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QUICK SUMMARY ��HIGH RISK DRUGS���

UK’S MOST INTENSIVE REVISION PROGRAMME

LONDON PHARMACIST NETWORK –

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AMIODARONE

  • Amiodarone has a very long half life. Can stay in body for months even after last dose.
  • Amiodarone can be taken with or without food.
  • Amiodarone is photosensitive and can lead to a blue-gray tone.
  • Avoid grapefruit juice
  • Corneal microdeposits
  • Thyroid function
  • Hepatotoxicity
  • Pulmonary toxicity, interstitial lung disease

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AMIODARONE

Monitoring points

    • Thyroid function test (before treatment and then every 6 months)
    • Liver function tests (before treatment and then every 6 months)
    • Serum K+ (measured before treatment)
    • Chest x-ray (measured before treatment)
    • IV use requires ECG (resuscitation facilities must be available)

DRUG INTERACTIONS – flecanaide, digoxin, warfarin, grapefruit juice,beta blockers, verapamil

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AMIODARONE�INTERACTIONS

Amiodarone interacts with Digoxin . Reduce digoxin by 50%.

Amiodarone increases the risk of muscle break down with simvastatin

Amiodarone increase rate of arrythmias with Lithium

Amiodarone increases risk of bleeding for patients taking warfarin

Amiodarone increases risk of bradycardia with betablockers . Patients heart rate is lowered.

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THEOPHYLLINE

  • Therapeutic range – 10mg – 20mg/L
  • Monitor two things – plasma conc., serum potassium
  • Theophylline must be prescribed by BRAND.
  • Theophylline can cause hypokalaemia
  • Symptoms of overdose – agitation, hyperglycaemia, restlessness, arrythmias, dilated pupils
  • Antidote is activated charcoal
  • Aminophylline is twenty times more potent than theophylline.

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THEOPHYLLINE

  • Check plasma concentration after 3 days if oral dose is adjusted.
  • Check plasma concentration 5 days after a patient is first started on theophylline.
  • Theophylline interacts with tobacco in cigarettes. Increase dose of theophylline if patient smokes and reduce dose if patient stops smoking.
  • Theophylline can interact with B2 agonists, corticosteroids, diuretics to increase risk of hypokalemia.
  • Theophylline can interact with quinolones to increase convulsions and seizures.
  • Theophylline levels can be reduced by inducers e.g. carbamazepine
  • Theophylline can cause seizures and palpitations

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DIGOXIN

  • Digoxin is a cardiac glycoside that increases the force of myocardial contraction and reduces conductivity within the av node.
  • Different bioavailabilities depending on form: IV - 100%, Tablets 50-90%, Elixir 75%)
  • ANTI-DOTE is DIGIFAB
  • Range is from 0.8mcg - 2mcg/L
  • Electrolyte imbalance that can cause digoxin toxicity
  • Hypercalcaemia e.f if patient is on high calcium or vit D
  • Hypokalaemia e.g if patient is on theophylline
  • Hypomagnesaemia e.g if patient is on PPI e.g omeprazole
  • Hypoxia e.g if patient has severe COPD or acute asthma attack

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DIGOXIN

Advise patients to report to doctor immediately if presence of

• Cardiac symptoms (arrhythmias and heart block)

• Neurological symptoms (weakness, lethargy, dizziness, headache, mental confusion and psychosis)

• Gastrointestinal symptoms (anorexia, nausea, vomiting, diarrhoea, abdominal pain; avoided by dividing larger doses)

• Visual symptoms (blurred and/yellow vision)

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DIGOXIN

Monitoring points

Serum electrolytes (K+ , Mg2+, Ca2+) (toxicity increased by electrolyte disturbance i.e. hypokalaemia, hypomagnesaemia, and hypercalcaemia)

Renal function (renal excretion of drug; reduce dose in renal impairment to reduce accumulation of metabolite)

Plasma-digoxin (mainly in renal impairment, blood should be taken at least 6 hours after dose)

Heart rate (should be maintained above 60 beats/min)

Renal impairment Reduce dose, monitor plasma concentration in renal impairment

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DIGOXIN�INTERACTIONS

Digoxin can interact with amiodarone , dronaderone and quinine. Reduce digoxin dose by half to reduce riak of digoxin digitalis.

beta-agonists e.g salbutamol can cause hypokalaemia which can increase digoxin toxicity

Digoxin concentration can be reduced by st Johns wart.

NSAIDs reduce kidney function which can increase levels of digoxin

Macroclides e.g clarithromycin are enzyme inhibitors which can increase levels of digoxin in patients leading to toxicity

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METHOTREXATE

  • DIHYDROFOLATE REDUCTASE

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  • TAKE WEEKLY

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  • 2.5MG STRENGTH VS 10MG STRENGTH

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  • HOW TO TAKE FOLIC ACID ??

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  • COUNSEL PATIENTS ON HOW TO TAKE ?

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METHOTREXATE ADVERSE EFFECTS

BLOOD DISORDER

LIVER TOXICITY

RESPIRATORY EFFECTS e.g. pneumonitis

PHOTOSENSITIVITY

DEHYDRATION

ASCITES

CONTRACEPTION AND CONCEPTION

OTHER SIDE-EFFECTS G.I IRRITATION TOXICITY withdraw if stomatitis, ANAEMIA, taste disturbance, dyspnoea

GIVE CALCIUM FOLINATE AS ANTIDOTE IN ACUTE TOXICITY

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METHOTREXATE DRUG INTERACTIONS

NSAIDS – reduce kidney function

ASPIRIN NOT OTC

PENICILLINS

TRIMETHOPRIM – antifolate can impair immune system severely.

CO-TRIMOXAZOLE

PPIs – especially omeprazole

QUINOLONES

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CYCLOSPORIN

POTENT IMMUNOSUPRESSANT

PRESCRIBE BY BRAND

PHOTOSENSITIVE- UV LIGHT, SUNLIGHT, SUN BEDS, SUN LAMPS

AVOID GRAPE-FRUIT JUICE

INTERACT WITH MACROLIDES CLARITHROMYCIN, ERYTHROMYCIN, CARBAMAZEPINE, ST JOHNS WORT, COLCHICINE

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CICLOSPORIN MONITORING

CHECK BLOOD CONCENTRATIONS

CHECK blood pressure twice before starting

CHECK blood lipids

LIVER FUNCTION

POTASSIUM AND MAGNESIUM LEVELS- risk of high K

KIDNEY FUNCTIONS

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NSAIDS

  • NSAIDS should be taken with food.
  • Prescribe a PPI alongside NSAIDS.
  • NSAIDs can cause constriction of airways especially if patient is asthmatic.
  • NSAIDs can increase the risk of fluid overload in patients with heart failure.
  • NSAIDs can cause bleeding , GI irritation and peptic ulcer.
  • Do not sell NSAIDs to patients with uncontrolled hypertension or patients taking methotrexate or if pregnant/ breastfeeding.

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NSAIDS

  • Nsaids can reduce EGFR which can increase toxicity of lithium , methotrexate etc
  • Increase risk of bleeding with SSRIs, DOACs, aspirin, heparins
  • Enhances effects of sulphonylureas
  • Nsaids can increase blood pressure .
  • Nsaids can increase INR with warfarin .

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Sodium valproate

  • “Valproate should not be used in female children and women of childbearing potential unless other treatments are ineffective or not tolerated. In this case, valproate must be prescribed and dispensed according to the valproate pregnancy prevention programme”.
    • NEW Under 55 years patients guideline.
    • Ensure patients receive Valproate PATIENT GUIDE.
    • Valproate should be dispensed in the original package.
    • Remind patients of risk in pregnancy, PPP & use highly effective contraception.
    • In case of suspected pregnancy, females should be advised NOT to stop taking the medication and contact their GP immediately.
    • Unborn babies exposed to valproate are at risk of neurodevelopmental disorders and congenital malfunctions - advise females accordingly
    • It can cause blood disorder symptoms, pancreatic and hepatic toxicity

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Phenytoin

GIVE SAME BRAND –bioequivalence

Plasma conc of 10 to 20 mg/ L or 40 to 80 micromole/litre

Can cause blood disorder, hirsutism?

Doctor to discontinue - if rash is noticed

contra-indicated in acute porphyrias

interacts with lidocaine, dronaderone, amiodarone, Azoles

Bradycardia and hypotension ,if hypotension occurs, reduce infusion rate or discontinue

pre-screening – Han Chinese patients –HLAB 1502- RISK OF s.j.s.

reduce dose or infusion rate in elderly, and in renal or hepatic impairment

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Aminoglycosides

ensure patients drinks adequate amount of water

Increased risk of toxicity in elderly, renal impaired patients

They are not absorbed from the gut although its possible in IBD/Liver disease

Loading dose may be calculated based on patient’s ideal body weight or renal function.

ONCE daily administration is preferred to multiple-daily dose regimens except in patients with endocarditis due to gram+ bacteria.

Monitor serum concentration to prevent excessive and sub-therapeutic concentrations – narrow therapeutic index

interacts with loop diuretics, vancomycin, ciclosporin

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WHY IS IDEAL BODY WEIGHT IMPORTANT ??

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Aminoglycosides

Side – effects

  • Ototoxicity
  • Nephrotoxicity
  • Skin reactions
  • histamine related adverse reactions – gentamicin
  • NB– Naseptin cream contains peanut oil . Check allergy!!
  • TROUGH AND PEAK CONCENTRATIONS
  • learn gentamicin and amikacin concentrations
  • monitor renal, auditory function and plasma concentration

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LITHIUM

LITHIUM may impair performance of skilled tasks (e.g. driving, machinery use)

same brand, avoid low sodium diet, correct hypothyroidism , check weight

A combination of symptoms such as visual disturbances, polyuria, muscle weakness, CNS disturbances, vomiting, diarrhoea, restlessness and stupor suggests LITHIUM OVERDOSE

Target of 0.4 – 1 mmol/ litre ----- after 12 hours after a dose as lithium is a narrow therapeutic index drug. What about elderly patients

Target 0.8 – 1 mmol/litre ------ is for acute acute episodes of mania , sub-syndromal symptoms and relapse cases

interactions – NSAIDs affect kidneys, diuretics, amiodarone, diltiazem , phenytoin

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HIGH RISK DRUG - CARBAMAZEPINE �

  • Therapeutic range: 4 to 12mg/L (20 to 50 micromol/litre); PRESCRIBE by brand-specific category
  • Toxicity (incoordination, blurred vision, double vision, drowsiness, nystagmus, ataxia, arrhythmias, nausea & vomiting, diarrhoea, hyponatraemia)
  • Blood disorders (fever, sore throat, unexplained bruising or bleeding)
  • Skin disorders (mouth ulcers, rash)
  • Hepatic disorders e.g. hepatitis (severe GI upset, fatigue, jaundice, dark urine)
  • Antiepileptic Hypersensitivity Syndrome (fever, rash, swollen lymph nodes)
  • Intrxs -Increased plasma concentration with acetazolamide, cimetidine, clarithromycin,
  • Decreased plasma concentration with phenytoin, rifabutin, St. John’s Wort
  • SREENING FOR Han Chinese and Thai patients for Allelle to reduce risk of SJS

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VANCOMYCIN

THERAPEUTIC RANGE – 10 TO 15MG/L

CONSELLING

Red mans syndrome – don’t infuse rapidly

Blood disorder symptoms

Auditory problems

kidney toxicity

MONITOR – serum K , full blood count, renal function , auditory function.

interactions – diuretics e.g loop diuretics and ciclosporin can affect vancomycin concentration

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YOU WILL SMASH THE GPHC EXAM !!!!

  • THE END