High Risk Drugs Flashcards
Is loading dose usually required with drugs with short or long half-life?
Drugs with long half-lives will take longer to reach steady state, therefore, require a loading dose to rapidly achieve target concentration for acute therapeutic response.
What is the indication of amiodarone?
Treatment of arrhythmias - but usually is not first line - it is used when other treatments have failed or is contra-indicated. (Initiated in hospital under specialist supervision).
What is the half life of amiodarone?
about 50 days
Loading doses may be required
What is the usual oral dose of Amiodarone?
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 200 mg daily or the minimum dose required to control arrhythmia.
What are the monitoring requirements for Amiodarone?
- Thyroid function
- Liver function
- Serum potassium
- Chest X-ray
- ECG (with intravenous use)
What are the warning signs to be aware of with amiodarone?
- signs and symptoms of hypo or hyperthyroidism
- impaired vision (optic neuritis, optic neuropathy)
- photophobia, dazzled by headlights at night (corneal micro deposits)
- progressive shortness of breath or cough (pneumonitis, pulmonary toxicity)
- clinical signs of liver disease e.g. jaundice
- Neurological effects of tremor, peripheral neuropathy (e.g. develop numbness and tingling in hands and feet)
- phototoxic skin reactions e.g. burning sensation followed by erythema, and persistent slate grey skin discoloration on light-exposed areas.
What advise should be given to people taking amiodarone?
- Advise patient to shield skin from direct sunlight and for several months after stopping treatment or to use a wide-spectrum sunscreen
- warn drivers that they may be dazzled by headlights at night
- warn patients that the clinical effects may occur up to a year after stopping the medicine.
As amiodarone has a long half-life, what advice should be given about drug interactions?
There is a potential for drug interactions for several weeks to months after treatment has been stopped.
Which drugs plasma concentration is increased when given with amiodarone?
Coumarins, dabigatran, digoxin, flecainide, phenindione and phenytoin.
Which drugs when given with amiodarone increases the risk of ventricular arrhythmias?
amisulpride, atomexetine, chloroquine, citalopram, disopyramide, escitalopram, haloperidol, hydroxychloroquine, levofloxacin, lithium, mizolastine, mefloquine, mocifloxacin, phenothiazine, pimozide, quinine, sulpride, telithromycin, tolterodine tricyclics
When amiodarone is given with either beta blockers, diltiazem or verapamil, what is there an increased risk of?
Increased risk of bradycardia, AV block and myocardial depression.
Interaction between amiodarone and simvastatin?
Increased risk of myopathy
What are the common indications of digoxin?
1) In atrial fibrillation (AF) and atrial flutter, digoxin is used to reduce the ventricular rate. However, a β-blocker or non-dihydropyridine calcium channel blocker is usually more effective.
2) In severe heart failure, digoxin is an option in patients who are already taking an ACE inhibitor, β-blocker and either an aldosterone antagonist or angiotensin receptor blocker. It is used at an earlier stage in patients with co-existing AF.
What is the mechanism of action of digoxin?
Digoxin is negatively chronotropic (it reduces the heart rate) and positively inotropic (it increases the force of contraction).
In AF and flutter its therapeutic effect arises mainly via an indirect pathway involving increased vagal (parasympathetic) tone.
- this reduces conduction at the atrioventricular (AV) node, preventing impulses from being transmitted to the ventricles, thereby reducing ventricular rate.
In heart failure what is the mechanism of digoxin?
In heart failure, it has a direct effect on myocytes through inhibition of Na+/K+ ATPase pump, causing Na+ to accumulate in the cell. As cellular extrusion of Ca2+ requires low intracellular Na+ concentrations, elevations of intracellular Na_ causes Ca2+ to accumulate in the cell, increasing contractile force.
What is digoxin dose decided by?
Dose is decided by ventricular rate at rest and persistent rate shouldn’t fall under 60.
Which patients do not require a loading dose?
Patients with heart failure and sinus rhythm don’t require a loading dose
Does digoxin have a long half life?
Yes so it is given once daily
Which type of impairment is most important in deciding the dose of digoxin?
Renal function
What can digoxin side effects be mixed with?
It can be hard to distinguish between side effect and deteriorating heart condition.
What range of digoxin does toxicity progress in?
Through the range 1.5mcg-3mcg/L.
Is regular monitoring required when on digoxin?
No - unless toxicity is suspected
What are the side effects of digoxin?
- Arrhythmias
- blurred vision
- Yellow vision
- conduction disturbances
- dizziness
- eosinophilia
- nausea and vomiting
- rash
When switching from IV digoxin to oral what dose change is needed?
Increase the dose by 20-33% so plasma concentration can be maintained
Which conditions is digoxin contraindicated in?
- constructive pericarditis
- hypertrophic cardiomyopathy
- intermittent heart block
- myocarditis
- second-degree AV block
- supraventricular arrhythmias e.g. wolff-parkinson syndrome.
Which patients should digoxin be used with caution?
Those with hyperkalaemia, hypokalaemia
Which electrolyte imbalance can potentiate toxicity of digoxin?
- hypokalaemia
- hypomagnesaemia
- hypercalcaemia
With digoxin what heart rate should be maintained?
at greater than 60 beats per minute
What should be monitored for those on digoxin treatment?
- serum electrolytes (K+, Mg2+ and Ca2+).
- renal function
- heart rate
What is the major route of elimination for digoxin?
- renal excretion; hepatic metabolism to active metabolites.
What are the warning signs of digoxin?
- Cardiac e.g. arrhythmias, heart block
- Neurological e.g. weakness, lethargy, dizziness, headaches, mental confusion, psychosis
- Gastrointestinal e.g. anorexia, nausea, vomiting, diarrhoea, abdominal pain
- Visual e.g. blurred and/ or yellow vision
Does digoxin + st John’s wort increase or decrease plasma concentration of digoxin?
Decrease
What other interactions is there to know of with digoxin?
Concomitant adminstration of acetazolamide, amphoterecin, loop diuretics or thiazides and related diuretics can cause hypokalaemia that increases the risk of cardiac toxicity and digoxin toxicity.
Which drugs increase plasma concentration of digoxin?
- alprazolamiodarone
- ciclosporin
- diltiazem
- itrazonazole
- lercanidipine
- macrolides
- mirabegron
- nicardipine
- nefidipine
- quinine
- spironolactone
- verapamil
How long does it taken for effect of digoxin with IV / oral?
IV = 30 mins Oral = about 2 hours
When rapid effect is needed, what is required?
A loading dose
What is the usual maintenance dose of digoxin?
125-250 micrograms
Digoxin with or without food?
Can be taken with or without food,
What can therapetic doses of digoxin cause on the ECG?
should note that therapeutic doses of digoxin can cause ST-segment depression (the ‘reverse tick’ sign) on the ECG. This is an expected effect and does not signify toxicity.
Why is digoxin rarely used now on its own for AF?
Because digoxin’s effect on ventricular rate in AF relies on parasympathetic (‘rest and digest’) tone, it tends to be lost during stress and exercise. Digoxin is therefore now rarely used on its own for AF, although it may be an option in sedentary patients.
For digoxin assay when should blood be taken?
At least 6 hours after the dose.
During digoxin therapy, it is essential to monitor serum potassium levels because….?
- Low potassium levels increase the chance of digoxin toxicity
Mrs. Chin is undergoing digoxin therapy and begins to complain of headache and studies revel a dysrhythmia. What is happening with this patient?
Digoxin toxicity
Mr. Ferris also complains of constipation. He complains that if he were allowed to eat his high fiber bran as often as he used to, he wouldn’t be constipated. What teaching should the nurse provide to Mr. Ferris?
Food high in fiber bind to digitalis and make it less effective
Which class/ type of drug is azathioprine?
Anti-metabolite/ Immunosuppressant
What are the main indications of azathioprine?
1) Maintenance of remission of Chron’s disease and ulcerative colitis (UC)
2) As a disease modifying agent in rheumatoid arthritis and autoimmune conditions not responding to corticosteroids or other standard treatments
3) To prevent organ rejection in transplant recipients
Is azathioprine pharmacologically active?
Azathioprine is a pro-drug. this means that itself it is not pharmacologically active but on metabolism it is converted to substances that are.
What is the main metabolite that azathioprine is converted to?
6-mercaptopurine which is further metabolised to active substances.
What is the MOA of azathioprine?
The active metabolites inhibit the synthesis of purines (notably the nucleosides adenine and guanine) and therefore inhibit DNA and ribonucleic acid (RNA) replication.
- Whereas most cells can ‘salvage’ or ‘recycle’ purines, lymphocytes are dependent on purine synthesis and so are particularly affected by azathioprine metabolites.
Which enzymes does the metabolism and elimination of azathioprine involve?
- Xanthine oxidase
- Thiopurine methyltransferase (TPMT)
The activity of the latter is reduced or absent in some individuals.
What is the most serious dose related effect of azathiopurine?
- Bone marrow suppression - which results most significantly in leukopenia and an increased risk of infection.
What may results in resolving bone marrow suppression associated with azathioprine?
- A reduction in dose or temporary break in therapy may resolve this.
With Azathioprine nausea is common, what can be done to reduce this?
By dividing the daily doses
What side effects (hypersensitivity) can occur with azathioprine?
- diarrhoea
- vomiting
- rash
- fever
- myalgia
- hypotension
- pancreatitis
What are some rare but serous side effects of azathioprine?
- veno-occlusive disease
- hepatoxicity
- increased risk of some tumours such as lymphoma
What should be performed before starting therapy with Azathioprine?
TPMT performing should be performed before starting therapy as it may help identify those at risk.
What is the effect of TPMT activity on prescribing azathioprine?
Absent TPMT activity = should not prescribe azathioprine
Reduced TPMT activity = treated only by specialist
What is the effect of Azathioprine dose in hepatic and renal impairment?
Dosage should be reduced