.g. left ventricular hypertrophy)
- Reduced oxygen carrying capacity of blood (e.g. anaemia)
What is Ohms Law?
Flow = Change in pressure / Resistance
What is Poiseuille’s Equation?
Q = R^4
How does Poiseuille’s Law relate to CCS?
Relationship between flow, pressure and resistance; combination of Ohm’s law and vessel resistance equation. Radius has to fall below 75% before symptoms
What are some differential diagnoses of chest pain?
Cardiac – ACS, Aortic dissection, pericarditis, myocarditis
Respiratory – PE, pneumonia, pleurisy, lung cancer
MSK – rib fracture, chest trauma, costochondritis (inflammation of the cartilage between the ribs and sternum)
GORD
Oesophageal spasm
Anxiety/panic attacks
How would you discuss a patients pain when taking a history for IHD?
SOCRATES:
Site
Onset
Character
Radiation
Associated symptoms
Time/Duration
Exacerbating features
Severity
What characteristics of chest pain suggest ischaemic cardiac pain?
- Heavy, tight pain
- Located centrally
- Provoked by cold weather, big meals, exertion
- Relieved by rest, GTN spray
- Associated SOB
What is exercise testing?
Patient undertakes mild exercise on a treadmill and ECG is run simultaneously - any abnormailites, refer patient to catheterisation lab
What is a Perfusion/ Myoview scan?
IV radio-labelled agent travels to the coronary arteries - areas of darkness signify a blockage.
What are Psychosocial factors?
Factors influencing psychological responses (cognitive; behavioural; emotional) to the social environment and pathophysiological changes
What is a Coronary Prone Behaviour Pattern?
Coronary prone behaviour is the collection of behaviours and attitudes associated with heart disorders especially coronary heart disease and cardiovascular disorders.
Give some examples of personality traits associated with Coronary Prone Behaviour Patterns?
- Aggressiveness/Anger (biggest risk factor)
- Ambition
- Competitiveness
- Hostility (biggest risk factor)
- Impatience
- Sense of time urgency
- Need for achievement
Give some psychosocial factors that increase the risk for CHD?
Depression and Anxiety
Low quantity and quality of social support
High demanding jobs/low control of jobs
What are the layers of the pericardium?
Outer Fibrous layer - Continuous with the central tendon of the Diaphragm
Serous layer:
Outer Parietal - lines the inner surface of the fibrous pericardium
Inner Visceral - forms the outer layer of the heart (Epicardium)
What is found between the parietal and Visceral pericardium?
What is the Function of this?
Pericardial cavity:
Contains 50ml of serous fluid to minimise the friction generated when the heart contracts
Which great vessels are Contained within the pericardium?
Roots of the great vessels:
Aortal
Pulmonary Artery
Pulmonary Veins
SVC
IVC
What are the main functions of the pericardium?
- Fixes the heartin the mediastinum and limits its motion.
- Prevents overfillingof the heart. The relatively inextensible fibrous layer of the pericardium limits the filling pressure and volume of the heart
- Lubrication. A thin film of fluid between the two layers of the serous pericardium reduces the friction generated by the heart as it moves within the thoracic cavity
- Protection from infection. The fibrous pericardium serves as a physical barrier between the muscular body of the heart and adjacent organs prone to infection, such as the lungs.
What is the purpose of the small reserve volume associated with the pericardial sac?
Volume of pericardial fluid changes based on the physiological state of the heart.
What is Cardiac Tamponade?
Reduction in cardiac output due to a raised intrapericardial pressure secondary to a pericardial effusion.
As there is a greater pressure, the heart chambers cannot expand during diastole reducing SV and CO
What are some signs associated with cardiac tamponade?
Beck’s Triad
Pulsus Paradoxus
Tachycardia and Hypotension
Soft heart sounds
What is Chronic pericardial effusion?
Slow accumulation of fluid allowing for adaptation of the parietal pericardium
Why does Chronic Pericardial Effusion rarely cause Cardiac Tamponade?
Increased compliance reduces the effect on diastolic filling and therefore slow accumulating effusion does not often cause tamponade.
Define Pericardial Effusion?
Accumulation of excess fluid in the pericardial cavity; the pericardial fluid contains blood components such as fibrin, RBCs and WBCs
Define Acute Pericarditis?
Inflammation of the pericardium commonly due to viral infection.
What are the different types of Pericarditis?
Acute
Chronic effusive
Chronic Constrictive
Who is typically affected by pericarditis?
Males - 20-50yrs
What are some of the main causes of pericarditis?
Infection - Coxsackie Virus
Dressler’s Syndrome
Autoimmune
Neoplastic
Metabolic
Traumatic
Iatrogenic - PCI
What are some infectious causes of pericarditis?
HEAP:
Herpes virus
Enterovirus (Coxsackie)
Adenovirus
Parovirus
What are some Autoimmune causes of Pericarditis?
Sjogren’s Syndrome
SLE
Rheumatoid Arthritis
Scleroderma
Systemic Vasculitides
What is Constrictive Pericarditis?
persistent inflammation of acute pericarditis causes the heart to be encased with a rigid fibrotic calcified pericardial sac which prevents adequate diastolic filling of the ventricles
How is Pericarditis diagnosed?
ECG: (diagnostic) - PeRicardiTiS (PR dep and ST elev)
Concave Saddle Shaped ST elevation (in all leads)
PR depression
ECHO - exclude pericardial effusion/tamponade
CXR - Bottle water silhouette
FBC - increased WCC
Chest Pain
ESR/CRP - High ESR may suggest aetiology
Pericardial Rub
What is the Pathology of Pericarditis?
Pericardium becomes acutely inflamed, with pericardial vascularisation and infiltration with polymorphonuclear leukocytes
A fibrinous reaction frequently results in exudate and adhesions within the pericardial sac, and a serous or haemorrhagic effusion may develop
If this fluid accumulation impacts the hearts function this is cardiac tamponade
What is the nature of the chest pain associated with pericarditis?
Sharp severe pleuritic chest pain - radiate to left shoulder due to phrenic nerve
Pain is relieved when sitting forward
Pain is exacerbated when lying flat or on inspiration
What are the symptoms of pericarditis?
Severe pleuritic chest pain
Dyspnoea
Cough/hiccups - phrenic involvement
Systemic disturbance - weight loss, joint pain, fever
What is Pericardial Rub?
Extra heart sound heard upon auscultation
One systolic - Two diastolic
Sound resembles scratching.
What are the signs of effusion associated with pericarditis?
Pulsus paradoxus
Kussmaul’s Sign - rise in JVP on inspiration
Tachycardia and Hypotension
soft heart sounds - effusion obscures beat and sounds
What is Beck’s Triad?
Three clinical signs associated with pericardial tamponade:
- Falling BP - Hypotension (weak pulse or narrow pulse pressure)
- Muffled heart sounds
- Raised jugular venous pressure.
What are some important differential diagnoses of pericarditis?
MI - has no pericardial rub/not related to lying down (ST elevation not saddle shaped)
pneumonia
Aortic Dissection
PE
What is the management for pericarditis?
Period of sedentary activity until resolution of inflammation
NSAIDS (2 weeks) + Gastric Protection (PPI)
Colchicine (3 weeks)
Consider Abx for bacterial aetiology
What is the Mechanism of action of Colchicine?
Inhibits migrations of neutrophils to site of inflammation to reduce risk of reoccurrence
What are some complications of pericarditis?
Pericardial effusion - cardiac tamponade
myocarditis
constrictive pericarditis
How is Pericardial Effusion Diagnosed?
Echocardiogram - Echo free space around heart
CXR – large heart
ECG – low voltage QRS complexes and sinus tachycardia
How is cardiac tamponade diagnosed?
ECHO - diagnostic
Beck’s Triad
ECG - varying QRS peaks
CXR - big globular heart
How is Cardiac Tamponade treated?
Urgent pericardiocentesis
How is Pericardial Effusion treated?
treat underlying cause
NSAIDS
Colchicine
What is the main cause of pericardial effusion?
Typically pericarditis
RF are all factors related to pericarditis
Name some environmental causes of Angina?
Emotional stress
Large meals
Cold weather
What is Poiseuille’s Law?
Resistance = 8lu/pi r^4
l - length of vessel
U - viscosity
R - radius of vessel
What is Crescendo Angina?
patients present with angina over a period of months that gets progressively worse
What is the prevalence of Angina in men and women?
Men - 5% (5000/100,000)
Women - 4% (4000/100,000)
What is a common side effect of nitrates in GTN?
headache due to vasodilation
What are some side effects of Calcium channel blockers?
postural hypotension
Swollen ankles
Flushing
What procedures may be involved in PCI?
Balloon Stent
Angioplasty with Stent
What is the most common cause of Pericarditis?
Viral infection
What are the various causes of pericarditis??
Idiopathic
Infection:
Viral (most common) – HIV, Coxsackie B, echovirus
Bacterial – TB
Fungal – Histoplasma spp.
Malignancy
MI
Autoimmune (immune system attacking the pericardium):
Sjogren’s
RA
SLE
Dressler syndrome (inflammation of pericardium after MI damaging it)
What is Pulsus Paradoxus?
An inspiratory decrease in systolic BP >10mmHg.
(not a paradox but exaggeration of normal physiology)
Caused by increased venous return to the right side of the heart during inspiration
The increased RV volume therefore occupies more space within the rigid pericardium and impairs LV filling
Paradox:
On physical exam, beats are detected on cardiac auscultation during inspiration which cannot be palpated at the radial pulse. This is associated with increased JVP (kussmauls sign)
What is cardiomyopathy?
A disease of the heart muscle tissue where there is impaired ability to contract and/or there is electrical conduction dysfunction.
what is the epidemiology of cardiomyopathy?
Generally they are inherited conditions but can be acquired
What are the general risk factors for cardiomyopathy?
Family history
Hypertension
Obesity
Diabetes
Previous MI
What are the 3 major determinants of myocardial performance?
Preload - the volume of blood entering the ventricles that causes a greater stretch on the ventricles.
Afterload - The pressure that must be overcome in order to eject blood from the ventricles during systole.
Contractility
What are the main types of cardiomyopathy?
Hypertrophic Cardiomyopathy (HCM)
Dilated Cardiomyopathy (DCM)
Arrhythmogenic Right/Left ventricular Cardiomyopathy (ARVC/ALVC)
Restrictive Cardiomyopathy.
What is the most common type of Cardiomyopathy?
Dilated Cardiomyopathy
What is Primary Cardiomyopathy?
Occurs when genes encoding proteins involved in the Myocardial tissue are dysfunctional resulting in poor/altered function myocardial cells and further pathology.
What is Secondary Cardiomyopathy?
Where the Myocardial cells structure and function becomes damaged through:
Toxins
inflammation
infection
systemic disorders
How are cardiomyopathies diagnosed?
ECHO
Some with MRI
Troponins may be elevated.
What is Dilated Cardiomyopathy?
Dilation/thinning of the ventricular walls (chamber enlargement) causing weakness of the ventricular myocardial cell contraction.
Systolic function is impaired leading to poorly ejected blood
Can result in biventricular congestive HF.
What are the Symptoms of Dilated Cardiomyopathy?
Can be Asymptomatic
May present as congestive heart failure.
Dyspnoea
Weakness
Fatigue
Oedema
Raised JVP
Pulmonary congestion
Cardiomegaly
3rd/4th Heart Sounds
What is the Aetiology of Dilated Cardiomyopathy?
Idiopathic - Gene mutations often in cytoskeletal genes.
Infection
Ischaemia
Alcoholism
Thyrotoxicosis
What is the epidemiology of DCM?
More common in males
35/100,000
Median age - 50
How is DCM diagnosed?
ECHO - Marked Dilatation
CXR - Cardiomegaly, pulmonary oedema
ECG - May have tachycardia/arrhythmias
What is the treatment for DCM?
Tx of underlying conditions - AF/ HF
Bed rest
Loop and Thiazide Diuretics for fluid overload
ACEi
Beta Blockers
Heart transplant
What is Hypertrophic Cardiomyopathy (HCM)?
Unexplained primary cardiac hypertrophy (often on LV wall and interventricular septum) leading to impaired diastolic filling and a reduced stroke volume. due to thick heart and reduced compliance
Which is the main issue in HOCM, Systole or diastole?
Diastole is main issue.
Enlarged heart walls. ventricles are stiff
LV does not relax properly and so diastolic filling is impaired.
What is the cause of HCM?
Autosomal Dominant mutation in Sarcomeric genes:
Beta-myosin heavy chain
Troponin T
alpha tropomyosin.
What are the symptoms of HCM?
Most may be asymptomatic
Variable dyspnoea
Chest pain / palpitations
Syncope
Sudden death
What are the main complications of DCM?
Progressive Heart Failure
Sudden Cardiac Death
What may be found upon examination of a patient with HCM?
Forceful Apex beat
Late ejection systolic Murmur (crescendo-decrescendo similar to AS)
S4 Heart sound - stiff ventricle so sound as blood hits non compliant wall.
Jerky Carotid pulse
Alpha wave in JVP.
What is the Epidemiology of HCM?
1/500
Men and black people more likely
What is the most common form of sudden cardiac death in the young population and atheletes?
Hypertrophic Cardiomyopathy
How is HCM diagnosed?
ECG - LVH, ST segment changes, DEEP T wave inversion
CXR - variable, left atrial enlargement
ECHO - large LV walls
What is the treatment of HCM?
Amiodarone - reduce risk of arrythmias and sudden death
Treat chest pain:
Beta blockers and CCB - Verapamil
Implantable cardioverter defibrillator
What medication is contraindicated in HOCM?
Digoxin
Digoxin can increase inotropy which may exacerbate heart symptoms in patients with HCM that have preserved systolic function
What is HOCM the most common cause of?
Most common cause of sudden death in young and adults (especially athletes)
What is a severe complication of HCM?
Sudden Death
What is Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC)?
Associated with Desmosome gene mutations
Fibro-fatty replacement of the RV myocytes leading to impaired ability of RV muscle to contract due to muscle cell loss.
What is Naxos disease?
A autosomal recessive genetic condition associated with ARVC and diffuse palmoplantar keratoderma and woolly hair
What are the symptoms of ARVC?
Arrythmias - main feature
Palpitations
Presyncope/syncope
RHF
Death possible on first presentation
What is the most common sustained arrythmia in HCM?
Atrial Fibrillation
What is the cause of ARVC?
Unknown but may be due to apoptosis, inflammation or genetics
What is the Epidemiology of ARVC?
1/2000
Mainly affects males
30-50% of cases have autosomal dominant genetic predisposition
How is ARVC diagnosed?
ECHO - RV wall Dimensions and abnormalities
RV angiography
ECG - In leads V1, 2 and 3, Epsilon wave, T wave inversion
MRI - fatty infiltration and fibrosis on RV wall.
How is ARVC treated?
Standard heart failure medication.
Beta blockers in asymptomatic patients.
Amiodarone - Tx for arrythmias
Heart transplant
What is the most frequent cause of heart transplants?
Dilated cardiomyopathy.
What is Restrictive cardiomyopathy?
Rigid Fibrotic Myocardium
Increased myocardial stiffness despite normal LV cavity size and function.
Increased stiffness restricts diastolic filling as the ventricle is incompliant.
What are the causes of Restrictive cardiomyopathy?
Granulomatous disease - Amyloidosis (Amyloid heart disease) / Sarcoidosis.
infiltrative myocardial disease
Loffler Endo(myo)carditis
Haemochromatosis
What is the epidemiology of Restrictive cardiomyopathy?
between 1/1000 to 1/1500
5% of all cardiomyopathies
Mainly affects the elderly, tropical Africa
What are the symptoms of restrictive cardiomyopathy?
Similar to constructive pericarditis
Features of RV failure
Dyspnoea
Elevated JVP
Hepatomegaly
Ascites
3rd and 4th heart sounds
What are the investigations for Restrictive cardiomyopathy?
ECHO - thickened ventricular walls, valves and atrial septum.
ECG - Low amplitude signals
MRI - to distinguish between cardiomyopathies.
What is the treatment for restrictive cardiomyopathy?
Tx underlying cause
Heart Transplant
What are the complications of restrictive cardiomyopathy?
Heart failure
sudden death
Poor prognosis.
What is the main feature of ARVC?
Arrhythmia
What do all cardiomyopathies carry a risk of?
Developing arrythmia
What is Takotsubo’s Cardiomyopathy?
Also known as ‘stress-induced cardiomyopathy’ or ‘broken-heart syndrome’.
A stressful event can lead to characteristic apical ballooning with transient systolic dysfunction.
Thought to be related to catecholamine-induced spasm of the small vessels in the microvasculature.
The condition preferentially affects postmenopausal women.
What is a channelopathy?
Gene mutations in genes that are involved in ion channel proteins resulting in channelopathies.
What can be a cardiovascular sign of channelopathies?
Arrythmias
Give some examples of cardiac Channelopathies
Long QT
Short QT
Brugada
Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT)
What is the major clinical sign of ARVC?
Ventricular Tachycardia
What is the commonest symptoms of channelopathies?
Recurrent Syncope
What is Brugada Syndrome?
A channelopathy caused by a mutation in the cardiac sodium channel gene
What are the symptoms of Brugada Syndrome?
Asymptomatic
May have syncope
Can cause sudden death
What are the common rhythmic abnormalities associated with Brugada Syndrome?
Ventricular fibrillation
Polymorphic Ventricular Tachycardia
What would the ECG look like with a patient with Brugada?
Characteristic ST elevation with partial RBBB pattern in V1 and V2
What is sudden cardiac death in young people often due to?
Inherited condition likely a cardiomyopathy or channelopathy
What conditions are included in Aortovascular syndromes?
Marfans
Vascular Ehler Danlos (EDS)
Loeys-Dietz
What is Diastolic Distensibility?
The pressure required to fill the ventricle to the same diastolic volume
What are the Consequences of Hypertension?
Stroke (ischaemic and haemorrhagic)
Myocardial Infarction
Heart failure
Chronic renal disease
Cognitive decline
Premature death
What are the different stages of clinical Hypertension?
- Define Stage 1 Hypertension.
Clinical = 140/90
Ambulatory = 135/85 - Define Stage 2 Hypertension
Clinical = 160/100
Ambulatory = 150/95 - Define severe Hypertension.
Clinical = 180/110
How is Hypertension treated?
Lifestyle modification
Antihypertensive drug therapy
Who should be offered antihypertensive drug treatment for hypertension?
Individuals aged 80 or below and individuals who have one or more of the following:
- Target organ damage
- Established CVD
- Renal disease
- Diabetes
- 10-year CVD risk of >20%
Describe mechanisms of BP control - targets for therapy
- Cardiac output and peripheral resistance
- Interplay between the RAAS and sympathetic nervous system (NA)
- Local vascular vasoconstrictor and vasodilator mediators
Describe the renin angiotensin-aldosterone system.
- Kidneys sense low BP and renin is released from juxtaglomerular cells.
- Renin converts angiotensinogen to angiotensin I
- ACE from the lungs converts angiotensin I to angiotensin II
- Angiotensin II (extremely potent vasoconstrictor) stimulates aldosterone release resulting in increased Na+ and thus water reabsorption which leads to increased blood volume and thus blood pressure
Describe the Sympathetic nervous system response to a drop in BP?
Drop in BP results in the release of noradrenaline,
leading to vasoconstriction and increased contractility of the heart
thus increasing peripheral resistance and cardiac output and thus BP.
Also results in renin release which further augments RAAS
What is the MOA of ACE inhibitors?
Prevent ACE converting angiotensin I to Angiotensin II and therefore inhibiting the CVS effects of Angiotensin II
Give examples of ACEis?
- Ramipril
- Enalapril
- Perindopril
- Trandolapril
What are the indications for ACE Inhibitors?
- Hypertension
- Heart Failure
- Diabetic nephropathy
What are the main Adverse effects of ACEi?
Related to reduced Angiotensin II:
Hypotension
Acute renal failure
Hyperkalaemia
Teratogenic effects in pregnancy
Related to increased Kinin Production:
Cough
Rash
Anaphylactoid reactions
Why are there side effects such as cough when using ACEi?
ACE breaks down bradykinin.
If ACE is inhibited then bradykinin levels increase
This can cause a persistent dry cough
What are Angiotensin II Receptor Blockers (ARBs)?
They block the receptors of angiotensin II preventing its binding and it inducing effects.
Give examples of ARBs?
- Candesartan
- Losartan
- Valsartan
- Telmisartan
What are the indications for ARBs?
- Hypertension (and when ACEi is contradicted due to cough)
- Diabetic nephropathy
- Heart failure (when ACEi contraindicated - acts on AT-1 receptor)
What are the ADRs associated with ARBs?
- Symptomatic hypotension (esp. in volume depleted patients)
- Hyperkalaemia
- Potential renal dysfunction
- Rash
- Angiooedema
- Teratogenic in pregnancy
What are Calcium Channel Blockers (CCBs)?
These block the calcium channels from allowing Ca entry into cardiomyocytes.
What are the indications for CCBs?
- Hypertension
- IHD (angina)
- Arrhythmias
Give examples of CCBs.
- Dihydropyridines (e.g.amlodopine, nifedipine, felodipine)
- Phenylalkylamines(e.g. verapamil)
- Benzothiozepines(e.g. diltiazem)
Give an example and explain the actions of Dihydropyridines?
Amlodipine:
Preferentially affect Vascular smooth muscle and act as peripheral arterial vasodilators
Give an example and explain the actions of Phenylalkylamines?
Verapamil:
Directly affects the heart - negatively chronotropic, negatively ionotropic
Give an example and explain the actions of Benzothiozepines?
Diltiazem:
Intermediate heart and peripheral vascular effects
What are the ADRs associated with CCBs?
Due to peripheral vasodilation (Dihydropyridines):
- Flushing
- Headache
- Peripheral oedema
- Palpitations
Due to negative chrontropic effect (Phenylalkylamines and Benzothiozepines):
- Bradycardia
- Atrioventricular block
- Postural hypotension
Due to negative ionotropic effect (Benzothiozepines)
- Worsening of HF
Verapamil causes constipation
What are Beta Blockers?
Beta adrenoceptor blockers that prevent the effects of adrenaline and noradrenaline in the sympathetic nervous system.
They work on B1 and B2 receptors.
Give examples of Beta Blockers?
- Bisoprolol
- Propranolol
- Atenolol
- Carvedilol
What are the indications for beta blockers?
- IHD - angina
- HF
- Arrhythmia
- Hypertension
Which beta blockers are B-1 selective?
Metoprolol
Bisoprolol
(Atenolol is mostly B1 but not entirely cardioselective)
Which beta blockers are non-selective?
Propranolol
Nadolol
Carvedilol
What condition is contraindicative for beta blockers?
Asthma
What are the ADRS associated with Beta blockers?
- Fatigue
- Headache
- Sleep disturbance
- Bradycardia
- Hypotension
- Cold peripheries
- Erectile dysfunction
What conditions can Beta blockers cause exacerbations of
Asthma
PVD - Claudication or Raynauds
Heart Failure - when given in standard doses or acutely
How do Diuretics reduce blood pressure?
Increased excretion of water, salt and metabolites in urine
What are the indictations for Diuretics?
- Hypertension
- Heart failure
What are the different classes of Diuretics?
Thiazide diuretics - act on distal tubule blocking Na/Cl exchanger
Loop diuretics - act on ascending loop of henle, blocks Na/K/2Cl (NKCC2) transporter
Potassium-sparing diuretics(Aldosterone antagonists) - Retain Potassium
Give examples of Diuretics of each class?
- Thiazide diuretics: bendroflumethiazide, hydrochlorothiazide
- Loop diuretics: furosemide, bumetanide
- Potassium-sparing diuretics: spironolactone, eplerenone
What are the ADRs associated with Diuretic?
- Hypovolaemia (mainly loop)
- Hypotension (mainly loop)
- Hypokalaemia
- Hyponatraemia
- Hypomagnesaemia
- Hypocalcaemia
- Hyperuricaemia (gout)
- Erectile dysfunction (thiazides)
- Impaired glucose tolerance (thiazides)
Give an alpha 1 adrenoceptor blocker used as an anti-hypertensive?
Doxazosin
Give examples of centrally acting antihypertensives?
Act on the CNS:
Moxonidine
Methyldopa
When may Methyldopa be used?
During pregnancy for gestational hypertension
