Week 7: Drugs to Treat Cardiovascular Disease and Affecting Haemostasis

Question 1

A 60 year old man is found to have a persistently raised blood pressure of around 200/115. He also has signs and symptoms of mild congestive cardiac failure.
PMH: Type II diabetes controlled by diet alone. Osteoarthritis of both knees. Medication: Naproxen 500 mg twice daily.

What factors might be contributing to his hypertension?

Answer 1

Ca 80% of Type II diabetes sufferers also have hypertension. Likely to indicate a poor diet and obesity. Osteoarthritis also linked to obesity, will also restrict movement and amount of exercise performed.

Naproxen with other NSAIDs can cause blood pressure increases.

Stress.

Question 2

A 60 year old man is found to have a persistently raised blood pressure of around 200/115. He also has signs and symptoms of mild congestive cardiac failure.
PMH: Type II diabetes controlled by diet alone. Osteoarthritis of both knees. Medication: Naproxen 500 mg twice daily.
Should you consider antihypertensive treatment at this level of blood pressure? What might he gain from effective control of his blood pressure?

Answer 2

He has severe hypertension, Yes

Heart failure is a likely result of his hypertension, reducing blood pressure should reduce the progression of heart failure by decreasing the afterload

Question 3

A 60 year old man is found to have a persistently raised blood pressure of around 200/115. He also has signs and symptoms of mild congestive cardiac failure.
PMH: Type II diabetes controlled by diet alone. Osteoarthritis of both knees. Medication: Naproxen 500 mg twice daily.

What drug might be most suitable for first line treatment?

Answer 3

NICE guidelines state “Offer people aged under 55 years step 1 antihypertensive treatment with an angiotensin-converting enzyme (ACE) inhibitor or a low-cost angiotensin-II receptor blocker (ARB).

Offer step 1 antihypertensive treatment with a calcium-channel blocker (CCB) to people aged over 55 years and to black people of African or Caribbean family origin of any age. If a CCB is not suitable, for example because of oedema or intolerance, or if there is evidence of heart failure or a high risk of heart failure, offer a thiazide-like diuretic.”

As he is over 55 with mild heart failure NICE guidelines suggest use of a thiazide diuretic.

Question 4

A 60 year old man is found to have a persistently raised blood pressure of around 200/115. He also has signs and symptoms of mild congestive cardiac failure.
PMH: Type II diabetes controlled by diet alone. Osteoarthritis of both knees. Medication: Naproxen 500 mg twice daily.

What target blood pressure would you aim for on treatment?

Answer 4

140/90 mmHg

Question 5

A 60 year old man is found to have a persistently raised blood pressure of around 200/115. He also has signs and symptoms of mild congestive cardiac failure.
PMH: Type II diabetes controlled by diet alone. Osteoarthritis of both knees. Medication: Naproxen 500 mg twice daily.

As he is over 55 with mild heart failure NICE guidelines suggest use of a thiazide diuretic as first line treatment. This achieves a blood pressure of around 160/100. What action would you take?

Answer 5

Add an ACE Inhibitor or Angiotensin-II receptor blocker (ARB).

Question 6

A 30 year old man has a medical examination for life assurance and is found to have a blood pressure of 170/110. He smokes 20 cigarettes daily and has no significant past medical history. His father had a myocardial infarct at the age of 50.

What additional information do you require?

Answer 6

Lifestyle; exercise and stress levels, diet.

Alcohol intake, recreational and over the counter drug use.

Question 7

A 30 year old man has a medical examination for life assurance and is found to have a blood pressure of 170/110. He smokes 20 cigarettes daily and has no significant past medical history. His father had a myocardial infarct at the age of 50.

What investigations would you carry out to find a cause for his hypertension?

Answer 7

Urea & electrolytes, creatinine for renal function
Blood sugars, cholesterol
Repeat monitor of BP

Question 8

A 30 year old man has a medical examination for life assurance and is found to have a blood pressure of 170/110. He smokes 20 cigarettes daily and has no significant past medical history. His father had a myocardial infarct at the age of 50. Similar blood pressure readings are obtained on several occasions. What action would you recommend?

Answer 8

Lifestyle changes; stop smoking, increase exercise, balanced diet and weight loss

Pharmacological intervention: an angiotensin-converting enzyme (ACE) inhibitor or angiotensin-II receptor blocker

Question 9

A 50-year-old man is admitted to hospital complaining of central, crushing chest pain. An acute anterior myocardial infarction is diagnosed. He receives treatment with aspirin, oxygen and thrombolysis. He makes an uncomplicated recovery. His only identifiable risk factor for coronary heart disease is smoking (20 cigarette-pack-year history) and his only significant previous medical history is of “asthma” for which he uses a salbutamol inhaler. 48 hours after admission he is asymptomatic, BP 110/78 mmHg, heart rate 102 beats per minute, respiratory and cardiovascular examinations are otherwise normal.

What drug treatments would you consider at this stage?

Answer 9

Aspirin and clopidogrel antiplatelet.

Beta-blockers, Ca channel blockers and ACE Inhibitors may be considered

Question 10

A 50-year-old man is admitted to hospital complaining of central, crushing chest pain. An acute anterior myocardial infarction is diagnosed. He receives treatment with aspirin, oxygen and thrombolysis. He makes an uncomplicated recovery. His only identifiable risk factor for coronary heart disease is smoking (20 cigarette-pack-year history) and his only significant previous medical history is of “asthma” for which he uses a salbutamol inhaler. 48 hours after admission he is asymptomatic, BP 110/78 mmHg, heart rate 102 beats per minute, respiratory and cardiovascular examinations are otherwise normal.

An echocardiogram confirms significant left ventricular dysfunction in spite of normal examination. You decide to initiate ACE inhibitor therapy.

What mechanisms underlie the beneficial therapeutic effect of ACE inhibitors in this clinical situation?

Answer 10

Reduce cardiac workload by acting indirectly as a vasodilator of the capacitance and resistance vessels to reduce blood pressure.

Question 11

A 50-year-old man is admitted to hospital for an acute anterior myocardial infarction. He makes an uncomplicated recovery. His only identifiable risk factor for CHD is smoking (20 cigarette-pack-year history) and his only significant previous medical history is of “asthma” for which he uses a salbutamol inhaler. 48 hours after admission he is asymptomatic, BP 110/78 mmHg, heart rate 102 beats per minute, respiratory and cardiovascular examinations are otherwise normal.

An echocardiogram confirms significant left ventricular dysfunction in spite of normal examination. You decide to initiate ACE inhibitor therapy.

What are the possible adverse effects of ACE inhibitors and how would you monitor the patient for these?

Answer 11

ACE inhibitors can cause hypotension (note this patient has normal blood pressure and maybe a risk here) and renal impairment. A persistent dry cough is a common side effect.

Question 12

A 50-year-old man is admitted to hospital for an acute anterior myocardial infarction. He makes an uncomplicated recovery. His only identifiable risk factor for CHD is smoking (20 cigarette-pack-year history) and his only significant previous medical history is of “asthma” for which he uses a salbutamol inhaler. 48 hours after admission he is asymptomatic, BP 110/78 mmHg, heart rate 102 beats per minute, respiratory and cardiovascular examinations are otherwise normal.

An echocardiogram confirms significant left ventricular dysfunction in spite of normal examination. You decide to initiate ACE inhibitor therapy.

What other pharmacological and non-pharmacological factors would you consider in the clinical treatment of this man?

Answer 12

Advise on giving up smoking

Consider statins – could be beneficial for secondary effects even if LDL-C is not a concern

Question 13

A 78-year-old lady is discharged from hospital following an episode of congestive cardiac failure secondary to ischaemic heart disease. Her previous medical history is otherwise unremarkable.
She is subsequently reviewed in out-patient clinic and describes dizziness on standing, and on exertion. Her medications are: Aspirin 150mg daily, Simvastatin 40mg nocte, Lisinopril 10mg daily, Bumetanide 3mg twice daily, Metolazone 2.5mg daily.
On clinical examination her BP is 105/65 mmHg supine, HR 90 beats per minute, jugular venous pressure not raised. On auscultation of her praecordium you hear a pan-systolic murmur of mitral regurgitation. She has no clinical sign of pulmonary or peripheral oedema.

Why is she experiencing dizziness? And how might you demonstrate this?

Answer 13

Orthostatic (or postural) hypotension

BP sitting vs standing, tilt table if available

Question 14

A 78-year-old lady has congestive cardiac failure secondary to ischaemic heart disease. In out-patient clinic she describes dizziness on standing, and on exertion. Her medications are: Aspirin 150mg daily, Simvastatin 40mg nocte, Lisinopril 10mg daily, Bumetanide 3mg twice daily, Metolazone 2.5mg daily.
On clinical examination her BP is 105/65 mmHg supine, HR 90 beats per minute, jugular venous pressure not raised. On auscultation of her praecordium you hear a pan-systolic murmur of mitral regurgitation. She has no clinical sign of pulmonary or peripheral oedema.

What biochemical abnormalities might you expect to find on blood testing?

Answer 14

Electrolyte imbalance and kidney function: urea and creatinine could be increased especially if she is showing signs of dehydration

Question 15

A 78-year-old lady has congestive cardiac failure secondary to ischaemic heart disease. In out-patient clinic she describes dizziness on standing, and on exertion. Her medications are: Aspirin 150mg daily, Simvastatin 40mg nocte, Lisinopril 10mg daily, Bumetanide 3mg twice daily, Metolazone 2.5mg daily.
On clinical examination her BP is 105/65 mmHg supine, HR 90 beats per minute, jugular venous pressure not raised. On auscultation of her praecordium you hear a pan-systolic murmur of mitral regurgitation. She has no clinical sign of pulmonary or peripheral oedema.

Answer 15

Reduce the diuretic dose:

intially stop metolazone and monitor situation from there.

Question 16

A 78-year-old lady has congestive cardiac failure secondary to ischaemic heart disease.
She is reviewed in clinic and describes dizziness on standing, and on exertion. Her medications are: Aspirin 150mg daily, Simvastatin 40mg nocte, Lisinopril 10mg daily, Bumetanide 3mg twice daily, Metolazone 2.5mg daily.
On clinical examination her BP is 105/65 mmHg supine, HR 90 beats per minute, jugular venous pressure not raised. On auscultation of her praecordium you hear a pan-systolic murmur of mitral regurgitation. She has no clinical sign of pulmonary or peripheral oedema.

Would a beta-blocker be appropriate in this situation?

Answer 16

Not immediately as the patient needs to stabilise, however a beta-blocker may be beneficial longer term.

Question 17

A 78-year-old lady has congestive cardiac failure secondary to ischaemic heart disease. In out-patient clinic she describes dizziness on standing, and on exertion. Her medications are: Aspirin 150mg daily, Simvastatin 40mg nocte, Lisinopril 10mg daily, Bumetanide 3mg twice daily, Metolazone 2.5mg daily.
On clinical examination her BP is 105/65 mmHg supine, HR 90 beats per minute, jugular venous pressure not raised. On auscultation of her praecordium you hear a pan-systolic murmur of mitral regurgitation. She has no clinical sign of pulmonary or peripheral oedema.

How might this problem be prevented in future?

Answer 17

Was the decision to add a second diuretic correct? This situation may have been avoided if only the loop diuretic was prescribed, however presumably the metolazone was considered necessary in this case.
Dual diuretics are more usually prescribed in hospital rather than primary care, presumably her blood pressure was reviewed prior to her discharge and wasn’t considered a problem, but if she had no oedema and a stable blood pressure could the metolazone have been discontinued on discharge?

Question 18

A 78-year-old woman presents with breathlessness. She has a history of IHD and severe bi-ventricular failure. Patient is dyspnoeic at rest with evidence of pulmonary oedema and severe peripheral oedema up to and including her abdominal wall.

What other information from the medical history is important?

Answer 18

Kidney or liver disease?
Urination problems
Current medication (diuretics show ADRs with NSAIDs, digoxin and lithium)
Allergy to Sulfa antibiotics (some loop diuretics also cause allergy)

Question 19

A 78-year-old woman presents with breathlessness. She has a history of IHD and severe bi-ventricular failure. Patient is dyspnoeic at rest with evidence of pulmonary oedema and severe peripheral oedema up to and including her abdominal wall.

What is the initial therapeutic management?

Answer 19

Oxygen maybe required to maintain blood saturation

Use diuretics to target hypervolaemia, this is likely to be combined with an ACE inhibitor to reduce the preload and afterload.

Question 20

A 78-year-old woman presents with breathlessness. She has a history of IHD and severe bi-ventricular failure. Patient is dyspnoeic at rest with evidence of pulmonary oedema and severe peripheral oedema up to and including her abdominal wall.

The treatment includes furosemide. What is furosemide’s mechanism of action?

Answer 20

A loop diuretic, it binds to and inhibits the Na-K-2Cl cotransporter on the luminal surface of the thick ascending limb of the loop of Henle. This inhibits Na+ reabsorption, and so also reduces water reabsorption.

Question 21

A 78-year-old woman presents with breathlessness. She has a history of IHD and severe bi-ventricular failure. Patient is dyspnoeic at rest with evidence of pulmonary oedema and severe peripheral oedema up to and including her abdominal wall. The treatment includes furosemide.

What route of administration would you consider? Why?

What are the potential biochemical consequences of furosemide?

Answer 21

Can be delivered i.v. or orally, orally takes 1 hour whereas i.v. starts working within 5 mins

Potential for hypokalaemia, while hyperglycaemia is a common side effect too.

Question 22

A 78-year-old woman presents with breathlessness. She has a history of IHD and severe bi-ventricular failure. Patient is dyspnoeic at rest with evidence of pulmonary oedema and severe peripheral oedema up to and including her abdominal wall. The treatment includes furosemide.
The treatment includes furosemide.

Would you consider alternative diuretics?

Answer 22

Other classes of diuretics exist and maybe more suitable for this patient. Could consider thiazides or potassium or calcium sparing diuretics if you are concerned about electrolyte imbalance

Question 23

A 72-year old man with hypertension was prescribed ibuprofen for acute gout 10 days ago. He presented to the ED with nausea and loss of appetite. His other drug therapy included: Ramipril 10 mg and Bendroflumethiazide 2.5 mg daily.

Admission investigations:
Na+ 134 mmol/l
K+ 4.2 mmol/l
Urea 22
Creatinine 360

Explain the potential causes for his renal failure.

Answer 23

Age. Hypertension can cause chronic kidney disease.

Increased uric acid levels in gout are exacerbated by bendroflumethiazide. Crystallisation of urea in kidney can cause renal damage.

ACE Inhibitors such as Ramipril can cause renal damage

Ibuprofen and other NSAIDs can cause chronic kidney failure, however this is usually over a more prolonged period of time.

Question 24

A 72-year old man with hypertension was prescribed ibuprofen for acute gout 10 days ago. He presented to the ED with nausea and loss of appetite. His other drug therapy included: Ramipril 10 mg and Bendroflumethiazide 2.5 mg daily.

Admission investigations:
Na+ 134 mmol/l
K+ 4.2 mmol/l
Urea 22
Creatinine 360

What other immediate investigations would you request? Detail your initial management plan.

Answer 24

Serum albumin and glucose
Urine analysis for proteinuria, haematuria and creatinine clearance
Ultrasound

eGFR = 15 ml/min/1.73m2 stage 4 point at which dialysis could be considered, along with ureamia

Consider using a different class of diuretic away from the thiazide, but maintain the Ramipril as ACE Inhibitors are generally preferred in kidney disease.

Corticosteriods make an alternative to ibuprofen for gout.

Give lifestyle advice regarding gout and renal failure in particular dietary changes

Question 25

A 68 yr old man with severe osteoarthritis of his right hip is admitted for an elective total hip replacement. He smokes 30 cigarettes a day and admits to drinking approximately 7 bottles of wine a week. Post operatively he complains of pain and swelling in his left leg and a left deep vein thrombosis is diagnosed. What precautions may have been taken to try and prevent his thrombosis occurring?

Answer 25

Physiotherapy | Anticoagulants

Question 26

A 68 yr old man with severe osteoarthritis of his right hip is admitted for an elective total hip replacement. He smokes 30 cigarettes a day and admits to drinking approximately 7 bottles of wine a week. Post operatively he complains of pain and swelling in his left leg and a left deep vein thrombosis is diagnosed. Once the deep vein thrombosis has been diagnosed, how would you initiate his treatment? What advice/counselling would you give to him about his treatment?

Answer 26

Anti-coagulants to prevent the clot enlarging Heparin for immediate effect, 24 hour dose of low molecular weight heparins. Switch to warfarin for oral use on discharge – need to check his arthritis medication for ADRs Compression stocking

Question 27

A 68 yr old man with severe osteoarthritis of his right hip is admitted to hospital for an elective total hip replacement. He smokes 30 cigarettes a day and admits to drinking approximately 7 bottles of wine a week. Post operatively he complains of pain and swelling in his left leg and a left deep vein thrombosis is diagnosed. After discharge from hospital, he comes back to the outpatient clinic complaining of increased and easy bruising. His INR is found to be greater than 10. What may have caused this? What options are available to you to treat this situation and what would you suggest is the best course of action?

Answer 27

Likely to be excess alcohol, but potentially use of a pain killer like aspirin or paracetamol or certain foods in diet.

Question 28

A 74-year old woman with stable angina. Her only medication is Aspirin 150mg a day. She complains of frequent symptoms of indigestion. Why might this be the case? What might the GP do to help her?

Answer 28

Aspirin can cause damage to stomach directly on ingestion and systemically. Clinical burden due to ulceration, haemorrhage and even perforation seen with long term high dose elderly users. Consider an alternative angina treatment eg Glyceryl Trinitrate (GTN) spray or calcium channel blocker

Question 29

A 74-year old woman with stable angina. Her only medication is Aspirin 150mg a day. It transpires that she is left to continue on Aspirin treatment. One day she is admitted to hospital with pleuritic chest pain and with a suspected, but unconfirmed diagnosis of pulmonary embolism. Whilst awaiting further investigation how would you manage her initially?

Answer 29

NICE guidelines state “if a patient has a ‘likely’ probability of PE, treatment with either low molecular weight heparin, or fondaparinux should be started while waiting for confirmation, and stopped if the scan result is negative”

Question 30

A 74-year old woman with a history of stable angina. Her only medication is Aspirin 150mg a day. It transpires that she is left to continue on Aspirin treatment. One day she is admitted to hospital with pleuritic chest pain and with a suspected, but unconfirmed diagnosis of pulmonary embolism. After her initial management she is noted to have widespread purpura. What might this be due to?

Answer 30

Could be a combination of the anticoagulant and aspirin

Question 31

A 74-year old woman with a history of stable angina consults her GP. Her only medication is Aspirin 150mg a day. It transpires that she is left to continue on Aspirin treatment. One day she is admitted to hospital with pleuritic chest pain and with a suspected, but unconfirmed diagnosis of pulmonary embolism. Prior to being discharged from hospital she starts to develop a chest infection and is treated with the antibiotic erythromycin according to bacterial sensitivity. Will this affect your subsequent management? If so, how and why?

Answer 31

Erythromycin inhibits the metabolism and subsequent clearance of warfarin from the body. Therefore she should not be started on warfarin before she has completed her antibiotic treatment.

Question 32

A 74-year old woman with a history of stable angina. Her only medication is Aspirin 150mg a day. Admitted to hospital with pleuritic chest pain and with a suspected diagnosis of pulmonary embolism. Prior to being discharged from hospital she starts to develop a chest infection and is treated with the antibiotic erythromycin according to bacterial sensitivity. One month after discharge she suffers a fall at home, resulting in a fracture of her left neck of femur. With respect to her current treatment, what are your main concerns for her?

Answer 32

Assuming the anticoagulation treatment is successful there will be concealed bleeding with haematoma around the fracture site. Depending on the severity this could cause anaemia requiring a blood transfusion. Potential bleeding elsewhere too and head or other injuries. She needs surgery but the risks of uncontrolled bleeding are high on warfarin. A target INR for surgery is <1.5 SIGN111 ‘Management of hip fracture in older people’ states “Withholding warfarin combined with administration of oral or intravenous vitamin K is recommended if reversal of the anticoagulant effects of warfarin to permit earlier surgery is deemed appropriate.”

Question 33

A 74-year old woman with a history of stable angina consults her GP. Her only medication is Aspirin 150mg a day. It transpires that she is left to continue on Aspirin treatment. One day she is admitted to hospital with pleuritic chest pain and with a suspected, but unconfirmed diagnosis of pulmonary embolism. Prior to being discharged from hospital she starts to develop a chest infection and is treated with the antibiotic erythromycin according to bacterial sensitivity. One month after discharge she suffers a fall at home, resulting in a fracture of her left neck of femur. The orthopaedic surgeons advise that the best treatment for her is to undergo pinning of her fracture within the next week if possible. How would you manage her anticoagulation therapy peri-operatively?

Answer 33

Hip fracture is best operated early, within 24 hours, but this would be dangerous in the presence of anticoagulation so there is a balance between the risks of surgical bleeding versus the possibility of DVT and or PE. Therefore warfarin must be withdrawn, but an alternative may be required. Plan: Refer to the hospital’s Anticoagulant guidelines Stop warfarin and administer vitamin K if appropriate (SIGN111), monitor INR daily. Bridge the anticoagulant gap with LMW heparin, starting at admission, stopping 12 hours before surgery and restarting 6–12 hours after surgery (NICE CG92). Operate once INR<1.5 Other considerations: Consult haematologist for latest advice on new anticoagulants that may be suitable or fresh frozen plasma administration to replace clotting factors

Question 34

A 65 year old man presents with central chest pain at sudden onset. His ECG shows acute 4 mm ST elevation in leads V2-V6. What further information do you need to plan his initial medical treatment?

Answer 34

Onset time – assess suitability for percutaneous coronary intervention (PCI, coronary angioplasty) Serial ECG changes Coronary angiography Troponin levels Previous cardiac history, especially if given streptokinase Other concurrent medications Results of FBC, urea & electrolytes, glucose and lipids blood tests

Question 35

A 65 year old man presents with central chest pain at sudden onset. His ECG shows acute 4 mm ST elevation in leads V2-V6. What immediate treatments would you give?

Answer 35

Oxygen if oxygen saturation is less than 94% Analgesia e.g. diamorphine injection Aspirin Sublingual GTN Then plan for percutaneous coronary intervention (PCI, coronary angioplasty) or thrombolysis (if PCI not available within 120 mins of thrombolysis) (NICE CG167) Later consider use of an ACE inhibitor or beta blocker and DVT prophylaxis.

Question 36

A 55 year old man presents with a 6 hour history of crushing central chest pain and ECG evidence of acute myocardial infarction. You consider immediate thrombolytic therapy. What are the options available and how would you decide which of the agents that are available to use?

Answer 36

Thrombolytic agents convert plasminogen to plasmin which acts as a fibrinolytic to dissolve clots. Options include: Streptokinase – original agent but with ADRs, including being antigenic and so for one use only Alteplase a recombinant tissue plasminogen activator rtPA, newer class of agents with fewer side effects that can be used after a previous dose of streptokinase.

Question 37

A 55 year old man presents with a 6 hour history of crushing central chest pain and ECG evidence of acute myocardial infarction. You consider immediate thrombolytic therapy. What complications of thrombolytic treatment might occur, how common are they and how should they be managed?

Answer 37

Risk of haemorrhage (especially cerebral and GI) Hypotension, antigenic reactions and even myocardial rupture. Most complications are rare e.g. estimates for cerebral haemorrhage and stroke around 1%. Allergic reaction with streptokinase can be managed with oxygen, antihistamines, steroids and if necessary adrenaline.

Question 38

A 55 year old man presents with a 6 hour history of crushing central chest pain and ECG evidence of acute myocardial infarction. You consider immediate thrombolytic therapy. Four hours later he develops difficulty finding his words and is noted to have right facial weakness with reduced power in the right arm. What might have caused this? What investigations would you carry out?

Answer 38

FAST: Face, Arm, Speech, Time A stroke caused by cerebral haemorrhage CT scan of head Later on swallow assessment, physiotherapy, speech therapy and further CT

Question 39

A 55 year old man presents with a 6 hour history of crushing central chest pain and ECG evidence of acute myocardial infarction. You consider immediate thrombolytic therapy. Four hours later he develops difficulty finding his words and is noted to have right facial weakness with reduced power in the right arm. The diagnosis of cerebral haemorrhage is confirmed. How common is this complication, and what factors predispose to it?

Answer 39

``` Around 1% Factors include: Previous history of a bleed or stroke Hypertension Recent head injury or recent neurosurgery ```

Question 40

What is the indication for dual diuretic therapy in heart failure?

Answer 40

Refractory heart failure, in cases where a loop diuretic has been insufficient to treat oedema and so the thiazide has been added to the treatment.

Question 41

A 65 year old man presents with central chest pain at sudden onset. His ECG shows acute 4 mm ST elevation in leads V2-V6. What information would you give the patient at this stage? How would you assess the effectiveness of your immediate treatment?

Answer 41

This is a serious life changing event – lifestyle changes Best results from PCI but this may not be available in which case thrombolysis will help. Explain risks vs benefits of procedures Often may undergo angio at a later date Plan for cardiac rehabilitation /physiotherapy

Question 42

A 65 year old man presents with central chest pain at sudden onset. His ECG shows acute 4 mm ST elevation in leads V2-V6. How would you assess the effectiveness of your immediate treatment?

Answer 42

``` Improvement in pain relief Improvement in serial ECGs Coronary angiography Monitor cardiac markers e.g. troponin Monitor for further complications e.g. heart failure ```

Question 43

True or false? High blood pressure very seldom causes symptoms.

Answer 43

True. It is therefore not a ‘disease’ but a risk factor for future vascular disease.

Question 44

List 3 organs impacted by hypertension

Answer 44

The organs affected by sustained hypertension are the brain, the heart, the arterial system, the kidney and the eye.

Question 45

True or false? Hypertension is rarely (<5%) secondary to a definable cause

Answer 45

True. Hypertension is rarely (<5%) secondary to a definable cause such as renal or endocrine disease or coarctation of the aorta. In most patients the basis is ‘essential’ or primary hypertension, which is often familial.

Question 46

Secondary causes of hypertension

Answer 46

Can be secondary to a definable cause such as renal (interstitial or renovascular) or endocrine (phaeochromocytoma, Conn’s, Cushing’s) disease or coarctation of the aorta.

Question 47

How oral contraceptive pills impact blood pressure?

Answer 47

raise BP the oral contraceptive pill and corticosteroids can raise the blood pressure, as can sustained high alcohol intake.

Question 48

How corticosteroids impact blood pressure?

Answer 48

raise BP the oral contraceptive pill and corticosteroids can raise the blood pressure, as can sustained high alcohol intake.

Question 49

How does sustained high alcohol intake impact blood pressure?

Answer 49

raise BP the oral contraceptive pill and corticosteroids can raise the blood pressure, as can sustained high alcohol intake.

Question 50

List two medications that can raise BP.

Answer 50

the oral contraceptive pill and corticosteroids can raise the blood pressure

Question 51

What two factors are considered important in determining whether drug therapy should be offered for hypertension

Answer 51

I. The sustained level of blood pressure II. The overall cardiovascular risk profile for e.g. For patients with diabetes, high blood pressure is particularly adverse and should be stringently controlled.

Question 52

Thresholds for drug treatment of hypertension

Answer 52

Sustained pressure ≥160 mm systolic and ≥100 mm diastolic justify drug treatment. At levels of 140-159 systolic and 90-99 diastolic, the decision depends on the overall cardiovascular risk profile (is there >15% risk of a cardiovascular event in the next 10 years?) and the presence or absence of end organ damage in the heart (LVH), eye or kidney. In the presence of diabetes, the treatment threshold is 140mm systolic or 90 mm diastolic, with a target level of <130/80mm on treatment.

Question 53

List 5 types of drugs used to treat hypertension

Answer 53

I. Thiazide Diuretics II. Beta-adrenoceptor blocking drugs III. Angiotensin converting enzyme (ACE) inhibitors IV. Calcium-channel blocking drugs V. Other agents for resistant hypertension or patients intolerant of other agents: angiotensin-II receptor antagonists, alpha-blockers, vasodilators and centrally acting drugs.

Question 54

Mechanism of thiazide diuretics in managing hypertension

Answer 54

``` Thiazide diuretics (e.g. bendrofluazide) have direct vasodilating properties as well as natriuretic action. ```

Question 55

Patient is prescribed thiazide diuretics for hypertension. What are some important side effects?

Answer 55

Side effects include gout, hypokalaemia and mild | impairment of glucose tolerance (all rare).

Question 56

Mechanism of beta blockers in managing hypertension

Answer 56

Beta-blockers (e.g. atenolol) have their main action on the heart by reducing myocardial contractility.

Question 57

Side effects of beta blockers

Answer 57

Side effects include cold extremities and impaired exercise capacity (fairly common), bronchospasm (important to avoid in asthmatic patients), precipitation of acute heart failure, bradycardia. Positively indicated with concurrent angina, chronic heart failure or past myocardial infarction.

Question 58

Mechanism of ACE inhibitors in managing hypertension

Answer 58

``` ACE inhibitors (e.g. lisinopril) lower angiotensin-II (A-II) levels and thereby cause vasodilatation and natriuresis. ```

Question 59

Why should renal function by monitored when starting a patient on ACE inhibitors?

Answer 59

``` First-dose hypotension can occur, especially in patients who are volume-depleted and/or on diuretics. Rarely, a sharp and potentially irreversible decline in renal function may occur in patients with (probably unsuspected) renal artery stenosis; renal function should be monitored when starting or increasing ACE inhibitor dose. ```

Question 60

Your patient is prescribed ACE inhibitors for hypertension but develops a significant dry cough. What suitable alternative medication could you use?

Answer 60

A-II receptor antagonists (e.g. losartan) do not cause cough but act otherwise similarly to ACE inhibitors – a suitable substitute

Question 61

Are ACE inhibitors indicted in a patient with hypertension and concurrent heart failure?

Answer 61

Yes ACE inhibitors are generally well tolerated, and positively indicated with concurrent heart failure.

Question 62

Which hypertensive medication is Positively indicated with concurrent angina?

Answer 62

Calcium-channel blocking drugs Dihydropyridines can cause vasodilator side effects

Question 63

Mechanism of Calcium channel blockers in managing hypertension

Answer 63

Calcium-channel blocking drugs are of three pharmacological classes. All are effective in lowering blood pressure but some (the dihydropyridines e.g. amlodipine) are predominantly vasodilators while others (e.g. diltiazem and verapamil) appear to act mainly or partially via an effect on myocardial contractility.

Question 64

Define heart failure.

Answer 64

Heart failure is a state ‘in which the heart fails to maintain an adequate circulation for the needs of the body despite an adequate filling pressure’.

Question 65

Starling’s law of the heart

Answer 65

The force developed in the myocardium depends on the degree to which the fibres are stretched (or the heart is filled). In heart failure the heart can no longer produce the same amount of force (or cardiac output) for a given level of filling.

Question 66

Use starling's law of the heart to explain the change that occurs in heart failure

Answer 66

Starling's Law of the Heart - The force developed in the myocardium depends on the degree to which the fibres are stretched (or the heart is filled). In heart failure the heart can no longer produce the same amount of force (or cardiac output) for a given level of filling.

Question 67

What two systems are activated in heart failure in an attempt to maintain cardiac output?

Answer 67

The sympathetic nervous system and the Renin-Angiotensin-Aldosterone System (RAAS) are both activated in heart failure in an attempt to maintain cardiac output. These have the effect of making an already struggling heart work.

Question 68

The sympathetic nervous system and the Renin-Angiotensin-Aldosterone System (RAAS) are both activated in heart failure in an attempt to maintain cardiac output. Why are these harmful in the context of heart failure?

Answer 68

These have the effect of making an already struggling heart work harder. In addition, angiotensin II can damage the heart and other organs.

Question 69

ACE inhibitors thus have | an indirect vasodilatory and diuretic effects. Explain how.

Answer 69

ACE inhibitors are used in the treatment of heart failure to prevent the production of angiotensin II which is a powerful vasoconstrictor and promotes the release of aldosterone from the adrenal cortex. Aldosterone causes salt and water retention in the kidneys, increasing blood volume. ACE inhibitors thus have an indirect vasodilatory and diuretic effect, both of which are beneficial in the treatment of heart failure.

Question 70

Goals of treatment of heart failure

Answer 70

``` o Symptomatic improvement o Delay progression of heart failure o Reduce mortality o Treat complications/associated conditions/cardiovascular risk factors ```

Question 71

Define Thrombosis

Answer 71

Thrombosis is the local coagulation or clotting of the blood in a part of the circulatory system.

Question 72

In what context is virchow's triad used? What comprises the triad?

Answer 72

Virchow’s triad indicates the main factors which predispose to thrombosis. Stasis Hypercoagulability Endothelial injury

Question 73

Does anticoagulation refer to venous or arterial thromboembolism?

Answer 73

both prevention and treatment of thromboembolism,

Question 74

What is prothrombin time?

Answer 74

The prothrombin time is the time taken for plasma to clot in the presence of an extrinsic tissue factor.

Question 75

How is prothrombin time reported in a standardised way?

Answer 75

In order to compare the clotting of a patient to a normal control The International Normalised Ratio (INR) is used. This gives a standardised measure of the prothrombin time ratio; PTtest:PTnormal allowing for the tissue factor used and is particularly used to monitor patients taking warfarin.

Question 76

Vitamin K promotes synthesis of prothrombin & which clotting factors?

Answer 76

VII, IX, X as well as proteins C and S

Question 77

Mechanism of action: Vitamin K antagonist anticoagulants

Answer 77

􀁸 Vitamin K promotes synthesis of prothrombin & Factors VII, IX, X (also Proteins C & S) 􀁸 Competitively antagonised by coumarin derivatives e.g. Warfarin

Question 78

Important Pharmacokinetics of Warfarin

Answer 78

GI absorption – oral dosing Causes dose dependent reduction in Vit. K dependent factors, but: 􀁸 Extreme variation in individual dose requirement 􀁸 Monitor dose by INR 􀁸 Differing degrees of anticoagulation, depending upon condition 􀁸 Heavily protein bound 􀁸 Gradual onset of activity. 􀁸 Persisting anticoagulant action on cessation of treatment 􀁸 Numerous drug interactions resulting in altered anticoagulant effect o The majority are potentiating, but some are inhibiting 􀁸 Hepatic metabolism by multiple CYP isoforms

Question 79

Warfarin has numerous drug interactions resulting in altered anticoagulant effect. Are most potentiating or inhibiting?

Answer 79

Most warfarin DDI are potentiating, leading to increased bleeds

Question 80

Adverse effects of warfarin

Answer 80

􀁸 Excessive bleeding/bruising/purpura | 􀁸 In pregnancy – teratogenicity

Question 81

Several of warfarin therapy

Answer 81

􀁸 Antagonism of therapy by administration of Vitamin K

Question 82

Heparin mechanism of action

Answer 82

􀁸 Linear mucopolysaccharide chains (glycosaminoglycans) of variable length and Molecular Weight 􀁸 Active site is a pentasaccharide sequence – this binds to Antithrombin 􀁸 Markedly increases antithrombin-mediated inhibition of predominantly Thrombin and Xa, (but also Factors Ixa, Xia XIIa)

Question 83

Important pharmacokinetics of Heparin

Answer 83

􀁸 Poor GI absorption – therefore administered iv/sc 􀁸 Rapid onset/offset of anticoagulant activity 􀁸 Variable bioavailability due to binding to plasma proteins 􀁸 Dose/effect monitored by APTT

Question 84

Contrast the dosing routes of warfarin vs heparin

Answer 84

warfarin - GI absorption – oral dosing heparin - Poor GI absorption – therefore administered iv/sc

Question 85

How is the dose/effect monitored in warfarin vs heparin?

Answer 85

Heparin 􀁸 Dose/effect monitored by APTT Warfarin 􀁸 prothrombin time via INR

Question 86

Compare the actions of heparin and warfarin after treatment is stoped

Answer 86

Heparin - Rapid onset/offset of anticoagulant activity Warfarin - Persisting anticoagulant action on cessation of treatment

Question 87

Adverse effects of heparin

Answer 87

􀁸 Bleeding/bruising 􀁸 Thrombocytopenia 􀁸 Osteoporosis (long term administration)

Question 88

Reversal of heparin therapy

Answer 88

􀁸 Protamine sulphate – causes dissociation of Heparin/Antithrombin complex and binds irreversibly to heparin

Question 89

3 categories of Antiplatelet agents

Answer 89

1. Thromboxane A2 inhibition: (e.g. Aspirin, Dipyridamole) 2. latelet ADP receptor antagonists: (e.g. Clopidogrel, Ticlopidine) 3. GpIIb/IIIa inhibitors:

Question 90

Give an example of an Antiplatelet agent that works via thromboxane A2 inhibition

Answer 90

Aspirin – inhibits cyclooxygenase and therefore platelet thromboxane A2 production. Also attenuates protective effect of gastric mucosal prostaglandins (through cyclocoxygenase inhibition) – gastric erosions/ulcers may occur. Dipyridamole – inhibits platelet phosphodiesterase – rising platelet 128eli levels inhibit Thromboxane A2 production.

Question 91

How does aspirin act as an anti platelet agent?

Answer 91

inhibits cyclooxygenase and therefore platelet thromboxane A2 production Thromboxane A2 liberated from activated platelets – causes platelet aggregation

Question 92

How does Clopidogrel act as an anti platelet agent?

Answer 92

ADP/ADP-receptor interaction – one of many stimuli for platelet aggregation.

Question 93

How do GpIIb/IIIa inhibitors: act as anti platelet agents?

Answer 93

Inhibit final common pathway of platelet aggregation – 3 classes: o Monoclonal antibodies to GpIIb/IIIa receptor o Peptide antagonists to GpIIb/IIIa receptor o ‘Non-peptide’ small molecule antagonists of GpIIb/IIIa receptor

Question 94

The normal clearance mechanism for thrombi is by which enzyme?

Answer 94

plasmin, a trypsin-like | enzyme which cleaves fibrin (and fibrinogen and several other coagulation factors including II, V and VIII).

Question 95

What is the role of plasmin?

Answer 95

The normal clearance mechanism for thrombi is by plasmin, a trypsin-like enzyme which cleaves fibrin (and fibrinogen and several other coagulation factors including II, V and VIII).

Question 96

What is plasmin formed from?

Answer 96

Plasmin is formed from the circulating precursor plasminogen, which binds to fibrin strands within a thrombus. The conversion of plasminogen to plasmin is achieved by a number of plasminogen activators. These activate plasminogen bound to fibrin. The fibrinolytic system is itself regulated by circulating inhibitors.

Question 97

What is the main underlying mechanism of fibrinolytic drugs?

Answer 97

Fibrinolytic drugs generate plasmin either themselves (e.g. tPA, approved name alteplase) or by binding to and activating endogenous plasminogen (e.g. the bacterial product streptokinase). The former mechanism works preferentially in the presence of fibrin and is therefore described as ‘clot specific’, whereas streptokinase causes a degree of fibrinolytic activity in the general circulation. The practical significance of this difference is uncertain.

Question 98

Which fibrinolytic mechanism is described as "clot specific"?

Answer 98

Fibrinolytic drugs generate plasmin either themselves (e.g. tPA, approved name alteplase) or by binding to and activating endogenous plasminogen (e.g. the bacterial product streptokinase). The former mechanism works preferentially in the presence of fibrin and is therefore described as ‘clot specific’,

Question 99

Why is streptokinase a potential allergen?

Answer 99

Streptokinase is a bacterial protein and therefore antigenic. It can cause allergic reactions (major in about 0.1% of treated patients) and cannot be used twice since it invariably generates blocking antibodies which persist for many years.

Question 100

In carefully selected patients, fibrinolytic drugs are used for the following 3 indications:

Answer 100

􀁸 Acute myocardial infarction 􀁸 Pulmonary embolism 􀁸 Major venous thrombosis Note: Trials have also examined the use of fibrinolytic agents in ischaemic stroke (where a haemorrhagic mechanism has been excluded by CT or MRI scan), but their use in this indication is not routine because of the associated risk of induced cerebral haemorrhage and narrow time-window of potential benefit

Question 101

Give 2 reasons why early treatment with fibrinolytic is important

Answer 101

- before the consequences of vascular occlusion become irreversible. - as they age, thrombi become more resistant to lysis. - The potential benefit of treatment declines continuously over time, whereas the risks (see below) remain constant. - The window of opportunity is within approximately 12 hours for coronary occlusion, rather longer for venous thrombo-embolism but only about 3 hours for ischaemic stroke.

Question 102

Major contra-indications for fibrinolytic therapy

Answer 102

active peptic ulcer or other potential bleeding source, recent trauma or surgery, history of cerebral haemorrhage or stroke of uncertain aetiology, uncontrolled hypertension, and coagulation defect. Age per se is not a contraindication. Streptokinase should not be given to a patient who has received it in the past.

Question 103

In the case of severe allergy or anaphylaxis in response to streptokinase, list 3 treatments that may be given

Answer 103

Severe allergy or anaphylaxis is treated with adrenaline, oxygen, intravenous fluids, an antihistamine and hydrocortisone as required.