HIGH RISK DRUGS Flashcards
What is steady state?
4 or 5 half-lives after initiation of therapy or a change in dosage.
What is a loading dose?
Higher initial dose to rapidly achieve therapeutic response. 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 half life of Amiodarone?
LONG - about 50 days. Loading dose may be required
What monitoring is needed for amiodarone?
Thyroid function, liver function, serum K, chest xray, ECG (with IV use)
What is the indication for amiodarone?
- Treatment of arrythmias, particularly when other drugs are ineffective or c/i (including paroxysmal supaventricular, nodal and ventricular tachycardias, AF and flutter, ventricular fibrillation associated with Wolff-Parkinson-White syndrome)
Warning signs for amiodarone?
- signs and symptoms of hypo/hyperthyroidism
- impaired vision (optic neuritis/neuropathy)
- photophobia, dazzled by headlights at night (corneal micro deposits)
- progressive s.o.b 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 discolouration on light-exposed areas
Action required when warning signs for amiodarone present?
- advise patient to shield skin from direct sunlight and for several months after stopping treatment or to use wide spec spf
- warn drivers that they may be dazzled by headlights at night
- warn patients that clinical effects may occur up to a year after stopping the medicine
Amiodarone interations?
Due to long half life, there is potential for drug interations to occur for several weeks to months after treatment stopped.
- Increased plasma conc of coumarins (warfarin), dabigatran, digoxin, flecainide, phenindione, phenytoin
- Increased risk of ventricular arrhythmias when given with amisulpride, atomoxetine, chloroquine, citalopram, disopyramide, excitalopram, haloperidol. hydroxychloroquine, levofloxacin, lithium, mizolastine, mefloquine, moxifloxacin, phenothiazines, pimozide, quinine, sulpiride, telithomycin, tolterodine, tricyclics
- Increased risk of bradycardia, AV block and myocardial depression when given with BBs, diltiazem, verapamil
- Increased risk of myopathy when given with simvastatin
What monitoring is needed for antihypertensives?
- Blood pressure
- heart rate
- renal function
- serum electrolytes
What are the warning signs for antihypertensives?
- water retention
- heaviness in the centre of chest triggered by effort or emotion
- depression
- extreme tiredness, thirst or excessive urination
- irregular heartbeat, muscle weakness, nausea
- pain or tightness in legs while exercising that dissapears at rest
- dizziness, light-headedness on standing, blurred vision (postural hypotension)
Action required when antihypertensive warning signs are present:?
- advise patient to report immediately to doctor
- advise patient to sit up and stand slowly first thing in the morning to prevent postural hypotension
- If dizziness experienced, avoid driving/operating machinery
- drink adequate (not excessive) volumes of fluids each day
- inform of potential interactions and check with pharmacist/doctor before taking any other new medication (incl OTC)
- advise patient on avoiding soluble OTC preparations e.g. analgesics due to high sodium content
- ensure the patient recieves the same brand of diltiazem or nifedipine MR prep each time
Antihypertensive interations?
- Diltiazem, verapamil, amlodipine, ranolazine and high dose statins can increased risk of myopathy. Recommended max daily dose of simvastatin 20mg with concomitant diltiazem, verapamil, amlodipine or ranolazine.
- Increased plasma conc of ivabradine, aliskerin CCBs when given with grapefruit juice
Carbamazepine indications?
- Epilepsy (focal and secondary generalised tonic-clonic seizures, primary generalised tonic-clonic)
- Trigeminal neuralgia
- prohylaxis of bipolar unresponsive to lithium
- adjunct in acute alcohol withdrawal
- ## diabetic neuropathy
What is the therapeutic range of carbamazepine?
4-12mg/L (20-50 micromol/L)
Monitoring for carbamazepine
FBC, renal function, LFT
Warning signs for carbamazepine?
- toxicity - incoordination, blurred vision. diplopia. drowsiness, nystagmus, ataxia, arrhythmias, n+v. diarrhoea, hyponatramia
- blood disorders e.g. leucopenia, thrombocytopenia (fever, sore throat, unexplained bruising or bleeding)
- skin disorders e.g. toxic epidermal necrolysis (mouth ulcers, rash)
- hepatic disorders e.g. hepatitis
- antiepileptic hypersensitivity syndrome - symptoms commonly seen are fever, rash, swollen lymph nodes
What is the major route of elimination for carbamazepine?
- hepatic metabolism
Action required for when carbamazepine warning signs are present?
- advise patient to report immediately to a doctor if any warning signs occur
- ensure patient recieves same brand of medicine each time
- ensure patient is aware of law regarding seizures and driving
- inform patinent of potential interations and they should check with pharm/doc before any new meds/OTCs
Carbamazepine interactions?
- Increased plasma conc with acetazolamide, cimeditine, clarithromycin, erythromycin, fluoxetine, isoniazid
- decreased plasma conc with phenytoin, rifabutin, st johns wort
- carbamazepine reduces plasma conc of antipsychotics, corticosteroids, coumarins, eplerenone, oestrogens, progestogens, simvastatin
- anticonvuslant effect antagonised by mefloquine, antipsychotics
- possible increased risk of convulsions when antiepileptics given with orlistat
What is systemic chemotherapy?
Oral, IV, SC, IM with aim of maximal therapeutic cytotoxic effect whilst avoiding extreme toxicity to normal healthy issues
What is regional chemotherapy?
Intrathecal, intraarterial which is aimed at delivering cytotoxics directly into cavity in which tumour is located or blood vessel supplying tumour therefore minimising side effects
Common side effects of chemo?
- Extravasation of IV drugs: leakage of cytotoxic drug from vein into subcutaneuos or subdermal tissue, which can lead to permanent tissue damage; refer to local guidlines for prevention and prompt managment
- N+V: can cause distress and may lead to refusal of treatment so prophylaxis of n+v is very important; drugs have varying emetogenic potential
- Bone marrow supression: (except vincristine and bleomycin) commonly occurs 7-10 days after administration, important to treat infection before or when starting cytotoxic, neutropenic sepsis is a medical emergency
- Other: oral mucositis, diarrhoea, fatugue, organ toxicities (e.g, neurotoxicity with vinca alkaloids so IV administration only, cardiotoxicity with anthracyclines), hyperericaemia, urothelial toxicity
Warning signs of neutropenic sepsis (from chemo)?
- feeling unwell and/or have temperature
- develop shivering episodes/flu like symptoms
- uncontrolled gum/nose bleeds or unusual bruising
- diarrhoea and/or uncontrolled vomiting
- develop mouth ulcers that stop patient eating/drinking
Action required for neutropenic sepsis?
- A&E immediately withot taking paracetamol or seeking advice (to avoid dangerous delay in start antibiotics)
- advise patient to report side effects to dr immediately
- for a drug that causes moderate-severe emesis, antiemetics should always be prescribed on a regular basis
- advise patient to maintain good oral hygeine (rinsing mouth more frequently and effective brushing of teeth with soft brush 2-3 times daily) to avoid mucositis
What is the therapeutic range for ciclosporins?
depends on clinical situation and indication for treatment. Loading doses may be required
Monitoring for ciclosporin?
- FBC, LFT, serum K and Mg, blood lipids, renal function (including creatinine, urea), BP, dermatological and physical examination
Warning signs for ciclosporin?
- neurotoxicity e.g. tremor, headache, encephalopathy (e.g. confusion, convulsions)
- blood disorders (signs of infection fever etc) e.g. leucopenia, thrombocytopenia
- liver toxicity e.g. jaundice, n+v, abdominal discomfort, dark urine
- nephrotoxicity e.g. elevated serum creatinine concentrations
- other signs of toxicity - vomiting, drowsiness, tachycardia
- hypertension
- headache
- gingival hyperplasia
Action required when warning signs of ciclosporin present ?
- advise patient to report immediately to a doctor if any warning signs occur
- hypertension is a common side effect of ciclosporin therapy. Advise patient to have their blood pressure monitored regularly
- warn patients they must not recieve immunisation with live vaccines
- brand-specific prescribing is recommended (if changing brand monitor closely for changes in ciclosporin level, serum creatinine and BP)
- avoid excessive UV light exposure - use wide spec spf (may reduce risk of secondary skin malignancies). Patients with atopic dermatitis and psoriasis should avoid use of UVB or PUVA
- advise patient to avoid high potassium diet and grapefruit juice. the oral solution formulations can be taken with orange or apple juices to improve taste
Ciclosporin interactions?
- increased plasma conc with clarithromycin, diltiazem, erythromycin, fluconazole, grapefruit juice, itraconazole, ketoconazole, miconazole, metoclopramide, verapamil, colchicine (with which concomitant use also increases risk of nephrotoxicity and myotoxocity) and tacrolimus (AVOID)
- decreased plasma conc with carbamazepine, orlistat, phenobarbital, phenytoin, rifampicin, st johns wort
- increased risk of hyperkalaemia when given with ACE inhibitors or ARBs, aldosterone antagonists
- increased risk of nephrotoxicity when give with NSAIDs and increased plasna conc of diclofenac
- increased risk of myopathy when given with atorvastatin, fluvastatin, pravastatin, rosuvastatin, simvastatin (avoid concomitant use)
Monitoring for corticosteroids?
- BP
- blood lipids
- serum K
- body weight and height in children and adolescents
- bone mineral density
- blood glucose
- eye exam (for intraocular pressure, cataracts)
- signs of adrenal suppression
Corticosteroid warning signs
- paradoxical bronchospasm (constriction of the airways)
- symptoms of uncontrolled asthma e.g cough, wheeze, tight chest
- frequent courses of antibiotics and/or oral corticosteroids
- adrenal suppression e,g. nausea, vomiting, weight loss, fatigue, headache, muscular weakness
- immunosuppression, e.g. chicken pox, measles, oral candidiasis, more serious infections e.g. TB, septicaemia, oculat fungal or viral infections
- psychiatric reactions e.g suicidal thoughts, nightmares, depression, insomnia
Action required when corticosteroid warning signs present ?
- report immediatly to doctor
- give patient steroid treatment card if long term. explain that they must not stop treatment abruptly after prolonged treatment (>3weeks)
- check patient is taking oral steroids in the morning as a single dose
- ensure patients rinse their mouth/clean teeth after using inhaled ccsteroids
- if the patient has not already had chicken pox/measles, advise them to avoid anyone with these infections
Corticosteroid interactions?
- metabolism of ccsteroids accelerated by carbamazepine, phenobarbital and rifamycins
- ccs may induce or enhance anticoagulant effect of coumarins
- high dosse ccs can impaire immune response to vaccines; avoid concomittant use with live vaccines
- ccs can mask GI effects of NSAIDS (incl aspirin); avoid concomitant use if possible and consider gastroprotection
- hypokalaemia can be severe when given with other drugs that lower serum K e.g loop and thiazide diuretics
- effects if antihypertensive and oral hypoglycaemic drugs are antagonised by glucocorticoids
what is the therapeutic range of digoxin?
1-2mcg/L. Loading dose may be required
Monitoring for digoxin?
- serum electrolytes (K, Mg, Ca) as electrolyte imbalance (hypokalaemia, hypomagnesaemia, hypocalcaemia) can potentiate toxicity, renal function, heart rate (maintained at greater than 60bpm)
Major route of elimination for digoxin?
Renal excretion; hepatic metabolism to active metabolites
Warning signs for digoxin?
- cardiac e.g. arrhythmias. heart block
- neurological e.g. weakness, lethargy, dizziness, headache, mental confusion, psychosis
- GI e.g. anorexia, nausea, vomiting, diarhoea, abdominal pain
- visual e.g. blurred and/or yellow vision
Action required when digoxin warning signs present?
- advise patient to report immediately to a doctor
- dosage forms have different bioavailabilities (change of dose required to maintain same plasma-digoxin conc). Please refer to manufacturer spc for more info
- IV: 100%
- tablet: 50-90%
- elixir: 75%
Digoxin interactions?
- increased plasma conc with alprazolamamiodarone, ciclosporin. diltiazem, itraconazole, lercanidipine, macrolides, mirabegron, nicardipine, nifedipine, quinine, sprionolactone and verapamil
- reduced plasma conc with st johns wort
- concomitant administration of acetazolamide, amphotericin, loop diuretics or thiazides and related diuretics can cause hypokalaemia that increases the risk of cardiac toxicity and digoxin toxicity
- drugs that impair renal function can affect the plasma digoxing conc e.g. NSAIDs. ACE inhibs
Diuretics monitoring?
- BP
- serum electrolytes (Na+, K)
- weight (as a measure of fluid loss)
Warning signs for diurtetics?
- heaviness in the centre of the chest
- water retention
- depression
- extreme tiredness. thirst or excessive urination
- irregular heartbeat, muscle weakness, nausea
- gout
Action required when diuretics warning signs present ?
- report to dr stat
- advise patient to sit up and stand slowly first thing in the morn to prevent postural hypotension and report to gp if hypotensive symptoms persist
- if dizziness experienced, advise patient to avoid drinking or operating machinery
- drink adequate amount of fluids each day
- interactions