Angina

Question 1

Stable angina

Sub-lingual GTN- Mechanism of action

Answer 1

• Nitrates are converted to NO
• NO increases cGMP synthesis and reduces Intracellular Ca2+ in vascular smooth muscle= relaxation and vasodilation
• This reduces cardiac work and myocardial oxygen demand by improving perfusion to cardiac muscle

Question 2

GTN spray- Adverse effects

Answer 2

• Flushing
• Headache
• Hypotension
• Tolerance
• Don’t use overnight- increase side effects (NOT needed)

Question 3

GTN- Contraindications

Answer 3

• Severe Aortic Stenosis- cause cardiovascular collapse
  
  • This is because the heart is unable to increase cardiac output sufficiently through the narrow valve area to maintain pressure
• Haemodynamic instability
• Hypotension

Question 4

GTN- important interactions

Answer 4

• Phosphodiesterase inhibitors (Sildenafil)
  
  • because of the enhanced hypotensive effect
• Anti-HTN- use with caution

Question 5

GTN- Communication

Answer 5

• Explain that you are prescribing a nitrate to relieve chest pain and or breathlessness
• May develop a headache when starting but should go
• Better at preventing than terminating angina pain, take before tasks that can bring on angina
• Because of postural Hypotension- it is a good idea to advise them to sit down and rest before and 5 minutes after taking GTN spray
• Tolerance can occur- make sure there is a nitrate free period every day during a time of inactivity (overnight)

Question 6

Beta blockers

Answer 6

See atrial fibrillation

Question 7

Calcium channel blockers

Common indications

Answer 7

1. All Calcium channel blockers can be used to control symptoms in people with stable angina, BB are the main alternative
2. Amlodipine is used for HTN
3. Diltiazem and verapamil are used to control cardiac rate in people with supraventricular arrhythmias including supraventricular tachycardia, atrial flutter and AF

Question 8

Calcium channel blockers

MOA

Answer 8

• CCB decrease Ca2+ entry into vascular and cardiac cells, reducing the intracellular calcium concentration
• This causes relaxation and vasodilation in arterial smooth muscle, lowering arterial pressure
• In the heart, CCB reduce Myocardial contractility
• Suppression cardiac conduction, particularly across the AV node, slowing ventricular rate
• Reduced cardiac rate, contractility and afterload reduce myocardial oxygen demand preventing angina
• CCB can broadly be divided into two classes. Dihydropyridines, including amlodipine and nifedipine, is relatively selective for the vasculature, whereas non-dihydropyridines are more selective for the heart. Of the non-dihydropyridines, verapamil is the most cardioselective, whereas diltiazem also has some effects on the vessels.

Question 9

CCB

Warnings

Answer 9

• Poor left ventricular function as they worsen HF
• AV nodal conduction delay in whom they may provoke complete heart block

Question 10

CCB

Interactions

Answer 10

• Non-dihydropyridine- should not be prescribed with a BB as both classes are negatively inotropic and chronotropic and together may cause HF, bradycardia and asystole

Question 11

CCB

Communication

Answer 11

• MR and SR should be swallowed whole and not crushed or chewed
• Common side effects- ankle oedema
  *

Question 12

CCB

Monitoring

Answer 12

• Treatment efficacy can be judged by regular BP monitoring for HTN, enquiry about chest pain for angina and by pulse rate from examination or ECG
• A 24-hour tape can be performed to review arrhythmias

Question 13

Nicorandil

Common indications

Answer 13

• For prevention and treatment of chest pain in people with stable angina
• First choice treatments for stable angina are BB and CCB
• These may be used if the other drugs can not be tolerated

Question 14

Nicorandil

MOA

Answer 14

• Nicorandil causes both arterial and venous vasodilation through its action as a nitrate (see nitrate) and by activating K-ATP channels
• Efflux of K through K/ATPase channels leads to hyperpolarisation of the cell membrane and subsequent inactivation of voltage-gated Ca2+ channels
• The net effect is a decrease in free intracellular calcium
• As Ca is required for smooth muscle contraction, relaxation and vasodilation occur
• The effect of this is to reduce cardiac preload and systematic and coronary vascular resistance
• This improves myocardial perfusion and decreases myocardial work as well as oxygen demand
• Clinically, this reduces the frequency and severity of angina attacks

Question 15

Nicorandil

Warnings

Answer 15

• You should not prescribe nicorandil for patients with poor:
  
  • Poor Left ventricular function
  • Hypotension
  • Pulmonary oedema

Question 16

Nicorandil
Interactions

Answer 16

• As with nitrates, the hypotensive side effects of nicorandil are significantly enhanced by phosphodiesterase inhibitors
• They should not be prescribed together

Question 17

Nicorandil

Communication

Answer 17

• Reduce attacks of chest pain
• Warn patient not to drive or use heavy machinary until angia symptoms are controlled and side effects of nicorandil, including dizziness and hypotension have settled

Question 18

Ranalozine

Indications

Answer 18

• Adjunctive therapy in the treatment of stable angina in patient inadequately controlled by first-line antianginal therapies

Question 19

Ranolazine

MOA

Answer 19

• Largely unknown
• Some antianginal effect is by inhibition of the late sodium current in cardiac cells
• This reduces intracellular sodium accumulation and consequently decreases intracellular calcium overload
• Reduction in cellular calcium overload is expected to improve myocardial relaxation and thereby decrease left ventricular diastolic stiffness
• Also significantly shortens QTc interval

Question 20

Ranolazine

Warnings

Answer 20

• Contraindicated in
  
  • Hypersensitivity
  • Severe renal impairment (<30mL/min)
  • Moderate-severe hepatic impairment
• Cautioned in
  
  • Elderly
  • Low body weight (<60kg)
  • Patients with moderate to severe CHF

Question 21

Ranolazine

Adverse effects

Answer 21

*

Question 22

Ranolazine

Interactions

Answer 22

• CYP inhibitors (Azoles, Clarithromycin, Diltiazem, Ciclosporin, Verapamil, Grapefruit)
• CYP inducers (Rifampicin, CBZ, Phenytoin, STW, Phenobarbital)
• Digoxin- increase in dig concentration meaning levels should be monitored on initiation and termination of treatment
• Statin- Increase statin concentration, increase risk of rhabdo
• Ciclosporin, sirolimus, tacrolimus-

Question 23

Ivabradine

Indications

Answer 23

• Treatment of angina in patients in normal sinus rhythm
• Mild to severe chronic HF

Question 24

Ivabradine

MOA

Answer 24

• Pure HR lowering agent
• Selective and specific inhibition of cardiac pacemaker If current that controls the spontaneous diastolic depolarisation in the sinus node and regulates HR
• Cardiac effects are specific to the sinus node
• Ivabradine can also interact with the retinal Ih which resembles cardiac If
• Patients can get phosphenes- described as transient enhanced brightness in a limited area of the visual field
• NB- reduce cardiac work, O2 consumption, No inotropic effect

Question 25

Ivabradine

Warnings- contraindications

Answer 25

• Hypersensitivity
• Resting HR <70 bpm
• Cardiogenic shock
• Acute MI
• Severe Hypotension (<90/50mmHg)
• Severe hepatic dysfunction
• Sino-atrial block
• Unstable angina
• CYP inhibitors
• Pregnancy/breastfeeding
• HF

Question 26

Ivabradine

Cautions

Answer 26

• AF
• Other arrhythmias
• Elderly
• Stop if no symptom improvement in angina
• hypotension
• Retinitis pigmentosa
• Intraventricular conduction defects

Question 27

Ivabradine

Adverse effects

Answer 27

• Tranient luminous phenomena (Phosphenes) - NB- counsel around driving
• Bradycardia
• AV block
• Different arrhythmias
• Uncontrolled `BP
  *

Question 28

Ivabradine

Interactions

Answer 28

• QT prolonging medicinal products
• CYP inhibitors
• CYP inducers
• Verapamil/Diltiazem- contra-indicated

Question 29

Ivabradine

Monitoring

Answer 29

• ECG- AF
• HR
• BP
• Monitor for visual disturbances