CV

Question 1

What test results would suggest thyrotoxicosis while using Amiodarone?

Answer 1

A raised T3 and T4 with a very low or undetectable TSH concentration suggests the development of thyrotoxicosis

Question 2

Which serum electrocyte concentration should be measured before the start of Amiodarone ?

Answer 2

Serum potassium

Question 3

What advise patients should be offered while taking Amiodarone ?

Answer 3

Advised to shield the skin from light during treatment and for several months after stopping Amiodarone. Not to drink grapefruit juice as this may increase the risk of side effects. Report any SOB or cough

Question 4

If patients are taking Amiodarone with sofosbuvir and
daclatasvir, simeprevir and sofosbuvir, or sofosbuvir and
ledipasvir, what advice should they be given?

Answer 4

Should be told how to recognise signs and symptoms of bradycardia and heart block and advised to seek urgent care if symptoms such as SOB, light headiness, palpitations, fainting, unusual tiredness, or chest pain develop.

Question 5

How does Amiodarone work?

Answer 5

Amiodarone has many effects on myocardial cells, including blockade of sodium, calcium and potassium channels, and antagonism of α- and β-adrenergic receptors. Amiodarone causes QT prolongation

Question 6

What adverse effects Amiodarone can cause when its taken chronically?

Answer 6

Lungs (pneumonitis)
Heart( bradycardia, AV block) 
Liver ( hepatitis)
Skin (photosensitivity and grey discolouration)
Thyroid abnormalities (hypo and hyper)
Corneal micro deposits

Question 7

Which drugs should be halved if Amiodarone is started and why?

Answer 7

Digoxin, diltiazem and verapamil. It increases these drugs conc.

Question 8

Monitoring requirements for Amiodarone?

Answer 8

Thyroid function test- before and after 6 months.
Liver function test- before and then every 6 months.
Chest x-ray and serum potassium before treatment

Question 9

What are the most common side effects with oral Amiodarone ?

Answer 9

Constipation
Corneal deposits
hypothyroidism
movement disorders
sleep disorders
taste altered
photosensitivity Reactions
vomiting

Question 10

Whats is Amiodarone loading and maintenance dose?

Answer 10

Adult: 200 mg 3 times a day for 1 week, then reduced to
200 mg twice daily for a further week, followed by
maintenance dose, usually 200mg daily or the
minimum dose required to control arrhythmia

Question 11

Describe clinical signs of hypothyroidism?

Answer 11

Hypothyroidism should be suspected if the following clinical signs occur: weight gain, cold intolerance, reduced activity, excessive bradycardia. The diagnosis is supported by an increase in serum usTSH and an exaggerated TSH response to TRH. T3 and T4 levels may be low. Euthyroidism is usually obtained within 3 months following the discontinuation of treatment. In life-threatening situations, amiodarone therapy can be continued, in combination with levothyroxine. The dose of levothyroxine is adjusted according to TSH levels.

Question 12

Describe clinical features of hyperthyroidism?

Answer 12

Hyperthyroidism may occur during amiodarone treatment, or, up to several months after discontinuation. Clinical features, such as weight loss, asthenia, restlessness, increase in heart rate, onset of arrhythmia, angina, congestive heart failure should alert the physician. The diagnosis is supported by a decrease in serum usTSH level, an elevated T3 and a reduced TSH response to thyrotropin releasing hormone. Elevation of reverse T3 (rT3) may also be found.

In the case of hyperthyroidism, therapy should be withdrawn.

Question 13

Combined therapy with the following drugs which prolong the QT interval is contra-indicated (see section 4.3) due to the increased risk of torsades de pointes; give examples?

Answer 13

• Class Ia anti-arrhythmic drugs e.g. quinidine, procainamide, disopyramide
• Class III anti-arrhythmic drugs e.g. sotalol, bretylium
• intravenous erythromycin, co-trimoxazole or pentamidine injection
• some anti-psychotics e.g. chlorpromazine, thioridazine, fluphenazine, pimozide, haloperidol, amisulpiride and sertindole
• lithium and tricyclic anti-depressants e.g. doxepin, maprotiline, amitriptyline
• certain antihistamines e.g. terfenadine, astemizole, mizolastine
• anti-malarials e.g. quinine, mefloquine, chloroquine, halofantrine.
• Moxifloxacin
Concomitant use of amiodarone with fluoroquinolones should be avoided (concomitant use with moxifloxacin is contraindicated).

Question 14

Drugs lowering heart rate or causing automaticity or conduction disorders are not recommended to be used with Amiodarone? give examples?

Answer 14

Combined therapy with the following drugs is not recommended:
- Beta blockers and heart rate lowering calcium channel inhibitors (diltiazem, verapamil); potentiation of negative chronotropic properties and conduction slowing effects may occur.

Question 15

Agents which may induce hypokalaemia are not recommended with Amiodarone. Give examples?

Answer 15

Stimulant laxatives, which may cause hypokalaemia thus increasing the risk of torsades de pointes; other types of laxatives should be used.Caution should be exercised over combined therapy with the following drugs which may also cause hypokalaemia and/or hypomagnesaemia, e.g. diuretics, systemi corticosteroids, tetracosactide, intravenous amphotericin.In cases of hypokalaemia, corrective action should be taken and QT interval monitored. In case of torsades de pointes antiarrhythmic agents should not be given; pacing may be instituted and IV magnesium may be used.

Question 16

What is the Effect of amiodarone on other medicinal products?

Answer 16

Amiodarone and/or its metabolite, desethylamiodarone, inhibit CYP1A1, CYP1A2, CYP3A4, CYP2C9, CYP2D6 and Pglycoprotein and may increase exposure of their substrates.

Question 17

Amiodarone is a P-gp inhibitor. Co administration with P-gp substrates is expected to result in an increase of their exposure: name drugs that are p-gp substrates?

Answer 17

Digitalis: administration of Amiodarone to a patient already receiving digoxin will bring about an increase in the plasma digoxin concentration and thus precipitate symptoms and signs associated with high digoxin levels. Clinical, ECG and biological monitoring is recommended and digoxin dosage should be halved. A synergistic effect on heart rate and atrioventricular conduction is also possible.

• Dabigatran: caution should be exercised when amiodarone is co administered with dabigatran due to the risk of bleeding. It may be necessary to adjust the dosage of dabigatran as per its label.

Question 18

Amiodarone inhibits CYP 2C9; which drugs would this affect?

Answer 18

Amiodarone raises the plasma concentrations of oral anticoagulants (warfarin) and phenytoin by inhibition of CYP 2C9:

• Warfarin: the dose of warfarin should be reduced accordingly. More frequent monitoring of prothrombin time both during and after amiodarone treatment is recommended.
• Phenytoin: phenytoin dosage should be reduced if signs of overdosage appear (resulting in neurological signs), and plasma levels may be measured.

Question 19

CYP P450 3A4 substrates :When such drugs are co-administered with amiodarone, an inhibitor of CYP 3A4, this may result in a higher level of their plasma concentrations, which may lead to a possible increase in their toxicity: name the drugs?

Answer 19

Ciclosporin: plasma levels of ciclosporin may increase as much as 2-fold when used in combination. A reduction in the dose of ciclosporin may be necessary to maintain the plasma concentration within the therapeutic range.

• Statins: the risk of muscular toxicity (e.g.rhabdomyolysis) is increased by concomitant administration of amiodarone with statins metabolised by CYP 3A4 such as simvastatin, atorvastatin and lovastatin. It is recommended to use a statin not metabolised by CYP 3A4 when given with amiodarone.
• Other drugs metabolised by cytochrome P450 3A4: examples of such drugs are lidocaine, tacrolimus, sildenafil, fentanyl, midazolam, triazolam, dihydroergotamine, ergotamine and colchicine.

Question 20

What effects of other drugs would be on Amiodarone?

Answer 20

CYP3A4 inhibitors and CYP2C8 inhibitors may have a potential to inhibit amiodarone metabolism and to increase its exposure.It is recommended to avoid CYP 3A4 inhibitors during treatment with amiodarone.Grapefruit juice inhibits cytochrome P450 3A4 and may increase the plasma concentration of amiodarone. Grapefruit juice should be avoided during treatment with oral amiodarone.