High risk meds Flashcards
What are high risk drugs?
Medicines that can cause significant harm to the patient, may cause serious side effects especially when administered incorrectly or when dose is calculated incorrectly.
May have a narrow therapeutic range.
What is the half life of amiodarone?
About 50 days - loading doses may be required
Monitoring required for Amiodarone?
Thyroid function, liver function, serum potassium, chest x ray, ECG (with iv use)
Warning sings associated with amiodarone?
- Signs of hypothyroidism OR hyperthyroidism
- Corneal microdeposits
- Progressive SOB (pulmonary toxicity)
- Clinical signs of live disease
- Neurological effects of tremor, peripheral neuropathy
- Phototoxic skin reactions
Interactions with amiodarone?
Increased plasma concentrations with:
dabigatran, digoxin, flecainide, phenindione, phenytoin
Increased risk of arrhythmias with amisulpride. atomoxetine, chloroquine, citalopram, disopyramide, escitalopram, haloperidol, hydroxychloroquine, levofloxacin, lithium, mizolastine, melfoquine, moxifloxacin, phenothiazines, pimozide, quinine, sulpiride, tricyclics
Increased risk of bradycardia when given with beta blockers, dilitazem, verapamil
Increased risk of myopathy when given with simvastatin
What monitoring is needed with ACE inhibitors and ARB’s
BP, renal function and electrolytes
Warning signs with ace inhibitors and ARB’s?
Postural hypotension (dizziness, blurred vision)
Jaundice
Abnormal renal function
Water retention
Confusion, nausea, vomiting and dehydration (AKI)
Actions required for ACE inhibitors and ARBS:
- 1 in 10 people taking ACE inhibitor will get a dry cough, can take 8-12 weeks to disappear
- Routine bloods - 1-2 weeks after initiation and 1-2 weeks after dose changes
- Preferably give dose at bedtime
- Drink plenty of water
- Stop medication during sick days
ACE and ARB interactions?
- Can both increase concentration of lithium
- Can both increase potassium levels (hyperkalaemia)
- Increased risk of renal impairment when both give with aliskiren
Monitoring required for antipsychotics
FBC U+E's LFT's fasting blood glucose blood lipids BP Weight ECG
Warning sings for antipsychotics
Hyperthermia, muscle rigidity, fluctuating levels of consciousness, tachycardia, labile BP
Remember for clozapine: intestinal immobility, agranulocytosis, myocarditis and the risk of stopping smoking
Actions required for antipsychotics:
- Repeat ECG periodically and dose reduce if QT interval is prolonged
- Maintain adequate fluid intake
- Increase doses slowly
- Half doses used for elderly
- Avoid prescribing more than 1 antipsychotic
- Dont stop abruptly
- Photosensitisation risk in higher dose
Antipsychotic interactions:
- Increased hypotensive effect with ACE inhibitors, ARBs, CCB’s and B blockers
- Increased sedation with antihistamines and anxiolytics
- Increased risk of QT prolongation with amiodarone, citalopram, escitalopram, methadone and macrolide antibiotics
- Increased extrapyramidal side effects with metoclopramide and amantadine
What are extra pyramidal side effects:
Akathisia: Feeling restless like you can’t sit still
Dystonia: When your muscles contract involuntarily
Parkinsonism: Symptoms are similar to Parkinson’s disease
Tardive dyskinesia: Facial movements happen involuntarily.
Monitoring required for azathioprine
FBC, Renal Function, Liver function
Warning signs with Azathioprine?
- Signs of hypersensitivity i.e. fever,
- Hypotension
- N+V
- Unexplained bruising or bleeding
Actions required with azathioprine?
- if taking concurrent allopurinol, reduce dose to 1/4
- Measure TPMT before initiation
- Counsel patient to report any signs or symptoms of bone marrow suppression i.e. bruising, bleeding, infection
- Dose reduce in elderly
Interactions with azathioprine:
Increased risk of anaemia with ace inhibitors
Anticoagulant effect of coumarins reduced
Increased risk of haem toxicity with allopurinol
Increased risk of generalised infection which could be life threatening with live vaccines
What is the therapeutic range of carbamazapine?
4-12mg/l
Monitoring required for carbamazpine?
FBC, renal function, liver function
Warning sings for carbamazapine?
Toxicity –> blurred vision, drowsiness, arrythmias, N+V, diarrhoea, hyponatraemia
- Blood disorders - sore throat?
- Skin disorders - rash, sore throat?
- Hepatic disorders e.g. hepatitis
- Antiepileptic hypersensitivity syndrome
Actions required for carbamazepine?
- Advise to contact doctor about warning signs immediately
- Ensure that they receive the same brand each time
- Ensure patient is aware of the law surrounding seizures and driving
- Inform about potential interactions and need to check with a pharmacist or doctor before starting any other meds
Interactions with carbamazepine?
- Increased plasma conc with acetazolamide, cimetidine, clarithromycin, erythromycin, fluoxetine, isoniazid
- Decreased plasma conc with phenytoin, rifabutin, St Johns wort
- Carbamazepine reduced plasma conc of antipsychotics, corticosteroids, coumarins, eplerenone, oestrogens, progestogens, simvastatin
- Anticonvulsant effect antagonised by mefloquine, antipsychotics
- Possible increased risk of convulsions when antiepileptics given with orlistat
Common side effects of chemo
Extravasation of IV drugs = leakage N+V Bone marrow suppression (except vincristine and bleomycin) Fatigue Oral mucositis Hyperuricaemia Organ toxicities
Warning signs of neutropenic sepsis?
- Feeling unwell with two temp reading of 37.5 and above
- Shivering/flu like symptoms
- Uncontrolled bleeding/bruising
- Diarrhoea and/or uncontrolled vomiting
- Mouth ulcers
Actions required for chemo meds?
- Advise to visit a+e if development of signs of neutropenic sepsis and not to take paracetamol
- Report side effects immediately to doctor
- Pxing of anti emetics
- Advise to maintain good oral hygiene
Monitoring required for ciclosporin?
FBC, liver function, serum electrolytes, blood lipids, renal function, BP, dermatological and physical examination
Warning signs for ciclosporin?
- Neurotoxicity
- Blood disorders
- Liver toxicity
- Nephrotoxicity
- Hypertension
- Headache
- Gingival hyperplasia
Actions required for ciclosporin?
- Report any warning signs immediately
- Advise regular BP monitoring due to common side effect of hypertension
- Warn not to receive live vaccines
- Brand specific prescribing is recommended
- Avoid excessive sunlight exposure
- Avoid high potassium diet and grapefruit juice
Ciclosporin interactions
Increased plasma concentration with:
Clarithromycin, diltiazem, erythromycin, fluconazole, grapefruit juice, itraconazole, ketoconazole, miconazole, metoclopramide, verapamil, colchicine and tacrolimus
Decreased plasma conc with carbamazepine, orlistat, phenobarbital, phenytoin, rifampicin, st johns wort
Increased risk of hyperkalaemia when given with ACE/ARB inhibitors
Increased risk of nephrotoxicity when given with NSAIDs and increased plasma conc of diclofenac
Ciclosporin increases plasma conc of digoxin
Increased risk of myopathy when given with statins
Monitoring required for corticosteroids
BP, blood lipids, serum K+, body weight and height in children and adolescents, bone mineral density, blood glucose, eye exam, signs of adrenal suppression
Warning signs for corticosteroids?
- Bronchospasm
- Symptoms of uncontrolled asthma
- Frequent courses of abx/steroids
- Adrenal suppression
- Immunosuppression
- Psychiatric reactions e.g. nightmares
Actions required for corticosteroids?
- Report any warning signs to doctor immediately
- Give steroid card if treatment long term and warn them not to stop treatment abruptly
- Check if taking in the morning as a single dose
- Ensure rinsing of mouth after inhaled corticosteroids
- Advise to avoid anyone with chickenpox if they haven’t had it
Steroid interactions=
Metabolism accelerated by carbamazepine, phenobarbital, phenytoin and rifamycins
May induce or enhance anticoagulant effect of coumarins
High dose corticosteroid can impair immune response to vaccines, avoid use with vaccines
Can mask GI effects of nsaids, avoid use and use gastro protection
Hypokalaemia when given with other drugs that reduce serum K+ i.e. loop and thiazide diuretics
Therapeutic range for digoxin?
0.8-2mcg/L
Monitoring required for digoxin?
Serum electrolytes (K, Ca and Mg) as electrolyte balance can potentiate toxicity Renal function HR
Warning signs for digoxin?
Cardiac - arrthymias/heart block
Neurological e.g. weakness, lethargy
GI - anorexia, N+V
Visual - blurred and or yellow vision
Actions required for digoxin?
Report any warning signs to doctor immediately
Remember different formulations have different bioavailability’s
Digoxin interactions:
Increased plasma concentration with alprazolamamiodarone, ciclosporin, dilitazem, itraconazole, lercanidipine, macrolides, mirabegron, nicardipine, nifedipine, quinine, spironolactone, verapamil
Reduced plasma concs with St Johns Wort
Admin with acetazolamide, amphotericin, loop diuretics or thiazides can cause hypokalaemia which can increase risk of cardiac toxicity and digoxin toxicity
Drugs that impair renal function can affect the plasma digoxin concentration e.g. nsaids, ace inhibitors
Gentamicin/Amikacin therapeutic range:
On hour peak serum conc should be: 5-10mg/l
Pre dose should be less <2mg/l
Gentamicin/Amikacin monitoring?
Renal function
Auditory and vestibular function (ototoxicity is irreversible)
Actions required for gent/amik
- Advise patient to report any warning sings immediately
- Encourage plenty of fluids before starting treatment
Gentamicin/Amikacin interactions
Increased risk of nephrotoxicity when aminoglycosides are given with ciclosporin, tacrolimus, vanc
Increased risk of ototoxicity when given with loop diuretics or vanc
Lithium therapeutic range:
- 4 - 1 mmol/l (maintenance)
0. 8- 1 mmol/l in acute episodes of mania
Lithium monitoring?
Serum lithium conc, renal function, cardiac function, thyroid function
Lithium warning sings?
- GI disturbances
- Visual disturbances
- CNS disturbances
- Fine tremor
- Incontinence
- Serum conc >2 = overdose and toxicity = seizures, coma, renal failure
- Signs and symptoms of hypothyroidism
- Signs and symptoms of renal dysfunction
- Signs and symptoms of benign intracranial hypertension
Action required for lithium:
-
- Importance of sticking to same brand
- Ensure constant water and salt intake
- Advise on interactions and to avoid alcohol
- Counsel on using machinery and driving with the risks of drowsiness
- Do not stop abruptly
Interactions with lithium:
Increased risk of toxicity with: ACE, ARBs, loop diuretics, thiazides, NSAIDs, K sparing diuretics, aldosterone antagonists, metronidazole, SSRI’s and tricyclics
Increased risk of ventricular arrhythmias with amiodarone
Risk of neurotoxicity with methyldopa, phenytoin, carbamazepine, diltiazem, verapamil
Increased risk of EPSE with clozapine, haloperidol , sulpiride, risperidone, flupentixol, zunclopenthixol
Methotrexate monitoring:
FBC, Renal function, Liver function
MTX warning signs
- GI toxicity
- Liver toxicity
- Blood disorders - bone marrow suppression, sore throat, ulcers
- Pulmonary toxicity
- Pregnancy and breastfeeding
MTX actions required:
- Ensure once weekly dosing on same day
- Counsel on importance of contraception
- Advise to avoid OTC preps containing NSAIDs and aspirin
- Avoid live vaccines
MTX interactions:
Increased plasma concentration and risk of hepatotoxicity with acitretin (avoid)
Excretion reduced by NSAIDs and penicillins therefore increased risk of toxicity. Also increased when given with ciprofloxacin, doxycycline, tetracycline, sulphonamides, ciclosporin, PPI’s and leflunomide
Increased risk of haem toxicity when given with co trimoxazole or trimethoprim
Monitoring with NSAIDs:
Blood pressure, renal function, liver function, haemoglobin in those with risk factors for GI bleeding
Warning signs for NSAIDs:
• Black stools or ‘coffee ground’ vomit, suggesting chronic gastrointestinal bleeding
• Iron deficiency anaemia, suggesting chronic gastrointestinal bleeding (e.g. fatigue, dizziness,
pale skin, shortness of breath)
• Progressive unintentional weight loss or difficulty swallowing
• Pregnancy and breastfeeding
• Swollen ankles or feet
• Unexplained, persistent recent-onset dyspepsia
• Worsening of asthma
Actions required for NSAID’s:
• Advise patient to report immediately to a doctor if any warning signs occur
• Check that the NSAID prescribed is suitable for the patient; accounting for GI and CVS risk, high dose or regular dose, appropriate duration of treatment
• Advise patient to take the lowest effective dose and for shortest period of time to control symptoms. Long-term treatment to be reviewed periodically
• All patients of any age prescribed NSAIDs for osteoarthritis or rheumatoid arthritis or patients
over 45 years who are prescribed NSAIDs for lower back pain should be co-prescribed gastro-
protection (e.g. a proton pump inhibitor)
• Recommend that oral NSAID is taken with or just after food
• Inform patient of potential interactions, the need to check with a pharmacist or doctor before taking any new medication (especially OTC NSAIDs)
NSAID interactions?
• Possible increased risk of convulsions when given with quinolones
• Possible enhanced anticoagulant effect of coumarins and phenindione
• Possible enhanced effects of sulfonylureas
• Increased risk of bleeding with dabigatran, heparins, SSRIs, venlafaxine, antiplatelets
• Increased risk of nephrotoxicity when given with ciclosporin, tacrolimus, diuretics (also antagonism of diuretic effect)
• May reduce excretion of lithium or methotrexate (increasing risk of toxicity)
• Increased side effects with concomitant use of other NSAIDs, aspirin
• NSAIDs antagonise hypotensive effect of beta-blockers, calcium-channel blockers, ACEI-
inhibitors, angiotensin-II receptor antagonists, alpha-blockers, nitrates
Therapeutic range for phenytoin:
Therapeutic Range: 10 to 20mg/L (or 40 to 80 micromol/litre)
Non-linear relationship between dose and plasma drug concentration: small changes in dose/ missed dose / change in drug absorption can result in marked change in plasma drug concentration
Monitoring requirements for phenytoin?
Serum concentration, ECG and blood pressure with intravenous use, liver function, full blood count, serum folate, vitamin D.
Phenytoin is highly protein bound; patients with impaired liver function, elderly or those who are gravely ill may show early signs of toxicity
Warning signs with phenytoin:
• Toxicity e.g. nystagmus, ataxia, slurred speech, hyperglycaemia, diplopia or blurred vision, confusion
• Skin disorders e.g. rash, toxic epidermal necrolysis
• Blood disorders (fever, sore throat, mouth ulcers, unexplained bruising or bleeding) e.g.
leucopenia, aplastic anaemia, megaloblastic anaemia
• Suicidal thoughts
• Low vitamin D levels e.g. rickets, osteomalacia
Actions required for phenytoin:
• Advise patient to report immediately to a doctor if any warning signs occur
• Use caution when dispensing:
–> Brand-specific prescribing recommended as preparations containing phenytoin sodium (100mg) are equivalent to those containing phenytoin base (92mg). The dose is the same for all phenytoin products when initiating therapy, but if switching between formulations, the difference in phenytoin content may be clinically significant
Phenytoin interactions:
- Increased plasma concentrations with amiodarone, chloramphenicol, cimetidine, disulfiram, diltiazem, fluconazole, fluoxetine, miconazole, topiramate, trimethoprim (also increased antifolate effect), metronidazole, clarithromycin, telithromycin (avoid during and 2 weeks after phenytoin)
- Reduced plasma concentrations with rifamycins, St John’s Wort, theophylline, itraconazole, ciclosporin
- Phenytoin accelerates metabolism of coumarins (possibility of reduced anticoagulant effect but enhancement also reported), corticosteroids, oestrogens, protestogens
- Anticonvulsant effect possibly antagonised by antipsychotics, mefloquine, SSRIs, tricyclics and tricyclic-related antidepressants
- Phenytoin possibly reduces plasma concentration of aripiprazole, itraconazole, oestrogens and progestogens (reduced contraceptive effect), theophylline and tricyclics
Monitoring requirements for tacrolimus:
Blood pressure, ECG (for cardiomyopathy), fasting blood glucose concentration, renal function, liver function, serum electrolytes (particularly K+), haematological, neurological (including visual) and coagulation parameters
Warning signs for tacrolimus :
• Neurotoxicity e.g. tremor, headache
• Nephrotoxicity e.g. elevated serum creatinine concentrations
• Eye disorders e.g. blurred vision, photophobia
• Skin disorders e.g. rash, toxic epidermal necrolysis
• Blood disorders (signs of infection such as fever, sore throat, mouth ulcers, also unexplained
bruising or bleeding) e.g. leucopenia, thrombocytopenia
• Hyperglycaemia – diabetes mellitus e.g. increased thirst or excessive urination
• Cardiovascular disorders – cardiomyopathy, arrhythmias, hypertension e.g. irregular heartbeat,
heaviness in the centre of chest triggered by effort or emotion
• Liver toxicity e.g. jaundice, nausea, vomiting, abdominal discomfort, dark urine
Actions required for tacrolimus:
• Advise patient to report immediately to a doctor if any warning signs occur
• Advise patient to avoid excessive exposure to UV light, including sunlight and to use a wide- spectrum sunscreen (may reduce risk of secondary skin malignancies)
• Oral tacrolimus medicines should be prescribed and dispensed by brand name only, to minimise switching between products to reduce risk of toxicity and graft rejection. Any
switching between brands requires careful supervision by an appropriate specialist
• Ensure patient understands the importance of taking immunosuppressants regularly
• Advise patient that tacrolimus may affect performance of skilled tasks (e.g. driving) and to
avoid undertaking risk activities if they feel unfit to do them
• Warn patients receiving tacrolimus that they must not receive immunisation with live vaccines
• Advise patient to avoid a high potassium diet and grapefruit juice
Tacrolimus interactions:
• Increased plasma concentrations with clarithromycin, diltiazem, erythromycin, fluconazole, grapefruit juice, itraconazole, nifedipine, omeprazole, ranolazine
• Reduced plasma concentration with phenobarbital, St. John’s Wort, rifampicin, phenytoin
• Increased risk of nephrotoxicity when given with aminoglycosides, amphotericin and NSAIDs
(especially ibuprofen), certain antivirals (e.g. aciclovir, ganciclovir)
• Tacrolimus increases plasma concentration of ciclosporin
• Increased risk of hyperkalaemia when given with potassium-sparing diuretics (e.g. amiloride,
spironolactone), potassium salts, angiotensin II receptor antagonist
Theophylline therapeutic range:
Therapeutic Range: 10 to 20mg/L (55 to 110micromol/L)
(although a plasma theophylline concentration of 5 to 15mg/L may still be effective) Loading doses may be required
Monitoring for theophylline:
Serum potassium, plasma theophylline concentration
Theophylline warning signs:
- Toxicity e.g. vomiting (may be intractable), agitation, restlessness, dilated pupils, sinus tachycardia, hyperglycaemia, severe hypokalaemia may develop rapidly, haematemesis, convulsions, cardiac arrhythmias
- Symptoms of uncontrolled asthma (cough, wheeze, tight chest)
- Frequent courses of antibiotics and/or oral corticosteroids
Actions required for theophylline:
• Advise patient to report immediately to a doctor if any warning signs occur
• Inform the patient of potential interactions with theophylline and the need to check with a pharmacist or doctor before taking any new medication (including OTC, prescribed or herbal
medicines)
• Advise patient to inform their GP before stopping or starting smoking
• Emphasise the importance of maintaining on the same brand of medicine and recommend
that the patient always checks when collecting their medicine from a pharmacy and when taking the medicine; the rate of absorption from modified-release preparations can vary between brands
Theophylline interactions:
- Potentially serious hypokalaemia may result from beta2 agonist therapy. Caution required in severe asthma, because this effect may be potentiated by concomitant use of theophylline, corticosteroids, and diuretics as well as hypoxia. Plasma potassium should be monitored in severe asthma
- Increased plasma concentrations with diltiazem, cimetidine, ciprofloxacin, erythromycin, oestrogens, fluvoxamine, verapamil
- Possible increased risk of convulsions when theophylline given with quinolones
- Reduced plasma concentrations with carbamazepine, primidone, phenobarbital and phenytoin, ritonavir
Vancomycin therapeutic range:
Therapeutic Range: Trough 10 to 15mg/L (15 to 20mg/L for endocarditis or less sensitive strains of methicillin-resistant Staphylococcus aureus or complicated infections caused by S. aureus).
Loading doses may be required.
Vancomycin monitoring requirements:
Serum potassium, full blood count, renal function, auditory function in elderly, urinalysis
Vancomycin warning signs:
• Hearing loss, vertigo, dizziness, tinnitus
• Flushing of the upper body (‘Red Man Syndrome’)
• Blood disorders (signs of infection such as fever, sore throat, mouth ulcers, also unexplained
bruising or bleeding) e.g. neutropenia, thrombocytopenia
• Phlebitis (irritant to tissue)
• Nephrotoxicity e.g. elevated serum creatinine concentrations
• Skin disorders e.g. rashes, toxic epidermal necrolysis, pruritus
Actions required for vancomycin:
Advise patient to report immediately to a doctor if any warning signs occur
Vancomycin interactions:
- Increased risk of nephrotoxicity and ototoxicity when vancomycin given with ciclosporin, aminoglycosides, polymixin antifungals
- Increased risk of ototoxicity when vancomycin given with loop diuretics
- Vancomycin enhances effects of suxamethonium
Monitoring for sodium valproate:
Liver function, full blood count, weight, BMI.
Sodium Valproate warning signs:
- Persistent vomiting, abdominal pain, anorexia
- Jaundice, oedema, malaise drowsiness
- Loss of seizure control
- Suicidal ideation or behaviour
Actions required for sodium valproate:
- All women of child bearing age must be enrolled in a pregnancy prevention programme. Prescribers should ensure the patient understands the risks associated with valproate use in pregnancy, the need to use effective contraception, the need for regular review of treatment and that the woman should rapidly consult her doctor if she is planning a pregnancy or becomes pregnant.
- Treatment in women of child bearing age should not have therapy initiated without a negative pregnancy test. They should also have regular pregnancy tests throughout therapy.
- Women of child bearing potential should use an effective method of contraception throughout treatment. A user independent contraceptive method such as an IUD or implant is preferred or two complementary forms of contraception including a barrier method should be used.
- Patients that are immobilised for long periods or have inadequate sun exposure or dietary intake of calcium should take vitamin supplementation.
- Category 2 antiepileptic, brand dispensing based on clinical judgement.
- Abrupt withdrawal should be avoided, the valproate dose should be reduced gradually over at least 4 weeks.
Sodium valproate interactions:
- Effects of other psychotropics such as antipsychotics, MAO inhibitors, antidepressants and benzodiazepines potentiated.
- Anticoagulant effect of warfarin increased.
- Metabolism of lamotrigine reduced and its half-life almost doubled, leading to increased lamotrigine toxicity particularly serious skin reactions.
- Erythromycin and cimetidine may increase valproic acid plasma levels by reducing hepatic metabolism.
- Anti-epileptics with enzyme inducing effect decrease valproic acid plasma concentrations.
Sulfasalazine monitoring:
Full blood count, renal function, urea and electrolytes, liver function
Sulfasalazine warning signs:
- Malaise, fever, sore throat and other signs of infection
- Unexplained bruising
- Jaundice
Sulfasalazine actions required:
• Advise patients that there maybe yellow-orange discoloration of the urine, other body fluids and the skin
• Advise patients that some soft contact lenses may be stained
• Patients should ensure they maintain an adequate fluid intake
• Oral sulfasalazine inhibits the absorption and metabolism of folic acid leading to folic acid
deficiency. This can be corrected using folic acid supplements
• Use with caution in patients with G-6-PD deficiency since it may cause haemolytic anaemia
Sulfasalazine interactions:
- Reduced absorption of digoxin resulting in sub-therapeutic plasma levels.
- Bone marrow suppression and leucopenia with 6-mercaptopurine or azathioprine.
