Ischaemic Heart Disease

Question 1

Angiotensin Receptor Blockers

Losartan, candesartan

Common indications

Answer 1

• NB ARBs are used when ACEI are not tolerated

1. HTN- 1st or 2nd line treatment to reduce risk of stroke MI and CVD
2. Chronic heart failure- 1st line treatment of all grades of HF to improve symptoms and reduce cardiac remodelling
3. Ischaemic heart disease- reduce risk of subsequent CV events such as MI and stroke
4. Diabetic neuropathy and CKD with proteinuria- to reduce proteinuria and progression of nephropathy

Question 2

ARB

MOA

Answer 2

• ARBs and ACEI have similar effects
• ACEI= inhibit angiotensin (AG) 1 => AG2
• ARBs= block action of AG2 on AT1-receptor
• AG2 is a vasoconstrictor and stimulates aldosterone secretion
• Blocking action reduces peripheral vascular resistance (afterload), which lowers BP
• It dilates the efferent glomerular arteriole, which reduces intraglomerular pressure and reduces progression of CKD
• Reducing aldosterone level promotes Na + H20 excretion
• This can help reduce venous return (pre-load), which has a beneficial effect in HF

Question 3

ARB

Adverse effects

Answer 3

• ARBs can cause hypotension (particularly after the first dose), hyperkalemia and renal failure. The mechanism is the same as for ACEI
• Patients most at risk of renal failure are those with renal artery stenosis, who rely on the constriction of the efferent arterioles to maintain glomerular filtration
• Unlike ACEI, ARBs are less likely to cause a dry cough, as they do not inhibit ACE and therefore do not affect bradykinin metabolism
• For the same reason, they are less likely to cause angioedema

Question 4

ARB

Warnings

Answer 4

• ARBs should be avoided in patients with renal artery stenosis or AKI
• Women who are pregnant or those breastfeeding
• Although ARB therapy is potentially valuable in some forms of CKD- lower doses should be used and the effect of renal function monitored closely

Question 5

ARB

Interaction

Answer 5

• Due to the risk of hyperkalaemia, avoid prescribing ARB with other potassium-elevating drugs- including potassium supplements and potassium-sparing diuretics
• In combination with other diuretics they may be associated with profound first-dose hypotension
• The combination of NSAIDs with ARBs increase the risk of renal failure

Question 6

ARBs

Communication

Answer 6

• Explain that you are offering treatment with medicine to improve their BP and reduce strain on their heart
• If a patient has previously not tolerated ACEI due to cough state this does not cause a cough
• State possibility of dizziness (Hypotension) due to low BP, particularly after the first dose
• Make sure they understand the need for blood test monitoring, explaining that ARBs can interfere with their kidney function and upset potassium balance
• Advise them to avoid taking OTC anti-inflammatories (e.g. ibuprofen) due to risk of kidney damage

Question 7

ARBs
Monitoring

Answer 7

• Monitor efficacy clinically, for example, reduced symptoms of breathlessness in HF or improved BP control in HTN
• For safety, check electrolytes and renal function before starting treatment
• Repeat 1-2 weeks into treatment and after increasing the dose
• Biochemical changes can be tolerated provided they are within certain limits, the creatinine concentration should not rise by more than 30%, the eGFR should not fall by more than 25%, and the potassium concentration should not rise above
• If any of these limits are exceeded, you should stop the drug and seek expert advice

Question 8

ACEI

Common indications

Answer 8

1. HTN- for 1^st or 2^nd treatment of HTN to reduce the risk of stroke, MI and death from CVD
2. Chronic HF- 1^st line treatment of all grades of HF, to improve symptoms and prognosis
3. Ischaemic heart disease- reduce the risk of subsequent CV events such as MI and stroke
4. Diabetic nephropathy and CKD with proteinuria- reduce proteinuria and progression of nephropathy

Question 9

ACEI

MOA

Answer 9

• ACEI block the action of the ACEI, to prevent the conversion of Angiotensin AG1 to AG2
• AG2 is a vasoconstrictor and stimulates aldosterone secretion. Blocking its action reduces peripheral vascular resistance (afterload), which lowers BP
• It particularly dilates the efferent glomerular arteriole, which reduces intraglomerular pressure and slows the progression of CKD
• Reducing the aldosterone level promotes sodium and water excretion
• This can help to reduce venous return (preload), which has beneficial effect in HF

Question 10

ARBs

Adverse effects

Answer 10

• Common side effects include hypotension (particularly after the first dose, persistent dry cough (increased levels of bradykinin, which are usually inactivated by ACE) and hyperkalemia (low aldosterone level promotes K retention)
• They can cause or worsen renal failure. This is particularly relevant in patients with renal artery stenosis, who rely on constriction of the efferent glomerular arteriole to maintain glomerular filtration
• It detected early, these adverse effects are usually reversible on stopping the drug
• Rare but important side effects include angioedema and anaphylactoid reactions

Question 11

ACEI

Warnings

Answer 11

• ACEI should be avoided in patients with renal artery stenosis or AKI. In women who are or could become pregnant and those who are breastfeeding.
• Although ACEI is potentially valuable in some forms of CKD- lower doses should be used and the effect on renal function monitored closely

Question 12

ACEI

Interactions

Answer 12

• Due to the risk of hyperkalaemia, avoid prescribing ACEI with other potassium-elevating drugs, including potassium supplements and potassium-sparing diuretics except under specialist advice for advanced HF
• In combination with other diuretics, they may be associated with first-dose hypotension
• The combination of an NSAID and an ACEI increases the risk of renal failure

Question 13

ACEI

Communication

Answer 13

• Explain that you are offering treatment with medicine to improve BP and reduce cardiac strain (remodelling)
• Advise patients about common side effects such as a dry cough, and about the possibility of dizziness due to low BP, particularly after the first dose
• Mention that, very rarely these medicines cause effects similar to severe allergic reactions and to stop taking and seek medical advice if they develop facial swelling and stomach pain
• Make sure they understand the need for blood test monitoring, explaining ACEI can interfere with kidney function and K balance
• Avoid NSAIDs due to risk of kidney damage

Question 14

ACEI

Monitoring

Answer 14

• Monitor efficacy e.g. SOB in HF patients
• For safety check electrolyte and renal function before starting treatment, repeat these after 1-2 weeks and then after increasing the dose and after increasing the dose
• Biochemical changes can be tolerated provided there within certain limits, the creatinine concentration should not rise by more than 30%
• K should not be above 6mmol/L

Question 15

Aspirin

Common indications

Answer 15

1. For the treatment of acute coronary syndrome and acute ischaemic, where rapid inhibition of platelet aggregation can prevent or limit arterial thrombosis and reduce subsequent mortality
2. For long-term CV secondary prevention of thrombotic arterial events in patient with cardiovascular, cerebrovascular and peripheral arterial disease
3. To reduce the risk of intracardiac thrombus of embolic stroke in AF where warfarin and NOACs are contraindicated
4. To control mild-to-moderate pain and fever

Question 16

Aspirin

MOA

Answer 16

• Thrombotic events occur when platelet-rich thrombus forms in atheromatous arteries and occludes the circulation
• Aspirin irreversibly inhibits COX to reduce production of pro-aggregatory factor thromboxane from arachidonic acid, reducing platelet aggregation and the risk of arterial occlusion
• The antiplatelet effect of aspirin occurs at low doses and lasts for the lifetime of a platelet (which does not have a nucleus to allow synthesis of new COX) and thus only wears off as new platelets are made

Question 17

Aspirin

Adverse effects

Answer 17

• The most common adverse effect of aspirin is GI irritation
• More serious effects include GI ulceration and haemorrhage and hypersensitivity including bronchospasm
• In regular high-dose therapy aspirin causes tinnitus
• Aspirin is life-threatening in overdose
• Features include hyperventilation, hearing changes, metabolic acidosis and confusion, followed by convulsions, CV collapse and respiratory arrest

Question 18

Aspirin

Warnings

Answer 18

• Aspirin should not be given to children U16 due to the risk of Reye’s syndrome, a rare but life-threatening illness that principally affects the liver and brain
• It should not be taken by people with aspirin hypersensitivity i.e. who have had bronchospasm or other allergic symptoms triggered by exposure to aspirin or another NSAID
• However, is not routinely contraindicated in Asthma
• Aspirin should be avoided in the third trimester of pregnancy when prostaglandin inhibition may lead to premature closure of the ductus arteriosus
• Aspirin should be used with caution in people with peptic ulceration (e.g. prescribe GI protection) or Gout as it may trigger an acute attack

Question 19

Aspirin

Interactions

Answer 19

• Aspirin acts synergistically with other antiplatelet agents, which although therapeutically beneficial can lead to increased risk of bleeding
• Thus, although it may be given with antiplatelet drugs (e.g. clopidogrel, dipyridamole) and anticoagulants (e.g. heparin, warfarin) in some situations (e.g. ACS) caution is required

Question 20

Beta-blockers

Common indications

Answer 20

1. Ischaemic heart disease- as a 1st line option to improve symptoms and prognosis associated with angina and ACS
2. Chronic HF- 1st line option to improve prognosis
3. AF- 1st line option to reduce the ventricular rate and in paroxysmal AF, to maintain sinus rhythm
4. Supraventricular tachycardia (SVT): 1st line option in patients without circulatory compromise to restore sinus rhythm
5. HTN- although not generally initial therapy, they may be used when other medicines (e.g. CCB, ACEI, thiazide) are insufficient or inappropriate

Question 21

Beta-Blocker

MOA

Answer 21

• B1-adrenoreceptors are located mainly in the heart, whereas B2-adrenoreceptors are found mostly in the smooth muscle of blood vessels and the airways.
• Via the B1-receptor, BB reduces the force of contraction and speed of conduction in the heart.
• This relieves myocardial ischaemia by reducing cardiac work and oxygen demand, and increasing myocardial perfusion.
• They improve prognosis in HF by protecting the heart from the effects of chronic sympathetic stimulation.
• Slow the ventricular rate in AD mainly by prolonging the refractory period of the AV node
• SVT often involves a self-perpetuating (re-entry) circuit that takes in the AV node; BB may break this and restore sinus rhythm
• In HTN- BB lower BP though many ways, one of which by reducing renin secretion from the kidneys.

Question 22

BB

Adverse effects

Answer 22

• BB commonly cause fatigue, cold extremities, headache and GI disturbance (e.g. nausea)
• They can cause sleep disturbance nightmares
• They may cause impotence in men

Question 23

BB

Warnings

Answer 23

• In patients with asthma, BB can cause life-threatening bronchospasm so should be avoided
• The effect is mediated by blockade of B2-adrenoreceptors in the airways
• BB are usually safe in COPD, although is prudent to choose a BB with mainly B1 action (bisoprolol, atenolol) rather than non-selective (propranolol)
• When used in HF, BB should be started at a low dose and increased slowly, as they may initially impair cardiac function
• They should be avoided in patients with haemodynamic instability and are contraindicated in heart block
• BB generally require dosage reduction in significant hepatic failure

Question 24

BB

Interactions

Answer 24

• BB must not be used with non-dihydropyridine calcium channel blockers (e.g. verapamil, diltiazem)
• This combination can cause HF, bradycardia and even asystole

Question 25

BB
Communication

Answer 25

• Explain the rationale for treatment as appropriate for the situation
• Discuss common side effects, including impotence where nessessary
• Warn patients with HF about the risk of initial deterioration in their symptoms, and advise them to seek medical attention if this occurs
• Warn patients with obstructive airway disease to stop treatment and seek medical advise if they develop any breathing difficulties

Question 26

BB

Monitoring

Answer 26

• Best guide to dosage is Pt symptoms and HR 55-60 BPM (50-90)

Question 27

Clopidogrel

Common indications

Answer 27

• Clopidogrel is generally prescribed with aspirin, although clopidogrel may be used alone where aspirin is contraindicated or not tolerated

1. ACS where rapid antiplatelet action can prevent limit arterial thrombosis and reduce subsequent mortality
2. To prevent occlusion of coronary artery stents
3. Long-term secondary prevention of thrombotic arterial events in patients with CV, cerebrovascular, peripheral arterial disease
4. To reduce risk of intracardiac thrombus and embolic stroke in AF where warfarin and NOAC are contraindicated

Question 28

Clopidogrel

MOA

Answer 28

• Thrombotic events occur when platelet-rich thrombus forms in atheromatous arteries and occludes the circulation
• Clopidogrel prevents platelet aggregation and reduces the risk of arterial occlusion by binding ADP receptors (P2Y12 subtype) irreversibly on the surface of the platelets.
• As this process is independent of the cyclo-oxygenase pathway, its action is synergistic with those of aspirin.

Question 29

Clopidogrel

Adverse effects

Answer 29

• The most common adverse effect of clopidogrel is bleeding, which can be serious, particularly if GI, intracranial or following a surgical procedure
• GI upset, including dyspepsia, abdo pain and diarrhoea, is also common
• As with other antiplatelet agents, clopidogrel can rarely affect platelet numbers as well as function causing thrombocytopenia

Question 30

Clopidogrel

Warnings

Answer 30

• Clopidogrel should not be prescribed for people with significant active bleeding and may need to be stopped for 7 days before elective surgery and other procedures
• It should be used with caution in patients with renal and hepatic impairment, especially where patients otherwise have an increased risk of bleeding

Question 31

Clopidogrel

Interaction

Answer 31

• Clopidogrel is a pro-drug that requires metabolism by hepatic P450 enzymes to its active form to have an antiplatelet effect
• P450 inhibitors may reduce its efficacy by inhibiting its activation
• Relevant examples include omeprazole, ciprofloxacin, erythromycin and some antifungals and some SSRIs
• Where gastroprotection with PPI is required for patients taking clopidogrel- lansoprazole and pantoprazole are preferred over omeprazole as they are considered less likely to inhibit clopidogrel activation
• Co-prescription of clopidogrel with other anti-platelet drugs (e.g. aspirin), anti-coagulation (e.g. heparin) or NSAIDs increase the risk of bleeding

Question 32

Clopidogrel

Communication

Answer 32

• Advise patients that the purpose of treatment is to reduce the risk of heart attacks or strokes and to prolong the life
• In those who are taking clopidogrel following the insertion of a drug-eluting stent, emphasise the importance of continuing treatment as directed, usually for 12 months, to make sure that the stent stays open and does not block and cause a heart attack
• Before starting therapy, check that the patient does not have any active bleeding
• Explain that if bleeding does occur while on treatment it might take longer than usual to stop
• Patients should report any unusual or sustained bleeding to their doctor

Question 33

Fibrinolytics (Alteplase, streptokinase)

Common indications

Answer 33

1. Acute ischaemic stroke- must be given within 4.5hrs of the onset of stroke
2. In acute STEMI- can reduce mortality when they are given within 12 hrs of the onset of symptoms in combination with antiplatelet agents and anticoagulants. However, PCI largely supersedes fibrinolytic
3. Massive PE with haemodynamic instability- Fibrinolytic drugs reduce clot size and pulmonary artery pressures, but there is no clear evidence that they improve mortality

Question 34

Fibrinolytics (Alteplase, streptokinase)

MOA

Answer 34

• Thrombolytic drugs catalyse the conversion of plasminogen to plasmin, which acts to dissolve fibrinous clots and re-canalise occluded vessels
• This allows reperfusion of affected tissue, preventing or limiting tissue infarction and cell death and improving patient outcomes

Question 35

Fibrinolytic drugs (Alteplase, Streptokinase)

Adverse effects

Answer 35

• Common effects: N&V, bruising around the injection site and hypotension
• Adverse effects that require treatment to be stopped include serious bleeding, allergic reaction, cariogenic shock and cardiac arrest
• Serious bleeding may require treatment with coagulation factors and antifibrinolytic drugs e.g. tranexamic acid but this is usually avoidable as fibrinolytic agents have a very short half-life
• Reperfusion of infarcted brain or heart tissue can lead to cerebral oedema and arrhythmias

Question 36

Fibrinolytic drugs (Alteplase, Streptokinase)

Warnings

Answer 36

• Contraindication BLEEDING: Recent haemorrhage, recent trauma, surgery, bleeding disorders, severe HTN and peptic ulcers
• Contraindications STROKE: intracranial haemorrhage must be excluded with a CT scan before treatment
• Previous streptokinase treatment is a contraindication to repeat dosing (although other fibrinolytic can be used) as development of anti-streptokinase Abs can block its effects

Question 37

Fibrinolytic drugs (Alteplase, Streptokinase)

Interactions

Answer 37

• The risk of haemorrhage is increased in patients taking anticoagulants and antiplatelet agents
• ACEI appear to increase the risk of anaphylactoid reactions

Question 38

Fibrinolytic drugs (Alteplase, Streptokinase)

Communication

Answer 38

• The decision to thrombolyse should be made by senior clinicians and the risk and benefits discussed with the patient and next of kin
• In acute stroke, explain that part of the brain is being starved of blood and oxygen due to a blocked artery, which will cause long-term damage
• Clot-busting drugs can prevent damage to the brain dissolving the blood clot and restoring blood flow to the brain
• Although the chance of death is increased initially after receiving a blot busting drug (due to bleeding), after the first week the chances of independent living are increased

Question 39

Fibrinolytic drugs (Alteplase, Streptokinase)

Monitoring

Answer 39

• Patients should be monitored in a high dependency area, with vital signs check every 15 minutes for the first 2 hrs
• This should include observation for signs of bleeding, anaphylaxis and in the case of acute stroke, neurological deterioration

Question 40

Statins

Common indications

Answer 40

1. Primary prevention of CVD- prevent events in people over 40 with a Qrisk3 of >20%
2. Secondary pervention of CVD- Prevent CVE in patients who already have evidence of CVD
3. Primary hyperlipidemia

Question 41

Statins

MOA

Answer 41

• Statins reduce serum ChE levels.
• They inhibit 3-hydroxy-3-methyl-glutaryl Coenzyme A (HMG CoA) reductase, an enzyme involved in making ChE.
• They decrease ChE production by the liver and increase the clearance of LDL-ChE from the blood, reducing LDL-ChE levels.
• They also indirectly reduce triglycerides and slightly increase HDL-ChE levels.
• Though these effects they slow the atherosclerotic process and may even reverse it

Question 42

Statins

Adverse effects

Answer 42

• Statins are generally safe and well tolerated
• The most common adverse effects are headache and GI disturbances
• Potentially more serious are their effects on muscle
• These can range from simple aches to more serious myopathy or rarely rhabdomyolysis
• They can also cause a rise in liver enzymes (Alanine transaminase [ALT], drug-induced hepatitis is a rare but serious adverse effects

Question 43

Statins

Warnings

Answer 43

• Statins should be used with caution in patients with existing hepatic impairment
• They are excreted by the kidneys, so the dose should be reduced in people with renal impairment
• You should avoid prescribing statins to women who are pregnant (ChE is essential for normal fetal development) or breastfeeding

Question 44

Statins

Interactions

Answer 44

• The metabolism of statins is reduced by P450 inhibitors (amiodarone, diltiazem, itraconazole, macrolides and protease inhibitors)
• This leads to accumulation of the statin in the body, which may put patients at increased risk of adverse effects
• Amlodipine has a similar interaction, although the mechanism is less clear. To reduce the risk, you may need to reduce the dose of the statin or if the other drug is being used for a short period only (e.g. a course of clarithromycin therapy) withhold statin

Question 45

Statins

Communications

Answer 45

• Explain you are prescribing medicine to lower ChE levels to reduce the risk of a MI or stroke in the future
• Advise Pts of common side effects and to seek medical help if they get muscle symptoms (e.g. pain or weakness)
• Ask the patient to come back for blood tests at 3, 12 months
• Advise them to keep alcohol intake to a minimum
• Those taking simvastatin and atorvastatin should avoid grapefruit juice, which inhibits the P450 enzymes that metabolise statins and may therefore increase the risk of side effects
• This is not the case for pravastatin and rosuvastatin

Question 46

Statins

Monitoring

Answer 46

• Primary prevention of CVD you should check lipid profile prior to treatment but thereafter this does not need to be check routinely
• Secondary prevention- baseline lipid profile is not necessary but efficacy should be monitored by checking ChE
• For safety check liver enzymes at baseline and again at 3 + 12 months
  
  • A rise in ALT up to 3x normal limit is acceptable but above requires discontinuation
  • The statin can be restarted at a lower dose when liver enzymes have returned to normal
  • You do not need to regularly check creatinine kinase, but should ask Pt to report muscle symptoms