1
Q
Aspirin - Main Indications
A
1)
- ACS: Angina
- Acute ischaemic stroke
2) Long-term secondary prevention of thrombotic arterial events in patients with :
- Cardivascular
- Cerebovascular
- Peripheral arterial disease
Historically, used to control mild-to-moderate pain and fever
2
Q
Aspirin - MOA
A
- Thrombotic events occur when platelet-rich thrombus forms in atheromatous arteries and occludes circulation.
- Aspirin irreversibly inhibits cyclooxygenase (COX) to reduce production of the pro-aggregator factor thromboxane from arachidonic acid, reducing platelet aggregation and the risk of arterial occlusion.
- Effect of aspirin occurs at low dose and lasts for lifetime of the platelet.
3
Q
Aspirin - Side Effects
A
GI irritation: - Peptic ulceration + Haemorrhage Hypersensitivity reactions: - Bronchospasm Regular high-dose - tinnitus Life-threatening in overdose: -hyperventilation, hearing changes, metabolic acidosis, confusion, convulsions , CVS collapse, reps arrest
4
Q
Aspirin - Contraindications
A
Should not be given:
- Children under 16 years (risk of Reye’s syndrome)
- People with aspirin hypersensitivity
- 3rd trimester of pregnancy
5
Q
Aspirin - Caution
A
- Peptic ulceration
- Gout (may trigger attack)
- Elderly
6
Q
Aspirin - Key interactions
A
Acts synergistically with antiplatelets and anticoagulants
8
Q
Aspirin - Patient Education
A
To minimise GI irritation taken after food.
Enteric-coated may help further but not useful in medical emergencies due to slower absorption
9
Q
Clopidogrel - Class of drug and Other examples
A
Anti-platelet drugs , ADP-receptor antagonists
E.g : Ticagrelor, Prasugrel
10
Q
Clopidogrel - Main Indications
A
1) ACS usually in combination with aspirin
2) Prevent occlusion of coronary artery stents - with aspirin
3) Long-term secondary prevention of thrombotic arterial events in patients with :
- Cardiovascular
- Cerebrovascular
- Peripheral arterial disease - alone or with aspirin
11
Q
Clopidogrel - MOA
A
- Prevent platelet aggregation and reduce risk of arterial occlusion by binding irreversibly to adenosine diphosphate (ADP) receptor .
- Synergistic with aspirin
12
Q
Clopidogrel - Side effects
A
- Bleeding
- GI upset - dyspepsia, abdominal pain & diarrhoea
- Can cause thrombocytopenia
13
Q
Clopidogrel - Contraindications
A
- Active bleeding
14
Q
Clopidogrel - Caution
A
- Must be stopped 7 days before elective surgery
- Renal and hepatic impairment
15
Q
Clopidogrel - Key interactions
A
- Clopidogrel is pro-drug that requires metabolism by hepatic cytochrome P450 enzymes to its active form to have an anti-platelet effect..
- -> Efficacy maybe reduced by CYP inhibitors by inhibiting activation.
- Antiplatelets and anticoagulants - increase risk of bleeding
16
Q
Clopidogrel - Monitoring
A
Clinical monitoring for adverse effect
17
Q
Clopidogrel - Patient Education
A
- Can be given with or without food
- Purpose of the treatment is to reduce risk of heart attacks or strokes
- Usually taken for 12 months
- stop if there is any active bleeding
18
Q
Statins - Main indications
A
1) Primary prevention of CVS events: to prevent CVS in people over 40 years with QRISK tool of >10%
2) Secondary prevention CVS events: 1st line along with lifestyle changes, to prevent CVS disease
3) Primary hyperlipidaemia: 1st line
19
Q
Statins - Examples
A
Simvastatin
Atorvastatin
Pravastatin
Rosuvastatin
20
Q
Statins - MOA
A
Reduce serum cholesterol levels by:
- Inhibit 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG CoA) reductase - enzyme involved in making cholesterol
- Decrease cholesterol production by the liver and increase clearance of LDL from blood.
- Also reduce triglycerides and slightly increase HDL
- These effects slow the atherosclerotic process.
21
Q
Statins - Side effects
A
- Headache
- GI disturbances
- Aches to serious myopathy; or rarely rhabdomyolysis
- rise in liver enzymes ; drug-induced hepatitis
22
Q
Statins - Contraindications
A
None
23
Q
Statins - Caution
A
- Hepatic impairment
- Renal impairment
- Pregnant (cholesterol essential in foetal development)
- Breastfeeding
24
Q
Statins - Key interactions
A
Metabolism of statins reduced by cytochrome P450 inhibitors:
- amiodarone
- diltiazem
- macrolides
- protease inhibitors
These lead to accumulation of the statin in the body which can increase risk of adverse effects.
Amlodipine
25
Q
Statins - Monitoring
A
Primary prevention :
- Check lipid profile before treatment and 3 months after treatment : aim for 40% reduction in non-HDL levels.
Secondary prevention:
- Check for target cholesterol levels.
Safety:
- Check liver enzymes at baseline and 3 & 12 months.
- Rise in ALT is normal upto 3 times upper limit of normal.
26
Statins - Patient Education
- Simvastatin is traditionally taken in the evening.
| - Inform patient that the medication is to reduce risk of heart attack or stroke
27
Warfarin - Main indications
1) Venous thromboembolism - Treatment and prevention of recurrence
2) To prevent arterial embolism in patients with AF or prosthetic valves.
- short- term for tissue valve replacement
- lifelong for mechanical valve replacement
28
Warfarin - MOA
Clot formation is driven by coagulation cascade.
- Warfarin inhibits hepatic production of vitamin K-dependent coagulation factors.
- It does this by inhibiting vitamin K epoxide reductase.
- the enzyme responsible for restoring vitamin K to its reduced form, necessary as a co-factor in the synthesis of these clotting factors.
29
Warfarin - How can it be reversed?
- Can be reversed by phytomenadione (vitamin K) or dried prothrombin complex
30
Warfarin - Side effects
- Bleeding
| - Epistaxis or retroperitoneal haemorrhage
31
Warfarin - Contraindications
- Immediate risk of haemorrhage
| - 1st trimester of pregnancy
32
Warfarin - Key interactions
- CYP inducers e.g phenytoin, carbamazpine, rifampicin : increases warfarin metabolism + risk of clots
- CYP inhibitors e.g. fluconazole, macrolides : decrease warfarin metabolism + increase bleeding risk
- Antibiotics - increase warfarin effect by killing gut flora that synthesise vitamin K.
33
Warfarin - Caution
- Liver disease : patients who are less able to metabolise the drug at risk
- later on pregnancy due to the risk of peripartum haemorrhage
34
Warfarin - Patient Education
- Advice patients it is balance between benefits (prevent clot) and risks (bleeding)
- Patient receive an anticoagulant book ('Yellow Book')
- ---------------------------------------------------
35
Warfarin - Prescription
- Usually taken with heparin (fast onset action). Heparin should. be stopped once INR is in target range.
- Doses are guided by INR
36
Warfarin - Monitoring
- INR is the prothrombin time of a person on warfarin divided by that of a non-warfarinised 'control'.
- Target INR varies by indication.
- Once stable dose of warfarin is established, INR measurement is less frequent.
37
Heparin - Types and Examples
Types:
- unfractionated heparin (UFH)
- low molecular weight heparin (LMWH)
Examples:
LMWH:
- enoxaparin
- dalteparin
38
Heparin - Main indications
1) Usually LMWH - primary prevention of DVT and PE (VTE).
- An option for VTE until oral anticoagulation is established.
2) ACS : LMWH is used with anti-platelet agents to reduce clot progression or maintain revascularisation
39
Heparin - MOA
- Antithrombin (AT) inactivates clotting factors (esp : IIa - thrombin and Xa), providing a natural break to the clotting process.
- Heparin act by enhancing the anticoagulant effect of AT.
Size of heparin molecule determines the specificity :
- UFH (large & small) - promotes inactivation of both IIa and Xa
- LMWH (smaller) - specific for factor Xa
40
Heparin - Side effects
- Main SE : haemorrhage
- Bruising at injection at site
- Hyperkalaemia
- Rare : immune reaction to heparin resulting in low platelet count and thrombosis (heparin-induced thrombocytopenia, HIT) - less likely with LMWH than UFH
41
Heparin - Contraindication
N/A
42
Heparin - Caution
Increased risk of bleeding:
- clotting disorders
- severe uncontrolled hypertension
- recent surgery or trauma
Withheld before and after invasive procedures : lumbar puncture & spinal anaesthesia.
Renal impairment : LMWH accumulate so low dose UFH should be used
43
Heparin - Key interactions
Combing with other antithrombotic drugs (warfarin) has an additive effect.
- Desired in ACS but has increased risk of bleeding so should be otherwise avoided
In major bleeding, protamine is an option to reverse heparin anticoagulation.
- Effective for UFH but less for LMWH
44
Heparin - Prescription
- Usually given SC
| - Depends on indication and body weight
45
Heparin - Monitoring
LMWH's effect is predictable
- In pregnancy and renal impairment : antifactor Xa activity is measured.
UFH is not predicatble
- Dosage is titrated against the activated partial thromboplastin ration (APTR: 1.5-2.5 target)
- FBC, baseline clotting and renal profiles done before treatment.
In prolonged therapy (>4 days) : platelet count and serum potassium concentration should be monitored.
- Risk of thrombocytopenia and hyperkalaemia increases with duration of therapy.
-Seek medical advice if platelt count drop significanlty : can signify HIT
46
Heparin - Patient Education
- In VTE prophylaxis, explain that you are offering a daily injection to reduce the risk of blood clots.
- Avoid activities that may increase their risk of bleeding
- Patient must be trained to take SC injection, or district nurse must administer.
47
Direct Oral Anticoagulants - Examples
- Apixaban
- Dabigatran
- Edoxaban
- Rivaroxaban
48
Direct Oral Anticoagulants - Main Indications
1) Venous thromboembolism : as treatment and prevention of recurrence. (secondary prevention)
2) Atrial Fibrillation : Prevent stroke and systemic embolism in patients with non-vulvular AF with at least 1 risk factor (prev stoke, symptomatic HF, DM or HTN)
49
Direct Oral Anticoagulants - MOA
The DOACs act on the final common pathway of the coagulation cascade, comprising factor X, thrombin and fibrin.
- Apixaban, edoxaban and rivaroxaban directly inhibit activated factor X (Xa), preventing conversion of prothrombin to thrombin.
- Dabigatran directly inhibits thrombin, preventing the conversion of fibrinogen to fibrin.
--> less effective in the arterial circulation as clots are mainly platelet driven - better prevented by antiplatelets
50
Direct Oral Anticoagulants - Adverse Effects
Most common : bleeding
- epistaxis, GI and GU haemorrhage
- increased risk of GI bleeding
(intraluminal drug accumulation causing local anticoagulant effect )
Other AE :
- Anaemia
- GI upset
- Dizziness
- Elevated liver enzymes
51
Direct Oral Anticoagulants - Contraindication
- Active, clinically significant bleeding
- Risk factors for major bleeding : peptic ulceration, cancer, and recent surgery or trauma.
- Pregnancy
- Breastfeeding
52
Direct Oral Anticoagulants - Caution
Hepatic or renal disease
- DOACs are excreted by mulptiple routes, including CYP enzyme metabolism and elimination in faeces and urine.
- So may need dose reduction or alternative .
53
Direct Oral Anticoagulants - Interactions
Other antithrombotic agents:
- increased risk bleeding
- e.g. heparin, antiplatelets and NSAIDs.
Macrolides, protease inhibitors, flucanazole.
- increased the effect of DOACs by affecting their metabolism and excretion.
Rifampicin and phenytoin
- decreased effect
54
Direct Oral Anticoagulants - Prescription
- Dosage and duration depends on indication.
| - Can be started without heparin treatment
55
Direct Oral Anticoagulants - Monitoring
Do not require monitoring
56
Direct Oral Anticoagulants - Patient Education
- Patient should have alert card.
57
Loop Diuretics - Examples
- Furosemide
| - Bumetanide
58
Loop Diuretics - Indications
1) Acute pulmonary oedema :
- for relief of breathlessness
- in conjunction with oxygen and nitrates
2) Chronic heart failure : symptomatic treatment of fluid overload
3) Other oedematous states: :
- e.g. due to renal disease or liver failure
- in combination with other diuretics
59
Loop Diuretics - MOA
- Acts on the ascending limb of the loop of henle
- inhibit the Na+/K+/2Cl- co-transporter.
- This protein is responsible for transporting sodium, potassium and chloride ions from the tubular lumen into the epithelial cell.
Water then follows by osmosis.
- loop diuretics prevents this effect.
- Also causes dilatation of capacitance veins.
- In acute HF : this reduces preload and improves contractile function of the 'overstretched' heart muscle.
60
Loop Diuretics - Adverse Effects
- Dehydration
- Hypotension
- Low electrolyte state
- Hearing loss & tinnitus
61
Loop Diuretics - Contraindication
- Hypovolaemia
| - Dehydration
62
Loop Diuretics- Caution
- Hepatic encephalopathy
- Hypokalaemia and/or hyponatraemia
- Gout (inhibited uric acid excretion)
63
Loop Diuretics - Interactions
Affect drugs that are excreted by the kidneys. E.g:
- Lithium levels are increased due to reduced excretion
- increased risk of digoxin toxicity - diuretic associated hypokalaemia
- increase the ototoxicity and nephrotoxicity of amino-glycosides
64
Loop Diuretics - Prescription
- oral and IV preparations
65
Loop Diuretics - Monitoring
For efficacy:
- Acute management: monitor symptoms (tachycardia, hypertension & oxygen requirement)
- Long-term therapy: monitor symptoms, signs and body weight (body loss of no more than 1kg/day)
For safety:
- periodic monitoring of serum sodium, potassium and renal function in first few weeks of therapy
66
Loop Diuretics - Patient Education
Explain:
- body is overloaded with water
- treatment will increase urine flow
- pass water more often
- provided doses are not taken late in the day, it should not affect them at night
67
Thiazide and Thiazide- Like Diuretics - Examples
- Bendroflumethazide
- Indapamide
- Chlortalidone
68
Thiazide and Thiazide- Like Diuretics - Indications
1) Hypertension : alternative 1st line when CCB would otherwise be used
2) Hypertension: add-on in patients whose BP not controlled by CCB plus ACEi or ARB
69
Thiazide and Thiazide- Like Diuretics - MOA
- Inhibit the Na+/Cl- co-transporter in the distal convoluted tubule of the nephron
- Prevents reabsorption of sodium and osmotically related water.
70
Thiazide and Thiazide- Like Diuretics - Adverse Effects
- Hyponatraemia
- Hypokalaemia
- Cardiac arrhytmias
- (may increase plasma conc of glucose, LDL and triglycerides)
- Impotence in men
71
Thiazide and Thiazide- Like Diuretics - Contraindications
- Hypokalaemia
72
Thiazide and Thiazide- Like Diuretics - Caution
- Hyponatraemia
| - Gout
73
Thiazide and Thiazide- Like Diuretics - Interactions
- Effectiveness may reduce NSAIDs (low dose aspirin is not a concern)
- Avoid loop diuretics (lower serum k+ conc)
74
Thiazide and Thiazide- Like Diuretics - Prescribing
- Oral
| - higher-dose increase side effects w/o improving HTN
75
Thiazide and Thiazide- Like Diuretics - Monitoring
Efficacy:
- patient's BP
- severity of oedema
- Measure patient's serum electrolyte conc before drug, 2-4 weeks into therapy and after any change in therapy
76
Thiazide and Thiazide- Like Diuretics - Patient Education
- Explain treatment with a 'water tablet' for their high BP.
- If they have leg swelling - tablet helps.
- Will make them pass urine more
- anti-inflammatory drugs like ibuprofen may reduce effectiveness of diuretics
- at review, ask male patients about impotence
77
Beta Blockers - Examples
- Bisoprolol
- Atenolol
- Propanolol
- Metoprolol
- Carvedilol
78
Beta Blockers - Indications
1) Ischaemic heart disease : improve symptoms and prognosis associated with - angina and ACS
2) Chronic HF: Bisoprolol and carvedilol used to improve prognosis
3) AF : reduce ventricular rate in paroxysmal AF - maintain sinus rhythm
4) Supraventricular tachycardia: In patients w/o circulatory compromise to restore sinus rhythm
5) HTN : used when other medications are insufficient or inappropriate
79
Beta Blockers - MOA
β1-adrenoreceptors are located mainly in the heart.
β2-adrenoreceptors are found mostly in smooth muscle of blood vessels and airways.
- β-blockers reduce force of contraction and speed of conduction in the heart.
- relieves myocardial ischaemia by reducing cardiac work and oxygen demand increasing myocardial perfusion
Improve prognosis in HF:
- 'protecting' the heart from chronic sympathetic stimulation
Slow the ventricular rate in AF:
- by prolonging the refractory period of AV node.
- through the same effect, they terminate SVT
In HTN :
- β-blockers lower BP by reducing renin secretion from the kidney, since this is mediated by β1-receptors
80
Beta Blockers - Adverse Effects
Common:
- Fatigue
- Cold extremities
- Headaches
- GI disturbances ( nausea)
Can cause:
- sleep disturbances & nightmares
- impotence in men
81
Beta Blockers - Contraindications
- Asthma
| - Heart block
82
Beta Blockers - Caution
- Heart Failure
- Haemodynamic instability
- Hepatic Failure
83
Beta Blockers - Interactions
Should not be used:
- non-dihydropyridine CCB (e.g. verapamil, diltiazem)
- this combo can cause HF, bradycardia and asystole
84
Beta Blockers - Prescription
Oral regular medication
| IV is available for rapid effect
85
Beta Blockers - Monitoring
Monitor patient's symptoms ( chest pain) and heart rate
86
Beta Blockers - Patient Education
- Explain the rationale for treatment
- Discuss common SE inc impotence
- In HF : warn risk of initial deterioration in their symptoms and advise to seek medical attention if this occurs.
- Obstructive airway disease: stop treatment if there is any breathing difficulty
87
α-blockers - Examples
- Doxazosin
- Tamsulosin
- Alfuzosin
88
α-blockers - Indications
1) Benign Prostatic Enlargement:
| 2) Resistant HTN: when other medicines are insufficient
89
α-blockers - MOA
Drugs are highly selective for α1-adrenoceptor.
- α1-adrenoceptors are found mainly in smooth muscle, including in blood vessels and the urinary tract.
- stimulation induces contraction; blockade induces relaxation
Therefore, α1-blockers causes: - vasodilatation
- a fall in blood pressure (BP)
- reduced resistance to bladder outflow
90
α-blockers - Adverse Effects
- Postural hypotension
- Dizziness
- Syncope
91
α-blockers - Contraindications
None
92
α-blockers - Caution
- Should not be used in existing postural hypotension
93
α-blockers - Interactions
- To avoid pronounced 1st dose hypotension, omit one or more antihypertensive tot avoid additive effect.
94
α-blockers - Prescription
- Doxazosin and tamsulosin is the most commonly prescribed
95
α-blockers - Monitoring
Efficacy:
- patient's urinary symptoms and/or BP
For tolerability and safety:
- enquire about symptom
- measure BP : lying and standing
96
α-blockers - Patient Education
Explain the treatment is for urinary symptoms or BP.
- may cause dizziness on standing
- take medicine at bedtime to minimise impact
97
Calcium Channel Blockers - Examples
- Amlodipine
- Nifedipine
- Diltiazem
- Verapamil
98
Calcium Channel Blockers - Indications
1) HTN: Amlodipine & Nifedipine used for 1st and 2nd line.
- Reduce risk of stroke, MI and death from CVD
2) Stable Angina : control symptoms
3) Supraventricular arrhythmias (SVT, Atrial flutter, AF): Diltiazem and Verapamil are used to control cardiac rate
99
Calcium Channel Blockers - MOA
- Decrease Ca2+ entry into vascular and cardiac cells
- Reducing intracellular calcium concentration.
- This causes relaxation and vasodilation in arterial smooth muscle, lowering arterial pressure.
- In the heart, calcium channel blockers reduce myocardial contractility.
- They suppress cardiac conduction, particularly across the atrioventricular (AV) node, slowing ventricular rate.
- Reduced cardiac rate, contractility and afterload reduce myocardial oxygen demand, preventing angina.
100
Calcium Channel Blockers - Adverse Effects
Amlodipine & Nifedipine - Common:
- Ankle swelling
- Flushing
- Headache
- Palpitations
```
Verapamil -
Common:
- Constipation
Less common:
- Bradycardia
- Heart Block
- Cardiac Failure
```
Diltiazem:
mixed vascular and cardiac actions.
101
Calcium Channel Blockers - Contraindications
Amlodipine & Nifedipine:
- Unstable angina
- Severe aortic stenosis
Verapamil & Diltiazem:
- AV nodal conduction delay
102
Calcium Channel Blockers - Caution
Verapamil & Diltiazem:
- poor left ventricular function
-
103
Calcium Channel Blockers - Interactions
- Should not be prescribed with β-blockers
104
Calcium Channel Blockers - Prescribing
....
105
Calcium Channel Blockers - Monitoring
Efficacy:
- regular monitoring of BP
Enquire:
- chest pain for angina
- pulse rate from examination or ECG
106
Calcium Channel Blockers - Patient Education
- Purpose of medication depending on indication
- Discuss other measure to reduce CV risk inc smoking cessation.
- Discuss common SE esp ankle oedema.
107
Calcium Channel Blockers - Classification
Two classes:
Dihydropyridines:
- E.g.: Amlodipine & Nifedipine,
- Relatively selective for the vasculature
Non-dihydropyridines:
- More selective for the heart.
- Verapamil is the most cardioselective
- Diltiazem has some effects on blood vessels also.
108
Angiotensin - converting enzyme inhibitors (ACEi) - Examples
- Ramipril
- Lisinopril
- Perindopril
109
ACEi - Indications
1) HTN : 1st or 2nd line. Reduce risk of stroke, MI & death from CVD
2) Chronic HF: 1st line, to improve symptoms & prognosis
3) Ischaemic heart disease: reduce CV events e.g. MI & stroke
4) Daibetic nephropathy & CKD with proteinuria: reduce proteinuria & progression of nephropathy
110
ACEi - MOA
- ACEi block the action of ACE, to prevent the conversion of angiotensin I to angiotensin II.
- Angiotensin II is a vasoconstrictor and stimulates aldosterone secretion.
- Blocking its action reduces peripheral vascular resistance (afterload), which lowers BP.
- 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 is beneficial in HF.
111
ACEi - Adverse Effects
Common:
- hypotension
- persistent dry cough
- hyperkalaemia
- renal failure
Rare:
- angioedema
- anaphylactoid reactions
112
ACEi - Contraindications
- Renal artery stenosis
- AKI
- Pregnancy
- Breastfeeding
113
ACEi - Caution
- CKD
114
ACEi - Interactions
- Avoid with other potassium -elevating drugs icluding potassium supplement and potassium-sparing diuretics due to risk of hyperkalaemia.
- Combination with NSAID increases the risk of nephrotoxicity
115
ACEi - Prescription
....
116
ACEi - Monitoring
Efficacy:
- Monitor clinically : reduced symptoms of breathlessness in heart failure or improved BP control in HTN.
- Check BP in 4 weeks
Safety:
- Check electrolytes and renal function before starting treatment.
- Check U & E 1-2 weeks after initiation and after each dose change
- ACE should be stopped if the serum creatinine concentration rises more than 30% or the estimated GFR falls more than 25%.
- If serum potassium rises above 5.0 mmol/L, stop other potassium-elevating and nephrotoxic drugs (see Important interactions).
- If, despite this, it remains above 5.0 mmol/L, reduce the dose of ACE inhibitor.
- If it exceeds 6.0 mmol/L, stop the ACE inhibitor and seek expert advice.
117
ACEi - Patient Education
- Explain medication is to improve blood pressure and reduce strain on their heart.
- Advise on common SE: dry cough, dizziness.
- Mention that, very rarely, this medicine can cause effects similar to severe allergic reactions; they should stop taking it and seek urgent medical advice if they develop facial swelling or stomach pains.
- Explain need for blood test monitoring.
- Explain that ACE inhibitors can interfere with their kidney function and upset potassium balance.
- Advise them to avoid taking over-the-counter antiinflammatories (e.g. ibuprofen) due to the risk of kidney damage.
118
Angiotensin Receptor Blockers - Examples
- Losartan
- Candesartan
- Irbesartan
119
ARBs - Indication
Usually used when ACEi are not tolerated due to cough.
1) HTN : 1st or 2nd line. Reduce risk of stroke, MI & death from CVD
2) Chronic HF: 1st line, to improve symptoms & prognosis
3) Ischaemic heart disease: reduce CV events e.g. MI & stroke
4) Daibetic nephropathy & CKD with proteinuria: reduce proteinuria & progression of nephropathy
120
ARBs - MOA
- ARBs have similar effects to ACE inhibitors.
- ARBs block the action of angiotensin II on the angiotensin type 1 (AT1) receptor.
- Angiotensin II is a vasoconstrictor and stimulates aldosterone secretion.
- Blocking its action reduces peripheral vascular resistance (afterload), which lowers blood pressure.
- 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 a beneficial effect in heart failure.
121
ARBs - Adverse Effects
- Hypotension (esp after 1st dose)
- Hyperkalaemia
- Renal failure
- Unlike ACEi, less likely to cause dry cough and angioedema
122
ARBs - Contraindications
- Renal artery stenosis
- AKI
- Pregnant
- Breastfeeding
123
ARBs - Caution
- Lower doses in CKD (renal function must be monitored closely)
124
ARBs - Interactions
- Avoid with other potassium -elevating drugs icluding potassium supplement and potassium-sparing diuretics due to risk of hyperkalaemia.
- Combination with NSAID increases the risk of nephrotoxicity
125
ARBs - Prescription
....
- Can be taken with or without food
- Best to take the 1st dose before bed to reduce symptomatic hypotension
126
ARBs - Monitoring
Efficacy:
- Monitor clinically : reduced symptoms of breathlessness in heart failure or improved BP control in HTN.
Safety:
- Check electrolytes and renal function before starting treatment.
- ACE should be stopped if the serum creatinine concentration rises more than 30% or the estimated GFR falls more than 25%.
- If serum potassium rises above 5.0 mmol/L, stop other potassium-elevating and nephrotoxic drugs (see Important interactions).
- If, despite this, it remains above 5.0 mmol/L, reduce the dose of ACE inhibitor.
- If it exceeds 6.0 mmol/L, stop the ACE inhibitor and seek expert advice.
127
ARBs - Patient Education
- Explain medication is to improve blood pressure and reduce strain on their heart.
- Advise on common SE: dry cough, dizziness.
- Explain if the previously had cough, ARBs does not cause cough.
- Explain need for blood test monitoring.
- Explain that ARBs can interfere with their kidney function and upset potassium balance.
- Advise them to avoid taking over-the-counter antiinflammatories (e.g. ibuprofen) due to the risk of kidney damage.
128
Mineralocorticoid Receptor Antagonist - Examples
AKA - Aldosterone anatonists
Examples:
- Spironolactone
- Eplerenone
129
MRA - Indications
1) Ascites & odema due to liver cirrhosis : spironolactone is the 1st line diuretic
2) Chronic HF :
130
MRA - MOA
- Aldosterone is a mineralocorticoid that is produced in the adrenal cortex.
- It acts on mineralocorticoid receptors in the distal tubules of the kidney to increase the activity of luminal epithelial sodium (Na+) channels (ENaC).
- This increases the reabsorption of sodium and water, elevating blood pressure, with a corresponding increase in potassium excretion.
- Aldosterone antagonists inhibit the effect of aldosterone by competitively binding to the aldosterone receptor.
- This increases sodium and water excretion and potassium retention.
- Their effect is greatest when circulating aldosterone is increased, e.g. in primary hyperaldosteronism or cirrhosis.
131
MRA - Adverse Effects
- Hyperkalaemia : can lead to muscle weakness , arrhythmias & even cardiac arrest
- Gynaecomastia
- Can cause liver impairment and jaundice
- Can cause Stevens–Johnson syndrome (a T-cell-mediated hypersensitivity reaction) that causes a bullous skin eruption.
132
MRA - Contraindications
- Severe renal impairment
- Hyperkalaemia
- Addison's disease
133
MRA - Caution
- Pregnancy or lactating women
134
MRA - Interactions
- Combination with other potassium-elevating drugs increases the risk of hyperkalaemia.
- However, this combination may be beneficial in HF.
- Avoided with potassium supplements.
135
MRA - Prescribing
....
- Should be taken with food
- Taken several days to start having an effect
136
MRA - Monitoring
Efficacy:
- Monitored by patient report of symptoms and clinical findings.
- E.g. reduction in ascites, oedema and/or blood pressure.
Safety:
- Monitored by checking renal function and serum potassium concentration.
- Due to the risk of renal impairment and hyperkalaemia.
137
MRA - Patient Education
- Warn men about the possibility of growth and tenderness of tissue under the nipples and impotence.
- Reassure them that such effects are benign and reversible, but acknowledge that they may be uncomfortable and embarrassing.
- Ask patients to return if they have troublesome side effects, as these may respond to dose reduction.
- Advise all patients that aldosterone antagonists can cause their potassium level to rise and reinforce the importance of attending for blood tests.
138
Nitrates - Examples
- Glyceryl Trinitrate (GTN)
| - Isosorbide mononitrate
139
Nitrates - Indications
1) Short acting (GTN)
- Acute angina
- Chest pain associated with ACS
2) Long acting (ISO)
- Prophylaxis of angina ( when beta-blocker & CCB is not tolerated)
3) IV Nitrate
- Pulmonary oedema (with furosemide & oxygen)
140
Nitrates - MOA
- Nitrates are converted to NO.
- NO increases cGMP synthesis & reduces intracellular Ca2+ in vascular smooth muscle cells causing them to relax.
- Results in venous & artial vasodilation.
- Which reduced cardiac preload & ventricular filling.
- Essentially reducing cardiac work & myocardial oxygen demand - relieving angina & cardiac failure.
- Nitrates can relieve coronary vasospasm & dilate collateral vessels --> improving coronary perfusion.
141
Nitrates - Adverse Effects
- Flushing
- Headaches
- Light- headedness
- Hypotension
-Prolonged use can lead to tolerance
142
Nitrates - Contraindications
- Severe Aortic stenosis
- Haemodynamic instability
- Hypotension
143
Nitrates - Interaction
Phosphodiesterase (PDE) inhibitors --> sildenafil
- prolong & enhance the hypotensive effect.
Used with caution for those with antihypertensive medication
144
Nitrates - Prescribing
- Stable angina - sublingual tablets or spray
| - ACS or HF - continuous IV infusion
145
Nitrates - Monitoring
- Best indication of efficacy is patients symptoms
| - Monitor BP
146
Nitrates - Patient Education
- Nitrate relieve chest pain and/or breathlessness
- Side effects
- Due to possible postural hypotension, advise patient to sit down and rest for 5 minutes
147
Digoxin - Indications
1) Atrial Fibrillation & Atrial flutter
- Reduce ventricular rate
2) Severe Heart Failure
- option for pt already on ACEo, BB, ARB
148
Digoxin - MOA
- Negatively Chronotropic --> reduces heart rate
- Positively Inotropic --> increases force of contraction
In AF = increased vagal (parasympathetic) tone
- reduces conduction at AV node --> prevents some impulses from being transmitted to the ventricle --> thus reducing ventricular rate
In Heart Failure = direct effect on myocytes through inhibition of Na+/K+ enzyme pump causing Na+ to accumulate in the cell.
- Cellular extrusion of Ca2+ requires low intracellular Na+ conc
- Elevation of intracellular Na+ causes Ca2+ to accumulate in the cell --> thus increasing contractile force
149
Digoxin - Adverse Effects
- Bradycardia
- GI disturbances
- Rash
- Dizziness
- Visual disturbance (blurred or yellow vision)
150
Digoxin - Contraindications
- 2nd degree heart block
- Intermittent complete heart block
- Ventricular arrhythmias
151
Digoxin - Caution
- Renal failure (digoxin is eliminated in kidneys)
- Hypokalaemia
- Hypomagnesaemia
- Hypercalcaemia
152
Digoxin - Interactions
Loop & thiazide diuretic
-->digoxin toxicity by hypokalaemia
Amiodarone, CCB, spironolactone, quinine
--> increase plasma conc of digoxin thus toxicity
153
Digoxin - Prescription
- Oral or IV
| - taken with or without food
154
Digoxin - Monitoring
- Monitor symptoms & heart rate
- Check ECG
- In acute setting -> regular cardiac monitoring
155
Digoxin - Patient Education
- Slow heart and make heart beat more strong
| - Common SE : sickness, diarrhoea, headache
156
Aspirin - Monitoring
Enquire about side effects
APPLIED PHARMACOLOGY💊
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