CARDIOVASCULAR Flashcards
What is the definition of Anaemia?
Reduction of red blood cells in circulation below normal range (mass) and deficiency in the oxygen-carrying capacity of the blood due to diminished erythrocyte mass.
What are the hemoglobin concentration criteria for men to be considered anemic?
Hb < 130
What are the hemoglobin concentration criteria for women to be considered anemic?
Hb < 120
What does MCV stand for and what does it indicate?
Mean corpuscular volume; it indicates red blood cell size.
What MCV value indicates macrocytic anemia?
> 100.
True or False: Acute bleed always show a drop in Hgb or Hct immediately.
False.
levels may initially appear normal because both RBCs and plasma are lost concomitantly. This discrepancy becomes evident once intravenous fluids restore or replenish the patient’s plasma volume
What physiological change occurs in pregnant women during the third trimester regarding RBCs?
RBCs expand by 25% but plasma volume increases by 50%, leading to ‘physiologic anemia.’
What is the effect of erythropoietin in the bone marrow?
Enhances the growth and differentiation of burst forming units-erythroid (BFU-E) and colony forming units-erythroid (CFU-E) into reticulocytes.
How long does a mature Red Blood Cell circulate in the peripheral blood?
100 to 120 days.
What are the three broad categories that anemia can be due to?
- Blood loss * Increased destruction of RBCs (hemolysis) * Decreased production of RBCs.
What are the types of normochromic, normocytic anemia?
- Anemias of chronic disease * Hemolytic anemias * Anemia of acute hemorrhage * Aplastic anemias.
What are the types of hypochromic, microcytic anemia?
- Iron deficiency anemia * Thalassemias * Anemia of chronic disease (rare cases).
What are the types of normochromic, macrocytic anemia?
- Vitamin B12 deficiency * Folate deficiency.
What serious complications may arise from severe anemia?
- Shock * Hypotension * Coronary insufficiencies * Pulmonary insufficiencies.
What factors should be considered in the patient’s history to evaluate for anemia?
- Bleeding history * Menstrual history * Prior intestinal surgery * Family history * Alcohol and nutritional questions * Liver and renal diseases * Environmental/work toxins (e.g., lead).
What percentage of the global population is affected by anaemia?
25%
Affects approximately 1.6 billion people globally.
What is the most common cause of anaemia?
Iron deficiency
When should pregnant women be screened for anaemia?
At their first booking visit and at 28 weeks
What is the minimum haemoglobin level required in the first trimester of pregnancy?
110 g/L
Who is more likely to develop anaemia during pregnancy?
Individuals with:
* Low iron stores pre-pregnant
* Pre-existing blood conditions
* Inflammatory disorders of the gut
* Multiple births
* Age > 20 years
* Previous birth < 12 months ago
What are the importance of iron in pregnancy?
- Maintain a healthy immune system
- Decrease blood loss impact at delivery
- Improve postnatal recovery
- Avoid decreased breast milk supply
- Reduce risk of low weight or premature delivery
- Mitigate post-natal depression
What form of iron is better absorbed?
Ferrous form
Which type of dietary iron has better absorption: heme or non-heme?
Heme iron
What are signs of anaemia?
- Pallor
- Tachycardia
- Flow murmur
- Oedema
- Enlarged heart
What are symptoms of anaemia?
- Cardiovascular: palpitations, angina, ankle swelling
- CNS: confusion, dizziness, headache
- Respiratory: shortness of breath
- Eyes: dimness of vision
- Ears: tinnitus
- Psychological: confusion, exacerbation of symptoms
Is routine iron supplementation recommended for all pregnant women?
No
What is the customary oral dose of elemental iron for iron-deficiency anaemia?
65 mg elemental iron (ferrous sulfate 200 mg) once daily
What are common adverse effects of iron supplements?
- Constipation
- Diarrhoea
- Epigastric pain
- Gastrointestinal irritation
- Nausea
What reduces the absorption of oral iron?
- Zinc or magnesium salts
- Calcium
- Tannins (in tea and coffee)
- Phytates
Which drugs can have reduced absorption when taken with oral iron?
- Tetracyclines
- Quinolones
- Bisphosphonates
What is the role of folic acid in the body?
Essential for DNA synthesis
What is the recommended daily supplement of folic acid during pregnancy?
400 mcg daily for the first 12 weeks
What is the increased daily dose of folic acid for women at risk of NTDs?
5 mg daily
What is venous thromboembolism (VTE) caused by?
Combination of stagnation of blood and hypercoagulability
Vascular injury is also a recognized causative factor but is not necessary for VTE development.
Name two examples of VTE.
- Deep vein thrombosis (DVT)
- Pulmonary embolism (PE)
What is often referred to as ‘red clots’?
RBCs and platelets dispersed in a fibrin mesh
What are some causes of stagnation or sluggishness of blood flow?
- Bed rest
- Surgery
- Reduced cardiac output (e.g., heart failure)
List risk factors that increase the risk of hypercoagulability.
- Surgery
- Pregnancy
- Oestrogen administration
- Malignancy
- Myocardial infarction
- Inherited or acquired disorders of coagulation
What is Virchow’s triad?
Presence of decreased blood flow (stasis), tendency to clot (hypercoagulability), and changes to the blood vessel wall
True or False: Venous thrombi require initial damage to develop.
False
Where do most venous thrombi begin?
In the valve cusps of the deep calf veins
What is a common complication of DVT?
Pulmonary embolism (PE)
DVT can also lead to post-thrombotic syndrome.
What are the symptoms of DVT?
- Tenderness
- Pain
- Oedema
- Warmth
- Skin discolouration
- Prominent superficial veins
How is DVT diagnosed?
Confirmed with D-dimer and/or duplex ultrasound
What is the definition of hospital-acquired VTE?
VTE occurring within 90 days of admission
What is the purpose of risk stratification tools in assessing VTE risk?
To assess individual patient risk of developing DVT
Name two methods of thromboprophylaxis.
- Mechanical (Non-pharmacological)
- Pharmacological
What drug is commonly used for DVT prevention?
LMWH
What is post-thrombotic syndrome characterized by?
Post-thrombotic syndrome (PTS), a long-term complication of deep vein thrombosis (DVT), is characterized by chronic pain, swelling, heaviness, and skin changes in the affected limb, potentially leading to venous ulcers in severe cases
What is the efficacy of compression stockings in preventing DVT?
May prevent asymptomatic DVT in general surgery and when immobile, but have not been shown to prevent pulmonary embolism
Compression stockings may also cause superficial thrombophlebitis in varicose veins and ischaemic complications in patients with peripheral vascular disease or diabetic neuropathy.
What is the duration of prophylaxis for general surgery?
Usually for 7 days, or when fully ambulant
Medical patients continue until no longer at risk.
What are the measures recommended for long distance air travel to reduce DVT risk?
Drink a lot of fluids, perform calf contractions each hour, and high-risk passengers should have LMWH immediately before departure
Moderate risk passengers should also use knee-length graduated compression stockings.
What are the objectives of treating an established venous thromboembolism?
To prevent thrombus extension/enlargement, pulmonary embolism (PE), post-thrombotic syndrome, and recurrent venous thromboembolism
What should be checked before starting therapy for DVT?
Check for and minimize predisposing factors, consider thrombophilia, and check baseline values (haemoglobin, platelets, APTT, and INR)
What are the treatment options for DVT?
Apixaban or rivaroxaban; if unsuitable, LMWH for 5 days followed by Dabigatran or LMWH concurrent with Warfarin for 5 days or until INR in range
UFH plus warfarin not routinely used except in renal impairment.
What are the three layers of cardiac muscle?
Endothelium, Myocardium, Epicardium
Endothelium is the inner layer lining the circulatory system, Myocardium is the heart muscle, and Epicardium is the outer layer.
What type of muscle is cardiac muscle classified as?
Striated muscle
Cardiac muscle has striations and is joined by intercalated disks.
What are the two types of junctions found in cardiac muscle?
Desmosomes, Gap junctions
Desmosomes provide mechanical connections, while gap junctions allow electrical connections.
What percentage of cardiac muscle contracts and conducts?
99% contracts, 1% conducts
The majority of cardiac muscle is involved in contraction, while a small percentage functions in conduction.
What triggers the heart beat?
Depolarisation via action potential
The electrical activity that leads to the heart beating is initiated by depolarisation.
Which nodes are regions of auto-rhythmicity in the heart?
SA node, AV node, Bundle of His, Purkinje Fibres
These structures are responsible for initiating and conducting electrical impulses in the heart.
What is the function of pacemaker cells?
Initiate and conduct action potentials
Pacemaker cells slowly drift to threshold to generate action potentials.
What is the normal pacemaker of the heart?
SA node
The SA node is responsible for setting the pace of the heart.
What opens during membrane depolarisation in ventricular action potentials?
Voltage gated Ca2+ channels
These channels play a crucial role in the contraction of cardiac muscle.
What is the role of calcium in excitation-contraction coupling?
Increases cytosolic calcium from sarcoplasmic reticulum
Calcium binds to troponin, initiating cross-bridge formation.
What can cause abnormal levels of K+ in the heart?
Altered resting potential, decreased cardiac contractility
High K+ levels can lead to reduced resting potential and inactivate Na+ channels, causing arrhythmias.
What is the effect of elevated Ca2+ levels in cardiac muscle?
Longer contractions
Elevated calcium can prolong the duration of contraction in cardiac muscle.
What is the cardiac refractory period?
The time during which the heart muscle cannot be re-excited
This period is crucial for preventing arrhythmias.
What are the mechanical events of the cardiac cycle?
Systole and Diastole
Systole refers to contraction, while diastole refers to relaxation of the heart.
What is stroke volume?
End diastolic volume - End systolic volume
Stroke volume is the amount of blood pumped by the heart with each beat.
What are the possible drug targets in the heart?
Receptors, Enzymes, Ion Channels, Carrier Proteins
These targets can be influenced by various cardiovascular drugs.
What class of antiarrhythmic drugs blocks sodium channels?
Class I
This class includes drugs like quinidine, procainamide, and flecainide.
What do Class II antiarrhythmic drugs do?
Block ß-adrenoceptors
Examples include atenolol and sotalol.
What is the effect of Class III antiarrhythmic drugs?
Prolong action potential and refractory period
These drugs help suppress re-entrant rhythms.
What is the primary effect of Class IV antiarrhythmic drugs?
Calcium channel antagonism
They impair impulse propagation in nodal and damaged areas.
True or False: Digoxin increases calcium and contractility.
True
Digoxin is used to enhance the force of cardiac contraction.
Fill in the blank: The typical ventricular action potential has _______ states for Na+ channels.
three
The states are closed, open, and refractory.
What is Torsades de Pointes?
A specific type of polymorphic ventricular tachycardia
It is often associated with prolonged QT interval.
What condition is associated with drug-induced Long QT syndrome?
Torsades de Pointes
This condition can lead to serious arrhythmias.
What is the primary function of the circulatory system?
Transporting materials, capillary exchange, transporting blood cells and immunoglobulins, regulation of body temperature and acid-base balance.
What occurs during blood flow through capillaries?
Exchange of oxygen and carbon dioxide takes place.
What is the pathway of blood returning from the systemic circuit?
Enters the right atrium through inferior and superior vena cava, moves into the right ventricle, then pumped to the lungs.
What is the pulmonary circuit?
The system of vessels that carries blood to and from the lungs for gas exchange.
What prevents backflow of blood into the right ventricle during diastole?
The semilunar valve.
What are the components of the pulmonary circulation?
Pulmonary trunk, left pulmonary artery, right pulmonary artery, pulmonary capillaries.
Where does blood with high oxygen concentration return after pulmonary circulation?
To the left atrium.
What is the aorta?
The largest artery in the body, originating from the left ventricle.
What are the main branches of the aorta?
- Ascending aorta
- Aortic arch
- Descending aorta
Which portion of the aorta passes through the diaphragm?
The descending aorta.
What are coronary arteries responsible for?
Feeding the heart with oxygenated blood.
What is the function of the fibrous connective tissue in blood vessels?
Providing structural support to the vessel.
What role does elastic connective tissue play in blood vessels?
Helps vessels expand and hold blood, applies pressure to push blood forward.
What is the role of smooth muscle in blood vessels?
Regulates vessel diameter to control blood flow.
What are the types of blood vessels?
- Arteries
- Arterioles
- Capillaries
- Veins
What is systole?
The phase in which the chambers contract and eject blood into the arteries.
What is diastole?
The phase in which the chambers relax and allow blood to fill them.
What is systolic pressure?
120 mmHg.
What is diastolic pressure?
Approximately 80 mmHg.
What is pulse pressure?
The difference between systolic and diastolic pressures.
What determines blood flow through a vessel?
The pressure gradient and vascular resistance.
Fill in the blank: The phase in the heart cycle when blood is ejected is called _______.
[systole]
Fill in the blank: Blood vessels are lined with a single layer of _______ cells.
[endothelial]
What is the pumping action of the heart known as?
The pumping action of the heart.
What is the normal systolic pressure in mmHg?
120 mmHg
What is the normal diastolic pressure in mmHg?
Approximately 80 mmHg
How is pulse pressure calculated?
The difference between systolic and diastolic pressures.
According to Ohm’s law, how is blood flow (Q) related to pressure gradient (ΔP) and vascular resistance (R)?
Q = ΔP / R
What are vasoactive substances?
Endogenous agents that increase/decrease blood pressure and heart rate.
Name one example of a vasoconstrictor.
- Catecholamines
- Angiotensin II
- Vasopressin
- Endothelin
- Thromboxane A2
Name one example of a vasodilator.
- Prostacyclin
- Nitric oxide
What is cardiac output (CO) defined as?
Heart rate (HR) multiplied by stroke volume (SV).
What is cardiac reserve?
The difference between cardiac output at rest and maximum volume of blood the heart pumps per minute.
What is stroke volume (SV)?
The volume of blood pumped out of each ventricle per beat (approximately 70 ml in a healthy heart at rest).
What occurs during ventricular contraction?
The ventricular myocardium contracts and squeezes down on the blood, causing rapid pressure increase.
What are the components of the electrical conduction system in the heart?
- Sino-atrial node (SA node)
- Inter-atrial pathway
- Inter-nodal pathway
- Atrioventricular node
- Bundle of His
- Bundle branches
- Purkinje fibres
What is the normal heart rate generated by the SA node?
70 to 75 beats/min.
What does depolarization mean in the context of the heart?
The reduction of a membrane’s resting potential so it becomes less negative.
What three factors control heart rate?
- Autonomic nervous system influence
- Catecholamines
- Body temperature
What neurotransmitter is released from sympathetic nerves to increase heart rate?
Norepinephrine
What effect does sympathetic stimulation have on heart rate?
Increases heart rate.
What effect does parasympathetic stimulation have on heart rate?
Decreases heart rate.
What is the function of stroke volume during a heartbeat?
The volume of blood pumped from the left ventricle per beat.
What are the two phases of a heartbeat?
- Systole
- Diastole
What is venous return?
The volume of blood returned to the right atrium per minute.
What is compliance (C) in relation to vascular blood volume (V) and intravascular pressure (P)?
C = V / P
What is the relationship between cardiac output (CO) and venous return (VR)?
CO = VR
What factors influence venous return (VR)?
- Blood volume
- Sympathetic stimulation of the veins
- Skeletal muscle activity
- Respiratory activity
What can cause low blood volume?
Haemorrhage or dehydration.
What blood pressure reading is considered hypertensive?
140/90 mmHg
Name one contributing factor to hypertension.
- Obesity
- Sedentary lifestyle
- Stress
- Smoking
- Excess alcohol or salt intake
What are some complications of hypertension?
- Atherosclerosis
- Stroke
- Aneurysm
- Heart failure
- Heart attack
- Kidney damage
What symptoms indicate hypotension?
- Dizziness
- Fainting
- Lack of concentration
- Blurred vision
- Nausea
- Cold and pale skin
- Rapid breathing
- Fatigue
- Thirst
- Depression
What is one treatment for hypotension?
- Consuming more salt
- Drinking more water
- Wearing compression stockings
- Drug medications (e.g., fludrocortisone, midodrine)
What are the three mechanisms that contribute to haemostasis?
- Vascular constriction
- Formation of platelet plug
- Blood coagulation
What triggers vascular constriction after a blood vessel injury?
- Sympathetic nerve reflexes
- Myogenic vasospasm
- Vasoconstrictors released from damaged tissue and platelets
What percentage of total blood volume does plasma form?
55 to 60%
What are the three major plasma proteins?
- Albumin
- Globulins
- Fibrinogen
What are the three major plasma proteins?
Albumin, Globulins, Fibrinogen
Albumin about 55%, Globulins about 38%, Fibrinogen synthesized in the liver
What is the primary function of Albumin?
Bind with various molecules in the blood and serve as a carrier protein
What types of globulins are present in plasma proteins?
Alpha, Beta, Gamma
Alpha and Beta globulins transport substances; Gamma globulins are antibodies
What role does Fibrinogen play in the blood?
Coagulation and thrombosis
What are erythrocytes commonly known as?
Red blood cells (RBCs)
What is the primary function of erythrocytes?
Transport oxygen to the tissues
What are the two components of haemoglobin?
Globin and Heme
How many heme groups are present in one molecule of haemoglobin?
Four
What does each heme group contain that is crucial for its function?
An iron atom that binds reversibly with oxygen
What is the average blood content of haemoglobin?
About 15 g/100 ml
What are the four blood groups?
Type A, Type B, Type AB, Type O
What are leukocytes commonly known as?
White blood cells (WBCs)
What is the normal range of leukocytes per microliter of blood?
4000 to 11,000 WBCs
What are some functions of leukocytes?
Destruction of pathogens, Fighting cancer cells, Phagocytosis of tissue wastes
What percentage of total WBCs do lymphocytes account for?
About 30%
What are the two types of lymphocytes?
B lymphocytes and T lymphocytes
What is the function of B lymphocytes?
Secrete antibodies
What is the role of T lymphocytes?
Play a role in the immune response
What are platelets?
Small, round or oval cell fragments formed in the red bone marrow
What is the primary function of platelets?
Contribute to stopping of bleeding
What do antiplatelet drugs do?
Inhibit platelet function and prevent the development of atherosclerosis and arterial thrombi
What is the best example of an antiplatelet drug?
Aspirin
What does aspirin inhibit?
Cyclo-oxygenase
How long does aspirin-induced inhibition of cyclooxygenase last?
7 to 10 days
What factors contribute to the prevention of blood clotting?
Smoothness of endothelial layer, Glycocalyx layer, Plasmin
What are anticoagulant drugs used for?
Prevent deep vein thrombosis and emboli formation
How is heparin administered?
Only by injection
What is the most commonly used oral anticoagulant drug in the US?
Warfarin
How does warfarin work?
Deactivates vitamin K involved in the synthesis of coagulation factors
What is the main function of the heart?
To pump blood through 60,000 miles of blood vessels
How many times does the heart contract in an average lifetime?
About 3 billion times
What is the average heart rate per day?
100,000 times
What organ is believed to be the first to become functional during fetal development?
The heart
What are the two main layers of the pericardium?
- Fibrous pericardium
- Serous pericardium
What is myocardium?
The muscle layer responsible for the heart’s pumping action
What can atherosclerosis or thrombosis in coronary arteries lead to?
Angina or myocardial infarction due to ischemia
What does heart failure result in?
- Fluid retention
- Pulmonary edema
- Renal insufficiency
- Hepatomegaly
- Shortened life expectancy
What is the epicardium?
The visceral layer next to the heart, inner layer of the pericardium
What are the three layers of cardiac muscle?
- Endothelium
- Myocardium
- Epicardium
What type of muscle is cardiac muscle?
Striated and branched, joined by intercalated disks
What are the two types of heart chambers?
- Atria
- Ventricles
What is the role of the right atrium?
Receives and holds deoxygenated blood
What distinguishes the left ventricle from the right ventricle?
The left ventricle has thicker walls because it pumps blood to the whole body
What separates the ventricles of the heart?
The interventricular septum
What is the function of the atrioventricular (AV) valves?
Ensures blood flows from the atria to the ventricles
What is the tricuspid valve?
The right AV valve located between the right atrium and right ventricle
What happens during systole?
The atrium pushes blood into the ventricle and the ventricle begins to contract
What are chordae tendineae?
Cord-like tendons connecting papillary muscles to the tricuspid and mitral valves
What is an electrocardiogram (ECG)?
A measure of the overall electrical activity of the heart
What does the P wave in an ECG represent?
Atrial depolarization
What causes the QRS complex in an ECG?
Ventricular depolarization
What is the function of the semilunar valves?
Prevent the flow back of blood into the ventricles
Fill in the blank: The _______ is the thick, membranous sac that surrounds the heart.
Pericardium
True or False: The left atrium holds deoxygenated blood.
False
How does blood flow from the body to the heart?
Blood flows from the body to the superior and inferior vena cava, then to the right atrium.
What valve does blood pass through from the right atrium to the right ventricle?
Tricuspid valve (right atrioventricular valve)
What is the route of blood from the right ventricle to the lungs?
Through the pulmonary valve to the pulmonary artery to the lungs.
What is the function of the left atrium in the circulatory system?
The left atrium receives oxygenated blood from the lungs via the pulmonary veins.
What valve does blood pass through from the left atrium to the left ventricle?
Bicuspid valve (mitral valve)
What is systolic dysfunction?
Loss of intrinsic contractility of the heart due to changes in signal transduction mechanisms.
What occurs in diastolic dysfunction?
The ventricle becomes stiffer, impairing ventricular filling.
What is the most common congenital abnormality of the heart?
Bicuspid aortic valve abnormality.
What condition is diagnosed when a person develops calcific aortic stenosis?
Bicuspid aortic valve abnormality.
What is myocardial infarction (MI)?
A heart attack resulting from a lack of blood flow and oxygen to the heart.
What triggers myocardial infarction?
Blockage of a coronary artery by atherosclerotic plaque.
What are common symptoms of myocardial infarction?
Angina pectoris, shortness of breath, irregular heartbeat, nausea, sweating.
What is the immediate treatment for myocardial infarction?
Supplemental oxygen, aspirin, nitroglycerine.
What is the long-term treatment for myocardial infarction?
Thrombolytic agents, balloon angioplasty, bypass surgery.
What is coronary artery disease?
A condition where plaque accumulates in the arteries, restricting blood flow.
What are risk factors for coronary artery disease?
Smoking, family history, hypertension, diabetes, obesity.
What are symptoms of congestive heart failure?
Breathlessness, fatigue, swollen legs.
What are common causes of heart failure?
Coronary heart disease, high blood pressure, cardiomyopathy.
What is angina pectoris?
Chest pain due to insufficient oxygenated blood to the heart.
What is the treatment for angina pectoris?
Nitroglycerine under the tongue.
What is a stroke?
A brain attack where a clot blocks blood flow through an artery.
What are the symptoms of a stroke?
Sudden paralysis, numbness, loss of speech and vision.
Fill in the blank: The heart works as two pumps, the right one pumps blood to the _______.
[pulmonary circulation]
Fill in the blank: The left ventricle pumps blood into the _______.
[aorta]
True or False: Heart failure means the heart has completely stopped working.
False
What is the leading cause of premature death and disability in the UK?
Cardiovascular disease (CVD)
CVD is a term that describes a group of disorders of the heart and blood vessels caused by atherosclerosis and thrombosis.
Define primary prevention in relation to cardiovascular disease.
Prevention of CVD in patients who have not yet developed clinical cardiovascular disease.
Define secondary prevention in relation to cardiovascular disease.
Prevention of recurrent events in patients who have already suffered the onset of clinical CVD.
What are the stages in the development of atherosclerosis?
Progression from a fatty streak to a plaque with a fibrous cap and necrotic lipid core.
What are the major modifiable risk factors for cardiovascular disease?
- Smoking
- Dyslipidaemia
- Hypertension
- Diabetes mellitus
- Obesity
- Physical inactivity
What are the non-modifiable risk factors for cardiovascular disease?
- Age
- Gender (M>F)
- Ethnicity (e.g., South Asian)
- Family history
- History of a previous cardiovascular event
What is absolute cardiovascular risk?
The risk of a person having a major cardiovascular event (MI or Stroke) in the next 5-10 years.
How often should the absolute cardiovascular risk of all adults be reviewed?
Every 5-10 years or more frequently if problems exist.
What is the purpose of using validated tools in cardiovascular risk assessment?
To identify patients with the greatest absolute risk of CVD.
What does the QRISK® 3 risk calculator include?
Additional risk factors such as CKD, SLE, migraine, corticosteroid use, atypical antipsychotics use, severe mental illness, erectile dysfunction, and a measure of systolic blood pressure variability.
True or False: Aspirin is recommended for primary prevention of cardiovascular disease.
False
What is the goal of managing multiple risk factors in cardiovascular risk management?
To reduce the patient’s level of cardiovascular risk.
What preventative strategies target primary prevention of cardiovascular disease?
- Smoking cessation
- Diet
- Dyslipidaemia management
- Hypertension management
- Diabetes mellitus management
- Physical activity
What are some secondary prevention strategies for cardiovascular disease?
- Antiplatelet therapy
- Statin therapy
- Beta blocker therapy
- ACE Inhibitor therapy
- Post MI management
What is the importance of assessing overall cardiovascular risk?
To understand the combined effects of multiple risk factors, as they can be cumulative or additive.
What lifestyle changes are recommended for high-risk cardiovascular patients?
- Frequent and sustained specific advice and support about diet and exercise.
- Pharmacotherapy about smoking cessation.
- Advice about BP and lipid lowering drug treatment.
What are the recommended blood pressure targets for patients with cardiovascular risk?
BP < 140/90 mmHg in general or <130/80 in all people with diabetes.
What are the targets for lipid levels in cardiovascular risk management?
- Total Cholesterol < 4 mmol/L
- LDL Cholesterol < 2 mmol/L
- HDL Cholesterol > 1 mmol/L
- Triglycerides < 2 mmol/L
What is the recommended review interval for response until targets are reached?
Every 6-12 weeks until targets reached or maximum tolerated dose is achieved.
What is the recommended review of CV risk for moderate risk patients?
Review of CV risk as per clinical guidelines or clinical need.
What is the appropriate advice for lifestyle changes in moderate risk patients?
- Specific advice on diet and exercise
- Smoking cessation advice
When should BP and/or lipid lowering therapy be considered?
If lifestyle measures for 3-6 months do not reduce CV risk or BP is persistently >160/100mmHg.
What should be reviewed every 6-12 months for low risk patients?
Review of CV risk.
What are the dietary recommendations for patients?
- Varied diet rich in vegetables, fruit, whole grains, lean meat, poultry, fish, eggs, nuts, seeds, legumes, beans, low-fat dairy
- Limit saturated and trans fats
- Limit salt intake to <6g per day
- Limit alcohol intake to <2 standard drinks per day
What is the goal for BMI in weight management?
BMI <25.
What is the goal for waist circumference in males and females?
- Male <94cm
- Female <80cm
How does smoking affect cholesterol levels?
Decreases levels of HDL cholesterol.
What is the risk increase of MI for heavy smokers?
4x risk of MI compared to non-smokers.
What are the goals for blood pressure in adults with CHD?
BP goal <130/80mmHg.
What is the recommended goal for LDL levels?
LDL <2.0mmol/l.
What are the lifestyle factors to consider for obesity management?
- Reduce weight through diet
- Increase exercise
What is the goal for alcohol consumption for hypertensive patients?
Limit intake to two (men) or one (women) standard drinks per day.
What should be the minimum physical activity goal per week?
At least 150 minutes of moderate-intensity physical activity.
What is the relationship between diabetes and CHD mortality?
Diabetes increases mortality with CHD by 2-3x in men and 6x in women.
What is the controversy surrounding aspirin use in primary prevention?
Generally NOT recommended for patients without history of CHD.
What constitutes secondary prevention in CHD?
Prevention of progression of disease in symptomatic patients.
What lifestyle changes are recommended for secondary prevention?
- Cessation of smoking
- Increased exercise
- Weight loss if overweight/obese
- Improving diet
- Moderating alcohol consumption
What is the recommended daily dose of Aspirin for patients post-MI?
75-150mg per day.
What should be considered for patients who cannot tolerate ACE inhibitors?
Use angiotensin II receptor blockers.
What are examples of ACE inhibitors?
- Ramipril
- Lisinopril
- Enalapril
- Captopril
- Perindopril
- Fosinopril
- Trandolapril
What is the goal for triglyceride levels?
Triglyceride <2.0mmol/l.
What are angiotensin II receptor blockers used for?
For patients who develop unacceptable side effects with ACEIs
Examples include Irbesartan, Candesartan, and Telmisartan.
Name three examples of ACEIs.
- Ramipril
- Lisinopril
- Enalapril
- Captopril
- Perindopril
- Fosinopril
- Trandolapril
These are commonly used ACE inhibitors.
When should beta blockers be started in post-acute coronary syndrome patients?
Unless contraindicated, start in most post-acute coronary syndrome patients and continue indefinitely
Examples include Carvedilol, Bisoprolol, and Metoprolol (extended release).
What benefits do beta blockers provide in heart failure patients?
Survival benefits in mild-moderate heart failure patients already taking ACEIs
Carvedilol, Bisoprolol, and Metoprolol are examples.
Are statins recommended for patients with coronary heart disease?
Yes, recommended for all patients with coronary heart disease
Statins are beneficial regardless of total or LDL cholesterol levels.
What are the agents of choice for lowering LDL-C?
Statins
Examples include Simvastatin, Atorvastatin, and Fluvastatin.
What are fibrates used for?
Effective for lowering triglyceride levels and raising HDL-C levels
Gemfibrozil is a common example.
What is hazardous about combining statins and fibrates?
Hazardous due to risk of myopathy
Specialist advice is required.
When is warfarin recommended post-MI?
Only for survivors of MI with high risk of systemic thromboembolism
This includes patients with AF, mural thrombosis, congestive heart failure, or previous embolisation.
Can warfarin be used in combination with aspirin?
Yes, but monitor patient closely for signs of bleeding
This is important for patient safety.
Is routine use of antiarrhythmics recommended post-acute coronary syndrome?
No, routine use is NOT recommended
Especially in patients with depressed left ventricular function.
What is amiodarone often chosen for?
To treat symptomatic ventricular tachycardia
It may reduce the incidence of arrhythmic death post-MI but has no effect on total mortality.
What is the role of calcium channel blockers in post-acute coronary syndrome?
Used as antianginal agents if beta blocker therapy is contraindicated
There is no evidence of preventing a secondary event.
Should oestrogens be used for coronary heart disease prevention?
No, should not be used for primary or secondary prevention
This is based on current guidelines.
Is there evidence to recommend antioxidants for coronary heart disease prevention?
No large scale trial to recommend antioxidants for prevention or treatment
Vitamins A, C, E, and beta-carotene fall into this category.
What is the mechanism of action of Aspirin?
Aspirin irreversibly inactivates COX-1 in platelets, reducing thromboxane A2 formation and platelet aggregation.
What is the net effect of Aspirin on platelet aggregation?
The net effect is zero due to the irreversible inactivation of COX-1 in endothelium, which increases platelet aggregation.
What is the difference between low and high doses of Aspirin?
Lower doses inhibit platelets, while higher doses inhibit both platelets and endothelial function.
What do Clopidogrel and Prasugrel inhibit?
They inhibit ADP-induced platelet aggregation by antagonizing the P2Y12 receptor.
What type of drugs are Clopidogrel and Prasugrel?
Pro-drugs.
What is a potential risk when combining Clopidogrel with certain PPIs?
Increased risk of bleeding; the combination should be discouraged unless essential.
What is the primary action of Nitric Oxide (NO) in the cardiovascular system?
NO primarily relaxes vascular smooth muscle (vasodilation) and inhibits platelet aggregation.
How do organic nitrates work?
They mimic the actions of endogenous NO by releasing NO or forming NO within tissues.
What are the side effects associated with organic nitrates?
Tolerance, headache, and postural hypotension.
How is Glyceryl Trinitrate (Nitroglycerin) administered?
It is absorbed buccally (under the tongue) for rapid effects.
What is the main effect of beta-adrenoceptor antagonists?
They block the binding of norepinephrine and epinephrine to beta-adrenoceptors, reducing heart rate, contractility, and arterial pressure.
What are the predictable unwanted effects of beta-blockers?
Bronchoconstriction, cardiac failure, bradycardia, and fatigue.
What do calcium channel blockers (CCBs) block?
They block cellular calcium entry through L-type channels.
Name the pharmacological effects of calcium channel blockers.
Reduced myocardial contractility, depressed electrical impulse propagation, and diminished vascular tone.
What is the effect of Verapamil?
It predominantly affects the heart, reducing cardiac output and heart rate.
What is the primary use of ACE inhibitors?
Heart failure and hypertension management.
What do ACE inhibitors do?
They inhibit the conversion of angiotensin I to angiotensin II, reducing vascular resistance.
What are the safety concerns associated with ACE inhibitors?
Hypotension, dry cough, renal artery stenosis, and hyperkalaemia.
What is the role of diuretics in heart failure management?
They increase urine output by promoting diuresis and relieve pulmonary and peripheral oedema.
List the different classes of diuretics.
- Thiazide
- Loop
- Potassium-sparing and aldosterone antagonists.
What effect do diuretics have on preload?
They reduce preload.
What is the effect of beta-blockers on the sympathetic nervous system in heart failure?
They reduce receptor down-regulation and attenuate catecholamine toxicity.
What is the paradoxical use of beta-blockers in heart failure?
They are used despite increased sympathetic nervous system activity and receptor down-regulation.
What do potassium-sparing and aldosterone antagonists reduce?
Pre-load and vascular volume
They also enhance Na+ excretion and may reduce afterload, improving ventricular ejection.
What is the mainstay of therapy among diuretics?
Loop diuretics
They are potent and act on the thick ascending loop of Henle.
What do loop diuretics inhibit?
Sodium-potassium-chloride cotransporter
This occurs in the thick ascending loop of Henle where ~25% of glomerular sodium is reabsorbed.
What do thiazide diuretics inhibit?
Sodium-chloride transporter
This occurs in the distal tubule, where only 10% of sodium is reabsorbed.
What electrolyte imbalance is associated with thiazides and loop diuretics?
Hypokalaemia
It is dose-dependent and can increase the chance of serious cardiac arrhythmias.
How can hypokalaemia be minimized?
By consuming vegetables (bananas) and potassium-sparing diuretics, e.g., Spironolactone
Supplements may also help.
Name a type of alpha blocker that is an α1 selective antagonist.
Prazosin, doxazosin, terazosin
Longer-acting agents like doxazosin and terazosin cause less tachycardia than non-selective α antagonists.
What effect do α1 selective antagonists have on lipid levels?
Decrease in LDL and increase in HDL
They are best to preserve erectile function.
What is the fourth class of RAS drugs?
Renin inhibitors
Aliskiren is a notable example, binding to the active site of Renin.
What is a unique characteristic of renin inhibitors like Aliskiren?
Only works in primates
Development difficulties limit its use in other species.
What side effects are associated with renin inhibitors?
Fatigue, headache, dizziness, diarrhea, nasopharyngitis, and back pain
They increase plasma renin concentration but not activity.
What is unknown regarding the effects of renin inhibitors?
Effects on renal function and potassium
Limited post-marketing observational data exists.
What are lipids?
Natural organic compounds that are derivatives of fatty acids and are hydrophobic
Found in all cells and contribute to cell function and structure.
Classify lipids into their types.
- Natural oils
- Fats and waxes
- Sterols (cholesterol) and steroids
What are fatty acids?
Carboxylic acids with a long aliphatic saturated or unsaturated chain
What is the formula for lauric acid?
CH3(CH2)10CO2H
What is the melting point of stearic acid?
69 ºC
What is hydrogenation of fats?
The forced addition of hydrogen into omega-6 polyunsaturated oils to solidify them at room temperatures
True or False: Hydrogenated fats are easier for the body to metabolize than natural fats.
False
What are the three forms of natural food fats?
- Saturated (butter, coconut oil)
- Monounsaturated (olive, canola oils)
- Polyunsaturated (sunflower omega-6, fish omega-3)
What is the importance of lipids in diets?
Source of energy and essential fat-soluble vitamins
List some general characteristics of lipids.
- Insoluble in water (hydrophobic)
- Soluble in non-polar solvents
- High energy content
- Produce geometric isomerism
What are the functions of lipids?
- Energy reserves
- Structure of cell membranes
- Regulate membrane permeability
- Hormone synthesis
Name examples of fatty acids.
- Oleic acid
- Linoleic acid
- Palmitoleic acid
- Arachidonic acid
What is cholesterol and where is it synthesized?
A steroid alcohol synthesized in the liver
What percentage of cholesterol is synthesized in the liver?
80%
What is the dietary recommendation for cholesterol intake?
<300 mg/d
What is the main precursor for cholesterol synthesis?
Hydroxymethylglutaryl-coenzyme A (HMG-CoA)
How does HDL cholesterol function in the body?
Picks up cholesterol accumulated in blood and transports it to the liver
What are triglycerides?
Dietary fats found in meats, dairy products, and cooking oils
What are chylomicrons?
The least dense lipoproteins that transport dietary fats from the intestine to tissues
What does LDL stand for and what is its role?
Low-density lipoprotein that takes cholesterol into cells and is correlated with heart disease
Fill in the blank: The fats we eat are dissolved by ______ in the intestine.
bile salts
What are the three types of lipoproteins mentioned?
- Chylomicrons
- VLDL (very low-density lipoprotein)
- LDL (low-density lipoprotein)
What is the average total body cholesterol?
150 g
What happens to 50% of cholesterol in the liver?
Converted to bile acids
What is saponification?
The hydrolysis of fats by alkali to form soaps
What is the role of essential fatty acids like linoleic and linolenic acids?
Precursors of important metabolites such as prostaglandins
What is VLDL?
Very low-density lipoprotein, transports fats from liver to tissues.
What does LDL stand for and its primary function?
Low-density lipoprotein, takes cholesterol into cells, correlated with heart disease.
What is the role of HDL?
High-density lipoprotein, picks up cholesterol from blood and peripheral tissues to deliver it to the liver for excretion.
What do chylomicrons and VLDL carry?
Triacylglycerols.
What do LDL and HDL carry?
Cholesterol.
What are the normal ranges for total cholesterol, LDL, and HDL?
Total cholesterol: <200 mg/dl, LDL: <130 mg/dl, HDL: >35 mg/dl.
Name the three main pathways for lipoprotein metabolism.
- Exogenous pathway: food lipids
- Endogenous pathway: lipids synthesized in the liver
- Reverse cholesterol transport: return of cholesterol from different tissues to liver.
What happens to dietary lipids in the small intestine?
They are packaged into chylomicrons that contain high TG, low cholesterol.
What causes elevated chylomicron concentration in hyperlipidemia?
Lipoprotein lipase deficiency.
How are lipoprotein disorders classified?
Primary: disorders not related to underlying disease; Secondary: disorders related to other diseases.
What is Familial hypercholesterolemia (FH)?
Results from over 500 different mutations of the LDL receptor gene.
What is the Fredrickson classification?
The most accepted classification for primary hyperlipidaemias.
What types are very common in Fredrickson classification?
- Type IIa
- Type IIb
- Type IV
What lipids are stored in adipocytes?
- Cholesterol
- Cholesteryl esters
- Triglycerides
What are some examples of lipid disorders?
- Acid lipase disease
- Fabry disease
- Gangliosidosis
- GM2 gangliosidoses
- Krabbe disease
- Lysosomal acid lipase deficiency
- Neuronal ceroid lipofuscinosis disease
- SMPD1-associated
- Niemann–Pick disease, type C
- Pelizaeus–Merzbacher disease
- Sandhoff disease
- Sulfatidosis
What are clinical symptoms of hyperlipidaemia?
Accumulation of lipid in tissues causing cell damage.
List some risks associated with hyperlipidemia.
- Heart disease
- Obesity
- Diabetes
- Kidney disease
- Fatty liver
- High blood pressure
- Thyroid disease
- Atherosclerosis
What are familial lipid disorders?
Rare disorders that run in families, causing very high levels of cholesterol.
What is the primary cause of familial hypercholesterolemia?
Defect of an LDL receptor (mutation) reducing cellular uptake of LDL by the liver.
What is primary hyperlipidemia?
Genetic (familial) disorder.
What is secondary hyperlipidemia?
Has different underlying causes such as diabetes and insulin resistance.
What is hypertriglyceridemia usually secondary to?
Another condition like obesity, excessive carbohydrate intake, alcohol, drugs, and acute pancreatitis.
What should patients do before lipid disorder analysis?
Fast for 12 hours and follow a ‘normal’ diet two weeks before tests.
What is the role of statins in cholesterol management?
Inhibit HMG-CoA reductase, controlling cholesterol production in the liver.
Name some statins used for hyperlipidemia.
- Pravastatin
- Simvastatin
- Atorvastatin
What do fibrates do?
Increase the synthesis of lipoprotein lipase, enhancing peripheral catabolism of VLDL and TGs.
What do bile acid sequestrants do?
Combine with bile acids in the intestine and reduce hepatic absorption of bile salts.
What is the consequence of elevated LDL?
Increased risk of cardiovascular disease.
Fill in the blank: Familial hypercholesterolemia is caused by a defect in the _______.
LDL receptor.
True or False: Homozygous familial hypercholesterolemia is rare.
True.
What are bile acid resins used for?
They are used to lower cholesterol levels.
What factors are associated with low HDL?
- Diabetes
- Smoking
- Menopause
- Obesity
- Male puberty
How do statins lower cholesterol?
By inhibiting the liver enzyme HMG-CoA reductase.
What is atherosclerosis?
A multifocal, immuno-inflammatory disease where plaque builds up in artery walls.
What are the components of atherosclerotic plaque?
- Fat
- Cholesterol
- Calcium
- Cellular waste products
- Fibrin
What are the treatment options for atherosclerosis?
- Surgery to remove plaques
- Stents to keep arteries open
- Medication and lifestyle changes
What are the worst consequences of atherosclerosis?
- Heart attack
- Stroke
What medications are used to lower cholesterol?
- Statins
- Niacin
- Fibrates (gemfibrozil, fenofibrate)
- Cholesterol-absorption inhibitors (Zetia)
What are the risk factors for hyperlipidemia?
- Genetic factors
- Age
- High saturated fat diets
- Smoking
- Alcohol intake
How does smoking affect HDL levels?
It lowers the HDL levels in the blood.
What lifestyle changes can help manage hyperlipidemia?
- Healthy diet with less than 30% calories from fat
- Limit high cholesterol meats
- Use low-fat dairy products
- Regular exercise
What is the recommended fat intake to prevent fatty acid deficiency?
Fats should provide 20-30% of total calories.
What are some symptoms of fatty acid deficiency syndromes?
- Dermatitis (dry, scaly skin)
- Hand tremors
- Inability to control blood pressure
True or False: Drug therapy is unnecessary for lowering cholesterol levels.
False
Fill in the blank: Atherosclerosis causes hardness and loss of _______ in artery walls.
elasticity
What medical conditions can raise cholesterol levels?
- Overweight and obesity
- Diabetes mellitus
- Metabolic syndrome
- Liver disease
- Kidney disease
What is the definition of dysrhythmia?
Abnormality of the cardiac rhythm usually caused by an impairment in impulse generation or conduction.
Dysrhythmia is the more accurate term to use as ‘Arrhythmia’ implies an absence of a rhythm.
How can dysrhythmias be classified by speed?
- Bradycardia (<60 bpm)
- Tachycardia (100-150 bpm)
- Flutter (150-350 bpm)
- Fibrillation (>350 bpm)
Tachydysrhythmias respond best to drug treatments.
What are the three main mechanisms that cause dysrhythmias?
- Inappropriate automaticity
- Triggered activity
- Re-entry mechanisms
These mechanisms can lead to various types of dysrhythmias.
What is inappropriate automaticity?
The ability of cells to spontaneously generate intermittent action potentials, which normally only occurs in specialized cells like those of the SA node.
Atrial or ventricular cells do not normally have this ability.
What can cause inappropriate automaticity?
- Ischaemia
- Electrolyte disturbances (especially hypokalemia)
These factors reduce the cell’s ability to control electrolyte flux across the cell membrane.
What occurs during triggered activity?
An impulse is generated during or just after repolarization due to a depolarizing oscillation of the membrane potential.
Early afterdepolarizations (EADs) and delayed afterdepolarizations (DADs) are examples of triggered activity.
What is the significance of reentry mechanisms in dysrhythmias?
They are a major cause of most tachydysrhythmias, including atrial and ventricular tachycardia, flutter, and fibrillation.
Reentry problems occur when electrical conduction in a portion of the heart is abnormally slowed.
What are the three main categories of dysrhythmias?
- Abnormal rates of sinus rhythm
- Abnormal/ectopic site of impulse initiation
- Disturbances of the conduction pathways
These categories help in the understanding and treatment of dysrhythmias.
What characterizes sinus tachycardia?
An abnormally fast heart rate >100 bpm, often a compensatory response to increased demand for cardiac output.
It can be caused by sympathetic activation, decreased parasympathetic activity, fever, and other factors.
What is sinus bradycardia?
Heart rate <60 bpm, often well tolerated in some individuals and may not require treatment unless it causes symptoms.
It can result from increased parasympathetic activity or certain medications.
What is sinus arrest?
Absence of impulse initiation resulting in flat ECG and zero cardiac output.
Common causes include myocardial infarction and electrolyte disturbances.
What are premature atrial complexes?
Extra heartbeats originating in the atria, often leading to atrial flutter or fibrillation.
Atrial flutter manifests at a rapid atrial rate of 240-350 bpm.
What is atrial fibrillation?
Completely disorganized and irregular atrial rhythm accompanied by irregular ventricular rhythm of variable rate.
It can lead to stagnation of blood in the atria and increased risk of thrombus formation.
What defines ventricular tachycardia (VT)?
Consists of 3 or more consecutive ventricular complexes at a rate of more than 100/min, often indicative of serious cardiac disease.
VT is a serious dysrhythmia that can compromise cardiac output.
What is ventricular fibrillation (VF)?
A rapid uncoordinated cardiac rhythm resulting in ventricular quivering and lack of effective contraction.
VF must be rapidly identified and treated with CPR and defibrillation.
What is Ventricular Fibrillation (VF)?
A rapid uncoordinated cardiac rhythm that results in ventricular quivering and lack of effective contraction.
ECG is rapid and erratic with no identifiable QRS complexes.
How must Ventricular Fibrillation be treated?
Rapidly identified and treated with CPR and defibrillation, followed by administration of antiarrhythmic drugs.
What is AV block?
A disturbance in conduction between the sinus impulse and its associated ventricular response, which may be abnormally slowed or completely blocked.
What are the three categories of AV block?
- 1st degree heart block
- 2nd degree heart block
- 3rd degree heart block
How is 1st degree heart block identified?
By a prolonged PR interval; rhythm is regular and each P wave is associated with a QRS complex.
What causes 1st degree heart block?
Often caused by drugs, myocardial ischaemia, and congenital heart defects.
What characterizes 2nd degree heart block?
Diagnosed when some AV impulses are not conducted to the ventricles.
What are the types of 2nd degree heart block?
- Mobitz type I (Wenckebach)
- Mobitz type II
What is Mobitz type I characterized by?
Progressive lengthening of the PR interval until one P wave is not conducted (dropped beat).
What is Mobitz type II characterized by?
Presence of nonconducted P waves (dropped beats) with a consistent PR interval.
What is 3rd degree heart block?
Pathologic lesion of the AV node, bundle of His, or bundle branches where no impulses are conducted from the atria to the ventricles.
What is bundle branch block (BBB)?
Abnormal conduction through the intraventricular bundle branches.
What are the factors that can prolong the QT interval?
- Genetics
- Electrolyte disturbances (↓K, ↓Mg, ↓Ca)
- ↑age
- Female gender
- Testosterone suppression
- Bradycardia
- CHF, CHD
- Drugs (e.g., Amiodarone, disopyramide)
What can result from prolonged QT interval?
Can predispose patients to Torsades de pointes, a potentially fatal ventricular arrhythmia.
What is Torsades de pointes?
A polymorphic ventricular tachycardia that is usually self-limiting but can recur if the underlying cause is not corrected.
What is Atrial Fibrillation (AF)?
Causes an irregular and often abnormally fast heart rate.
What are common causes of Atrial Fibrillation?
- Other heart conditions (e.g., hypertension, pericarditis)
- Other medical conditions (e.g., overactive thyroid gland, type 2 diabetes)
- Can occur without other conditions (lone atrial fibrillation)
What is the estimated overall population prevalence of AF in England?
2.5%.
How does AF affect stroke risk?
Increases the risk of stroke by 5-fold when compared with people without AF.
How is AF classified according to the pattern of episodes?
- Paroxysmal AF
- Persistent AF
- Permanent AF
What is the diagnosis process for AF?
Suspect AF in people with an irregular pulse and symptoms like palpitations, chest discomfort, breathlessness, syncope, or dizziness.
What is a major problem with antiarrhythmic agents?
Many antiarrhythmics may be pro-arrhythmic, potentially exacerbating rhythm problems or causing new arrhythmias.
What are common adverse effects of antiarrhythmic drugs?
- GI disturbances (diarrhoea, nausea, vomiting)
- Hypotension
- Heart failure
- CNS effects (tremors, headache, depression, hallucinations)
- Visual disturbances
- Hypersensitivity reactions
What non-drug therapies are used to treat arrhythmias?
- Radiofrequency ablation
- Direct current cardioversion
- Defibrillation
- Pacemakers
What is tachycardia?
A condition characterized by an abnormally fast heart rate.
Torsades de pointes can occur with drugs that prolong cardiac repolarization, such as Sotalol and amiodarone.
What are some non-drug therapies used to treat arrhythmias?
- Radiofrequency ablation
- Direct current cardioversion
- Defibrillation
- Pacemakers
- Internal cardioversion defibrillators (ICDs)
What is the overall aim of Antiarrhythmic Drug Therapy?
To control the frequency and severity of arrhythmias and maintain Sinus Rhythm (SR) as much as possible.
What is the ultimate goal of antiarrhythmic therapy?
- Restore normal SR and conduction
- Prevent more serious and potentially lethal arrhythmias from occurring
How do antiarrhythmics function?
- Decrease conduction velocity
- Change the duration of the effective refractory period (ERP)
- Suppress abnormal automaticity
Name some commonly used antiarrhythmic drugs.
- Flecainide
- Isoprenaline
- Lignocaine
- Sotalol
- Verapamil
- Adenosine
- Amiodarone
- Atropine
- Digoxin
- Disopyramide
- Esmolol
How can antiarrhythmic drugs be classified clinically?
- Act on supraventricular arrhythmias (e.g., verapamil hydrochloride)
- Act on both supraventricular and ventricular arrhythmias (e.g., amiodarone hydrochloride)
- Act on ventricular arrhythmias (e.g., lidocaine hydrochloride)
What is the Vaughan Williams classification used for?
To classify antiarrhythmic drugs based on their effects on cardiac electrophysiology.
What are Class I agents in the Vaughan Williams classification?
Agents that block fast Na channels and delay the rise in phase 0 of the action potential, further divided into three subgroups: * Class Ia (Disopyramide) * Class Ib (Lidocaine) * Class Ic (Flecainide)
What are Class II agents in the Vaughan Williams classification?
Beta-blockers that inhibit the effects of the sympathetic nervous system by blocking beta-adrenoceptors.
What is a common side effect of Class III agents?
Prolongation of the effective refractory period by prolonging the action potential duration.
What are the side effects of Disopyramide?
- Negative inotropic effects
- Anticholinergic effects (dry mouth, blurred vision, constipation)
- Severe arrhythmias
- Prolonged QT interval
- Exacerbation of heart failure
- Proarrhythmic effects
What is the mechanism of action (MOA) of Lidocaine?
Acts primarily on the Na channel, shortens phase 3 repolarization, and suppresses arrhythmias caused by abnormal automaticity.
What is a significant side effect of Flecainide?
Severe potential for proarrhythmic effect, especially in people with poor left ventricular function.
What are the main uses of Beta Blockers in arrhythmia treatment?
- Treatment of increased sympathetic-induced arrhythmias (stress and exercise-induced)
- Treatment of AF and flutter
- AV nodal tachycardia
What is the main action of Esmolol?
Ultra-short-acting beta1 selective beta-blocker used for short-term control of ventricular rate in AF/flutter.
What are the adverse effects of Amiodarone?
- Pulmonary fibrosis
- Photosensitivity reactions
- Hyper/hypothyroidism
- Elevated transaminases and liver toxicity
- Peripheral neuropathy
- Corneal microdeposits
- Skin pigmentation (Grey Man Syndrome)
What drug interactions are associated with Amiodarone?
- Inhibits CYP2C9 and CYP2D6, increasing concentrations of drugs metabolized by these enzymes
- Can cause bradyarrhythmias when administered with other agents that slow cardiac conduction
What is the mechanism of action of calcium channel blockers?
Block the movement of Ca ions during phase 2 of the action potential.
What effect do Class IV agents have on digoxin levels?
They can increase digoxin levels and increase risk of digoxin toxicity.
If using together, halve the digoxin dose and monitor for bradyarrhythmias and ECG changes.
What are the non-dihydropyridine calcium channel blockers mentioned?
Verapamil and Diltiazem.
These are used in the management of SVTs, AF, and atrial flutter.
What is digoxin used for?
Control of heart problems such as arrhythmias including AF and management of heart failure symptoms.
Usually used with other medicines.
What are the main effects of digoxin on the heart?
- Increased contractile force (positive inotrope)
- Decreased conduction through the AV node (negative dromotrope)
- Decreased Heart Rate (negative chronotrope)
- Disturbance of cardiac rhythm
What is the bioavailability of digoxin from tablets?
60-80% bioavailability.
From liquid, it is 70-85%.
What is the half-life (T1/2) of digoxin in patients with normal renal function?
20-50 hours.
Much longer in renal impairment.
What is a major precaution when using digoxin?
Renal impairment can decrease elimination.
Other considerations include hypothyroidism, hyperthyroidism, electrolyte abnormalities, and elderly patients.
What are common adverse effects of digoxin?
- Anorexia
- Nausea
- Vomiting
- Diarrhoea
- Blurred vision
- Visual disturbances
What ECG changes may indicate digoxin toxicity?
- Prolonged PR interval
- ST depression
- T wave inversion
What is the therapeutic range for digoxin?
0.5-2 mcg/L.
Toxic effects can occur even within this range.
What is the management for severe digoxin toxicity?
Use digoxin-specific immune antigen binding fragment (Fab) known as Digibind.
Dose reductions or withdrawal may also be necessary.
What is adenosine used for?
Effective in acute treatment and for terminating supraventricular tachycardia (SVT).
What is the mechanism of action (MOA) of adenosine?
Depresses SA node activity and slows conduction through the AV node.
What are some non-pharmacological therapies for arrhythmias?
- Radiofrequency ablation
- Direct current cardioversion
- Defibrillation
- Pacemakers
- Internal cardioversion defibrillators (ICDs)
True or False: Digoxin has a wide therapeutic index.
False.
Digoxin has a very narrow therapeutic index.
Fill in the blank: The half-life of digoxin is ______ in patients with renal impairment.
[much longer]
What is the overall prevalence of atrial fibrillation (AF) in the UK?
1.6%
It may be higher, approximately 3%, in other countries.
What major health issues are linked to atrial fibrillation (AF)?
- Mortality
- Morbidity from heart failure
- Stroke
- Thromboembolism
What impact does atrial fibrillation (AF) have on the NHS annually?
Costs over £2.2 billion each year
What are the potential complications of impaired cardiac performance due to AF?
- Myocardial ischaemia
- Tachycardia-induced cardiomyopathy
- Hypotension
- Heart failure
How does atrial fibrillation (AF) increase the risk of thrombotic stroke?
Stasis of blood in the atria leading to the formation of clots
What is the CHA2DS2-VASc score used for?
To assess stroke risk in people with AF
What is the ORBIT score used for?
To assess the risk of bleeding when considering anticoagulation in people with AF
What are the recommended anticoagulants for patients with valvular AF?
Warfarin
What anticoagulants are recommended for patients with non-valvular AF?
Assess stroke risk using the CHA2DS2-VASc scoring system
What is the significance of a CHA2DS2-VASc score of 2 or more?
Offer anticoagulants
What should be considered for a CHA2DS2-VASc score of 1 in men?
Consider anticoagulants
What is the risk of stroke in patients with non-valvular AF compared to a matched population?
5x more likely
What is the risk of stroke in patients with valvular AF compared to a matched population?
17x more likely
What are the newer anticoagulants available for AF management?
- Dabigatran
- Rivaroxaban
- Edoxaban
- Apixaban
What is the effectiveness of low-dose dabigatran compared to warfarin?
As effective as warfarin with low risk of bleeding
What is the stroke risk reduction percentage in patients with non-valvular AF taking warfarin?
50-80%
What is the risk factor for bleeding associated with high blood pressure?
Hypertension (SBP > 160 mmHg)
What are some modifiable risk factors for bleeding in AF patients?
- Hypertension
- Anaemia
- Labile INR
What is the maximum score for the CHA2DS2-VASc risk assessment?
9
What does a CHA2DS2-VASc score of 0 indicate?
No anticoagulants
What is the risk of major bleeding associated with warfarin therapy?
About 1% of patients per year
What is the recommended management for patients with AF requiring anticoagulation?
Identify and correct reversible bleeding factors
What does the ORBIT score assess?
Patient’s risk of bleeding
What factors contribute to the ORBIT score?
- Haemoglobin levels
- Age
- Bleeding history
- GFR
What are the clinical implications of using warfarin compared to newer anticoagulants?
Both are effective options for stroke prevention in AF
What should be the basis for selecting an anticoagulant for an individual patient?
Shared decision-making considering patient-specific factors
What are patient-specific factors in medication management?
Patient preference, Tolerability, Potential for DIs, Likely compliance/adherence to medication and monitoring requirements, Concomitant medications, Monitoring Requirements.
What are the advantages of Warfarin?
- Gold standard therapy for >50yrs
- Long half-life
- Cheap, effective antidote available (Vit K)
- Prescribers familiar with its management and DIs
- Potentially better compliance due to once daily dosing
- Well established guidelines for reversal in emergencies.
What are the disadvantages of Warfarin?
- Narrow therapeutic index
- Unpredictable therapeutic response
- Multiple drug-drug and drug-food interactions
- Slow onset and offset of action; transient procoagulant effect on initiation
- Frequent INR monitoring required
- Dietary restrictions
- Bridging therapy required on initiation and temporary cessation.
What are the advantages of DOACs?
- Specific coagulation enzyme target
- Rapid onset of action
- Predictable therapeutic response
- Fixed dosing
- Fewer drug-drug or drug-food interactions
- As effective as warfarin with lower intracranial haemorrhage risk
- Less likelihood of uncommon warfarin-related side effects
- No need for bridging
- Regular coagulation monitoring is not required
- No dietary restrictions.
What are the disadvantages of DOACs?
- Shorter half-life
- Accumulation in renal impairment
- No evidence for efficacy (and some evidence for harm) in patients with valvular AF
- No reliable anticoagulation monitoring available
- New drug interactions – CYP450, P-glycoprotein inhibitors/inducers
- Lack of long-term safety data and signals for new unexpected side effects
- No commercially available antidote for factor Xa inhibitors; expensive reversal agent for dabigatran (idarucizumab)
- Higher drug costs to the government
- Twice daily dosing (Dabigatran and apixaban) less forgiving to non-adherence, potentially increasing thromboembolic risk
- Monitoring of renal function and dosage adjustment in renal impairment is required.
- Contraindicated in severe renal impairment
- Not indicated in patients with valvular AF.
- Risk of non-detection of suboptimal patient adherence
- Inability to titrate doses
- Cannot easily assess the degree of anticoagulation
- Lack of prescriber awareness, risking bleeding or thromboembolic events due to unknown potential for long-term side effects.
- Reversal of anticoagulation more complicated in patients with bleeding or requiring emergency surgery.
What is the recommended approach for managing atrial fibrillation when DOACs are not tolerated?
Warfarin is used when DOACs are not tolerated, not suitable, or contraindicated.
What is CHA2DS2-VASc used for?
Estimating stroke risk in patients with atrial fibrillation.
What does a CHA2DS2-VASc score of 2 or greater indicate?
Anticoagulant therapy is recommended.
What does a CHA2DS2-VASc score of 1 indicate for men and women?
Men - Consider OAC; Women - No OAC.
What are the two treatment considerations for atrial fibrillation?
- Prophylaxis against thromboembolism
- Treatment of the arrhythmia.
What is the first-line drug class for rate control in atrial fibrillation?
Beta blockers.
What are the two strategies for managing atrial fibrillation?
- Rate Control
- Rhythm Control.
What should be assessed for thromboembolic risk in a patient with atrial fibrillation?
CHA2DS2-VASc score.
What is the maximum score for CHA2DS2-VASc?
9.
Fill in the blank: Women with a CHA2DS2-VASc score of 0 should receive _______.
No anticoagulant.
Fill in the blank: Patients with clear contraindications to OACs may be considered for _______.
LAA occluding devices.
What are the common signs and symptoms experienced by patients with atrial fibrillation?
Palpitations, breathlessness, dizziness.
What is the clinical implication of having moderate or severe mitral stenosis?
Increased stroke risk and need for anticoagulation.
What are the normal lab results for patients with atrial fibrillation on admission?
FBC, LFTs, U&Es, and renal function normal.
Fill in the blank: The duration of action for many anticoagulant agents is _______.
Variable.
What counseling should a patient discharged on a beta blocker and an anticoagulant receive?
Information on medication adherence, potential side effects, and monitoring.
What is Ischaemic Heart Disease (IHD)?
A condition also known as Coronary Heart Disease (CHD) or Coronary Artery Disease (CAD), characterized by reduced blood supply to the heart muscle.
What are the learning objectives related to IHD?
- Explain causes and pathophysiology related to IHD
- Discuss risk factors and preventive measures for IHD
- Distinguish between different types of IHD
- Discuss pharmacological and non-pharmacological management of IHD
What is the spectrum of disorders in IHD?
Ranges from Chronic Stable Angina to Unstable Angina and Acute Coronary Syndromes (ACS), including Myocardial Infarction (MI), STEMI, and NSTEMI.
What causes myocardial ischaemia?
An imbalance between supply and demand of oxygen and nutrients to the myocardium.
What is the definition of ischaemia?
A deficiency of oxygen and nutrients in the tissues due to inadequate blood supply.
How does ischaemia differ from hypoxia and hypoxemia?
- Hypoxia: Low oxygen levels in tissues
- Hypoxemia: Lack of oxygenation in the blood
- Ischaemia: Deficiency of oxygen and nutrients due to reduced blood flow
What is a major cause of Coronary Heart Disease?
Atherosclerosis, which involves progressive narrowing of the arterial lumen.
What are the less common causes of cardiac ischaemia?
- Abnormalities of blood O2 content (e.g., respiratory failure)
- Poor perfusion pressure through coronary arteries (e.g., hypotension, hypovolaemia)
- Issues with microcirculation
What are some non-modifiable risk factors for atherosclerosis?
- Age (>45 years for men, >55 years for women)
- Gender (male)
- Family history of premature CHD
What are target lipid levels for patients with increased cardiovascular risk?
- Total cholesterol <4.0mmol/L
- LDL cholesterol: target levels vary
- HDL cholesterol >1.0mmol/L
- Triglycerides <2.0mmol/L
What are some common modifiable risk factors for atherosclerosis?
- Hypertension
- Cigarette smoking
- Diabetes
- Obesity
- Physical inactivity
- Poor diet (atherogenic)
Which lipoprotein is associated with the highest risk of atherosclerosis?
Low-density lipoprotein (LDL) is high in cholesterol and has the highest risk.
What is the role of high-density lipoprotein (HDL) in atherosclerosis?
Decreases risk of atherosclerosis by transporting cholesterol from peripheral tissues back to the liver.
What are the atherogenic effects of nicotine?
- Augments conversion of LDL to oxidized LDL
- Decreases HDL levels
- Enhances platelet adhesiveness
What is the first step in atherosclerotic plaque formation?
Chronic endothelial injury that creates a point of entry for LDL.
What occurs during step 2 of atherosclerotic plaque formation?
Endothelial dysfunction leads to increased permeability and recruitment of leukocytes.
What happens in step 3 of atherosclerotic plaque formation?
Macrophages and foam cells release inflammatory mediators, leading to smooth muscle proliferation and lipid core formation.
What is a significant reduction in blood flow associated with atherosclerotic plaque?
Occurs when the plaque occupies 75% or more of the lumen.
What is thrombus formation?
The process of blood clotting that can occur in blood vessels.
How do atherosclerotic plaques form?
Atherosclerotic plaques increase in size gradually over years and progressively occlude the lumen of the blood vessel.
What blood flow reduction occurs with atherosclerotic plaques?
Significant reduction in blood flow can occur when the plaque occupies 75% or more of the lumen.
Where can clinically significant atherosclerotic plaques be located?
Anywhere within the 3 major coronary arteries or major secondary branches.
What is ‘triple vessel disease’?
A condition affecting the right coronary artery, left anterior descending coronary artery, and left circumflex coronary artery.
Are the extent and severity of atherosclerotic diseases good predictors of ischaemia severity?
No, they are often not good predictors of the severity of the resulting ischaemia.
What characterizes stable plaques?
They are usually asymptomatic or associated with exercise-induced angina (stable angina pectoris).
What can unstable plaques lead to?
Thrombus formation or total occlusion of the blood vessel.
What are risk factors for increased plaque instability?
Active inflammation in the plaque, large lipid core with a thin cap, endothelial denudation, fissured or ruptured cap, severe stenosis.
What is ischaemia of cardiac cells?
Occurs when the O2 supply fails to meet the metabolic demand.
Why do myocardial cells require a continuous supply of O2?
They are unable to store much energy in the form of ATP.
What are critical factors that decrease myocardial O2 supply or increase demand?
Rate of coronary perfusion (reduced) and myocardial workload (increased).
What can impair coronary perfusion?
Large, stable atherosclerotic plaque, acute platelet aggregation, thrombosis, vasospasm, failure of autoregulation.
What can increase myocardial workload?
Heart rate, preload, afterload, contractility.
What is acute coronary syndrome (ACS)?
Occurs when sudden obstruction of coronary blood flow results in acute myocardial ischaemia.
What typically leads to acute coronary syndrome?
Rupture of a vulnerable atherosclerotic plaque.
What are the common symptoms of chronic stable angina?
Retrosternal heaviness, pressure or pain, with or without radiation to the arms, neck, or jaw.
How is chronic stable angina triggered?
By activities that increase myocardial O2 demand, such as exercise or emotional stress.
What distinguishes unstable angina from chronic stable angina?
Unstable angina is characterized by sudden worsening of angina symptoms.
What is Prinzmetal angina?
A form of unstable angina due to coronary vasospasm, resulting in spontaneous attacks of angina at rest.
What are the treatment goals for chronic stable angina?
Limit angina attacks, protect against future ischaemic syndromes, reduce risk of atherosclerotic progression.
What is the average number of angina attacks in chronic stable angina?
About 2 per week.
What is the typical duration for relief from angina discomfort?
Relieved by rest within 1-5 minutes.
What are the three main treatment aims for chronic stable angina?
Symptomatic treatment, prevent future ischaemic events, reduce atherosclerotic progression.
What is the primary goal of reducing the frequency of administration of acute therapy?
To manage cardiovascular risk factors effectively
This includes lifestyle modifications such as diet and exercise.
What are the aims of medical treatment in managing cardiovascular issues?
To reduce cardiovascular morbidity and mortality
This includes identifying and treating cardiovascular risk factors.
What are the pharmacological treatment aims?
To reduce preload, augment coronary circulation, decrease oxygen demand, and stop active thrombus formation
This helps in preventing myocardial infarction (MI), pulmonary embolus (PE), or deep vein thrombosis (DVT).
What are the common revascularisation techniques?
- Angioplasty
- Stent Insertion
- Coronary artery bypass graft (CABG)
These techniques are used to improve blood flow to the heart.
Which drug groups are commonly used in the treatment of chronic stable angina?
- Organic nitrates
- Beta Blockers
- Calcium Channel Blockers
- Potassium Channel Activators
- Antiplatelet drugs
- Ivabradine
- Ranolazine
- Perhexilene (not used in UK)
These drugs have various mechanisms and effects on coronary circulation.
What is the mechanism of action of organic nitrates?
Nitrates are converted to nitric acid, increasing cGMP levels, leading to vasodilation
They are potent vasodilators affecting all vascular beds, primarily venous.
What is the effect of nitrates on myocardial blood flow?
Nitrates can dilate large epicardial vessels, increasing heart perfusion and reducing workload and preload
They also help in pooling blood in peripheral veins, decreasing venous return to the heart.
What is Glyceryl Trinitrate (GTN) used for?
To treat acute angina attacks
GTN can be administered sublingually for rapid action.
What is the duration of action for Isosorbide Dinitrate (ISDN)?
T1/2 = 45 minutes, with a peak time of 6 minutes
It is used for both acute treatment (sublingually) and long-term prophylaxis.
What are common adverse effects of organic nitrates?
- Headache
- Dizziness
- Reflex tachycardia
- Flushes
Most side effects are due to vasodilation in other tissues.
What is nitrate tolerance?
Reduction in efficacy of nitrate prophylaxis over time, with large inter-patient variability
It may be due to impaired conversion of nitrates to nitric oxide.
What is the best treatment for preventing nitrate tolerance?
Providing a nitrate-free period of about 8 hours
This can be achieved through once daily dosing or removing patches at night.
What should a patient do if they experience chest pain while in a nitrate-free period?
They should take their GTN
It is important to manage acute symptoms even during a nitrate-free period.
How should Glyceryl Trinitrate (GTN) be administered during an angina attack?
The patient should sit down and place 1 tablet or spray under the tongue
This helps prevent fainting if blood pressure drops.
How should transdermal GTN patches be applied?
To a clean, dry, hairless area of skin, usually on the chest
Avoid applying creams or lotions before patch application.
What precautions should be taken with GTN storage?
Keep in original glass container, well closed, below 25°C, and replace every 8 weeks after opening
GTN is volatile and should not be exposed to heat.
What should a patient do if they do not feel relief from chest pain after the first GTN dose?
Place a second tablet under the tongue and allow it to dissolve
If pain persists after two doses, seek immediate medical help.
What should be done before applying a fresh patch to the same area of skin?
Wait several days before applying a fresh patch to the same area of skin.
How should old patches be disposed of?
Dispose of the old patch carefully, out of the reach of children.
What is Isosorbide Mononitrate primarily used for?
Most UK products are SR products taken orally once daily.
What should be avoided if nitrates have been taken in the last 24 hours?
Avoid use of Sildenafil (Viagra) or similar products.
Name important examples of beta blockers.
- Atenolol
- Metoprolol
- Propranolol
What is the effect of beta blockers in exertional angina?
Reduce the severity and frequency of attacks.
What do beta blockers competitively block?
The actions of catecholamines (adrenaline, noradrenaline) upon the Beta-adrenoceptors.
List some cardiac conditions for which beta blockers are widely used.
- IHD
- Angina
- Hypertension
- Secondary prevention post-MI
- Antiarrythmic (some)
- Heart Failure (some and with provisos)
What happens when α1 adrenoceptors are stimulated?
The opposite effect will occur if α1 adrenoceptors are blocked.
What is the effect of β1 agonists?
They stimulate β1 adrenoceptors.
What do β2 agonists do?
Stimulate β2 adrenoceptors.
What is the primary mechanism of beta blockers in chronic stable angina?
Reduce left ventricular work and oxygen use.
What are the two types of beta blockers based on selectivity?
- Cardioselective
- Non-selective
What is intrinsic sympathomimetic activity (ISA) in beta blockers?
These are partial agonists that stimulate the receptor while blocking it.
Which beta blockers are examples of those with intrinsic sympathomimetic activity?
- Pindolol
- Oxprenolol
What type of beta blockers may be preferred in patients with hepatic impairment?
Water-soluble, renally eliminated beta blockers.
What effect does alpha 1 blockade provide?
Additional vasodilating properties.
What are common adverse effects of beta blockers?
- Dizziness
- Tiredness
- Bradycardia
- Bronchospasm
- Cold hands and feet
- Fatigue
- Impotence
What should not be done suddenly regarding beta blockers?
Do not suddenly stop taking beta blockers.
What is the mechanism of action of calcium channel blockers (CCBs)?
Block inward current of Ca2+ ions into cells.
What are the two main groups of calcium channel blockers?
- Dihydropyridines
- Non-Dihydropyridines
What is the main effect of dihydropyridines?
Act mainly on vascular smooth muscle.
What is a significant adverse effect of calcium channel blockers?
- Headaches
- Oedema in hands, face, and feet
- Reflex tachycardia
- Bradycardia and heart block
What does Nicorandil act as?
An ATP-dependent potassium channel activator.
What is Nicorandil?
An ATP-dependent potassium channel activator with arterial and venous vasodilatation properties.
It improves myocardial oxygen balance and decreases angina.
What is the mechanism of action of Nicorandil?
Activates potassium channels found in cardiac, smooth muscle, and skeletal muscle cells.
It also has a nitrate moiety.
What are common adverse effects of Nicorandil?
Headache, dizziness, lethargy, myalgia.
Uncommon effects include painful oral and perianal ulcers.
What is Ivabradine used for?
Improving symptoms and exercise capacity in anginal patients.
Its effect on cardiovascular outcomes and mortality is unclear.
What is the mode of action of Ivabradine?
Selective sinus node inhibitor that lowers heart rate at the SA node without negative inotropic effects.
Reduces heart rate by ~10 bpm.
What are the contraindications for Ivabradine?
HR <60 bpm, artificial pacemaker, sick sinus syndrome, 3rd degree heart block, NYHA class III & IV heart failure, hepatic impairment.
It is cautioned with grapefruit juice and CYP3A4 inhibitors.
What side effects are associated with Ivabradine?
Luminous effects, blurred vision, bradycardia, AV block, ventricular extrasystoles.
Luminous effects are common, especially in the first two months of treatment.
What is the mode of action of Ranolazine?
Improves relaxation of the myocardium and reduces left ventricular diastolic stiffness.
It is mediated through inhibition of the late inward Na+ current in cardiac cells.
What is Perhexiline used for?
Refractory angina in patients unsuitable for revascularization.
Not used in the UK but utilized in some other countries.
What is the dosing regimen for Perhexiline?
200 mg BD for 3 days, then 200 mg daily with monthly levels taken.
Maintenance is usually 100-400 mg daily.
What is the role of Low dose Aspirin in secondary prevention?
Reduces mortality in patients with unstable angina and incidence of MI.
Aspirin should be considered for all angina patients where benefits outweigh risks.
What are Thienopyridines?
Clopidogrel and Ticlopidine, which show superior efficacy in preventing ischemic events compared to aspirin.
They have less GI effects but can cause rash and diarrhea.
What is the effect of statins in secondary prevention?
Confer a relative risk reduction of 0.79 for all-cause mortality and 0.75 for cardiovascular mortality.
Statins should be offered to all patients with stable angina.
What is the aim of acute therapy for angina?
To relieve pain as soon as possible by stopping activity and administering SL GTN.
Max 3 doses in 15 mins.
What is the first line therapy for chronic stable angina?
Low dose Aspirin + Beta blocker + SL GTN.
Aspirin is replaced with Clopidogrel if the patient is allergic.
What should be done if a beta blocker is contraindicated?
Substitute with a non-dihydropyridine CCB (e.g., Diltiazem, Verapamil) and/or long-acting nitrate.
A non-dihydropyridine CCB should not be added to a beta blocker.
What should be added if a patient on a beta blocker experiences frequent angina attacks?
Add a dihydropyridine CCB (e.g., Amlodipine) and/or a long-acting nitrate.
This is because the beta blocker will counteract tachycardia caused by the dihydropyridine.
What is the general treatment regimen for CSA prophylaxis?
Low dose Aspirin + Beta blocker + GTN SL prn.
Consider statin therapy as well.
What is the second line agent if a beta blocker is contraindicated?
A nitrate
The patient should not be taking Verapamil plus Amlodipine.
What is the purpose of third line therapy in treatment regimens?
Additional agents are then added as required
Revascularisation methods are also considered.
What is revascularisation?
A procedure considered for treatment of angina that is currently used much earlier than in the past.
What does refractory angina refer to?
Angina not responding to standard drug therapy.
List the methods of revascularisation.
- PCTA
- Stenting
- CABG
What is heart failure?
An abnormality of cardiac structure or function leading to the heart’s inability to deliver oxygen at a rate commensurate with tissue requirements.
What is the 5-year mortality rate for heart failure?
About 50%.
What are the two types of dysfunction in heart failure?
- Systolic dysfunction
- Diastolic dysfunction
What is systolic dysfunction characterized by?
Reduced cardiac output and significantly reduced ejection fraction (less than 45%).
What does diastolic dysfunction often result from?
Hypertrophy and stiffening of the myocardium.
What is ‘high-output’ failure?
A condition where even increased cardiac output is insufficient to meet the body’s demands.
What does CHF stand for?
Congestive heart failure.
What are the classifications of ejection fraction in heart failure?
- Reduced ejection fraction: EF < 40%
- Mildly impaired EF: EF 40-49%
- Preserved ejection fraction: EF ≥ 50%
What are common signs of heart failure?
- Elevated jugular venous pressure
- Hepatojugular reflux
- Third heart sound
- Laterally displaced apical impulse
What are common symptoms of heart failure?
- Breathlessness
- Orthopnoea
- Fatigue
- Reduced exercise tolerance
What is the role of the renin–angiotensin–aldosterone system (RAAS) in heart failure?
It causes further myocardial injury and has detrimental effects on blood vessels and organs.
What is a compensatory mechanism in heart failure?
Increase in blood volume, heart rate, and cardiac muscle mass.
Fill in the blank: Heart failure leads to _______.
circulatory failure.
What are the four primary factors affecting cardiac performance?
- Preload
- Afterload
- Heart Rate
- Contractility
What is preload in the context of heart failure?
The filling pressure of the heart, typically increased due to blood volume and venous tone.
What is afterload?
The resistance against which the heart must pump blood.
How does heart rate impact cardiac output?
An increase in heart rate helps maintain cardiac output during heart failure.
What happens to contractility in chronic low-output heart failure?
There is a reduction in intrinsic contractility.
What is myocardial remodeling?
Dilation and slow structural changes in the stressed myocardium.
What can excessive myocardial hypertrophy lead to?
Ischemic changes, impairment of diastolic filling, and alterations in ventricular geometry.
True or False: The natriuretic peptide system has a protective function in heart failure.
True.
What is the impact of sympathetic activity in heart failure?
Increases heart rate and contractility but also increases workload and afterload.
What is the significance of cellular changes in heart failure?
They include changes in calcium handling and adrenergic receptors, leading to reduced contractility.
Fill in the blank: The systemic responses in heart failure create a pathophysiological ‘______ cycle’.
vicious.
What are fundamental causes of heart failure?
Mechanisms causing increased hemodynamic burden or reduction in oxygen delivery to the myocardium.
What are precipitating causes of heart failure?
Conditions that worsen underlying heart disease, such as fever or further narrowing of valves.
What is the fundamental cause of increased hemodynamic burden or a reduction in oxygen delivery to the myocardium?
Mechanisms (biochemical and physiologic)
These mechanisms can lead to conditions like myocardial or coronary insufficiency.
What are examples of precipitating causes of heart failure?
- Further narrowing of valves
- Fever
- Anaemia
- Infection
- Medications (chemotherapy, NSAIDs)
These causes alter homeostasis in heart failure patients.
What are the types of genetic cardiomyopathies that can cause heart failure?
- Dilated cardiomyopathy
- Arrhythmic right ventricular cardiomyopathy
- Restrictive cardiomyopathy
These genetic factors are significant in the aetiology of heart failure.
What are the classifications of heart failure according to McMurray et al.?
- Valvular heart disease
- Myocardial disease
- Endocardial disease
- Pericardial disease
- High output states
- Arrhythmia
- Conduction disorders
- Volume overload
- Congenital heart disease
These classifications help in understanding the aetiology of heart failure.
What is the NHS Stage A of heart failure?
At high risk for HF, but without structural or functional abnormality
No signs or symptoms are present at this stage.
What are the characteristics of Class I heart failure according to the NYHA classification?
No symptoms during normal activities
Patients experience no limitation of physical activity.
What is the mortality rate for patients with heart failure at 30 days post-hospitalization?
10.4%
This rate increases significantly over the following years.
What are some non-pharmacological measures for managing heart failure?
- Dietary sodium and fluid restriction
- Physical activity as appropriate
- Attention to weight gain
These measures help manage symptoms and improve quality of life.
What are the main pharmacological treatments for heart failure?
- Diuretics
- Vasodilators
- Inotropic agents
- Anticoagulants
- Beta-blockers
- Digoxin
These medications aim to limit and reverse heart failure manifestations.
What is the role of ACE inhibitors in heart failure treatment?
They block the enzyme ACE, which cleaves angiotensin I to form angiotensin II
This action leads to vasodilation and improved survival in heart failure patients.
What are the effects of angiotensin receptor blockers (ARBs) in heart failure?
- Similar effects to ACE inhibitors
- Substitute for ACE inhibitors in intolerant patients
- Do not increase bradykinin levels
ARBs provide a complete blockade of angiotensin II action.
What are the common adverse effects of vasodilators?
- Headache
- Hypotension
- Tachycardia
These side effects are important to monitor in patients receiving vasodilator therapy.
What are the first-line agents for diuretic therapy in heart failure?
- Loop diuretics (furosemide, bumetanide, torsemide)
Choice of agent may depend on individual pharmacokinetics.
What is the function of inotropic agents in heart failure?
To increase the force of cardiac contractions
These agents are used intravenously in acute settings for patients with low cardiac output.
Which beta-blockers have shown benefit in heart failure?
- Bisoprolol
- Carvedilol
- Long-acting metoprolol succinate
These medications are recommended for all patients with chronic, stable heart failure.
What is the mainstay of therapy for acute heart failure?
Vasodilators
They help reduce preload, afterload, and cardiac workload.
What is the role of diuretics in heart failure management?
Relieve pulmonary congestion and peripheral oedema, reducing preload and cardiac workload
They do not improve survival rates.
What are potassium-sparing diuretics, and how are they used?
Decrease potassium secretion and are often used with loop diuretics
Monitoring of renal function and potassium levels is essential.
What is the main effect of potassium-sparing diuretics?
Decrease potassium secretion and have weak diuretic and antihypertensive effects when used alone.
Examples include spironolactone and amiloride.
Why are potassium-sparing diuretics often used with loop diuretics?
To mitigate potassium loss and enhance diuretic effects while requiring careful renal function and potassium monitoring.
Loop diuretics can lead to significant potassium depletion.
What are other forms of diuretics that have weak diuretic effects?
Carbonic anhydrase inhibitors and osmotic diuretics.
These are not as potent as loop or potassium-sparing diuretics.
What is the mechanism of action of spironolactone?
Antagonizes aldosterone at intracellular cytoplasmic receptor sites, rendering the spironolactone-receptor complex inactive.
This results in potassium retention and sodium excretion.
In which patients are aldosterone antagonists recommended?
For patients with moderately severe and severe heart failure and reduced left ventricular (LV) systolic function.
Aldosterone antagonists help manage fluid overload in heart failure.
How does eplerenone compare to spironolactone?
Eplerenone has comparable actions to spironolactone but may have fewer endocrine effects.
Both are aldosterone receptor antagonists.
Are calcium channel blockers (CCBs) generally recommended in heart failure?
No, they are generally contraindicated but may be used cautiously in specific cases.
CCBs may be suitable for heart failure with normal left ventricular ejection fraction.
What are the potential benefits of using CCBs in heart failure?
They may improve exercise tolerance via their vasodilatory properties.
This can help alleviate symptoms in certain heart failure patients.
What are examples of alpha/beta adrenergic agonists?
Epinephrine and norepinephrine.
These are used in the management of acute heart failure.
What does CVS stand for?
Cardiovascular System
What are the main components of the cardiovascular system?
- Heart
- Arteries
- Veins
- Capillaries
What is the primary function of the cardiovascular system?
Maintaining homeostasis through heart’s pumping activity and blood movement
What is the difference between haemodynamics and haemostasis?
Haemodynamics refers to blood flow and pressure regulation, while haemostasis refers to the process of blood clotting.
Define the cardiac cycle.
Sequence of events that occurs when the heart beats.
What are the two major phases of the cardiac cycle?
- Diastole phase
- Systole phase
What happens during the diastole phase?
The heart ventricles are relaxed and fill with blood.
What occurs during the systole phase?
The ventricles contract and pump blood out of the heart.
What is the equation for cardiac output (CO)?
CO = SV x HR
What does SV stand for in the cardiac output equation?
Stroke Volume
What is the normal range for cardiac output?
~5 L/min
What is the normal heart rate (HR) range for adults?
80-100 beats per minute (bpm)
Fill in the blank: Stroke Volume (SV) is calculated as _______.
End Diastolic Volume (EDV) - End Systolic Volume (ESV)
What does EDV represent?
Amount of blood collected in a ventricle during diastole
What does ESV represent?
Amount of blood remaining in a ventricle after contraction
What is preload in the context of the cardiovascular system?
The end diastolic pressure when the ventricle has become filled
What is afterload?
The amount of resistance the heart must pump against when ejecting blood
What is contractility influenced by?
Preload; the greater the stretch, the more forceful the contraction.
List some conditions that increase cardiac output.
- Anxiety and excitement
- Eating
- Exercise
- High environmental temperature
- Pregnancy
- Epinephrine
List some conditions that decrease cardiac output.
- Sitting or standing from lying position
- Rapid arrhythmias
- Heart disease
What are the two specialized types of cardiac muscle cells?
- Contractile
- Autorythmic
What role does the sympathetic nervous system (SNS) play in heart regulation?
Activated by stress, anxiety, excitement, or exercise to increase heart rate.
What is the effect of the parasympathetic nervous system (PNS) on heart rate?
Mediated by acetylcholine to oppose the SNS and decrease heart rate.
True or False: Hypocalcemia increases heart irritability.
False
What does haemodynamics study?
Blood flow and the physical laws governing blood flow in blood vessels.
What are the four types of blood vessels?
- Arteries
- Arterioles
- Capillaries
- Veins
What is blood pressure?
The force exerted by blood against the vessel wall.
What is the normal range for systolic blood pressure?
100-120 mmHg
What is the normal range for diastolic blood pressure?
70-80 mmHg
What is venous return?
Amount of blood returning to the heart.
What mechanisms assist venous return?
- Skeletal muscle pump
- Respiratory pump
- Sympathetic venoconstriction
What can cause compensatory responses to decreased blood pressure?
Initial treatment with a vasodilator.
What are the major classes of antihypertensive drugs?
- Acting on Renin angiotensin system
- Acting on sympathetic nervous system
- Vasodilators
- Diuretics
Name three types of drugs that act on the Renin angiotensin system.
- Angiotensin converting enzyme inhibitors (ACEI)
- Angiotensin receptor antagonists (ARB)
- Renin antagonists
List examples of Angiotensin-Converting Enzyme (ACE) inhibitors.
- Captopril
- Enalapril
- Lisinopril
- Benazepril
- Fosinopril
- Perindopril
- Quinapril
- Ramipril
What are Angiotensin II antagonists also known as?
Angiotensin receptor blockers (ARBs)
Provide examples of Angiotensin receptor blockers (ARBs).
- Losartan
- Valsartan
- Olmesartan
- Irbesartan
- Eprosartan
- Candesartan
- Telmisartan
What is the mechanism of action for beta-adrenergic blockers?
Reduced heart rate and cardiac output
True or False: Alpha-1 selective blockers cause more reflex tachycardia than non-selective antagonists.
False
Fill in the blank: Centrally acting drugs include ______ and ______.
Methyldopa, Clonidine
What are the therapeutic uses of beta-adrenergic blockers?
- Hypertension
- Inhibition of renin release
- Migraine
- Hyperthyroidism
- Angina pectoris
- Myocardial infarction
What is a potential advantage of methyldopa?
Causes reduction in renal vascular resistance
List the adverse effects of alpha non-selective blockers.
- Reflex tachycardia
- Postural hypotension
- Nasal stuffiness
- Nausea
- Vomiting
- Inhibition of ejaculation
What are the effects of calcium channel blockers (CCBs)?
- Vascular smooth muscle relaxation (vasodilation)
- Decreased myocardial force generation (negative inotropy)
- Decreased heart rate (negative chronotropy)
- Decreased conduction velocity within the heart (negative dromotropy)
Give examples of diuretics used in hypertension.
- Thiazides (hydrochlorothiazide, chlorthalidone)
- Loop diuretics (furosemide, torsemide)
- Potassium-sparing diuretics (amiloride, triamterene, spironolactone)
What is the primary therapeutic use of Sodium Nitroprusside?
Hypertensive emergencies
What is the effect of hydralazine on blood vessels?
Dilates arteries more than veins
True or False: Dihydropyridines are most vaso-selective and have the least cardiac effect.
True
What cardiovascular effects does Phenoxybenzamine have?
- Prevents vasoconstriction of peripheral blood vessels
- Treatment of pheochromocytoma
- Inhibits cardiac arrhythmias induced by adrenaline
Define the term ‘reflex tachycardia’.
Increase in heart rate due to baroreceptor reflex in response to blood pressure drop
What is the significance of beta-1 selective blockers in patients with COPD?
Possibly safer as they have less impact on bronchial smooth muscle
Fill in the blank: The mechanism of action for centrally acting drugs primarily involves ______ peripheral vascular resistance.
Reducing
List the clinical features of beta-adrenergic blockers in hypertension.
- Moderate fall of BP
- Block rise in BP due to exercise
- Less likely to aggravate peripheral vascular disease
What is the primary action of direct vasodilators?
Dilate arterioles
What is one of the common side effects of hydralazine?
Reflex tachycardia
What condition is Methyldopa primarily used for?
Hypertension during pregnancy
What are the adverse effects of using direct vasodilators?
- Dizziness
- Headache
- Hypotension
- Flushing
- Angina
- Tachycardia
Fill in the blank: Calcium channel blockers bind to ______ type calcium channels.
L-
What is the primary action of Sodium Nitroprusside?
Release nitric oxide
This leads to vasodilatation by activating the guanylyl cyclase-cGMP-PKG pathway.
How does Sodium Nitroprusside affect afterload?
↓ afterload
It reduces arterial resistance leading to decreased cardiac O2 demand.
What is a significant side effect of Sodium Nitroprusside?
Hypotension
Rarely, it can convert to cyanide and thiocyanate.
For what conditions is Sodium Nitroprusside primarily used?
Hypertensive emergencies, controlled hypotension during surgery, reversible cardiac dysfunction
It is effective for short-term control of hypertension (up to 72 hours).
What is the mechanism by which diuretics affect blood pressure?
Alters sodium and water balance
Increased Na+ retention raises total peripheral resistance (TPR).
What is the typical reduction in blood pressure from diuretics?
10–15 mmHg
This effect is due to the alteration in sodium and water balance.
Name an example of a loop diuretic.
Furosemide
Other examples include Torsemide and Bumetanide.
What are thiazide diuretics commonly used for?
Moderate hypertension
Examples include Chlorothiazide, Chlorthalidone, and Hydrochlorothiazide.
What effect does angiotensin II have on peripheral resistance?
Altered peripheral resistance
It causes direct vasoconstriction and enhances peripheral noradrenergic neurotransmission.
What are the two types of pressor responses induced by angiotensin II?
Rapid pressor response and slow pressor response
These responses include vascular and cardiac hypertrophy.
What drugs interfere with the Renin-Angiotensin-Aldosterone System (RAAS)?
ACE inhibitors, ARBs, Renin inhibitors
Examples include Captopril, Losartan, and Aliskiren.
What is the role of aldosterone in blood pressure regulation?
Increased Na+ reabsorption by proximal tubule
This action contributes to increased blood pressure.
Fill in the blank: Diuretics reduce blood pressure by altering sodium and water _______.
balance
True or False: Loop diuretics are typically used for moderate hypertension.
False
Loop diuretics are used for severe hypertension.
What is a common side effect of diuretics?
Na+ and water retention
This can lead to increased blood pressure.
What is the effect of increased sympathetic discharge on blood pressure?
Increased blood pressure
This is due to catecholamine release from the adrenal medulla.
What does dyslipidaemia refer to?
Disordered lipid levels in the blood
It includes disorders of lipoprotein metabolism, such as overproduction or deficiency of lipoproteins.
What is hyperlipidaemia?
Elevated plasma cholesterol or triglyceride levels or both
It is present in all hyperlipoproteinaemias.
List the primary forms of hyperlipidaemias.
- Chylomicronemia
- Hypercholesterolemia
- Dysbetalipoproteinaemia
- Hypertriglyceridemia
- Mixed hyperlipoproteinemia
- Combined hyperlipoproteinemia
What diseases can cause secondary hyperlipidaemias?
- Diabetes mellitus
- Pancreatitis
- Renal disease
- Hypothyroidism
What are common manifestations of dyslipidaemias?
- Elevation of Total Cholesterol (TC)
- Increased Low-density Lipoprotein (LDL-C) cholesterol
- Increased Triglyceride (TG) concentrations
- Decrease in High-density Lipoprotein (HDL-C) cholesterol
What are primary hyperlipidaemias?
Familial, inherited disorders
These disorders are genetic in origin.
What are secondary hyperlipidaemias?
Acquired disorders caused by various other diseases or medications
What skin manifestations can occur with hyperlipidaemias?
- Xanthomas
- Xanthelasma
- Corneal arcus
What are the steps of atherosclerotic plaque formation?
- Infiltration of LDL-C into arterial walls
- Entrapment of LDL-C in artery walls
- Modification of LDL-C
- Uptake of modified LDL-C by macrophages
- Foam cell formation
- Fatty streak formation
- Conversion to fibrous plaques
What is the normal Total cholesterol level for healthy individuals?
Below 5.0 mmol/L or below 193 mg/dL
What dietary modifications can help manage lipid disorders?
- Decrease intake of saturated fats/cholesterol
- Increase proportion of mono- and polyunsaturated fatty acids
What is the recommended BMI for weight reduction in managing lipid disorders?
Less than 23 kg/m²
What types of exercises are recommended for managing lipid disorders?
- Brisk walking
- Jogging
- Cycling
- Swimming
What are the classes of lipid-lowering agents?
- HMG-CoA reductase inhibitors (Statins)
- Fibric acid derivatives (Fibrates)
- Bile acid sequestrants (Resins)
- Nicotinic acid (niacin)
- Cholesterol absorption inhibitors (2-Azetidiones)
What is the mechanism of action for statins?
Competitive inhibitors of HMG-CoA reductase, decreasing cholesterol synthesis
This leads to increased uptake of LDL from the blood.
What are the common adverse effects of statins?
- Elevated liver enzymes
- Myopathy
- Rhabdomyolysis
What is the therapeutic use of fibrates?
Lowering serum triglycerides and LDL levels, increasing HDL levels
What is the mechanism of action of nicotinic acid (niacin)?
Inhibits lipolysis in adipose tissue, reducing free fatty acid production
It lowers both cholesterol and triglycerides.
What are common adverse effects of nicotinic acid?
- Intense cutaneous flush
- Nausea
- Abdominal pain
- Hyperuricemia
How do bile acid sequestrants work?
They bind bile acids in the intestine, leading to increased conversion of cholesterol to bile acids
What is the primary mechanism of bile acid sequestrants?
They lower bile acid concentration, increasing conversion of cholesterol to bile acids.
What effect does the activation of hepatic uptake of LDL have?
It leads to a fall in cholesterol-containing particles and lowers plasma LDL levels.
What conditions are bile acid sequestrants useful for treating?
Type IIA and type IIB hyperlipidemias.
What additional condition can cholestyramine relieve?
Pruritus caused by accumulation of bile acids in biliary stasis.
What is colesevelam indicated for besides hyperlipidemias?
Type 2 diabetes mellitus due to its glucose-lowering effects.
What are the most common side effects of bile acid sequestrants?
GI disturbances, such as constipation, nausea, and flatulence.
What vitamins may be impaired in absorption by bile acid sequestrants?
Fat-soluble vitamins A, D, E, and K.
What contraindications exist for bile acid sequestrants?
Biliary/bowel obstruction, serum triglycerides >300-500 mg/dL, history of hypertriglyceridemia-induced pancreatitis.
What is the action of Ezetimibe?
It inhibits absorption of dietary and biliary cholesterol in the small intestine.
What is the effect of Ezetimibe on LDL cholesterol levels?
Lowers LDL cholesterol by approximately 15-17%.
In which patients is Ezetimibe often used?
As an adjunct to statin therapy or in statin-intolerant patients.
What are the contraindications for Ezetimibe?
Hypersensitivity and coadministration with statins in active liver disease.
What is the primary therapeutic use of Omega-3 polyunsaturated fatty acids?
For triglyceride lowering.
What common side effects are associated with Omega-3 fatty acids?
GI effects (abdominal pain, nausea, diarrhea) and a fishy aftertaste.
What effect can Omega-3 fatty acids have when taken with anticoagulants or antiplatelets?
Increased bleeding risk.
What is the role of HMG CoA reductase (Statins) in cholesterol synthesis?
It is a rate-limiting step and the most potent medication for controlling hyperlipidemia.
What effect do fibrates have on lipase activity?
They increase lipase activity, lowering triglyceride levels and elevating HDL-C.
What is the effect of Niacin on triglycerides and HDL-C?
Lowers triglycerides and LDL-C while increasing HDL-C levels.
How do bile acids sequestrants like colestipol and cholestyramine reduce LDL-C levels?
By eliminating bile acids/bile salts through forming a complex in the intestine.
What effect does Ezetimibe have on free cholesterol absorption?
It inhibits free cholesterol absorption from the intestine.
What is haemostasis?
The process that stops bleeding in a blood vessel.
What are the two main factors involved in normal hemostasis?
Extrinsic and intrinsic factors.
What is the primary role of platelets in hemostasis?
To adhere to macromolecules in the sub-endothelial regions and aggregate to form the primary haemostatic plug.
What is fibrin?
The insoluble protein that is essential to clot formation.
Define thrombosis.
The formation of a clot in a vessel when blood flow is impeded.
What are the three primary factors that influence pathological clot formation?
- Abnormality in blood flow
- Abnormalities of surface in contact with blood
- Abnormalities of clotting components
What is venous thrombosis primarily composed of?
Fibrin and erythrocytes.
What is deep vein thrombosis (DVT)?
The most common type of venous thrombosis occurring in the lower extremities.
What causes arterial thrombosis?
Atherosclerosis or arrhythmias, such as atrial fibrillation.
List the anticoagulants used in the treatment of thrombi.
- Heparin (UFH)
- Low-molecular-weight heparins (LMWH)
- Warfarin
- Various other NOACs
What is the purpose of thrombolytic therapy?
Rapid lysis of already formed clots.
What does plasminogen convert to?
Plasmin.
What can disturb the balance of the fibrinolytic system?
Activation with thrombolytic drugs.
What are the common unwanted effects of thrombolytic drugs?
- Hemorrhage
- Pyrexia
- Anaphylactic reaction
What is the principal adverse effect associated with thrombolytic therapy?
Bleeding due to fibrinogenolysis or fibrinolysis.
What is the half-life of alteplase?
5 to 10 minutes.
True or False: The older thrombolytic agents are clot-selective.
False.
What is the significance of concurrent administration of heparin and warfarin with thrombolytic drugs?
To reduce reocclusion but increases the risk of bleeding.
What is Tenecteplase (TNK-tPA)?
A thrombolytic agent with a longer half-life than alteplase.
Fill in the blank: The fibrinolytic system involves the removal of _______ as wounds heal.
fibrin
What is the most common type of venous thrombosis?
Deep vein thrombosis (DVT).
What is the role of the endothelium in the fibrinolytic system?
It releases plasminogen activator inhibitor-1 (PAI-1), which inactivates t-PA.
What is the role of fibrinolysis at the site of vascular injury?
Fibrinolysis occurs to help dissolve blood clots that form at the site of vascular injury
It is a crucial process for restoring normal blood flow after an injury.
What condition may occur and should be monitored with laboratory tests when using thrombolytic therapy?
Hypofibrinogenemia
This condition refers to lower than normal levels of fibrinogen in the blood.
How do second- and third-generation thrombolytic agents compare to others in terms of fibrinogenolysis?
They cause less extensive fibrinogenolysis
However, the incidence of bleeding remains similar for all thrombolytic agents.
What may necessitate the stoppage of thrombolytic therapy?
Life-threatening intracranial bleeding
This type of bleeding requires immediate medical intervention.
What treatments might be administered in the case of life-threatening intracranial bleeding?
- Whole blood
- Platelets
- Fresh frozen plasma
- Protamine (if heparin is present)
- An antifibrinolytic
These treatments aim to manage the bleeding and restore hemostasis.
What are absolute contraindications for the use of thrombolytic drugs?
- Active bleeding
- Cardiopulmonary resuscitation (possible trauma to thorax)
- Intracranial trauma
- Vascular disease
- Cancer
These conditions pose significant risks when administering thrombolytic therapy.
What are some relative contraindications for thrombolytic therapy?
- Uncontrolled hypertension
- Earlier central nervous system surgery
- Any known bleeding risk
These conditions may increase the risk of complications with thrombolytic therapy.
What is the recommendation for patients aged 60 to 80 years with persistent stage 1 hypertension?
Provide lifestyle advice/intervention and discuss starting an anti-hypertensive.
What conditions warrant the offering of antihypertensives to patients with persistent stage 1 hypertension?
- Diabetes mellitus
- Established CVD
- Renal disease
- Estimated 10 year CVD (QRISK) of >10%
What is the recommendation for patients with persistent stage 2 hypertension?
Offer antihypertensive and still provide lifestyle advice and intervention.
What is the main risk associated with alpha blockers?
Cause severe orthostatic hypotension.
What are the effects of centrally acting alpha 2 antagonists?
Severe orthostatic hypotension and sedation.
What side effect is particularly associated with ACE inhibitors?
Orthostatic hypotension.
What side effects are linked to thiazide diuretics?
- Orthostatic hypotension
- Hypokalaemia induced weakness
- Hyponatraemia
What complications can antianginals cause?
- Hypotension
- Paroxysmal hypotension
- GTN causes syncope due to sudden BP drop
What cardiovascular effects are associated with non-cardioselective beta-blockers?
- Bradycardia
- Hypotension
- Carotid sinus hypersensitivity
- Orthostatic hypotension
- Vasovagal syndrome
What is a key risk factor for falls in older adults?
Polypharmacy (taking 4+ medications).
What is fludrocortisone and its mechanism of action?
A synthetic mineralocorticoid that increases plasma volume and cardiac output by sodium retention.
What is gestation-induced hypertension?
High blood pressure found later in pregnancy, indicating secondary hypertension.
What are the symptoms of pre-eclampsia?
- Swelling in face/hands/ankles
- Severe headache
- Blurred vision
- Abdominal pain
What is the first-line treatment for hypertension in pregnancy?
Beta-blockers, primarily labetalol.
What should be considered for patients under 40 with hypertension?
Referral to cardiology for specialist investigation into aetiology.
What defines postural (orthostatic) hypotension?
Sustained reduction of systolic BP of at least 20 mmHg or diastolic BP of 10 mmHg within 3 minutes of standing.
What is the risk associated with a systolic blood pressure of 110 mmHg or below in older people?
Increased risk of falls.
What is the initial treatment step for patients under 55 years of age and not of African or Caribbean heritage?
ACE inhibitor or angiotensin receptor blocker.
What are the target blood pressure goals for patients under 80 years old?
Aim for <140/90 mmHg.
What is the effect of weight reduction on blood pressure?
1 mmHg reduction in BP per 1 kg weight loss.
What lifestyle change can lead to a reduction of 3-4 mmHg in blood pressure?
Alcohol cessation.
What is the classification for stage 1 hypertension according to clinic blood pressure?
Ranging from 140/90 mmHg to 159/99 mmHg.
Each 10 mmHg reduction in BP reduces CVD risk by approximately what percentage?
~20%.
What is the risk of CHF in patients with hypertension?
Increased sixfold
CHF stands for Congestive Heart Failure.
What is classified as Stage 1 hypertension?
Clinic blood pressure ranging from 140/90 mmHg to 159/99 mmHg
ABPM refers to Ambulatory Blood Pressure Monitoring and HBPM refers to Home Blood Pressure Monitoring.
What defines Stage 2 hypertension?
Clinic blood pressure of 160/100 mmHg or higher, but less than 180/120 mmHg
ABPM daytime average or HBPM average blood pressure of 150/95 mmHg or higher.
What is Stage 3 (Severe) hypertension?
Clinic systolic blood pressure of 180 mmHg or higher or clinic diastolic blood pressure of 120 mmHg or higher.
At what systolic and diastolic levels is hypertension diagnosed?
Systolic 140, Diastolic 90.
What age group should consider antihypertensive drug treatment in addition to lifestyle advice?
Adults under 60 years old with persistent Stage 1 hypertension.
What percentage of men and women in the UK are diagnosed with hypertension?
31% of men and 26% of women.
What is the leading risk factor for death worldwide according to WHO?
Hypertension.
What percentage of hypertension cases are classified as ‘essential’?
90-95%.
How is hypertension diagnosed?
Measure blood pressure.
What are common symptoms of hypertension?
Often asymptomatic, but may include:
* Headache
* Visual disturbances
* Swelling of the macula.
What should be done if the first blood pressure measurement is >140/90 mmHg?
Repeat the measurement.
How is a diagnosis of hypertension confirmed?
Clinic BP of >140/90 mmHg or ABPM/HBPM average of >135/85 mmHg.
What is the purpose of Ambulatory Blood Pressure Monitoring?
Provides a better overview of patients’ blood pressure in a day-to-day setting.
What is the typical discrepancy between clinical measurements and ABPM?
Average clinical measurements are 10/5 mmHg higher than ABPM.
What should be done if ABPM is not tolerated?
Advise Home Blood Pressure Monitoring (HBPM).
How should home blood pressure be measured?
Patient measures BP at set times, repeating each measurement twice, 1 minute apart.
What should be done with the first day’s readings in HBPM?
Discard the first day’s worth of readings.
What is hypertension (HPT)?
A persistent elevation of SBP > 140 mm Hg and/or DBP > 90 mm Hg or taking antihypertensive medication
Defined by NICE/JNC-8 and ACC/AHA guidelines.
What percentage of adults in the UK had hypertension?
30%
Includes 15% with untreated hypertension.
What is considered a condition of hypertension?
Blood pressure rises to a level likely to cause injury or adverse outcome.
What are the common diseases associated with hypertension?
- Stroke
- Myocardial infarction
- Vascular disease
- Chronic kidney disease
What percentage of hypertension cases are classified as essential hypertension?
90-95%
Also known as primary hypertension.
What is a significant risk factor for developing hypertension?
Genetic predisposition
More common in patients of African or Caribbean ethnicity.
What is the public awareness level regarding hypertension?
61% goes undiagnosed.
What factors are involved in blood pressure regulation?
- Baroreceptor reflex
- Sympathetic nervous system
- Renin-angiotensin aldosterone system (RAAS)
- Hormonal mediators
- Vascular reactivity
- Circulatory volume
- Blood viscosity
- Cardiac output
- Blood vessel elasticity
What are the circadian changes in blood pressure?
Greatest on waking, increases during morning, declines during the day, lowest during sleep.
What may contribute to the pathogenesis of essential hypertension?
- Genetic predisposition
- Excess dietary salt intake
- Adrenergic tone
How does age affect blood pressure in individuals diagnosed with hypertension?
Most individuals will have increasing blood pressure as they age.
What is the prognosis for mild to moderate untreated hypertension?
Risk of atherosclerotic disease in 30% and organ damage in 50% within 8-10 years.
What is the diagnosis of hypertension based on?
Repeated, reproducible increase in blood pressure.
What device is used for blood pressure measurement?
Sphygmomanometer.
What are the two types of hypertension?
- Primary (essential) hypertension
- Secondary hypertension
What percentage of hypertension cases are secondary hypertension?
2-10%.
What are modifiable risk factors for primary hypertension?
- Overweight/Obese
- Diabetes
- Smoking
- Alcohol
- Lack of exercise
- Cold/low temperature
- Stress
What are non-modifiable risk factors for primary hypertension?
- Age
- Race
- Family history
What is the lifetime risk of developing hypertension for those aged 55 and older with normal BP?
90%.
What is the classification of blood pressure for adults aged 18 years or older?
- Normal: SBP < 120 mm Hg, DBP < 80 mm Hg
- Prehypertension: SBP 120-139 mm Hg, DBP 80-89 mm Hg
- Stage 1: SBP 140-159 mm Hg, DBP 90-99 mm Hg
- Stage 2: SBP ≥ 160 mm Hg or DBP ≥ 100 mm Hg
What characterizes hypertensive emergencies?
Evidence of impending or progressive target organ dysfunction.
What defines isolated systolic hypertension (ISH)?
SBP of ≥140 mmHg and DBP <90 mmHg.
What is white coat hypertension?
Persistently above 140/90 mmHg in clinic/office while lower at home.
What is masked hypertension?
Normal clinic BP but elevated 24-hour ambulatory BP load (≥135/85 mmHg).
What are the consequences of untreated hypertension?
- Thickening of the arteries
- Narrowing of lumen of small arteries
- Deterioration of atherosclerosis
- Development of small aneurysms
- Left ventricular hypertrophy
- Proteinuria
- Retinopathy
What is the primary type of hypertension in the patient scenario?
Essential hypertension.
What stage of hypertension is Ms TSP in based on the given BP readings?
Stage 1 hypertension.
Why was Ms TSP unaware of her hypertension?
Hypertension is often asymptomatic.
What damage can high pressure in the heart and arteries cause?
Damage likely due to excessive mechanical stretch and load.
What is manifested as thickening of the arteries?
Hypertension (HTN)
Hypertension leads to various vascular changes.
What type of circulation is particularly affected by narrowing of the lumen of small arteries?
Renal circulation
This is a significant consequence of hypertension.
What condition is characterized by the deterioration of atherosclerosis?
Cardiac Ischaemia and angina
These conditions are linked to the effects of hypertension.
What is one of the consequences of hypertension that involves small aneurysms?
Development of small aneurysms in cerebral arteries
This can lead to serious complications such as stroke.
What is a common renal complication associated with hypertension?
Proteinuria
This indicates kidney damage due to hypertension.
True or False: Malignant hypertension develops rapidly and causes organ damage.
True
It can lead to fatal outcomes if not treated.
What is a significant risk associated with hypertension leading to stroke?
Intracerebral haemorrhage
This can occur due to the rupture of aneurysms in cerebral arteries.
What are the target organ complications (TOC) of hypertension?
- Retinal damage
- Renal failure
- Heart failure
These complications arise from chronic hypertension.
What is the ideal Body Mass Index (BMI) range for Asians?
18.5 to 23.5 kg/m²
Maintaining a healthy BMI is part of non-pharmacological management.
What does the American Heart Association recommend for sodium intake?
Less than 1500 mg per day
This is crucial for managing hypertension.
Fill in the blank: The DASH diet is high in _______ and low in sweets and red meat.
fruits, vegetables, whole grains, poultry, and fish
This dietary approach helps in controlling blood pressure.
What is the first step in the management of hypertension?
Non-pharmacological management
Lifestyle changes are essential before medication.
What are the first-line pharmacological treatments for hypertension?
- Thiazide diuretics
- Long-acting calcium channel blockers (CCB)
- Angiotensin-converting enzyme (ACE) inhibitors
- Angiotensin II receptor blockers (ARBs)
These medications are typically initiated based on individual patient profiles.
What is the goal for blood pressure in patients aged 60 years and older?
SBP < 150 mm Hg and DBP < 90 mm Hg
This is a recommendation from evidence-based guidelines.
In what population should initial antihypertensive treatment include a thiazide-type diuretic?
The general nonblack population, including those with diabetes
This is part of evidence-based recommendations for hypertension treatment.
What should be the goal blood pressure for patients with chronic kidney disease (CKD)?
SBP < 140 mm Hg and DBP < 90 mm Hg
This is crucial for managing hypertension in CKD patients.
What is the main objective of hypertension treatment?
To attain and maintain goal blood pressure
Regular monitoring and adjustments are necessary.
What is hypertensive urgency?
A severe increase in BP not associated with acute end-organ damage
Patients with grade III or IV retinal changes should be admitted.
What is hypertensive urgency?
A severe increase in BP which is not associated with acute end-organ damage/complication
Includes patients with grade III or IV retinal changes (accelerated and malignant hypertension).
What should be the initial treatment goal for a patient with hypertensive urgency?
About a 25% reduction in BP over 24 hours but not lower than 160/90 mmHg
Oral drugs proven to be effective are used.
What is required for patients with hypertensive urgency?
Admission to the hospital
BP measurement should be repeated after 30 minutes of bed rest.
What are some complications of severe hypertension that classify as hypertensive emergencies?
- Acute heart failure
- Dissecting aneurysm
- Acute coronary syndromes
- Hypertensive encephalopathy
- Subarachnoid haemorrhage
- Acute renal failure
Occur in patients with BP < 180/110 mmHg, particularly if the BP has risen rapidly.
What is the recommended BP reduction for patients with hypertensive emergencies?
10%-25% within certain minutes to hours but not lower than 160/90 mmHg
This is best achieved with parenteral drugs.
Which antihypertensive drug classes could be used as first-line therapy for an African-American patient with hypertension and diabetes?
- ACE inhibitors
- ARB
- Calcium channel blockers
- Beta-blockers
Which antihypertensive drug class could be used as a first-line therapy for an African-American patient with hypertension, CKD, and diabetes?
- ACE inhibitors
- Thiazide diuretics
- Calcium channel blockers
- Beta-blockers
What is the appropriate classification for a patient with SBP 200 mmHg and DBP 120 mmHg who also presented with kidney failure?
Hypertensive emergency
Other options include resistant hypertension, hypertensive urgency, and asymptomatic severe hypertension.
Which drug would be suitable for treating a patient in a hypertensive emergency?
- Nicardipine
- Sodium nitroprusside
- Labetalol
- Nitroglycerine
What are some further reading topics related to hypertension?
- HTN and Diabetes
- HTN and CVD
- HTN and Cerebrovascular events
- HTN Emergencies
- HTN in Paediatrics
- HTN in Pregnancy
- Pulmonary HTN
What is the definition of Dysrhythmia?
Abnormality of the cardiac rhythm usually caused by an impairment in impulse generation or conduction
Dysrhythmia is the more accurate term to use as ‘Arrhythmia’ implies an absence of a rhythm.
What are the types of Dysrhythmias based on speed?
- Bradycardia (<60 bpm in sedentary adult)
- Tachycardia (100-150 bpm)
- Flutter (150-350 bpm)
- Fibrillation (>350 bpm)
Tachydysrhythmias respond best to drug treatments.
What is inappropriate automaticity?
The ability of cells to spontaneously generate intermittent action potentials
Atrial or ventricular cells do not normally have this ability, but in inappropriate automaticity, they acquire it.
What are the common factors that disturb heart rhythm?
- Ischaemia/Hypoxia
- Electrolyte imbalances
- Trauma
- Inflammation
- Drugs
What is triggered activity in the context of arrhythmogenesis?
Occurs when an impulse is generated during or just after repolarisation due to a depolarising oscillation of the membrane potential
Early afterdepolarisations (EADs) and delayed afterdepolarisations (DADs) are examples.
What are the three main categories of Dysrhythmias?
- Abnormal rates of sinus rhythm
- Abnormal/ectopic site of impulse initiation
- Disturbances of the conduction pathways
What is Sinus Tachycardia?
Abnormally fast heart rate >100 bpm, often a compensatory response to increased demand for cardiac output
Treatment aims at correcting the underlying cause.
What characterizes Atrial Fibrillation (AF)?
Completely disorganised and irregular atrial rhythm accompanied by irregular ventricular rhythm of variable rate
AF causes stagnation of blood in the atria and the risk of thrombus formation.
What is Ventricular Tachycardia (VT)?
Consists of 3 or more consecutive ventricular complexes at a rate of more than 100/min
It is a serious dysrhythmia, usually indicative of serious cardiac disease.
What is Ventricular Fibrillation (VF)?
A rapid uncoordinated cardiac rhythm resulting in ventricular quivering and lack of effective contraction
Must be rapidly identified and treated with CPR and defibrillation.
What defines 1st degree heart block?
Identified by a prolonged PR interval, with each P wave associated with a QRS complex
Often caused by drugs, myocardial ischaemia, and congenital heart defects.
What is Mobitz type I 2nd degree heart block?
Associated with progressive lengthening of the PR interval until one P wave is not conducted
This pattern repeats, causing QRS complexes to occur in groups.
What is Mobitz type II 2nd degree heart block?
Identified by nonconducted P waves with a consistent PR interval
It is usually associated with a pathological lesion of the bundle of His.
What characterizes 3rd degree heart block?
No impulses are conducted from the atria to the ventricles, showing a junctional or ventricular escape rhythm
Pacemaker is usually required.
What is Wolff-Parkinson-White syndrome?
A congenital abnormality of the conduction system with accessory pathways that provide alternative pathways for depolarisation
This can lead to reentry and the development of SVT.
What does the QT interval on an ECG represent?
Ventricular depolarisation and repolarisation
Normally <440 milliseconds.
What is Torsades de pointes?
A polymorphic ventricular tachycardia, usually self-limiting but can recur if the underlying cause is not corrected.
What is haloperidol?
An antipsychotic medication used to treat various mental health conditions
Haloperidol is often referenced in the context of drug interactions affecting the QT interval.
Name three antibiotics that may inhibit the metabolism of other drugs and prolong the QT interval.
- Clarithromycin
- Erythromycin
- Moxifloxacin
What condition can prolonged QT interval predispose a patient to?
Torsades de pointes
What is Torsades de pointes?
A polymorphic ventricular tachycardia that can be potentially fatal
What emergency treatments are available for Torsades de pointes?
- Isoprenaline
- Magnesium
- Cardiac pacing
- Electrical cardioversion
What should be considered when managing dysrhythmias with anti-arrhythmic agents?
Advantages and disadvantages of treatment options
What is a major limitation of anti-arrhythmic therapy?
Efficacy is limited and may fail to work in many patients
What are common adverse effects of anti-arrhythmic agents?
- GI disturbances
- Hypotension
- Heart failure
- CNS effects
- Visual disturbances
- Hypersensitivity reactions
True or False: Many anti-arrhythmics may be pro-arrhythmic.
True
What are some non-drug therapies increasingly used to treat arrhythmias?
- Radiofrequency ablation
- Direct current cardioversion
- Defibrillation
- Pacemakers
- Internal cardioversion defibrillators (ICDs)
What is the ultimate goal of antiarrhythmic drug therapy?
Restore normal sinus rhythm and conduction
Antiarrhythmic drugs aim to decrease conduction velocity, change the duration of the effective refractory period, and _______.
[suppress abnormal automaticity]
According to the Vaughan Williams classification, which class of agents blocks fast Na channels?
Class I agents
What are the subgroups of Class I antiarrhythmic agents?
- Class Ia
- Class Ib
- Class Ic
What is the mechanism of action of Class III agents?
Block K channels, prolonging the plateau of phase 2 and increasing the refractory period
What is the main use of Class II agents, specifically beta blockers?
Treatment of increased sympathetic-induced arrhythmias
What is a significant side effect of Sotalol?
Proarrhythmic effects including Torsades de pointes
What does amiodarone treat?
Serious tachyarrhythmias refractory to other treatments
What is a notable side effect of amiodarone related to the lungs?
Pulmonary fibrosis
What is the main action of digoxin on the heart?
- Increased contractile force
- Decreased conduction through the AV node
- Decreased heart rate
Fill in the blank: Digoxin is a _______.
[cardiac glycoside]
How does digoxin increase contractile force?
By binding to Na⁺-K⁺-ATPase, leading to increased intracellular Ca²⁺
What are common side effects of Class I agents?
- Negative inotropic effects
- Anticholinergic effects
- Severe arrhythmias
- Prolonged QT interval
What is the mode of action of Class Ib agents like lidocaine?
Acts primarily on the Na channel and shortens phase 3 repolarization
What is the main use of Class Ic agents like flecainide?
Management of SVT, paroxysmal AF or atrial flutter, and refractory ventricular arrhythmias
What is the relationship between amiodarone and CYP450 enzymes?
Amiodarone is a potent inhibitor of CYP-450
Which two calcium channel blockers are classified as non-dihydropyridines?
- Verapamil
- Diltiazem
What is the role of the Na⁺-K⁺ pump during repolarisation?
Expels Na⁺ and transports K⁺ into the cardiac cell
What occurs to intracellular Na⁺ during repolarisation?
Accumulation inhibits the extrusion of Ca²⁺ ions
What is essential for linking electrical excitation to mechanical contraction in myocardial cells?
Free Ca²⁺ ions
How do increased Ca²⁺ ions affect myocardial contraction?
Increases coupling of actin and myosin, resulting in more forceful contraction and increased CO
How does digoxin affect Na⁺ and K⁺ transport in myocardial cells?
Inhibits active transport by inhibiting Na⁺-K⁺-ATPase
What are the negative chronotropic and dromotropic actions of digoxin?
Decreases heart rate (↓HR) and conduction velocity
What is automaticity in cardiac tissue?
Inherent ability to initiate and propagate an impulse without electrical stimulation
What effect does therapeutic dose of digoxin have on automaticity?
Decreases automaticity and increases resting potential of atrial tissue and AV node
What can occur with increased plasma digoxin concentrations?
Severe bradycardia and heart block
What happens at toxic digoxin concentrations?
Increases sympathetic NS activity and automaticity, leading to arrhythmias
What is the effect of digoxin on conduction velocity?
Decreases conduction velocity
What is indicated by prolonged PR interval on an ECG?
Sign of digoxin toxicity
What is the bioavailability of digoxin from tablets?
60-80%
What is the half-life of digoxin in patients with normal renal function?
20-50 hours
What are some precautions when using digoxin?
- Renal impairment
- Hypothyroidism
- Hyperthyroidism
- Electrolyte abnormalities
- Elderly
What are common adverse effects of digoxin?
- Anorexia
- Nausea
- Vomiting
- Diarrhoea
- Blurred vision
- Visual disturbances
What is the therapeutic range for digoxin?
0.5-2 mcg/L
What is the management for severe digoxin toxicity?
Use of digoxin-specific immune antigen binding fragment (Fab) (Digibind)
What is the mechanism of action of adenosine?
Depresses SA node activity and slows conduction through the AV node
What is radiofrequency ablation used for?
Management of arrhythmias, especially SVTs
What is the typical success rate of radiofrequency ablation?
Approximately 90%
What is direct current cardioversion used for?
Restoring heart’s natural rhythm in patients with atrial flutter or AF
What is required before DC cardioversion?
Patient is briefly anaesthetised
What is defibrillation performed to correct?
Life-threatening fibrillations of the heart
What is the common indication for temporary pacing?
Post-MI with new bundle branch block
What are permanent pacemakers implanted for?
- Complete heart block
- Sick sinus syndrome
- Second degree AV block
What do internal cardioversion defibrillators (ICDs) do?
Monitor cardiac rate and rhythm and deliver shocks if VT is detected
What happens if anti-tachycardia pacing fails in ICDs?
The device discharges an internal shock to terminate the arrhythmia
What is the overall prevalence of Atrial Fibrillation (AF) in the UK?
1.6%
AF prevalence is approximately 3% in other countries.
What is the increased risk of stroke in patients with Atrial Fibrillation?
Nearly 500% increase
Strokes associated with AF tend to be more severe.
What percentage of all strokes is attributed to Atrial Fibrillation?
15-20% of all strokes
What is the annual cost of AF to the NHS?
Over £2.2 billion
What is the mortality rate of people with AF compared to those in Sinus Rhythm?
2x higher
What are the main cardiac causes of Atrial Fibrillation?
- Hypertension
- Valvular heart disease
- Ischemic heart disease
- Endocarditis
- Myocarditis
- Cardiomyopathy
- Pericarditis
What are the main non-cardiac causes of Atrial Fibrillation?
- Pyrexial illness
- Excessive alcohol consumption
- Thyrotoxicosis
- Diseases of the pleura
- Pulmonary circulation issues
What is ‘Lone AF’?
AF with a structurally normal heart and all other investigations are normal
What is the typical ventricular rate in Atrial Fibrillation?
50 to 200 beats per minute
What are common symptoms of Atrial Fibrillation?
- Palpitations
- Shortness of breath
- Syncope
- Chest pain
What is the significance of an irregularly irregular pulse?
It suggests the presence of Atrial Fibrillation
How is Atrial Fibrillation diagnosed?
Confirmed by ECG showing no P wave, a chaotic baseline, and an irregular ventricular rate
What is the CHA2DS2-VASc score used for?
To assess stroke risk in patients with Atrial Fibrillation
What is the primary goal of Atrial Fibrillation management?
Prophylaxis against thromboembolic complications and treatment of the arrhythmia
What anticoagulant is recommended for patients with valvular AF?
Warfarin
What is the risk of stroke in patients with non-valvular AF compared to a matched population?
5x more likely
What newer anticoagulants are available for AF management?
- Dabigatran
- Rivaroxaban
- Edoxaban
- Apixaban
What is the efficacy of aspirin compared to anticoagulants in stroke prevention?
About 20% reduction in stroke risk versus placebo
What are the risk factors for bleeding in AF patients requiring anticoagulation?
- Hypertension
- Anaemia
- Advanced age
- Labile INR
- Impaired renal function
- Impaired liver function
- History of major bleeds
- Concomitant medications
What scoring system does NICE recommend for assessing bleeding risk?
ORBIT score
What is the maximum score for the CHA2DS2-VASc scoring system?
9
What is the age threshold for additional points in the CHA2DS2-VASc score?
Age 75 years or over
What is the significance of the ORBIT score in AF management?
It assesses the patient’s risk of bleeding
What is the ORBIT score used for?
To assess bleeding risk in patients with atrial fibrillation
The ORBIT score evaluates factors such as hemoglobin levels and bleeding history.
What are the risk group categories based on the ORBIT score?
Low, Medium, High
Risk groups correspond to scores: 0-2 (Low), 3 (Medium), 4-7 (High).
What factors are included in the HAS-BLED score?
- Hypertension (>160mmHg systolic)
- Abnormal liver or renal function
- Stroke history
- History of bleeding
- Labile INR
- Age >65 years
- Drugs (antiplatelets or NSAIDs)
Each factor contributes 1-2 points to the score.
When should anticoagulants be offered according to CHA2DS2-VASc scores?
Score 2 or more (men and women)
Score 1 in men: consider anticoagulants; score 1 in women: no anticoagulants.
What are the advantages of Warfarin?
- Gold standard therapy for >50 years
- Long half-life
- Cheap, effective antidote available (Vit K)
- Familiarity among prescribers
- Potentially better compliance due to once daily dosing
Warfarin has established guidelines for emergency reversal.
What are the disadvantages of Warfarin?
- Narrow therapeutic index
- Unpredictable response
- Multiple interactions
- Slow onset and offset
- Frequent INR monitoring required
- Dietary restrictions
Bridging therapy is needed on initiation and cessation.
What are the advantages of DOACs?
- Specific coagulation enzyme target
- Rapid onset of action
- Predictable response
- Fixed dosing
- Fewer interactions
Lower risk of intracranial hemorrhage compared to Warfarin.
What are the disadvantages of DOACs?
- Shorter half-life
- Accumulation in renal impairment
- No reliable monitoring
- Lack of long-term safety data
- Higher drug costs
DOACs are less forgiving to non-adherence.
What is the primary goal of rate control in atrial fibrillation management?
To control the ventricular rate during episodes of AF
Aim is to maintain a ventricular rate <110bpm at rest.
What medications are typically used for rate control in AF?
- Beta blockers (e.g., Bisoprolol, Atenolol, Metoprolol)
- Non-dihydropyridine calcium channel blockers (e.g., Diltiazem, Verapamil)
Digoxin can be added if monotherapy is ineffective.
What factors favor rhythm control in atrial fibrillation?
- Younger, active, highly symptomatic patients
- Paroxysmal or early persistent AF
Rhythm control is less favored in asymptomatic patients.
What are the two treatment strategies for managing atrial fibrillation?
- Rate control
- Rhythm control
Choice depends on patient symptoms and AF type.
What is the recommended duration for anticoagulation before elective cardioversion?
2-6 weeks
This allows intra-arterial thrombus to dissolve.
What is the CHA2DS2-VASc score used for?
To assess stroke risk in patients with atrial fibrillation
Factors include age, sex, and medical history.
Fill in the blank: The maximum score for CHA2DS2-VASc is _______.
9
What is a key consideration before attempting cardioversion in AF?
Assessing the risk of thromboembolism
Anticoagulation is necessary prior to elective cardioversion.
In the event of a patient with AF requiring anticoagulation, what is the preferred agent?
NOAC (Novel Oral Anticoagulant)
Warfarin is used when NOACs are contraindicated.
What is the significance of the AFFIRM trial regarding AF management?
Showed no statistical difference in mortality or quality of life between rate control and rhythm control groups
There was a trend favoring the rate control arm.
What factors are considered when selecting an anticoagulant for a patient?
- Patient preference
- Tolerability
- Potential for drug interactions
- Likely compliance/adherence
- Monitoring requirements
Shared decision-making is essential.
What differentiates Angina from Acute Coronary Syndrome (ACS)?
Angina is a syndrome of reversible myocardial ischaemia without cell necrosis; ACS involves permanent damage to the myocardium due to myocardial ischaemia
Angina features include central chest pain and shortness of breath.
What is the primary cause of Myocardial Infarction (MI)?
Permanent occlusion of a coronary blood vessel usually due to plaque rupture and thrombus formation
What are the common features of Myocardial Infarction?
Rapid necrosis of myocardial tissue starting within 30 mins of occlusion, leading to permanent necrosis after 6-12 hours
What characterizes a Q-wave myocardial infarction?
ST segment elevation on ECG at admission, with Q waves developing later
What distinguishes Non-Q-wave myocardial infarction from unstable angina?
No ST segment elevation on ECG at admission, distinguished retrospectively by persistence of ECG changes and rise in serum markers
What is the new terminology for Q-wave myocardial infarction?
ST segment elevation myocardial infarction (STEMI)
What is the new terminology for Non-Q-wave myocardial infarction?
Non-ST segment elevation myocardial infarction (NSTEMI)
What does the diagnosis of unstable angina, minor myocardial damage, and non-STEMI represent?
A continuum with prognosis and treatment closely related to serum troponin levels
What is required for the diagnosis of myocardial infarction (MI)?
Careful clinical evaluation, particularly of chest pain characteristics and risk assessment, along with accurate ECG interpretation
What are the common presentations of Acute Coronary Syndrome (ACS)?
Chest pain at rest, recurrent chest discomfort, dyspnoea, diaphoresis, nausea and vomiting
Atypical pain is more common in women, diabetics, and the elderly.
What should be done in acute management of chest pain?
Seek medical help, access to defibrillator, administer Aspirin 300mg, oxygen, GTN, and IV morphine if required
What is the aim of treatment for STEMI?
Relieve pain, achieve coronary reperfusion, minimize infarct size, prevent complications, and allay anxiety
What defines STEMI on an ECG?
Persistent ST-segment elevation of >1mm in 2 contiguous limb leads or >2mm in 2 contiguous chest leads
What is the preferred method of reperfusion therapy for STEMI?
Percutaneous Coronary Intervention (PCI)
Fibrinolysis is an alternative but generally less preferred.
What factors influence the choice of reperfusion therapy?
Time delay to PCI and time from presentation to balloon inflation
What are cardiac troponins?
Specific cardiac structural proteins released during myocyte injury
When should cardiac troponins be measured to exclude myocardial injury?
6-8 hours after onset of chest pain
True or False: Creatinine kinase is only elevated when muscle fibers are damaged in the heart.
False
Creatinine kinase is found in other organs as well.
What factors determine the choice of reperfusion therapy in STEMI management?
Factors include:
* Time delay to PCI
* Time from presentation to balloon inflation
* Time from onset of symptoms until medical contact
* Time to hospital fibrinolysis
* Contraindications to fibrinolytic therapy
* Location and size of infarct
* Presence of cardiogenic shock
* Other special circumstances
Guidelines suggest fibrinolysis if time is >120 mins from presentation to balloon inflation.
What are absolute contraindications to thrombolysis in STEMI?
Absolute contraindications include:
* Active bleeding (excluding menses)
* Significant closed head or facial trauma within 3 months
* Suspected aortic dissection
* Prior intracranial hemorrhage
* Ischemic stroke within 3 months
* Known structural cerebral vascular lesion or malignant intracranial neoplasm
These contraindications prevent the use of thrombolytic therapy due to high risk of complications.
What are relative contraindications to thrombolysis in STEMI?
Relative contraindications include:
* Concurrent anticoagulants
* Non-compressible vascular punctures
* Recent major surgery (<3 weeks)
* Traumatic or prolonged (>10 mins) CPR
* Recent internal bleeding (within 1 month)
* Active peptic ulcer
* History of chronic, severe, poorly controlled hypertension
* Ischemic stroke (>3 months), dementia, or intracranial abnormality
* Pregnancy
These factors may increase the risk of bleeding or other complications during thrombolysis.
What are the options for fibrinolytic therapy?
Fibrinolytic therapy options include:
* Streptokinase
* Alteplase
* Tenecteplase
Reteplase is also an option but is not used in the UK.
What are the characteristics of Streptokinase as a fibrinolytic agent?
Streptokinase characteristics:
* Cheap
* Antigenic
* Given as an infusion
* Not to be given if previous exposure >5 days
Risk of antibodies against Streptokinase increases with prior exposure.
What advantages do alteplase and tenecteplase have over streptokinase?
Advantages include:
* Better reduction in mortality if given within 6 hours of symptom onset
* Alteplase is superior to streptokinase in patients under 75 years if used within 4 hours of chest pain onset
* Tenecteplase is convenient as it is given as boluses
* Tenecteplase has a lower rate of bleeding compared to alteplase
These agents are more fibrin-specific, leading to better outcomes.
What are the major side effects of thrombolytics?
Major side effects include:
* Major hemorrhage (intracerebral and gastrointestinal)
* Minor bleeding around injection sites
* Allergic reactions
Major hemorrhage is uncommon but serious, while minor bleeding usually responds to local compression.
What are common complications in the management of STEMI?
Common complications include:
* Persistent or recurrent pain
* Left ventricular failure
* Cardiogenic shock
* Arrhythmias
Each complication is treated appropriately as they occur.
What is the first objective in the evaluation of NSTEMI/NSTEACS?
The first objective is to determine whether ACS is the actual cause of the patient’s presentation
This involves assessing for prolonged or recurrent chest discomfort and atypical symptoms.
What atypical symptoms may present in patients with ACS?
Atypical symptoms include:
* Neck, jaw, back, or epigastric discomfort
* Excessive sweating (diaphoresis)
* Nausea and vomiting
Atypical presentation is more common in the elderly, diabetics, and women.
What is used to evaluate the short-term risk of adverse outcomes in NSTEMI/NSTEACS?
Patients are evaluated based on their 6-month risk of death or MI
High-risk features indicate a predicted 6-month mortality >3%, while low-risk features indicate <3%.
What scoring system is used to assess 6-month mortality or risk of CV events?
The GRACE scoring system is used to assess 6-month mortality or risk of CV events
This scoring system helps guide management decisions based on risk stratification.
What comorbidities can increase the risk of developing CVD?
- Hypertension
- Diabetes mellitus (including pre-diabetes/metabolic syndrome)
- Chronic kidney disease
- Atrial fibrillation
- Rheumatoid arthritis
- Some mental health disorders
- Socioeconomic status
- Lack of social support
What are the two categories of risk factors for CVD?
- Modifiable
- Non-modifiable
List some non-modifiable risk factors for CVD.
- Age
- Gender
- Family history
- Ethnic background
List some modifiable risk factors for CVD.
- Smoking
- Cholesterol level
- Unhealthy diet
- Sedentary lifestyle/lack of physical activity
- Alcohol intake above recommended levels
- Overweight and obesity
What is primary prevention in the context of CVD?
Individuals at high risk of developing CVD may benefit most from risk factor modification.
What is the NHS Health Check programme designed to do?
Identify people at high risk of CVD through different free health checks.
What did a systematic review reveal about systematic offers of health checks?
They are not likely to be beneficial and may lead to unnecessary tests and treatments.
What is secondary prevention for CVD?
People who already have CVD can benefit from risk factor modification and cardiac rehabilitation (where appropriate).
What is a population-based strategy to prevent CVD?
This strategy may influence lifestyle modification, e.g., diet, and is beneficial as CV deaths also occur in people who are not at high risk.
What are the three divisions of strategies to prevent the development or worsening of CVD according to NICE guidelines?
- Primary prevention
- Secondary prevention
- Population-based interventions
What do risk calculators estimate?
The likelihood of CV disease in people who have not already developed major atherosclerotic disease.
What is the purpose of the score generated by risk calculators?
- Guide decision-making and choice of intervention
- Assess patients’ cardiovascular risks to identify the need for lifestyle changes and medication
Name some risk calculators used for assessing CVD risk.
- QRISK®
- Framingham
- Joint British Societies (JBS)
- QRISK Assessment Tool
What are the pros of using validated risk calculators?
They are used to assess an individual’s 10-year CVD risk.
What are the limitations of risk calculators?
- Not used for people who already have CVD or are at high risk of developing it
- Not suitable for people aged 85 years or above
- May overestimate or underestimate risk in certain populations
What is the QRISK®3?
The recent version of the QRISK® risk calculator.
What should be used if the clinical system does not use QRISK®3?
QRISK®2 should be used.
What is the Framingham Risk Calculator used for?
Predicting an individual’s risk of heart disease.
What are the pros of the Framingham Risk Calculator?
- Used data from the Framingham Heart Study
- Includes multiple ranges for blood pressure values
What are some cons of the Framingham Risk Calculator?
- Applicability in certain specific populations may be limited
- Overestimates risk in populations with a low incidence of CAD
- Underestimates risk in women
What questions does the JBS3 Risk Calculator help address?
- Why should I start CVD risk reduction?
- When should I start?
- What should I do?
What does the JBS3 Risk Calculator demonstrate about risk factor reduction?
Delay in risk factor reduction reduces the benefits that could be gained.
What is the normal heart rate in BPM?
70 BPM
Define bradycardia.
Heart rate < 60 BPM
Define tachycardia.
Heart rate > 100 BPM
What is the native pacemaker of the heart?
SA node (60-100 BPM)
What is the heart rate of the AV node?
50-60 BPM
What is the heart rate of the Bundle of His?
50-60 BPM
What is the heart rate of Purkinje fibers?
30-40 BPM
How is the transmission of cardiac impulse characterized?
Spreads rapidly through atria, delayed at AV node (0.1 s), spreads rapidly via Purkinje fibers to endocardial surfaces of ventricles
What is the role of the autonomic nervous system in heart rate control?
Controls heart rate through parasympathetic (vagal activity) and sympathetic activity
What is the duration of the SA node impulse?
30 ms
What is the duration of the AV node impulse?
130 ms
What is the duration of the Bundle of His impulse?
30-40 ms
What is the duration of the Purkinje fibers impulse?
30-40 ms
What is defined as any change from normal sinus rhythm?
Cardiac arrhythmia
List some causes of arrhythmias.
- Increased sinus node automaticity
- Decreased sinus node automaticity
- Escape rhythms
- Enhanced automaticity of latent pacemakers
- Triggered activity
- Conduction abnormalities/block
What is sinus tachycardia?
Heart rate > 100 BPM, driven by the sinus node
What are some pathological causes of sinus tachycardia?
- Acute hyperthyroidism
- Heart failure
- Haemorrhage
- Fever
- Anaemia
- Hypovolemia
- Drug induced
What is sinus bradycardia?
Heart rate < 60 BPM, often seen during sleep or in fit athletes
What is sinus arrest?
Missing beats (PQRST complex) with otherwise normal ECG
What characterizes sick sinus syndrome?
SA node fails to excite the atria regularly, resulting in a slow resting heart rate
What is sinus arrhythmia?
Normal phenomenon with subtle change in heart rate with each respiratory cycle
What are the two major causes of conduction abnormalities?
- Depolarisation
- Abnormal anatomy
What is Wolff-Parkinson-White syndrome?
A condition where there is a bypass of the AV node with a short PR interval but wide QRS
What characterizes first-degree AV block?
Slowing of conduction through the AV node with an unusually long PR interval
What occurs in second-degree AV block?
Intermittent block where the PR interval lengthens until the AV node fails completely
What is a bundle branch block?
Failure of the ventricular conduction system, often at high heart rates
What does right bundle branch block indicate?
Conditions such as pulmonary embolus, chronic lung disease, cardiomyopathy, and can occur in healthy individuals
What does left bundle branch block usually indicate?
Underlying cardiac pathology such as dilated cardiomyopathy or coronary artery disease
What is third-degree (complete) block?
Failure of conduction between atria and ventricles, where supraventricular impulses no longer trigger ventricular contraction
What are the symptoms of third-degree block?
- Bradycardia
- Signs of congestive heart failure
- Altered mental status
- Hypotension
What is required for a re-entrant circuit to form?
Unidirectional block and slowed conduction
What characterizes atrial flutter?
Rapid regular atrial activity (180-350 BPM) with many impulses reaching the AV node but not conducting to ventricles
What are potential treatments for atrial flutter?
- Electrical cardioversion
- Pacemaker
- Pharmacological therapy
- Catheter ablation
What is atrial fibrillation?
Chaotic rhythm with atrial rate of 350-600 discharges per minute and irregular ventricular response
What are some causes of atrial fibrillation?
- Enlarged atria
- Heart failure
- Hypertension
- Coronary artery disease
- Thyrotoxicosis
- Alcohol
What is the ventricular rate in atrial fibrillation?
140-160 BPM
Atrial fibrillation can lead to irregular ventricular rates due to wandering re-entrant circuits.
What are some causes of atrial fibrillation?
- Enlarged atria
- Heart failure
- Hypertension
- CAD
- Thyrotoxicosis
- Alcohol
Enlarged atria increase the likelihood of developing atrial fibrillation.
Why is atrial fibrillation considered dangerous?
Rapid ventricular rates reduce cardiac output and can lead to blood stasis, resulting in thrombus/emboli.
What are the treatment options for atrial fibrillation?
- Antiarrhythmic drugs
- Electrical cardioversion
- Catheter ablation
- Maze procedure
What characterizes ventricular tachycardia (VT)?
It can be sustained or non-sustained and is associated with structural heart disease, MI, and heart failure.
What is the heart rate range for ventricular tachycardia?
100-200 BPM
What are the symptoms of ventricular tachycardia?
- Syncope
- Pulmonary oedema
- Cardiac arrest
What is ventricular fibrillation (VF)?
A life-threatening condition characterized by disordered rapid stimulation of the ventricles, leading to loss of cardiac output.
What can trigger ventricular fibrillation?
- Heart disease
- Low K+
- Electric shock
- Some drugs
VF often initiated by episodes of ventricular tachycardia.
What is the primary treatment for ventricular fibrillation?
Prompt electrical defibrillation
What is an ICD?
An implantable cardioverter defibrillator similar to a pacemaker but delivers larger shocks to the heart.
What are congenital long-QT syndromes?
Conditions characterized by prolonged ventricular repolarization, which can lead to ventricular arrhythmias.
What is the mechanism behind LQT1?
Decreased K+ current due to mutations in the KCNQ1 gene.
What is the inheritance pattern of LQT1?
Autosomal dominant and autosomal recessive
What is the primary effect of class I antiarrhythmic drugs?
Sodium channel blockade
What are the three subtypes of Class I antiarrhythmic drugs?
- 1a: Sodium channel blockade with lengthened refractoriness
- 1b: Sodium channel block with reduced refractoriness
- 1c: Sodium channel block with little effect on refractory period
What is the mechanism of action for Class II antiarrhythmic drugs?
Catecholamine blockade
What does Class III antiarrhythmic drugs aim to do?
Lengthen the refractory period
What are the adverse effects of Amiodarone?
- Photosensitive rash
- Thyroid abnormalities
- Pulmonary fibrosis
- Corneal deposits
What is the primary function of Class IV antiarrhythmic drugs?
Calcium channel blockade
What is the role of adenosine in cardiac function?
Acts as a vasodilator and slows conduction through the AV node.
How does digoxin affect cardiac function?
Inhibits Na+/K+ ATPase, increasing intracellular Ca2+ and enhancing contractility.
What is a significant risk associated with digoxin?
Low therapeutic index leading to ectopic arrhythmias and heart block.
What is the primary treatment for digoxin overdose?
Use FAB fragment of antibody (Digibind)
What is the mechanism of action of atropine?
Muscarinic antagonist used to treat sinus bradycardia.
What is the effect of isoprenaline?
β receptor agonist used in heart block.
What does the choice between drugs and electroconversion depend on?
The type of arrhythmia and its self-sustaining nature.
What type of receptor agonist is Isoprenaline?
β receptor agonist
What condition can Calcium chloride be used to treat?
Ventricular tachycardia
What condition can Magnesium sulphate be used to treat?
Ventricular fibrillation (torsades de pointes)
What is a key choice when treating arrhythmias?
Choice between drugs and electroconversion
What type of electric shock is applied externally for arrhythmias?
Direct current (DC) electric shock
What happens once many atrial/ventricular arrhythmias begin?
They are self-sustaining
What is the result of a successful electric shock in treating arrhythmias?
Heart depolarised, ectopic focus extinguished, SA node resumes as dominant pacemaker
How quickly do the effects of electroconversion occur?
Immediate
What are the drawbacks of using drugs for arrhythmias?
Adverse effects and unpredictability
What types of tachycardia can be treated with electroconversion?
Supraventricular tachycardia, ventricular fibrillation, atrial fibrillation/flutter
What can drugs be used for in the context of arrhythmias?
To prevent relapse
What are the main objectives of anti-arrhythmic drug treatment?
Reduce morbidity and reduce mortality.
Ventricular arrhythmias lead to 70,000 deaths per year in the UK.
What is the main challenge in the treatment of chronic/episodic arrhythmias?
Notoriously difficult.
What occurs during Phase 0 of the cardiac action potential?
Rapid depolarisation due to Na+ influx.
What occurs during Phase 1 of the cardiac action potential?
Short repolarisation due to K+ efflux.
What happens during Phase 2 of the cardiac action potential?
Delay in repolarisation due to Ca2+ entry via L-type channels.
What is the function of Phase 3 in the cardiac action potential?
Rapid repolarisation due to K+ efflux.
What is the role of Phase 4 in the cardiac action potential?
Automaticity through slow depolarisation.
What is the pacemaker potential in the SA node primarily driven by?
If slow Na+ current.
Fill in the blank: The _______ period is the time during which a second action potential cannot be initiated.
absolute refractory
What are the major modes of action of anti-arrhythmic drugs?
- Decrease slope of Phase 4 (slow rate)
- Increase threshold potential (slow Phase 0)
- Increase refractory period (lengthen action potential)
- Impair conduction (prevent re-entry)
What is the Vaughan-Williams classification?
A classification system for anti-arrhythmic drugs.
What characterizes Class I anti-arrhythmic drugs?
Sodium channel blockade.
What is the effect of Class II anti-arrhythmic drugs?
Catecholamine blockade.
What is the primary action of Class III anti-arrhythmic drugs?
Lengthening of refractoriness.
What do Class IV anti-arrhythmic drugs do?
Calcium channel blockade.
What is a key feature of Class 1a anti-arrhythmic drugs?
Sodium channel blockade with lengthened refractoriness.
Name an example of a Class 1a anti-arrhythmic drug.
Quinidine, disopyramide, or procainamide.
What is characteristic of Class 1b anti-arrhythmic drugs?
Sodium channel block with reduced refractoriness.
Name an example of a Class 1b anti-arrhythmic drug.
Lidocaine.
What distinguishes Class 1c anti-arrhythmic drugs?
Sodium channel block with little effect on refractory period.
Name an example of a Class 1c anti-arrhythmic drug.
Flecainide.
What is the action of Class III anti-arrhythmic drugs like Amiodarone?
Prolongs cardiac action potential.
What are the adverse effects of Amiodarone?
- Photosensitive rash
- Thyroid abnormalities
- Pulmonary fibrosis
- Corneal deposits
What is a potential risk of Class III anti-arrhythmic drugs?
They can be pro-arrhythmic.
What is the primary action of Class IV anti-arrhythmic drugs like Verapamil?
Slow conduction in SA and AV nodes.
What is a unique feature of Adenosine as an anti-arrhythmic agent?
Acts via A1 receptors on the AV node.
What is the mechanism of action of Digoxin?
Inhibits Na+/K+ ATPase.
What conditions is Digoxin useful in treating?
- Atrial fibrillation
- Atrial flutter
- Heart failure
What is the elimination route and half-life of Digoxin?
85% unchanged by kidneys; half-life is 36 hours.
What is the treatment for Digoxin overdose?
Use FAB fragment of antibody (Digibind).
What is the Maze procedure used for?
Treatment of atrial fibrillation when drugs do not control the condition.
What is the purpose of catheter ablation?
Creates a scar that is electrically inactive to stop arrhythmias.
True or False: Drugs can be used to prevent relapse of arrhythmias.
True.
What are the session objectives related to stroke and TIA?
- Discuss the pathophysiology associated with stroke and TIA.
- Identify signs, symptoms, and risk factors.
- Outline the pathway for diagnosis.
- Formulate an appropriate treatment plan.
How many people in the UK are living post-stroke?
1.2 million
What is the annual incidence of first or repeat strokes in the UK?
140,000 people
What percentage of strokes are due to cerebral infarction?
85%
What percentage of strokes are due to cerebral haemorrhage?
15%
What is the incidence of first-ever TIA in the UK?
Approximately 50/100,000 people per year
What percentage of all deaths in the UK are caused by stroke?
7%
What is the mortality rate for haemorrhagic stroke compared to ischaemic stroke?
35–40% higher
What is the prognosis for recurrent stroke at 1 year after the first stroke?
11.1%
What is the risk of recurrent stroke within 30 days after TIA?
7.5–12%
What percentage of people experience long-term altered arm function after stroke?
Approximately 40%
What are the non-modifiable risk factors for stroke?
- Age
- Gender
- Ethnicity
Name some modifiable risk factors for stroke.
- Hypertension
- Diabetes Mellitus
- Atrial Fibrillation
- Cholesterol
- Smoking
- Obesity
- Low physical activity
- Alcohol intake
- Stress
What are common symptoms of stroke?
- Rapid onset
- Slurred speech
- Facial droop
- Unilateral weakness
- Confusion
- Difficulty speaking or understanding
- Loss of coordination or balance
- Visual disturbance
- Hearing loss
What is a Transient Ischaemic Attack (TIA)?
Neurological dysfunction caused by focal brain ischemia without evidence of acute infarction.
What is the typical duration of TIA symptoms?
Most < 20 mins per attack
What does the acronym FAST stand for in stroke recognition?
- Facial droop
- Arm weakness
- Speech difficulties
- Time to call emergency services
What is the primary management for TIA?
Stat 300mg Aspirin
What is the first-line antiplatelet therapy for secondary prevention after TIA?
Clopidogrel 75mg OD
What is the typical starting dose for atorvastatin for lipid modification?
40mg OD
What imaging is used to diagnose acute stroke?
- Computed Tomography (CT)
- Magnetic Resonance Imaging (MRI)
- Cerebral Angiography
What percentage of strokes in the UK are ischaemic?
Approximately 85%
What is the most common cause of intracerebral haemorrhage?
Hypertension
What is the common symptom of a haemorrhagic stroke?
‘Thunderclap’ headache
What are the main goals of stroke therapy?
- Minimise injury
- Maximise recovery
- Restore perfusion
What is the prognosis for disability after a haemorrhagic stroke at 6 months?
40% have difficulty with basic self-care
What cranial nerve is primarily responsible for facial muscle movement?
Facial nerve (cranial nerve 7)
What type of stroke accounts for 10% of strokes in the UK?
Subarachnoid haemorrhage
What is the purpose of the ROSIER score?
To assess the likelihood of stroke in patients
What is the purpose of atorvastatin in stroke management?
To reduce non-HDL by >40%
Atorvastatin is commonly prescribed at a dose of 20-80mg OD, with a usual starting dose of 40mg OD.
What imaging technique is used to exclude differential diagnosis in acute stroke?
Computed Tomography (CT)
CT scans are essential for ruling out other conditions before treatment.
What is the role of Magnetic Resonance Imaging (MRI) in stroke diagnosis?
Identify responsible blood vessel and show ischaemic changes over time
MRI is preferred for confirming transient ischaemic attacks (TIA).
What does the Electrocardiogram (ECG) help assess in stroke patients?
Underlying heart conditions
ECGs can identify arrhythmias or other cardiac issues contributing to the stroke.
What is the significance of time in ischaemic stroke management?
Time is essential for effective treatment, such as thrombolysis
Rapid intervention can significantly improve outcomes.
What is the first-line treatment for ischaemic stroke within 4.5 hours of symptom onset?
Alteplase
Alteplase activates plasmin production to degrade fibrin clots.
What is the maximum time frame for thrombectomy in ischaemic stroke?
Up to 24 hours if signs of posterior circulation occlusion are present
Thrombectomy is a surgical procedure to remove the clot.
What is the recommended dosage of aspirin for antiplatelet therapy after stroke?
Aspirin 300mg daily for 14 days
If dysphagia is present, alternative administration methods should be used.
What trial demonstrated the efficacy of clopidogrel compared to aspirin?
CAPRIE trial
Clopidogrel reduced ischaemic events with an ARR of 0.51%.
What is the target systolic blood pressure for managing acute haemorrhagic stroke?
130-140mmHg for at least 7 days
This target helps in managing intracranial pressure and reducing further bleeding.
What is the purpose of using nimodipine in subarachnoid haemorrhage (SAH) management?
To prevent vasospasm
Nimodipine is administered at 60mg every 4 hours.
What is the Glasgow Coma Scale threshold for surgical intervention in acute intracerebral haemorrhage?
Below 8
Surgical intervention is rare unless there are significant deficits.
What is the role of decompressive hemicraniectomy in haemorrhagic stroke?
Performed within 48 hours of symptom onset
It is indicated if there are signs of significant brain infarction.
What are some common complications following a stroke?
- Aphasia
- Dysarthria
- Dysphagia
- Emotionalism
- Dyspraxia
- Impaired Cognition
- Depression
- Anxiety
These complications can significantly affect rehabilitation and recovery.
What percentage of stroke patients experience dysphagia?
40-78%
Dysphagia increases the risk of aspiration pneumonia and malnutrition.
What is the appropriate method to check the placement of a nasogastric tube?
pH testing
A pH of 5.5 or below indicates correct placement for feeding.
What types of enteral feeding tubes are mentioned?
- Nasogastric (NG)
- Nasojejunal (NJ)
- Percutaneous endoscopic gastrostomy (PEG)
- Percutaneous endoscopic jejunostomy (PEJ)
- Percutaneous endoscopic gastro-jejunostomy (PEGJ)
Each type has specific indications for use based on patient needs.
What should be administered after feeding through enteral tubes to prevent blockage?
Flush with water
Flushing helps dislodge any potential blockages and prevents interactions.
What is the volume used for some medicines and after feeds?
30ml
What helps prevent interactions of medicine-medicine and medicine-feeds?
Flushing the tube before and after medication administration
What should be considered in fluid restricted patients?
Interactions of medicines with feeds
What should be done to ensure remanent gastric acid is not in the tube?
Flush before and after aspiration
What are the two main consequences for drug absorption via the stomach when an enteral feeding tube is in place?
- Drugs bypass the stomach and normal enteral route * Reduced time in the stomach
What happens to drug absorption when an enteral tube terminating in the jejunum is used?
The acid environment of the stomach is bypassed, resulting in partial or no absorption
What can reduce drug absorption when administered via enteral feeding tubes?
Surgery or acute illness
What can inhibit absorption of medications administered via enteral tubes?
Gastric motility
Which prokinetics can help with gastric motility issues?
- Metoclopramide * Erythromycin * Mirtazapine
What is the guidance for administering several medications through enteral tubes?
Administer each drug separately
What should be done if the enteral tube becomes blocked?
Flush the tube with warm water
What are some complex methods not often used for tube blockage?
- Sodium bicarbonate * Pancrex V
Are injectable drugs suitable for use down the tube?
Some injectable drugs are suitable, like vancomycin and hyoscine
What should never be added to feeds?
Medication
Why should medication not be added to feeds?
It alters drug dosage and risks under/over-dosing
Is it possible to add medication to soft food to aid swallowing?
Sometimes, but not in product licence
When adding medication to food, when should it be done?
To the first mouthful of food
What should not be used to administer drugs due to potential interactions?
Grapefruit juice
