increases metabolism of the OCP, reducing its clinical eff ectiveness; other forms of contr aception should be used in such circumstances \200 Excretion quinidine reduces the renal clearance of digoxin, resulting in higher than anticipated levels of serum digoxin and incr easing the risk of digoxin side eff ects and/or toxicity. Pharmacodynamic interactions occur when two or more agents have affi nity for the same site of drug action, such as: \200 Salbutamol and propranolol (a non-specifi c B-blocker) hav e opposing eff ects at the B-adrenergic receptor; clinical eff ect is determined by the rel ative concentrations of the two agents and their receptor affi nity. Drugs which commonly h ave interactions include digoxin, warfarin, antiepileptics, many antibiotics, antidepressan ts, antipsychotics, theophylline and amiodarone. If in doubt, look in the BNF. Reporting adverse drug reactions The Yellow Card Scheme has been running for over 40 years, and is coordinated by the Medicines and Healthcare products Regulatory Agency (MHRA). Duri ng drug development, side eff ects with a frequency of 1:1000 or greater (more common) are likely to be identifi ed, so the Yellow Card Scheme is important in detecting rarer side ef f ects once a drug is in general use and all doctors have a duty to contribute to this. Yel low tear-out slips in the back of the BNF are completed and sent off and used to monitor ad verse drug reactions. The forms can be completed by any healthcare worker and even by patie nts. Common drug reactions such as constipation from opioids, indi- gestion from NSAIDs, an d dry mouth with anticholinergics are well rec- ognised and considered minor eff ects and d o not need reporting. Sinister drug eff ects such as anaphylaxis, hemorrhage, severe skin reactions etc must be r eported via the Yellow Card Scheme, irrespective of how well documented they already are. A ny suspected reaction from a new drug (drugs marked with an inverted triangle ( ) in the BN F) must also be reported by this scheme. _OHFP.indb 171 _OHFP.indb 171 30/05/2014 16:18 30/05/2014 16:18 172 CHAPTER 4 Prescribing Special considerations Every prescription should be carefully considered with specifi c ref l ection of the patient in question. If in doubt, consult the BNF or speak to the pharmacis t or a senior. There are some groups of patients for whom prescriptions must be even more c arefully considered. Patients with liver disease The liver has tremendous capacity and rese rve so liver disease is often severe by the time the handling of most drugs is altered. The liver clears some drugs directly into bile (such as rifampicin) so these should be used ca utiously if at all. The liver also manufactures plasma proteins and hypoproteinaemia can re sult in increased free fractions of some agents (phenytoin, warfarin, prednisolone) and res ult in exaggerated pharmacodynamic responses. Hepatic encephalopathy can be made worse by s edative drugs (night sedation, opioids etc), and fl uid overload by NSAIDs and corticostero ids is well documented in liver failure. Hepatotoxic drugs (such as methotrexate and isotre tinoin) should only be used by experts as they may precipitate fulminant hepatic failure an d death. Patients with estab- lished liver failure have an increased bleeding tendency so a void IM injections and employ caution if using any anticoagulant drugs. Paracetamol can be used in liver disease, but consider a reduced dose; consult BNF/pharmacist. Special conside rations for patients with liver disease are listed under each drug monograph in the BNF. Patients with renal disease Patients with impaired renal function should only be given neph rotoxic drugs with extreme caution as these may precipitate fulminant renal failure; these include NSAIDs, gentamicin, lithium, ACEi, and IV contrast. Any patient with renal disease (impairment or end-stage renal failure) will have altered drug handling (metabolism, cleara nce, volume of distribution etc) and more careful thought must be given when prescribing fo r the patients with GFR <60ml/min, and senior input sought when GFR <30ml/min (BNF, pharmac ist or senior); the amount, dosing frequency, and choice of drug needs careful thought. Rem ember that a creatinine in the \200\230normal \200\231 range does not mean normal renal fu nction, see b p373. Special considerations for patients with renal disease are listed under each drug monograph in the BNF. Pregnant patients Many drugs can cross the placenta and have eff ects upon the fetus. In th e fi rst trimester (weeks 1 \200\22312) this usually results in con- genital malformations, and in the second (weeks 13 \200\22326) and third trimesters (weeks 27 \200\22342) usually results in growth retardation or has direct toxic eff ects upon fetal tissues. There are n o totally \200\230safe \200\231 drugs to use in pregnancy, but there are drugs known to be particularly troublesome. The minimum dose and the shortest duration possible should be us ed when prescribing in pregnancy and all drugs avoided if possible in the fi rst trimester. \200 Drugs considered acceptable penicillins, cephalosporins, heparin, ranitidine, paracetamol, codeine Drugs to avoid tetracyclines, streptomycin, quinolones, warfarin, thiazides, ACEi, lithium, NSAIDs, alcohol, retinoids, barbiturates, opioids, cytotoxic drugs and phenytoin. Special considerations for pregnant patients are listed under each drug mono- graph in the BNF. OHFP.indb 172 OHFP.indb 172 30/05/2014 16:18 30/05/2014 16:18 173 CONTROLLED DRUGS Breastfeeding patient As with pregnant patients, drugs given to the mother can get into bre ast milk and passed on to the feeding baby. Some drugs become more concentrated in breast m ilk than maternal plasma (such as iodides) and can be toxic to the child. Other drugs can s tunt the child \200\231s suckling refl ex (eg barbiturates), or act to stop breast milk pro duction altogether (eg bromocriptine). Speak to a pharmacist before prescribing any drug to a mother who is feeding a child breast milk. Special considerations for patients who are b reastfeeding are listed under each drug monograph in the BNF. Children see the British National Formulary for Children. Neonates are more unpredictable i n terms of pharmacokinetics and pharmacodynamics than older children; prescriptions for thi s age group should be undertaken by experienced neonatal staff and drugs double- checked pr ior to administration. After the fi rst month or two the gut, renal system and metabolic pa thways become more predictable. Almost all drug doses still need to be calculated by weight (eg mg/kg) or by body-surface area (BSA). There are a few drugs which should never be pres cribed in children by a non-specialist, including tetracycline (causes irreversible stainin g of bones and teeth), aspirin (predisposes to Reye \200\231s syndrome); others should be u sed with caution such as prochlorperazine and isotretinoin. Always consult the BNF for chil dren when prescribing for pediatric patients. Controlled drugs Controlled drugs (CDs) are those drugs which are addictive and most often abused or stolen, and are subject to the prescription and storage requirements of the Misus e of Drugs Regulations 2001; they include the strong opioids (morphine, diamorphine, pethid ine, fentanyl, alfentanil, remifentanil, methadone), amphetamine-like agents (methyl- pheni date (Ritalin ), and cocaine (a local anesthetic). These agents are stored in a locked cab inet and a record of their use on a named patient basis is required to be kept by law. Some other drugs may be kept in the CD cupboard such as concentrated KCl, ketamine, benzodiazep ines and anabolic steroids, but this is not a legal requirement and will depend upon local policy. The weaker opioids (codeine, tramadol) are not treated as controlled drugs though t hey are still often misused. Prescribing controlled drugs for in-patients is just like prescribing any other drug and th e benefi ts should be balanced against potential side eff ects for each individual patient. Morphine, diamorphine and pethidine are the most commonly prescribed CDs on the ward. As w ith all prescrip- tions, write the details clearly and make sure a maximum dose and a minim al interval between doses is documented (see b p86 for management of pain). Controlled drug s for TTOs see b p78. _OHFP.indb 173 _OHFP.indb 173 30/05/2014 16:18 30/05/2014 16:18 174 CHAPTER 4 Prescribing Enzyme inducers and inhibitors The term enzyme inducers is used to describe agents (usually drugs, but not always) which alter the activity of hepatic enzymes, namely the cyto- chrom e P450 enzymes which are involved in phase 1 metabolism (typi- cally oxidation, reduction a nd hydrolysis reactions). Agents which induce cytochrome P450 activity result in increased metabolism of aff ected drugs and reduced activity of aff ected drugs; inhibitors of cytoch rome P450 have the reverse eff ect and result in exaggerated drug responses as more of the aff ected drug remains available to exert its eff ect. Common inducers and inhibitors are l isted here. Inducers Table 4.1 shows drugs that induce metabolic enzymes. Each of the drugs on the left can induce the enzymes so that all of the drugs on the right (and any of the other drugs o n the left) will have reduced plasma levels: Table 4.1 Enzyme inducers Enzyme inducers Plasma levels reduced Phenobarbital/barbiturates Rifampicin Phenytoin Ethanol (chronic use) Carbamazepine Warfarin Oral contraceptives Corticosteroids Ciclosporin (all drugs on left) Inhibitors Table 4.2 shows some drugs which inhibit enzymes. Each of the drugs on the left can infl uence the metabolic enzymes responsible for breaking down the drug on the right; t his has the eff ect of increasing the plasma level of this latter drug, exaggerating its bi ological eff ect: Table 4.2 Enzyme inhibitors Enzyme inhibitors Plasma levels increased Disulfi ram Chloramphenicol Corticosteroids Cimetidine MAO inhibitors Erythromycin Ciprofl oxacin Warfarin Phenytoin Tricyclic antidepressants Amiodarone, phenytoin, pethidine Pethidine The ophylline Theophylline OHFP.indb 174 OHFP.indb 174 30/05/2014 16:18 30/05/2014 16:18 175 ENDOCARDITIS PROPHYLAXIS Endocarditis prophylaxis 1 Adults and children with structural cardiac conditions Regard pe ople with the following cardiac conditions as being at risk of developing infective endocar ditis: \200 Acquired valvular heart disease with stenosis or regurgitation \200 Valve r eplacement \200 Structural congenital heart disease, including surgically corrected or p p y palliated structural conditions, but excluding isolated atrial septal defect, fully repaire d ventricular septal defect or fully repaired patent ductus arteriosus, and closure devices that are judged to be endothelialised Hypertrophic cardiomyopathy \200 Previous infective endocarditis. Advice Off er people at risk of infective endocarditis clear and consistent information abo ut prevention, including: \200 The benefi ts and risks of antibiotic prophylaxis, and an explanation of why antibiotic prophylaxis is no longer routinely recommended The importance of maintaining good oral health \200 Symptoms that may indicate infective endocarditis and when to seek expert advice The risks of undergoing invasive procedures, including non-medical procedures such as body piercing or tattooing. When to off er prophylaxis Do not off er antibiotic prophylaxis against infective endocardi tis: \200 To people undergoing dental procedures \200 To people undergoing non-dental p rocedures at the following sites: upper and lower gastrointestinal tract \200 genitourinary tract; this includes urological , gynecological, and obstetric procedures, and childbirth upper and lower respiratory tract; this includes ear, nose, and throat procedures and bronchoscopy. Do not off er chlorhexidine mouthwash as prophylaxis against infec- tive endocarditis to pe ople at risk undergoing dental procedures. Managing infection \200 Investigate and treat promptly any episodes of infection in peopl e at risk of infective endocarditis to reduce the risk of endocarditis developing. Off er an antibiotic that covers organisms that cause infective endocarditis if a person at risk of infective endocarditis is receiving antimicrobial thera py because they are undergoing a gastrointestinal or genitourinary procedure at a site wher e there is a suspected infection. 1 NICE clinical guidelines available at (cid:27)guidance.nice.org.uk/CG64 _OHFP.indb 175 _OHFP.indb 175 30/05/2014 16:18 30/05/2014 16:18 176 CHAPTER 4 Prescribing Night sedation Patients develop tolerance and dependence to hypnotics (sedating drugs) if t hey are taken long term. They are only licensed for short-term use and should be avoided if possible. Causes of insomnia Anxiety, stress, depression, mania, alcohol, pain, coughing, nocturia (d iuretics, urge incontinence), restless leg syndrome, steroids, aminophylline, SSRIs, benzod iazepine/opioid withdrawal, sleep apnoea, poor sleep hygiene, levothyroxine. Try to dose regular medications so that stimulants (steroids, SSRIs, amino- phylline) are g iven early in the day, whilst sedatives (tricyclics, antihistamines) are at night. Encourag e sleep hygiene (below), ear plugs, eye shades and treat any causes of insomnia. Sleep hygiene Avoid caff eine in evening (tea, coff ee, chocolate), alcohol, nicotine, dayt ime naps, cerebral activity before sleep; encourage exercise, light snack 1 \200\2232h befo re bed, comfortable and quiet location (ear plugs and eye shades), routine. If the patient is still unable to sleep and there is a temporary cause (eg post-op pain, no isy ward) then it is appropriate to prescribe a one-off or short course ( \211 5d) of hypn otics (Table 4.3). Some patients may be on long- term hypnotics; these are usually continue d in hospital. If long-term hyp- notics are stopped the dose should be weaned to minimize w ithdrawal. Table 4.3 Common oral hypnotics Diazepam 5 \200\22315mg/24h Signifi cant hangover eff ect, useful for anxious patients Shorter action than diazepam, le ss hangover Temazepam 10 \200\22320mg/24h Zopiclone 3.75 \200\2237.5mg/24h Less dependence and risk of withdrawal than diazepam and less hangover eff ect Contraindications Respiratory failure and sleep apnoea. Side eff ects Include hangover (mor ning drowsiness), confusion, ataxia, falls, aggression and a withdrawal syndrome similar to alcohol withdrawal if long-term hypnotics are stopped suddenly. Discharge If a patient is not on hypnotics when they enter hospital they should not be on hypnotics when they leave. It is bad practice to discharge patients with supplies of addictive and unnecessary medicat ions. Violent/aggressive patients See b p105 for emergency sedation. Pre-op sedation Diazep am and temazepam can be used for sedation before a procedure or anesthetic; this is usually prescribed by the anaesthe- tist 1 \200\2232h beforehand. Midazolam is a rapidly acting IV sedative; it should only be used by experienced doctors under monitored conditions (sats, RR, BP, and cardiac monitor) with a crash trolley available. Give 1 \200\2232mg boluses the n wait 5min for the full response before repeating; >5mg is rarely needed. OHFP.indb 176 OHFP.indb 176 30/05/2014 16:18 30/05/2014 16:18 177 STEROID THERAPY Steroid therapy Steroids given for >3wk should never be abruptly discontinued as this can p recipitate an Addisonian crisis (b p332). Patients can need >60mg prednisolone per day for severe infl ammatory disease and this must be converted to an appropriate IV corticosteroid dose if they are unable to take regular PO doses (Table 4.4). Long-term steroid use should prompt consideration of osteoporosis prophylaxis (b p437). Table 4.4 Conversion of oral prednisolone to IV hydrocortisone Suggested hydrocortisone dose1 Normal prednisolone dose \211 60mg/24h PO 20 \200\22350mg/24h PO \211 20mg/24h PO 100mg/6h IV 50mg/6h IV 25mg/6h IV Steroid conversion (see BNF 6.3.2) These are equivalent corticosteroid doses compared to 5m g predni- solone, but do not take into account dosing frequencies or mineralo- corticoid ef f ects: \200 Hydrocortisone 20mg; usually given IV 6 \200\2238h \200 Methylprednisolone 4mg; usually given once daily \200 Dexamethasone 750micrograms; usually given once daily . Withdrawing steroid therapy It is an art and must be performed gradually if steroids have b een used for >3wks. Large doses (>20mg prednisolone or equivalent) can be reduced by 5 \200 \22310mg/wk until dose is 7.5mg prednisolone/d. Thereafter the doses must be reduced more s lowly, eg by 2.5mg/wk until the dose is 2.5mg/d. Thereafter reduce the dose by eg 1mg/wk do wn to zero. Aim to taper dose to zero over 6 \200\2238wk. Steroid side eff ects and treatment and monitoring options GI ulceration Infections and reactivation of TB Low threshold for culturing samples or CXR Skin thinning/poor wound healing Pressure care and wound care Na+ and fl uid retention Hype rglycaemia Osteoporosis (b p437) Hypertension Consider PPI or H2-receptor antagonist Twice-daily BPs Twice-daily BMs if taking high-dose steroids Bone protection (Ca2+ + bispho sphonate) Twice-daily BPs 1 If patients with known adrenal insuffi ciency, or those who have been on any dose of oral corticosteroids for >3wks present unwell, consider an initial dose of 100mg hydrocortisone IV STAT, then d/w senior as to regular steroid dose. If unable to tolerate PO administratio n, ensure equivalent IV steroids given, as per steroid conversion box. _OHFP.indb 177 _OHFP.indb 177 30/05/2014 16:18 30/05/2014 16:18 178 CHAPTER 4 Prescribing Topical corticosteroids Topical steroids are used in the treatment of many infl ammatory sk in diseases. As with corticosteroids given orally or intravenously, the mechanism of action is complex. Corticosteroids off er sympto- matic relief but are seldom curative. The least potent preparation (see Table 5.20 b p219) should be used to control symptoms. Withdrawal of topical steroids often causes a rebound worsening of symptoms and the patient should be warned about this. The amount of steroid needed to cover various body parts is shown in Fig . 4.4. Always wash hands after applying topical steroids. Side eff ects local thinning of the skin, worsening local infection, striae and telangiecta sia, acne, depigmentation, hypertrichosis; systemic rarely adrenal suppression, Cushing \200\231s syndrome (subsequent withdrawal of topical steroids can precipitate an Addisonian crisis). Potency see b p219 for a list of the common topical steroids used arranged by pot ency. ONE adult fingertip unit (FTU)* Number of \201ngertip units (FTUs) Age Face & neck 21/2 Arm & hand 4 Leg & foot 8 Trunk (front) 7 Trunk (back) inc. buttocks 7 Adult Children: 3 \200\2236 months 1 \200\2232 years 3 \200\2235 years 6 \200\22310 years 1 11/2 11/2 2 1 11/2 2 21/2 11/2 2 3 41/2 1 2 3 31/2 11/2 3 31/2 5 Fig. 4.4 Amount of topical steroid required to treat various body parts. * One adult fi nge rtip unit (FTU) is the amount of ointment or cream expressed from a tube with a standard 5m m diameter nozzle, applied from the distal crease on the tip of the index fi nger. Reproduc ed with permission from Long, C.C. and Finlay, A.Y. (1991) Clinical and Experimental Dermat ology, 16: 444 \200\2237. Blackwell Publishing. OHFP.indb 178 OHFP.indb 178 30/05/2014 16:18 30/05/2014 16:18 179 EMPIRICAL ANTIBIOTIC TREATMENT Empirical antibiotic treatment Choice of suitable antibiotic depends upon likely pathogen a nd its usual antimicrobial sensitivity, patient factors (age and coexisting disease), drug availability, and local guidelines. Some common infections and suggested antibiotic regimen s are listed below (suitable for an oth- erwise healthy 70kg adult); more detailed options, including choices for patients with penicillin allergies are listed on b p649. Local antib iotic guidelines are written to ensure the most appro- priate antibiotics are used prior to knowing the pathogen and its antimi- crobial sensitivities. Taking cultures prior to comme ncing antibiotic therapy is impor- tant as it allows subsequent therapy to be more specifi cally tailored. However, cultures should not delay treatment in the septic patient. Urinary tract Co-amoxiclav 625mg/8h PO Cellulitis Wound infection Meningitis Flucloxacillin 1g/6h PO/IV As for cellulitis if after clean surgery; for dirty surgery or trauma, use co-amoxiclav 1.2g/8h IV Ceftriaxone 4g IV STAT then 2g/12h IV for 5-10d. Con sider addition of amoxicillin 2g/4h IV if patient >50yr, pregnant or immunocompromised and/ or vancomycin 1g/12h IV if pneumococcal meningitis suspected As for meningitis + aciclovir 10mg/kg/8h IV Encephalitis Endocarditis Acute presentation: fl ucloxacillin 2g/6h IV + gentamicin 5mg/kg/24h IV Indolent presentation: benzylpenicillin 1.2g/4h IV + gentamicin 5mg/kg/24h IV Septic arthritis Co-amoxiclav 1.2g/8h IV Pneumonia b pp 276 \200\2237 Amoxicillin 500mg \200\2231g/8h PO Community-acquired (CAP), CURB65=0-1 CAP, CURB65=2 Amoxicillin 1g/8h PO/IV + clarithromycin 500mg/12h PO/IV Co-amoxiclav 1.2g/8h IV + clarithr omycin 500mg/12h IV Co-amoxiclav 1.2g/8h IV (if severe: Tazocin 4.5g/8h IV) Co-amoxiclav 1.2g/8h IV + metronidazole 400mg/8h PO or 500mg/8h IV CAP, CURB65 \211 3 Hospital-acquired Aspiration pneumonia Septicaemia Co-amoxiclav 1.2g/8h IV + gentamicin 5mg/kg IV STAT Urinary tract sepsis Intra-abdominal sepsis Tazocin 4.5g/8h IV Meningococcal sepsis Ceftr iaxone 4g IV STAT then 2g/24h IV Neutropenic sepsis Skin/bone source Severe sepsis/septic s hock, no clear focus Tazocin 4.5g/8h IV + gentamicin 5mg/kg/24h IV Flucloxacillin 2g/6h IV Tazocin 4.5g/8h I V + gentamicin 5mg/kg STAT _OHFP.indb 179 _OHFP.indb 179 30/05/2014 16:18 30/05/2014 16:18 180 CHAPTER 4 Prescribing Clostridium diffi cile (C. diff ) Bacteriology C. diffi cile is a Gram-positive spore-formi ng anaerobic bacillus, which colonizes the intestines of some individuals (often those in l ong-term care). The use of antibiotics alters the balance of the gut fl ora, and can allow the overgrowth of C. diffi cile. Transmission via the faeco \200\223oral route. The spores are heat-resistant and can lay dormant in the environment for long periods. They are resist ant to stomach acid and germinate once in the colon. Symptoms diarrhea and abdominal pains are the commonest features of C. diffi cile overgrowth; when severe this can evolve into ps eudomem branous colitis. In the elderly and frail this can result in dehydration and even d eath. Detection is through urgent testing of stool as soon as suspicion of C. dif- fi cile arises.1 Currently this involves a 2-stage process, with a rapid, screening test for a C. d iffi cile protein (or PCR for the C. diffi cile toxin gene), followed by a more specifi c i mmunoassay for the C. diffi cile toxin. Speak to the laboratory if there is any doubt. Cons ider an urgent AXR to rule out toxic megacolon. Treatment is with metronidazole 400mg/8h PO or vancomycin 125mg/6h PO initially. More intensive regimens including higher doses of ora l vancomycin, metronidazole IV or vancomycin PR may be required in patients who fail to res pond or who relapse after initial treatment. Fecal transplantation (introduction of a suspe nsion prepared from the fresh feces of a screened donor either directly into the colon via enema or colonoscope, or through the upper GI tract after NJ delivery) is emerging as a hig hly eff ective, if cosmetically unappealing, method of treatment for refractory cases.2 Bar rier nursing and thorough hand hygiene are impor- tant to prevent transmission to other pat ients (the spores are resistant to alcohol hand gels so thorough hand washing with soap is essential).3 Surveillance as C. diffi cile is now regarded as a major cause of hos- pital-a cquired infections (HAI); local infection control teams should be made aware if a case is i dentifi ed or even suspected; they will often advise ward and medical staff on how the pati ent should be managed. p g Ecology, Clostridium diffi cile and antibiotics Intestinal carriage of Clostridium diffi ci le does not equate with disease \200\223 what matters is when C. diffi cile is able to out grow other com- mensal bacteria in the colon to the detriment of normal colonic ecology. He nce controlling the transmission of C. diffi cile is not suf- fi cient. Instead, we need to avoid perturbations in the colonic fl ora through the indiscriminate use of broad-spectrum antibiotics. As part of this approach, most trusts are limiting the use of cephalosporins, quinolones, and clindamycin, as well as drawing up helpful guidelines regarding antibiotic selection. Always check local antibiotic guidelines and consider risk and benefi t before prescribing any antibiotics. 1 Bristol Stool Chart types 5-7 stool not attributable to an underlying condition (eg overf l ow) or therapy (eg laxatives) from hospital patients aged >2 years, all community patients aged >6 5 years, and from community patients aged <65 years, wherever clinically indicated. See DH guidance at (cid:27)www.gov.uk/government/uploads/system/uploads/attachment_data/ \201 le/ 215135/dh_133016.pdf 2 See Rohlke and Stollman, Therap Adv Gastroenterol 2012 5:403 for a g ood review of trial data, available free at (cid:27)www.ncbi.nlm.nih.gov/pmc/articles/PMC3491681 3 Much emphasis is rightly placed on the prevention of in-hospital C. diffi cile transmissi on, with all sorts of policies introduced in the name of infection control. However, commun ity trans- mission appears to be at least as important, if not more so; see, for example, E yre, D.W. et al. NEJM 2013 369:1195 available free at (cid:27)www.nejm.org/doi/full/10.1056 /NEJMoa1216064 OHFP.indb 180 OHFP.indb 180 30/05/2014 16:18 30/05/2014 16:18 Chapter 5 Pharmacopeia 181 Pharmacopeia 182 _OHFP.indb 181 _OHFP.indb 181 30/05/2014 16:18 30/05/2014 16:18 182 CHAPTER 5 Pharmacopeia Pharmacopeia Users are advised to always check local prescribing guidelines and formularies and to consult the BNF when prescribing drugs. ACEi angiotensin-converting enzyme inhibito r Dose see Table 5.1, and see Table 5.2 on how to commence a patient on an ACEi Indications heart failure, hypertension, diabetic nephropathy, prophy- laxis of cardiovascular events Caution pregnancy and breastfeeding, patients already taking diuretics, renal artery stenos is/renal impair- ment, aortic stenosis, hyperkalaemia, known allergy to ACEi. May not be ef f ective in African-Caribbean patients SE postural hypotension, renal impairment and hyperk alaemia, dry cough, taste disturbance, urticaria and angioedema. If cough is problematic fo r the patient, consider AT II receptor antagonist, or other antihypertensive agent BNF 2.5. 5.1. Table 5.1 ACEi BNF 2.5.5.1 Dose initially 5mg/24h PO up to max 40mg/24h PO Dose initially 10mg/24h PO up to max 40mg/2 4h PO Dose initially 5 \200\22310mg/24h PO up to max 80mg/24h PO Dose initially 4mg/24h PO up to max 8mg/24h PO Enalapril Fosinopril Lisinopril Perindopril erbumine Perindopril arginine Dose initially 5mg/24h PO up to max 10mg/24h PO Dose initially 1.25 \200\2232.5mg/24h PO up to max 10mg/24h PO Ramipril Table 5.2 Starting an ACE inhibitor Patients with signifi cant comorbidity and/or taking other antihypertensive medications, as well as the frail and elderly, may need more cautious management when starting an ACEi and when increasing the dose Check U+E, document starting BP, identify target BP Before starting First dose Start with lowest dose and consider giving at bedtime to limit any problems with fi rst-dos e hypotension Increase dose daily/alternate days as BP allows, monitor U+E daily/alternate days In hospital In community Check U+E and BP at 7 \200\22310d after starting therapy or increasing dose. Increase dose every 14d until target BP reached Acetylcysteine (Parvolex ) amino acid derivative Dose 150mg/kg (max 16.5g) in 200ml 5% glu cose IVI over 15min; then 50mg/ kg (max 5.5g) in 500ml 5% glucose IVI over 4h; then 100mg/k g (max 11g) in 1l 5% glucose IVI over 16h Indication mainly used in known or sus- pected pa racetamol overdose Caution asthma SE allergic-like reactions, rash, bronchospasm, anaphylax is BNF emergency treatment of poisoning. OHFP.indb 182 OHFP.indb 182 30/05/2014 16:18 30/05/2014 16:18 183 pharmacopeia Actrapid insulin see insulins. Adenosine nucleoside (antiarrhythmic) Dose 6mg rapid IV bo lus; if needs repeated dose 12mg rapid IV bolus, then 12mg rapid IV bolus Indication suprav entricular tachycardia CI 2nd/3rd degree heart block, sick sinus syndrome (unless pacemaker fi tted), long QT syndrome, COPD/asthma Caution pregnancy, recent MI, pericarditis, heart block, bundle branch block, accessory pathway, hypovolaemia, valvular lesions SE nausea, si nus pause, bradycardia/asystole, fl ushing, angina, dizziness BNF 2.3.2. Adrenaline (epinephrine); anaphylaxis catecholamine Dose 0.5mg/STAT IM (0.5ml of 1:1000); r epeat after 5min if inadequate response Indication suspected anaphylaxis; if in doubt give it Caution cerebro- and cardiovascular disease SE iHR, iBP, anxiety, sweats, tremor, arrhyt hmias BNF 3.4.3. Adrenaline (epinephrine); cardiac arrest catecholamine Dose 1mg/STAT IV (10ml of 1:10,000); repeat as per ALS algorithm Indication cardiac arrest Caution as above SE as above BNF 2.7 .3. Aggrastat glycoprotein IIb/IIIa inhibitor see tirofi ban. Alteplase plaminogen activa tor see fi brinolytics. Amiloride potassium-sparing diuretic Dose 5-10mg/24h PO (max 20mg/24h PO) Indication oedema , potassium conservation when used as an adjunct to thiazide or loop diuretics for hyperten sion, con- gestive cardiac failure, hepatic cirrhosis with ascites CI hyperkalaemia, anuria , Addison s disease Caution renal impairment, DM, pregnancy and breastfeeding SE abdominal pain, GI disturbances including bleeding BNF 2.2.3. Aminophylline; IV theophylline/methylxanthine Dose Loading: 5mg/kg (based on ideal body wei ght) in 100ml 0.9% saline IVI over 20min. Maintenance: 0.5mg/kg/h, make up 500mg in 500ml 0 .9% saline (con- centration = 1mg/ml) IVI Indication reversible airways disease, severe acu te asthma Caution avoid loading dose if patient taking oral theophyl- line; cardiac disease , hypertension, epilepsy SE tachycardia, palpitations, arrhythmia, convulsions Info theophy lline is only available as an oral prepa- ration; aminophylline consists of theophylline an d ethylenediamine which simply improves the drug s solubility BNF 3.1.3. Stop infusion 15min prior to sampling, take sample 4 \200\2236h after commencing an infusio n 10 \200\22320mg/l (55 \200\223110micromol/l); toxic >20mg/l (>110micromol/l); signs of to xicity arrhythmia, anxiety, tremor, convulsions (OHAM3 b p731) Monitoring aminophylline (theophylline) _OHFP.indb 183 _OHFP.indb 183 30/05/2014 16:18 30/05/2014 16:18 184 CHAPTER 5 Pharmacopeia Amiodarone; cardiac arrest class III antiarrhythmic Dose 300mg IV/STAT after third shock if patient remains in VF/pulseless VT Indication VF/pulseless VT BNF 2.7.3. Amiodarone; arrhythmias class III antiarrhythmic Dose oral loading: 200mg/8h PO for 1wk, th en 200mg/12h PO for 1 wk, then 200mg/24h PO as maintenance dose, IV loading: initially 5mg/ kg over 20 \200\223120min IVI (with ECG monitoring) then further infusion if necessary of u p to 1.2g over 24h IVI Indication SVT, nodal and ventricular tachycardias, atrial fi brilla tion and fl utter, ventricular fi brillation (see above) CI bradycardia, sino-atrial heart block, thyroid dysfunction, iodine sensitivity Caution preg- nancy, breastfeeding, thyroid disease, hypokalaemia, heart failure, elderly, bradycardia SE N+V, taste disturbance, raise d transaminases, jaundice, bradycardia, hypotension, pulmonary toxicity, corneal deposits, skin discol- ouration Info monitor LFTs and TFTs every 6mth BNF 2.3.2. Amlodipine see calcium-channel blockers. Amoxicillin beta-lactam Dose 500mg \200\2231g PO/IV 8h Indication infection CI penicillin a llergy Caution glandular fever, CMV infection, ALL/CLL SE N+V, diarrhea, rash BNF 5.1.1.3. Ampicillin beta-lactam Dose 500mg \200\2231g PO/IV 6h Indication infection CI penicillin al lergy Caution glandular fever, CMV infection, ALL/CLL SE N+V, diarrhea, rash BNF 5.1.1.3. Antacids/Alginates Dose see Table 5.3 Indications acid refl ux disease Caution hepatic and renal impairment; if symptoms are severe or persist seek expert opinion SE depends upon pre paration used, see Table 5.3 Info the sodium load in these preparations can be signifi cant and they should be used with caution in patients with hepatic impair- ment. The alginates increase the viscosity of the stomach contents and can protect the oesophageal mucosa from acid attack; the raft-forming alginates fl oat on the surface of the stomach contents and m ay further reduce the symptoms of refl ux BNF 1.1.1/1.1.2. Table 5.3 Antacids BNF 1.1.1; alginates BNF 1.1.2 Classi \201 cation eg Alu-Cap Dose 1 capsule 4 times daily and at bedtime CI hypophosphataemia, neonates SE constipation Dose 10ml 3 times daily in water CI hypophosphataemia SE diarrhea, belching (d ue to CO2 liberation) Aluminum hydroxide Magnesium carbonate Magnesium trisilicate Dose depends upon preparation, see BNF 1.1.1 CI and SE see magnesium carbonate eg Peptac Dose 10 \200\22320ml after meals and at bedtime SE u sually none eg Gastrocote Dose 5 \200\22315ml 4 times daily (after meals and at bedtime) SE usually none Alginate raft-forming suspensions Other alginate preparations OHFP.indb 184 OHFP.indb 184 30/05/2014 16:18 30/05/2014 16:18 185 pharmacopeia Antiemetics Dose see Table 5.5 Indications N+V see Table 5.4; not all antiemetics are eff e ctive for all causes of N+V Caution and SE see Table 5.5 Info it is important to establish the cause of N+V BNF 4.6. Table 5.4 Causes of N+V and suggested antiemetic BNF 4.6 Likely cause Suggested antiemetics Pregnancy Post-operative Promethazine, prochlorperazine, metoclopramide In no particular order: 5HT3 antagonists, an tihistamines (eg cyclizine), dexamethasone, phenothiazines (eg prochlorperazine), metoclopr amide. Bowel obstruction Treat the cause. Avoid metoclopramide Motion sickness Hyoscine hydrobromide, promethazine, cyclizine Vestibular disorders Cytotoxic chemotherapy Betahistine (see BNF 4.6), antihistamine (eg cinnarizine, see BNF 4.6), phenothiazine (eg p rochlorperazine) Pre- and post-treatment with domperidone or metoclopramide; add in dexamet hasone, 5HT3 antagonists. See BNF 8.1 Depends upon cause. See b p91 Palliative care Table 5.5 Antiemetic classi \201 cation BNF 4.6 Antihistamines Cinnarizine, cyclizine, promethazine Cyclizine Dose 50mg/8h PO/IV/IM CI heart failure SE drowsiness, pain on injection, urinary retention, dry mouth, blurred vision Phenothiazines Chlorpromazine, droperidol, perphenazine, prochlorperazine, trifl uoperazine Prochlorperazine Dose consult BNF; 10mg/8h PO, 12.5mg/24h IM, 3 \200\2236mg/12h BUCCAL CI P arkinson \200\231s, epilepsy SE extrapyramidal eff ects, hypotension, drowsiness, agitation Dopamine antagonists Domperidone, metoclopramide Metoclopramide Dose 10mg/8h PO/IV/IM CI avoid in patients <21y (especially 5) and in bowel obstruction SE extrapyramidal eff ects Granisetron, ondansetron, palonosetron 5HT3 antagonists Ondansetron Dose 4 \200\2238mg/8h PO/IV/IM CI QT prolongation SE constipation, headache, fl ushing, bra dycardia, hypotension Dexamethasone, benzodiazepines, hyoscine hydrobromide, nabilone, neur okinin receptor antagonists Miscellaneous _OHFP.indb 185 _OHFP.indb 185 30/05/2014 16:18 30/05/2014 16:18 186 CHAPTER 5 Pharmacopeia Antihistamines H1 receptor antagonists Dose see Table 5.6 Indications symptomatic relief of allergy (eg hayfever, allergic rhinitis, urticaria) Caution avoid if possible in pregnancy and breastfeeding; consult BNF if renal or hepatic impairment; all antihistamines have the potential to cause sedation, some more so than others (see Table 5.6); the sedating antihi stamines also possess signifi cant antimuscarinic activity and should be used with caution in prostatic hypertrophy, urinary retention, and in patients with angle-closure glaucoma SE drowsiness, headache, antimuscarinic eff ects Info the drugs in this section are all antag onists at H1 receptor; cimetidine and ranitidine antagonists at the H2 receptor and are use ful for gastric acid suppression (see ranitidine) BNF 3.4.1. Table 5.6 Antihistamines BNF 3.4.1 Non-sedating antihistamines; acrivastine, cetirizine, desloratadine, fexofenadine, levoceti rizine, loratadine, mizolastine, rupatadine Dose 10mg/24h PO Cetirizine Caution halve dose if eGFR <30ml/min Dose 5mg/24h PO Dose 10mg/24h PO Desloratadine Loratadine Sedating antihistamines; alimemazine, chlorphenamine, clemastine, cyproheptadine, hydroxyzi ne, ketotifen, promethazine Chlorphenamine (chlorpheniramine) Dose 4mg/4 \200\2236h PO (max 24mg/24h); 10mg/8h IV/IM (over 1min if given IV) Arthrotec NSAID see diclofenac. Asacol aminosalicylate see mesalazine. Aspirin; antipla telet NSAID Dose anti-platelet 75mg/24h PO; ACS/MI 300mg/STAT PO; non-haemorrhagic stroke 3 00mg/24h PO for 14d then 75mg/24h PO Indication secondary prevention of thrombotic cerebrov ascular and cardiovascular events CI active bleeding, children under 16 (Reye \200\231s syn drome) Caution pregnancy, breastfeeding, asthma, peptic ulceration, concomitant use of othe r anticoagulants SE bronchos- pasm, GI irritation/hemorrhage BNF 2.9. Aspirin; analgesic/antipyretic NSAID Dose 300 \200\223900mg/4 \200\2236h PO; max 4g/24h Ind ication pain, pyrexia CI as above Caution as above SE as above BNF 4.7.1. OHFP.indb 186 OHFP.indb 186 30/05/2014 16:18 30/05/2014 16:18 187 pharmacopeia AT II receptor antagonists Dose see Table 5.7; commence therapy in the same way as starting an ACEi (see b p182) Indications patients intolerant of ACEi; heart failure, hypertension, diabetic nephropathy, prophylaxis of cardiovascular events Caution pregnancy and breast- f eeding, renal artery stenosis/renal impairment, aortic stenosis, hyperkalaemia, known aller gy to ACEi. May not be eff ective in African- Caribbean patients SE postural hypotension, r enal impairment and hyperkalaemia, taste disturbance, urticaria and angioneurotic oedema; c ough can occur but is less common than with ACEi BNF 2.5.5.2. Table 5.7 AT II receptor antagonists BNF 2.5.5.2 Dose initially 4-8mg/24h PO up to max 32mg/24h PO Dose initially 75 \200\223150mg/24h PO up to max 300mg/24h PO Dose initially 25 \200\22350mg/24h PO up to max 100mg/24h PO Dose init ially 80mg/24h PO up to max 320mg/24h PO Candesartan Irbesartan Losartan Valsartan Atenolol see beta-blockers. Atorvastatin HMG CoA reductase inhibitor see statins. Atropine; bradycardia anticholinergic Dose 500micrograms/ STAT IV every 3 \200\2235min; max 3mg/24h Indication bradycardia CI glau- coma, myasthenia gravis, pyloric stenosis, prostatic enlarg ement Caution Down s syndrome, GORD SE transient bradycardia, antimuscarinic eff ects (cons tipation, urinary urgency and retention, pupil dilatation/loss of accommodation, dry mouth) BNF 15.1.3. Atropine; cardiac arrest anticholinergic Dose 3mg/STAT IV Indication non-shock able cardiopulmonary arrest Caution none in the arrest situation SE as above Info atropine is no longer recommended for routine use in non-shockable cardiopulmonary arrest (see 2010 Resuscitation Guidelines) BNF 2.7.3. Bactroban antibacterial see mupirocin. Beclometasone