THE ULTIMATE PRE-REG BNF NOTES
IMPORTANT MONITORING DRUGS 1. AMIODARONE Treatment of arrhythmias arrhythmias Loading Dose: 200mg tds for 7 days, then 200mg bd for 7 days then 200mg daily maintenance. Important side side effects: effects: Nausea, Vomiting, Taste disturbance, Pulmonary toxicity, Reversible
corneal micro-deposits, Phototoxicity, Slate grey discolouration, Tremor, Sleep disorder, Hypo/hyperthyroidism, Jaundice.
Monitoring: LFTs, Thyroid function tests required before treatment, then every 6 months. Measure
serum potassium concentration before treatment. Chest x-ray required before treatment. ECG monitoring and resuscitation facilities must be available during intravenous use.
A very long half life – life – there there is potential for drug interactions to occur for several weeks (or even months) after treatment has stopped.
The Drugs
The Interaction
Amiodarone and Warfarin
Amiodarone inhibits Warfarin metabolism – metabolism – enhanced enhanced anticoagulant effect
Amiodarone and β Blockers
Increased risk of bradycardia, AV block and myocardial depression
Amiodarone and Lithium
Risk of ventricular arrhythmias
Amiodarone and Digoxin
Plasma conc. of Digoxin increased by Amiodarone
2. DIGOXIN A cardiac glycoside – glycoside – used used in AF, tachycardias and heart failure. A positive positive inotrope inotrope – – increases increases the force of myocardial contraction and reduces conductivity within the AV node. Desired serum concentration: 1-2mcg/L 1-2mcg/L (1.5mcg-3mcg/L (1.5mcg-3mcg/L indicates toxicity) Monitoring: Serum electrolytes (especially potassium) and Renal function. A n a r r o w t h e r a p e u t i c i n d e x , Possibility of Digitalis toxicity, made worse by hypokalaemia. Managed by giving potassium sparing diuretic or potassium supplements. Note: Elderly more susceptible to digitalis toxicity. Important side side effects: effects: Nausea, Vomiting, Diarrhoea, Dizziness, Blurred vision.
The Drugs
The Interaction
Digoxin and Amiodarone
Plasma conc. of Digoxin increased by Amiodarone
Digoxin and Erythromycin
Plasma conc. of Digoxin increased by Erythromycin (enzyme inhibitor)
Digoxin and Rifampicin
Plasma conc. of Digoxin reduced by Rifampicin (enzyme inducer)
Digoxin and St. John’s Wort
Plasma conc. of Digoxin reduced by St. John’s Wort (enzyme inducer)
Digoxin and Diuretics
Increased toxicity of Digoxin if hypokalaemia occurs with Loop & Thiazides
Digoxin and Calcium channel blockers
Plasma conc. of Digoxin increased by Calcium channel Blockers
3. LITHIUM Treatment and prophylaxis prophylaxis of mania, bipolar disorder and recurrent depression depression A n a r r o w t h e r a p e u t i c i n d e x and and requires monitoring. Desired serum concentration 0.4-1mmol/litre. (of or above 1.5mmol/L may be fatal and toxic) Toxic effects: Tremor, ataxia (shaky movements), Dysarthria (speech disorder), Nystagmus
(rapid involuntary movements of the eyes), Renal impairment and convulsions, Blurred vision. Monitoring: Measure Lithium serum concentration every 3 months, measure Renal and Thyroid function every 6 to 12 months, Maintain Sodium levels.
Counselling: Maintain adequate fluid intake and avoid dietary changes which reduce or increase
sodium intake. The Drugs
The Interaction
Lithium and ACE inhibitors
Excretion of lithium reduced by ACE inhibitors – inhibitors – Risk Risk of lithium toxicity
Lithium and NSAIDs
Excretion of lithium probably reduced by NSAIDs – NSAIDs – Risk Risk of lithium toxicity
Lithium and Diuretics
Excretion of lithium reduced by Loop and Thiazide – Thiazide – Sodium Sodium depletion
Lithium and Amiodarone
Risk of ventricular arrhythmias
4. METHOTREXATE Treatment of moderate to severe active active rheumatoid arthritis, Crohn’s disease, malignant disease, Psoriasis. Blood dyscrasias: full blood count needed before starting treatment and patient needs to be
advised to report any sore throat, signs of infection, bruising or mouth ulcers.
Liver toxicity/cirrhosis: LFTs (and renal) needed before starting treatment and patient needs to be
advised to report any nausea, vomiting, abdominal discomfort or dark urine)
Pulmonary toxicity: Patients need to be advised to report any shortness of breath, cough or fever. Aspirin and other NSAIDs: NSAIDs: If aspirin or NSAIDs taken at the same time, the dose of
Methotrexate needs to be carefully monitored, as leads to rise in Methotrexate levels. Care with OTC.
Oral Dose: 7.5mg once weekly weekly and a maximum weekly dose dose of 20mg. A folate antagonist - treatment with folic acid (5mg) helps to prevent Methotrex ate-induced mucositis or myelosuppression. Don’t give folic acid at the same time.
Side effects: GI ulceration and bleeding, hepatoxicity.
5. PHENYTOIN Treatment of epilepsy (all except absence) absence) and neuropathic pain. A n a r r o w t h e r a p e u t i c i n d e x . Relationship between dose and plasma concentration is non
linear. Small dosage increase may produce large plasma concentrations and hence toxic effects. Therefore monitoring is required.
Desired serum concentration: 10-20mg/L Monitoring: Full blood counts, liver function. Side effects: Nausea, Vomiting, Constipation, Gingival hypertrophy, Rash, Acne, Hirsutism
(coarse pigmented hair on face) Coarse faeces, blood or skin disorders.
Counselling: Look out for signs of blood or skin disorders (Fever, sore throat, rash, mouth ulcers,
bruising, bleeding, Leucopoenia) + Take with or after food. The Drugs
The Interaction
Phenytoin and NSAIDs
Effects of Phenytoin enhanced by NSAIDs
Phenytoin and Amiodarone
Amiodarone inhibits metabolism of Phenytoin
Phenytoin and Warfarin
Phenytoin accelerates metabolism of Warfarin
Phenytoin and Cimetidine
Cimetidine inhibits the metabolism of Phenytoin
Phenytoin and Fluoxetine
Plasma concentration of Phenytoin increased by Fluoxetine
Phenytoin and St. Johns Wort
St. Johns Wort (an enzyme inducer) reduces plasma conc. of phenytoin
6. THEOPHYLLINE A bronchodilator for asthma or COPD A n a r r o w t h e r a p e u t i c i n d e x . Theophylline’s toxic dose is close to its therapeutic dose.
Note: Potentially serious hypokalaemia may result from concomitant use of theophylline.
Desired plasma concentration of 10-20mg/L (above 20mg/L can lead to severe side effects) Side effects: Tachycardia, Palpitation, nausea, GI, Headache, convulsions Monitoring: Plasma theophylline concentration, Lung function tests
The Drugs
The Interaction
Theophylline and Quinolones
Increased risk of convulsions
Theophylline and St. Johns Wort
Plasma conc. of theophylline reduced by St. Johns Wort
Theophylline and Rifampicin
Plasma conc. of theophylline reduced by Rifampicin
Theophylline and Cimetidine
Plasma conc. of theophylline increased by Cimetidine
Theophylline and Fluconazole
Plasma conc. of theophylline increased by Fluconazole
7. WARFARIN Anticoagulant (takes at least 48 to 72 hours for anticoagulant effect to develop fully). Highly protein bound to albumin 99% If INR is too high, there is a risk of bleeding, therefore Warfarin needs to be stopped. If INR is too low, there is a risk of blood clotting, therefore Warfarin dose needs to be increased. Dose: For rapid anticoagulation: an initial dose of 10mg of the first day, Daily maintenance dose: 3-9mg. Side effects: Haemorrhage, Rash, Hypersensitivity, Alopecia, Diarrhoea, Unexplained drop in
haematocrit (packed cell volume), Purple toes, Skin necrosis, Jaundice, Hepatic dysfunction.
Monitoring: INR, Renal function Counselling: Take at the same time each day, avoid major dietary changes (especially involving
salads and vegetables) as it can affect the anticoagulant effect, report any signs of bleeding or spontaneous bruising. The Drugs
The Interaction
Warfarin and NSAIDs
Anticoagulant effect enhanced by NSAIDs (can cause bleeding)
Warfarin and Fluconazole
Anticoagulant effect enhanced by Fluconazole (can cause bleeding)
Warfarin and Statins
Anticoagulant effect enhanced by Statins (can cause bleeding)
Warfarin and Ciprofloxacin
Anticoagulant effect enhanced by ciprofloxacin/erythromycin/metronidazole
Warfarin and Griseofulvin
Anticoagulant effect reduced by Griseofulvin
Warfarin & St. John’s Wort
Anticoagulant effect reduced by St. John’s Wort
Warfarin and Antiepileptics
Anticoagulant effect reduced by Antiepileptics
Warfarin and Alcohol
Anticoagulant control affected with alcohol consumption
Warfarin & Cranberry Juice
Anticoagulant effect enhanced by cranberry juice
Warfarin and Vitamin K
Anticoagulant effect antagonised by vitamin K
IMPORTANT INTERACTIONS Enzyme Inducers and Inhibitors: Enzyme Inhibitors – Inhibit cytochrome P450 enzyme, resulting in decreased metabolism of other drugs. This increases the concentration of the other drug which can cause toxic high levels of it. Enzyme Inducers – Induces cytochrome P450 enzyme to work. This results in increased metabolism of other drugs. This decreases the concentration of the other drug as it is broken down by the enzymes. This then leads to a decrease in the effect of this other drug. ENZYME INDUCERS
ENZYME INHIBITORS
Carbamazepine
Ciprofloxacin
Barbiturates
Erythromycin
Phenytoin
Cimetidine
Griseofulvin
Sodium Valproate
St John’s Wort
Fluoxetine
Rifampicin
Ketoconazole
Smoking
Fluconazole
Alcohol
Grapefruit juice
Alcohol and Interactions: Alcohol + Metronidazole = Disulfiram-like interaction where intensive support therapy may be required. (See counselling section on Disulfiram) Alcohol + Warfarin = Major changes in consumption of alcohol may affect anticoagulant control of coumarins. Alcohol + MAOI = Beverages containing tyramine can cause hypertensive crisis when taken with MAOI. Alcohol and Mirtazapine or Tricyclic antidepressants – Increased sedative effect.
Combined oral contraceptives and Interactions The effectiveness of combined oral contraceptives is considerably reduced by interaction with enzyme inducing drugs because they increase metabolism of the contraceptives. (Enzyme inducers: Carbamazepine, Phenobarbital, Primidone, Phenytoin, Topiramate, Ritonavir, Griseofulvin, Rifampicin, Rifabutin, St John’s Wort). Additional contraceptive precautions should be taken for at least 4 to 8 weeks after stopping treatment. A ‘tricycling’ method whereby daily intake of 50mcg ethinylestradiol (unlicensed) 3 or 4 packs in a row without a break and then having a 4 day pill free interval can be used by women treated with these drugs but effectiveness is uncertain. Rifampicin and Rifabutin are such potent enzyme inducers that IUD is always recommended. Some antibacterials that do not induce liver enzymes (Ampicillin, Amoxicillin, Doxycycline) may reduce the efficacy of combined oral contraceptives by impairing the bacterial flora responsible for recycling ethinylestradiol from the large bowel (risk is small). For these, additional precautions are required for duration of treatment and for 7 days after stopping treatment (if this is in the last 7 days of the packet, omit the pill free period). However NO need for extra precautions if a woman is taking the pill and has been
on the SAME antibacterial course exceeding 3 weeks. This is because the bacterial flora develops resistance. If the antibiotic is changed, then YES additional precautions are necessary. Also NO precautions are necessary if a woman is STARTING the COC and has been on antibiotic therapy for 3 weeks or more. For contraceptive patches, additional contraception is required for 7 days after stopping treatment with non-enzyme inducing antibacterial drugs (except tetracycline). However no need for extra precautions if a woman is using the patches and has been on the SAME antibacterial course exceeding 3 weeks. If the antibiotic is changed, then YES additional precautions are necessary. Also NO precautions are necessary if a woman is STARTING the COC and has been on antibiotic therapy for 3 weeks or more. IBNF page 434
Progestogen only contraceptives and Interactions Progestogen only contraceptives are not affected by antibacterials that are not enzyme inducers. However their efficacy is reduced by enzyme inducer drugs. In this case additional protection is needed for duration of treatment and for 4 weeks afterwards.
Sympathomimetics and Interactions Pseudoephedrine + MAOI = hypertensive crisis Pseudoephedrine + Beta Blockers = increased risk of hypertension
Orlistat and A l l i Orlistat + Amiodarone = Orlistat possibly reduces plasma conc of amiodarone Orlistat + Anticoagulants = Need to monitor anticoagulant effect of coumarins Orlistat + Diabetes = Avoid concomitant use of Acarbose as its effects work on GI Orlistat + Ciclosporin = Orlistat possibly reduces absorption of cicloporin (black dot)
Pharmacokinetic Interactions These occur when one drug alters the absorption, distribution, metabolism, or excretion of another drug, thus increasing or reducing the amount of drug available to produce its pharmacological effects. Affects absorption – reduced amount of absorption can result in ineffective therapy. Changes in protein binding and distribution – One drug can displace another drug from a protein binding site increasing its proportion free to diffuse from plasma to its site of action. Affects metabolism – Effects on liver cytochrome P450 enzymes. Affects renal excretion – NSAIDs delay the excretion of Methotrexate possibly causing serious toxicity.
Pharmacodynamic Interactions This is where effects of one drug are changed by the presence of another drug at its pharmacological site of action. Synergistic effect causing combined toxicity – sedative + sedative, antihypertensive drug + drugs causing hypotension, potassium sparing diuretics + K+ supplements. Antagonistic effect causing opposite effects – Warfarin + Vitamin K Affects drug transport mechanisms - nortriptyline inhibiting the uptake of adrenaline into adrenergic neurones. Disturbances in fluid and electrolyte balance - cardiac glycoside + potassium depleting diuretics, Lithium + thiazide diuretics causing sodium depletion.
POPULAR DRUG INDICATIONS and FACTS TO KNOW GI, CVS, CNS see separate notes Gastro Intestinal System H e l i c o b a c t e r p y l o r i Infection Eradication of H. pylori reduces recurrence of gastric and duodenal ulcers and o the risk of re-bleeding. The presence of H. pylori should be confirmed before starting treatment. o o First Line Therapy is a seven day treatment of: 1. Proton Pump Inhibitor (twice daily dose) 2. Plus 2 Antibiotics given twice daily - Clarithromycin - Amoxicillin or Metronidazole The above regimen eradicates H. pylor i in about 85% of cases. BNF page 50 o
Cardiovascular System For Hypertension People younger than 55 years and Caucasians respond better to an ACE inhibitor or angiotensin II receptor antagonists. People aged over 55 years & afro-Caribbean (any age) first line treatment is thiazide diuretics or calcium channel blockers. BNF page 105 For Heart Failure An ACE inhibitor titrated to a ‘target dose’ combined with a licensed beta blocker plus a diuretic to reduce fluid overload. Low doses of spironolactone reduce symptoms and mortality. Digoxin improves symptoms and exercise tolerance. BNF page 114 Colestyramine for hyperlipidaemia is a bile acid sequestrant which binds to bile acids and promotes hepatic conversion of cholesterol into bile acids. Counselling: Other drugs should be taken at least 1 hour before or 4 – 6 hours after bile acid sequestrants to reduce possible interference with absorption. Colesevelam and a statin can be taken at the same time. BNF page 166
Respiratory System BTS Guidelines (Table Page 174 BNF) – see separate Respiratory notes Tiotropium (Antimuscarinic bronchodilator) only indicated for COPD and not asthma.
Central Nervous System Orlistat ( an d A l l i ) – See separate OTC RPSGB guidance. Metoclopramide under 20 years old – Use restricted to severe intractable vomiting of a known cause, vomiting of radiotherapy and cytotoxics, aid to GI intubation, premedication; also dose should be determined on the basis of body-weight. BNF page
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Migraine – 5HT1 agonists such as naratriptan and sumatriptan are used for treatment of acute migraines. Beta blockers, pizotifen, clonidine, methysergide, sodium valproate, topiramate, TCAs and cyproheptadine are prophylactic treatments. Prophylaxis is required if a patient suffers more than 2 attacks per month, suffers an increasing frequency of headaches, suffers significant disabil ity despite treatment for migraine attacks, cannot take suitable treatments for migraine attacks. BNF page 277
Infections Meningitis (Blind Therapy) - following urgent transfer to hospital; Use Benzylpenicillin or Cefotaxime (if penicillin allergy) For Lower Urinary Tract Infection - Trimethoprim or Nitrofurantoin or Amoxicillin or oral Cephalosporin - for 3 to 7 days. Tuberculosis – Treat with 4 drugs (Isoniazid, Rifampicin, Pyrazinamide, Ethambutol) in the initial phase for 2 months or possibly longer. Treat with 2 drugs (Isoniazid and Rifampicin) for a further 4 months. Note: Ethambutol can cause colour blindness. High Anaerobic activity – Metronidazole.
Endocrine System Insulin – is given by subcutaneous injection but soluble insulin is given intravenously and is reserved for urgent treatment. Insulin may be required for both type 1 and 2 diabetes. It is needed for all patients with ketoacidosis and for those whose symptoms include: rapid onset of symptoms, substantial weight loss, weakness, ketonuria (ketone bodies in urine), and f irst degree relative who has diabetes. BNF page 427 Short acting sulphonylureas (Gliclazide and Tolbutamide) – Work by increasing insulin secretion by B cells. Considered for patients who are not overweight or for those where Metformin is CI. BNF page 435 Long acting sulphonlyureas (chlorpropamide and glibenclamide) - associated with greater risk of hypoglycaemia; hence should be avoided in the elderly and the short acting ones are preferred. BNF pag e 435 Biguanide - Metformin – Works by decreasing gluconeogenesis and increasing peripheral utilisation of glucose. It is first line therapy for diabetics. It does not cause weight gain hence good for overweight or obese patients. Produces normoglycaemia rather than hypoglycaemia. BNF page 437 Pioglitazone and Rosiglitazone - Work by decreasing peripheral insulin resistance Acarbose – Works by delaying digestion and absorption of starch and sucrose from the gut by inhibiting intestinal alpha glucosidases. Usually add on therapy. BNF page
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Diabetic Ketoacidosis (a hyperglycaemic emergency) - Symptoms include nausea, vomiting, abdominal pain, extreme thirst, blurred vision and can be life threatening. Treatment: a. Soluble Insulin by intravenous infusion (because subcutaneous insulin may be slow and erratic); b. Sodium chloride intravenous infusion fluid replacement; c. Potassium chloride is included in the infusion to prevent hypokalaemia induced by insulin. BNF page 443 Hypoglycaemia (caused by low blood glucose levels) - Causes: Too much insulin, little carbohydrate, delayed meals, too much exercise, hot weather, stress, alcohol. Symptoms include tremor, sweating, anxiety, paleness, irritability, feeling faint, stomach ache, headache, tingling sensation and blurred vision. Treatment for conscious patient: oral sugar following a carbohydrate snack. Treatment for unconscious patient: IV glucose infusion or Glucagon injection, followed by complex carbohydrates once conscious. Note: Hypoglycaemia can be masked by beta blockers and this can be dangerous. BNF pag e 444 ACE inhibitor - may have a specific role in the management of diabetic nephropathy in type 2 diabetes and may minimise decline of renal function. BNF page 115 Levothyroxine - For hypothyroidism – Initial dosing: If metabolism increases too rapidly this causes diarrhoea, nervousness, rapid pulse, insomnia, tremors and sometimes angina pain where there is latent myocardial ischemia. The dose needs to be reduced or withheld for one to two days then restarted again. BNF page 448 Read Pages 451 to 387 455 on Steroids
Corticosteroids - Important Indications: Replacement therapy for Addison’s disease, Acute adrenal insufficiency, hypopituitarism, anti-inflammatory treatment, immunosupression. Important Points: a. Prolonged use increases susceptibility to infections and severity of infections. b. Unless they have already had chickenpox, patients using oral or parenteral therapy are at risk of severe chickenpox. c. Special care is required to avoid exposure to measles. d. Long term dosing can lead to adrenal suppression, psychiatric reactions and growth restriction in children. e. Until one year after stopping steroids, patients must mention that they had taken steroids. Withdrawal: This must be gradual if a patient has received repeated courses of systemic corticosteroids particularly if taken for longer than 3 months, if the patient has taken a short course within one year of stopping long-term therapy, if there are other possible causes of adrenal suppression, if the patient received more than 40mg daily prednisolone (or equivalent), if the patient has been given repeated doses in the evening (e.g. mimicking the normal diurnal rhythm), if the patient has received more than 3 weeks treatment. HRT – for treatment of menopausal symptoms such as vaginal atrophy, vasomotor instability (heat, sweating) and menopausal osteoporosis. HRT can be used in women with early natural or surgical menopause before the age of 45. For early menopause, HRT can be given until the approximate age of natural menopause (i.e. until the age of 50). Experience in treating women over 65 with HRT is limited. RISKS: Increased risk of breast cancer within 1 to 2 years of initiating treatment. Increased risk of endometrial cancer (depends on dose and duration of oestrogen only HRT) hence progestogen can be added cyclically for 10 days in a 28 day cycle. Increased risk of ovarian cancer (although small) with long term combined use of HRT or oestrogen-only HRT. Increased risk of DVT and pulmonary embolism with combined or oestrogen only HRT. Risk of stroke and CHD also found. Note: HRT does not provide contraception and a woman is considered potentially fertile for 2 years after her last menstrual period if she is under 50 and for 1 year if she is over 50 years old. BNF page 458 and see BNF p age 505 for reasons to stop HRT Bisphosphonates (Alendronic acid, Disodium etidronate, Risedronate sodium) – Work by reducing bone turnover. They are used for the treatment of osteoporosis and for corticosteroid induced osteoporosis. Alendronic acid dose for postmenopausal osteoporosis is 70mg once weekly. BNF page 480
Gynaecology Combined oral contraceptive – BNF p age 502. Mechanisms: The oestrogen works by inhibiting ovulation, and changes the endometrial environment. The progestogen works by also inhibiting ovulation but to a lesser extent. Progestogen inhibits fallopian tube motility, changes the endometrial environment and thickens the cervical mucus which is hostile to sperm. Risk of DVT: Increased risk particularly during the first year. Risk increases with age and obesity. This risk is increased by travelling for long periods with immobility. Advice wearing graduated compression hosiery or exercising during the journey. Missed pill: If a pill is missed it should be taken as soon as remembered and the next one at the normal time. (A missed pill is one that is more than 24 hours late). If ONE pill is missed, it should be taken as soon as remembered and no further precautions are necessary. If 2 or more pills missed (especially in the first 7 days of the packet), protection is compromised. Take an active pill when remembered and then resume normal pill taking but barrier contraception for 7 days after. If these 7 days run beyond the end of the packet, the pill free interval should be omitted. EHC may be needed. Vomiting and diarrhoea: If vomiting occurs within 2 hours of taking COC, another pill should be taken. If
vomiting and diarrhoea is severe and lasts more than 24 hours, additional precautions should be used for 7 days. Risks: Small risk of breast cancer and cervical cancer but risk of ovarian and endometrial cancer reduced). First time users: Start on day 1 of menstruation. If started on day 4 or later then additional precautions necessary for 7 days. Changing to COC containing a different progestogen: Complete the whole packet then for the new pack start the very next day without the 7 day break. If the pill free break is taken then barrier methods should be used for 7 days after taking the new brand. Changing from POP to COC: Start on first day of menstruation for full protection. If taken for amenorrhoea then start at any time but barrier protection needed for first 7 days. After childbirth: Start 3 weeks after birth (risk of thrombosis if started earlier) If started later than 3 weeks, then barrier methods needed for first 7 days. After abortion or miscarriage: Start on the same day. For patches See BNF page 503
COC or HRT should be stopped immediately if: a. Sudden severe chest pain b. Sudden breathlessness c. Unexplained swelling or severe pain in calf of one leg d. Severe stomach pain. e. Serious neurological effects e.g. vision loss, seizure, bad fainting, numbness. f. Hepatitis, jaundice, liver enlargement g. Blood pressure above systolic 160mmHg and diastolic 95mmHg h. Prolonged immobility after surgery or leg injury i. Detection of a risk factor e.g. DVT in the family, art erial disease, migraine Progesterone Only Contraceptive: These may be suitable where COC is contraindicated but do have a higher failure rate. They are suitable for older women, heavy smokers, hypertension and heart disease, diabetics and migraine sufferers but still need to be cautioned. Staring routine: One tablet daily, starting on day one of cycle. Changing from COC: Start on the day following completion of COC course without a break. After childbirth: Start at any time after 3 weeks of birth (increased risk of breakthrough bleeding if started earlier). Breastfeeding: Lactation is not affected; in fact POP is preferred contraceptive for breast feeding. Missed Pill: If a pill is forgotten, it should be taken as soon as remembered and carry on with the next one at the right time. If the pill was more than 3 hours overdue (12 hours for Cerazette) then a woman is not protected. Continue normal pill taking but other forms of contraception (barrier methods) should be used for the next 2 days. Diarrhoea and vomiting: If vomiting occurs within 2 hours of taking POP, another one should be taken as soon as possible. If a replacement pill is not taken within 3 hours of the normal time or if severe diarrhoea and vomiting occur for a longer duration of time then extra precautions should be taken for 2 days after recover. Risks: Small risk of breast cancer. BNF page 509
Musculoskeletal and Joint diseases Acute attacks of Gout – Treated with high doses of NSAIDs such as diclofenac, an etoricoxib, indometacin, ketoprofen, naproxen or sulindac. C o l c h i c i n e is alternative (e.g. for patients with heart failure who cannot take NSAIDs or for patients on anticoagulants). Aspirin is not indicated in gout. A l l o p u r i n o l and U r i c o s u r i c s are not effective in treating an acute attack but used for prophylaxis of gout. Never start a prophylactic drug during an acute attack as it can make it worse; start them 1 to 2 weeks after the acute attack has settled. BNF page 641 Read Pages 642 to 644 BNF on NSAIDs
NSAIDs – Note about GI: etoricoxib and celecoxib are COX-2 selective and hence have fewer GI side effects. Azapropazone (non-selective) is associated with the highest risk of GI effects and Ibuprofen (non selective) with the lowest. Other nonselective (COX-1 and 2) NSAIDs include piroxicam, ketoprofen, indometacin, naproxen and diclofenac have intermediate risk for GI effects. Note about asthma: NSAIDs can worsen asthma due to bronchospasm being a side effect. Note about Cardio: COX-2 selective inhibitors are associated with an increased risk of thrombotic events and should not be used in preference to non-selective NSAIDs unless specifically indicated. Note about renal: NSAIDs can impair renal function and therefore need to be used in caution. Note about Heart failure: All NSAIDs are contraindicated in severe heart failure. Note about Peptic Ulcers: NSAIDs are contraindicated in peptic ulcers but those patients in need of NSAIDs i.e. for severe rheumatism can be given a PPI for prophylaxis of GI ulceration and bleeding. BNF page 644
Read Page 658-659 BNF on Methotrexate
POPULAR DRUGS AND THEIR SIDE EFFECTS Gastro Intestinal System Magnesium containing antacids - Laxative effect and can cause belching due to carbon
dioxide liberation.
Aluminium containing antacids - Constipating effect. Hyoscine (antimuscarinic) - Constipation, Transient Bradycardia, Reduced bronchial secretions, Urinary urgency and retention, Dilatation of pupils (problematic for patients with angle closure glaucoma), Photophobia, Dry mouth, Flushing, Dryness of the skin.
H2 Receptor Antagonists - Diarrhoea, GI disturbance, Altered Liver Function Tests, Headache, Dizziness, Rash, Tiredness.
Proton Pump Inhibitors - GI disturbances, Headache. Liquid paraffin - anal seepage, granulomatous reactions (especially from the emulsion), lipoid pneumonia and interference with the absorption of fat-soluble vitamins.
Cardiovascular System Thiazide Diuretics - Mild GI disturbance, Postural hypotension, Altered plasma lipid
concentrations, Hypokalaemia, Hyponatraemia (low sodium in the blood), Hypomagnesaemia, Hypercalcaemia, Hyperglycaemia, Hyperuricaemia and Gout (uric acid). Less common – impotence.
Loop Diuretics - Mild GI disturbance (nausea), Hypotension, Hypokalaemia, Hyponatraemia (low sodium in the blood), Hypomagnesaemia, Hypocalcaemia, Hyperglycaemia (less common than with thiazides), Hyperuricaemia, Gout (uric acid).
Potassium Sparing Diuretics - Hyperkalaemia Beta Blockers - GI disturbance, Bradycardia, Heart Failure, Hypotension, Peripheral vasoconstriction (cold hands and feet), Bronchospasm, Dyspnoea, Headache, Fatigue, Sleep disturbance (Nightmares), Sexual dysfunction, Pins and needles , Dizziness, Interference with glucose tolerance.
ACE Inhibitors - Can cause profound hypotension and renal impairment, Persistent dry cough, Angioedema, Rash, Pancreatitis, Upper Respiratory symptoms, GI disturbances, Altererd LFTs (jaundice), Hyperkalaemia, Hypoglycaemia, Blood disorders, Taste disturbance.
Angiotensin II Receptor Blockers - Dizziness (if taking high dose diuretics as well) , Hyperkalaemia (occasional) , Angioedema (occasional). Nitrates - Postural Hypotension, Tachycardia, Throbbing Headache, Dizziness, Flushing. Calcium channel Blockers – Oedema (Notably of the ankles). Aspirin - Bronchospasm, Gastro-intestinal bleeding (PPI can be added). Statins - Myositis, Myalgia and Myopathy (Muscle Effects) - Serious, Liver toxicity, GI disturbance (flatulence, abdominal pain).
Respiratory System Beta2 Agonists - Fine tremor, Nervous tension, Headache, Muscle cramps, Palpitations,
hypokalaemia.
Antimuscarinic Bronchodilators (Ipratropium, Tiotropium) - Dry mouth. Inhaled corticosteroids - Oral candidiasis, Hoarseness, Adrenal suppression. Antihistamines - Antimuscarinic side effects – urinary retention, dry mouth, blurred vision, constipation and sedation with the older generation.
Central Nervous System Benzodiazepines - Drowsiness, Light-headedness the next day, Amnesia, In elderly: Confusion
and ataxia, Dependence.
Antipsychotic (chlorpromazine) – Marked Sedative effects, Moderate antimuscarinic effects, Moderate extrapyramidal effects – see CNS Notes.
Antipsychotic (prochorperazine) – Marked Extrapyramidal effects, fewer sedative effects, fewer antimuscarinic effects.
Atypical Antipsychotics (e.g. Amisulpride, Olanzapine) - Weight gain, Dizziness, Postural hypotension, Extra-pyramidal effects (usually mild) , Hyper-glycaemia and diabetes. Tricyclic antidepressants - Dry mouth, Sedation, Blurred vision, Constipation, Nausea, Difficulty with urination, Cardiovascular side effects, Sweating, Tremor, Rashes, Hypersensitivity reactions, Confusion, Suicidal behaviour.
SSRI’s - Gastro-intestinal effects, Anorexia/weight loss or opposite, Hypersensitivity reactions, Urticaria, Angioedema, Anaphylaxis, Arthralgia, Myalgia, Photosensitivity.
Mirtazapine – Increased appetite and weight gain, oedema, sedation, nausea, vomiting, dizziness, headache – which commonly lead to the need for withdrawal but this should be done over several weeks.
Venlafaxine – GI disturbance, headache, anxiety, dizziness, sleep disturbance – which commonly lead to the need for withdrawal but this, should be done over several weeks. Orlistat – oily leakage from rectum, flatulence, faecal urgency, liquid or oily stools, faecal incontinence, abdominal distension and pain (minimised by reduced fat intake), tooth and gingival disorders, respiratory infections, fatigue, anxiety, headache, menstrual disturbance, UTI, hypoglycaemia.
Metoclopramide – Extrapyramidal side effects. 5HT1 agonists (Naratriptan, Sumitriptan) – Tingling, heat, heaviness, pressure, or tightness of any part of the body, flushing, dizziness, weakness.
Opioids – Nausea, vomiting, constipation, dry mouth, biliary spasm, respiratory depression in larger doses.
Infections Penicillin, Flucloxacillin, Amoxicillin, Ampicillin, Co-amoxiclav, Co-fluampicil
Hypersensitivity reactions can be fatal (uticaria, fever, joint pains, rashes, angioedema, anaphylaxis.)
Cephalosporins (Cefaclor, Cefalexin) - Hypersensitivity reactions (0.5-6.5% of penicillin allergic patients will also be allergic to cephalosporins), diarrhoea and antibiotic associated colitis (more likely with higher doses), nausea, vomiting, abdominal discomfort, headache, liver problems.
Tetracyclines (Tetracyline, Doxycycline, Lymecycline, Minocycline, Oxytetracycline) - nausea, vomiting, diarrhoea, Dysphagia, oesophageal irritation. Aminoglycosides (Gentamicin, Neomycin) – Ototoxicity (inner ear or balance of hearing toxicity) and nephrotoxicity.
Macrolides (Erythromycin) – Nausea, vomiting, abdominal discomfort and diarrhoea (Clarithromycin - also dyspepsia and tongue/tooth discolouration. Smell and taste disturbances).
Clindamycin – Diarrhoea (discontinue treatment as associated with fatal antibiotic associated colitis), abdominal discomfort, oesophageal ulcers.
Trimethoprim - GI effects, pruritus, rashes, hyperkalaemia. Rifampicin - GI effects (diarrhoea – antibiotic associated colitis reported, anorexia, nausea, vomiting), hepatic disorders, coloured bodily fluids (urine red).
Metronidazole - GI effects, taste disturbance, furred tongue, oral mucositis, and anorexia. Quinolones (Ciprofloxacin) - Nausea, vomiting, dyspepsia, abdominal pain, diarrhoea, headache, dizziness, rash, sleep disturbances.
Nitrofurantoin - Anorexia, nausea, vomiting, diarrhoea, acute and chronic pulmonary reactions. Terbinafine – Abdominal discomfort, anorexia, nausea, diarrhoea, headache, rash and urticaria.
Endocrine System Insulin - fat hypertrophy at injection site, hypoglycaemia (heavy sweating, shakiness, dizziness,
visual disturbance, tingling of hands and lips, speech disturbance)
Sulphonylureas - Weight gain, GI effects (nausea, vomiting, diarrhoea, constipation), hypoglycaemia.
Biguanides (Metformin) - Anorexia, nausea, vomiting, diarrhoea, abdominal pain, metallic taste, vitamin B12 deficiency.
Levothyroxine – Diarrhoea, vomiting, angina pain, arrhythmias, palpitation, tachycardia, tremor, restlessness, excitability, insomnia, headache, flushing, sweating, fever, heat intolerance, weight loss, muscle cramps, transient hair loss in children.
Carbimazole – nausea, mild GI disturbance, headache, rash, bone marrow suppression (neutropenia, agranulocytosis)
O r a l c o r t i c o s t e r o i d s : Euphoria, nightmares, insomnia, irritability, mood lability, suicidal thoughts, psychotic reactions, immunosupression, adrenal suppression. Mineralocorticoids - Hypertension, sodium and water retention, potassium and calcium loss. Glucocorticoids - Diabetes, osteoporosis, muscle wasting and weakness, peptic ulceration and perforation, Cushing’s syndrome (moon face, striae, acne occurs with higher doses and is reversal on withdrawal), growth suppression in children, GI effects, menstrual irregularities, hirsutism, weight gain, increased susceptibility to infection, insomnia, glaucoma, uticaria, skin atrophy, myocardial rupture following MI or congestive heart failure, hypersensitivity, thromboembolism, nausea, malaise, hiccups, headache, vertigo.
Gynaecology Combined Oral Contraceptives: Nausea, vomiting, abdominal cramps, changes in body
weight, liver impairment, hepatic impairment, fluid retention, and hypertension.
Progestogen-only Contraceptives: Menstrual irregularities, nausea, vomiting, headache, dizziness, breast discomfort, depression, skin disorders, disturbance of appetite, weight changes, changes in libido.
Musculoskeletal and Joint Diseases NSAIDs - GI discomfort, nausea, diarrhoea, bleeding and ulceration, hypersensitivity
(bronchospasms), headache, dizziness, nervousness, depression, drowsiness, insomnia, vertigo, hearing disturbance, photosensitivity, blood disorders, fluid retention, renal failure.
Methotrexate – anorexia, abdominal discomfort, dyspepsia, GI ulceration and bleeding, diarrhoea plus many more.
DRUGS THAT COLOUR BODILY FLUIDS Dantron (Co-danthramer) – Urine Red Sulfasalazine – Urine Orange Triamterene (potassium sparing) – Urine may look slightly blue in some lights Rifampicin – Urine Orange/Red Nitrofurantoin – Urine Orange/Brown Levodopa – Urine and other bodily fluids coloured Dark Red
DRUGS THAT CAUSE CONTACT SENSITISATION or PHOTOTOXICITY
Chlorpromazine - Healthcare professionals should avoid direct contact with this medication and tablets should not be crushed and solutions shoul d be handled with care. This is due to the risk of contact sensitisation. Avoid direct sunlight due to photo sensitisation. BNF page 221 Amiodarone – Causes phototoxicity and slate-grey skin discolouration. Due to the phototoxic reactions, patients should shield the skin f rom light during treatment and for several months after discontinuing treatment. A wide-spectrum sunscreen to protect against wide spectrum UV and visible light should be used. BNF page 94 Doxycycline - photosensitivity Azapropazone (NSAID) – photosensitivity.
CSM WARNINGS and ADVICE Gastro-Intestinal System Sucralfate - Bezoar formation (a mass of swallowed foreign material within the stomach) has been
reported and should therefore be used in caution for seriously ill patients. Extra care with those receiving concomitant enteral feeds or those with predisposing conditions such as delayed gastric emptying. BNF page 54 Pancreatin high strength preparations data recommendations. See BN F page 79-80
Cardiovascular system Beta-blockers (including cardioselective) should not be given to patients with history of asthma or
bronchospasm. However, in rare situations where there is no alternative a cardioselective betablocker is given with extreme caution under specialist care. BNF pag e 98 This is also true for the case of Beta-blocker eye drops . BNF page 687
Sotalol - The use of sotalol should be limited to the treatment of ventricular arrythmias or prophylaxis of supraventricular arrhythmias. It should no longer be used for angina, hypertension, thyrotoxicosis or for secondary prevention after myocardial infaction; when stopping sotalol for these indications, the dose should be reduced gradually. BN F page 99/104 Heparin - Hyperkalaemia: Inhibition of aldosterone secretion by heparin (including low molecular weight heparins) can result in h yperkalaemia; patients with diabetes mellitus, chronic renal f ailure, acidosis, raised plasma potassium or those taking potassium-sparing drugs seem to be more susceptible. The risk appears to increase with duration of therapy and the CSM has recommended that plasma-potassium concentration should be measured in patients at risk of hyperkalaemia before starting heparin and monitored regularly thereafter, particularly if heparin is to be continued for longer than 7 days. BNF page 140 Lipid-lowering drugs - Rhabdomyolysis associated with lipid-lowering drugs such as fibrates and statins is rare (1 case in every 100000 treatment years) but can be increased in those with renal impairment and possibly in those with hypothyroidism. Concomitant treatments with drugs that increase plasma-statin concentration increase the risk of muscle toxicity; concomitant treatment with a fibrate and a statin may also be associated with an increased risk of serious muscle toxicity. BNF pag e 162-164
Respiratory System Salbutamol - The CSM has advised that potentially serious hypokalaemia may result from beta 2
agonist therapy. Particular caution is required in severe asthma because this effect may be potentiated by concomitant treatment with theophylline and its derivatives, corticosteroids, and diuretics, and by hypoxia. Plasma-potassium concentration should therefore be monitored in severe asthma. BNF p age 177-178
Inhaled corticosteroids - The height of children receiving prolonged treatment of corticosteroids should be monitored. Large volume spacer devices should be used for administering inhaled corticosteroids under 5 year old children. BNF p age 186-188 Leukotriene receptor antagonists - Churg-Strauss syndrome (severe asthma with increased eosinophil count) has occurred very rarely in association with the use of leukotriene receptor antagonists; in many of the reported cases the reaction followed the reduction or withdrawal of oral corticosteroid therapy. The CSM has advised that prescribers should be alert to the development of eosinophilia, vasculitic rash, worsening pulmonary symptoms , cardiac complications, or peripheral neuropathy. BNF page 192 Bee and Wasp Allergen extracts/Grass and tree pollen extracts - The CSM has advised that facilities for cardiopulmonary resuscitation must be immediately available and patients monitored closely for one hour after each injection. BN F page 197-198
Central Nervous System Benzodiazepines a. Are indicated for short term relief (two to four weeks only) of anxiety that is
severe, disabling, or subjecting the individual to unacceptable distress, occurring alone or in association with insomnia or short-term psychosomatic, organic, or psychotic illness. b. The use of benzodiazepines to treat short-term ‘mild’ anxiety is inappropriate and unsuitable. c. They should be used to treat insomnia only when it is severe, disabling, or subjecting the individual to extreme distress. BNF page 210
Atypical Antipsychotics and Stroke – Olanzapine and Risperidone are associated with an increased risk of stroke in elderly patients with dementia. BNF page 219
Clozapine - a. Withdrawal b. Agranulocytosis c. Myocarditis and Cardiomyopathy d. GI obstruction. See Guidanc e BNF page 226 Hyponatraemia and Antidepressants - Hyponatraemia which is a low blood sodium concentration (usually in the elderly and possibly due to inappropriate secretion of antidiuretic hormone) has been associated with all types of antidepressants; however, it has been reported more frequently with SSRIs than with other antidepressants. The CSM has advised that hyponatraemia should be considered in all patients who develop drowsiness, confusion, or con vulsions while taking an antidepressant. BNF pag e 235
Depressive illness in Children - SSRI’s citalopram, escitalopram, paroxetine, and sertraline, and for mirtazipine and venlafaxine are unfavourable for under 18 years olds as clinical trials have failed to show efficacy and an increase in harmful outcomes. Only fluoxetine was found to be effective in clinical trials. Children and adolescence should be monitored carefully for suicidal behaviours. BNF page 242
Fluvoxamine - The CSM has advised that concomitant use of fluvoxamine and theophylline or aminophylline should usually be avoided. BNF page 242
Paroxetine - Extrapyramidal effects (including orofacial dystonias) and withdrawal syndrome are reported to the CSM more commonly with paroxetine than with other SSRIs. Also, the recommended dose for the treatment of depression, social anxiety disorder, generalised anxiety disorder, and post traumatic stress disorder is 20mg daily. For OCD and panic disorder it is 40mg daily. There is no evidence that higher doses are more effective. BNF pag e 245
Sumatriptan - Following reports of chest pain and tightness (coronary vasoconstriction) CSM has emphasised that sumatriptan should not be used in ischaemic heart disease or Prinzmental’s angina, and that use with ergotamine should be avoided. BNF page 277 Lamotrigine - Serious skin reactions including Steven-Johnson syndrome and toxic epidermal necrolysis have developed especially in children. Most rashes occur in the first 8 weeks. Rash is sometimes associated with hypersensitivity syndrome. Consider withdrawal if rash or signs of hypersensitivity syndrome develop. Factors associated with increased risk include concomitant use of valproate, initial lamotrigine dosing higher than recommended, and more rapid dose escalation than recommended. BNF page 290 Topiramate has been associated with acute myopia with secondary angle-closure glaucoma, typically occurring within one month of starting treatment. Choroidal effusions resulting in anterior displacement of the lens and iris have also been reported. The CSM advises that if raised intra-ocular pressure occurs then seek medical ophthalmic advice, use appropriate measures to reduce IOP and stop topiramate as rapidly as feasible. BNF pag e 294
Vigabatrin is associated with visual field defects. The CSM has advised that onset of symptoms varies from 1 month to several years after starting treatment. In most cases, visual field defects have persisted despite discontinuation. Product literature advises visual field testing before treatment and
at 6 month intervals; a procedure for testing visual fields in those with a developmental age of less than 9 years is available from the manufacturers. Patients should be warned to report any new visual symptoms that develop and those with symptoms should be referred for urgent ophthalmic opinion. Gradual withdrawal of vigabatrin should be considered. BNF pag e 297
Dopamine Receptor Agonists – The CSM has advised that ergot-derived dopamine receptor agonists, bromocriptine, cabergoline, lisuride and pergolide have been associated with pulmonary, retroperitoneal, and pericardial fibrotic reactions. Before starting treatment with these ergot derivatives it may be appropriate to measure the erythrocyte sedimentation rate and serum creatinine and to obtain a chest X-ray. Patients should be monitored for dyspnoea, persistent cough, chest pain, cardiac failure, and abdominal pain or tenderness. BNF p age 302 Buproprion (Zyban) - The CSM has issued a reminder that bupropion is contra-indicated in patients with a history of seizures or of eating disorders, a CNS tumour, or who are experiencing acute symptoms of alcohol or benzodiazepine withdrawal. Bupropion should not be prescribed to patients with other risk factors for seizures unless the potential benefit of smoking cessation clearly outweighs the risk. Factors that increase the risk of seizures include concomitant administration of drugs that can lower the seizure threshold (e.g. antidepressants, antimalarials [such as mefloquine and chloroquine], antipsychotics, quinolones, sedating antihistamines, s ystemic corticosteroids, theophylline, tramadol), alcohol abuse, history of head trauma, diabetes, and use of stimulants and anorectics. BNF page 316
Infections Flucloxacillin - Very rarely, cholestatic jaundice and hepatitis may occur up to several weeks after
treatment with Flucloxacillin has been stopped. Administration for more than 2 weeks and increasing age are risk factors. CSM remind that flucloxacillin should not be used in patients with a history of hepatic dysfunction associated with flucloxacillin, it should be used with caution in patients with hepatic impairment and careful enquiry should be made about hypersensitivity reactions to betalactam antibacterials. BNF pag e 342 Co-Amoxiclav - CSM has advised that cholestatic jaundice can occur either during or shortly after the use of co-amoxiclav. An epidemiological study has shown that the risk of acute liver toxicity was about 6 times greater with co-amoxiclav than with amoxicillin. Cholestatic jaundice is more common in patients above the age of 65 years and in men; these reactions have only rarely been reported in children. Jaundice is usually self-limiting and very rarely fatal. The duration of treatment should be appropriate to the indication and should not usually exceed 14 days. BNF page 344
Linezolid - Haematopoietic disorders (thrombocytopenia, anaemia, leucopenia, and pancytopenia – simultaneous decrease in the blood cells) have been reported in patients receiving linezolid. It is recommended that full blood counts are monitored weekly. Close monitoring is recommended in patients who a. Receive treatment for more that 10 to 14 days. b. Have pre-existing myelosupression. (may need to stop treatment unless considered essential) c. Are receiving drugs that may have adverse effects on haemoglobin, blood counts, or platelet function. d. Have severe renal impairment. BNF page 366
Linezolid – Severe optic neuropathy may occur rarely, particularly if used for longer than 28 days. It is recommended that visual impairment is reported immediately, evaluated promptly and monitored regularly (if treatment is longer than 28 days). BNF p age 366
Co-trimoxazole is associated with rare but serious side effects e.g. Stevens-Johnson syndrome (serious allergic skin reaction) and blood dyscrasias (blood problems), notably bone marrow depression and agranulocytosis (marked decrease in number of granulocyte white blood cells). It should only be used where there is good reason. See BNF page 367
Quinolones – Tendon damage (including rupture) has been reported with patients receiving quinolones. Tendon damage may occur within 48 hours of starting treatment. CSM reminds that a. Quinolones are CI in patients with tendon disorders relating to quinolones use, b. Elderly patients are more prone to tendinitis, c. The risk of tendon rupture is increased by the concomitant use of corticosteroids. d. If tendinitis is suspected, the quinolones should be discontinued. BNF page 376
Quinolones in Children – cause arthropathy (Joint disorders) in the weight bearing joints of immature animals. Therefore generally not recommended in children and growing adolescence. However, the significance of this effect in humans is uncertain and in some specific circumstances short term use of quinolones in children may be justified. Nalidixic acid is used for UTIs in children over 3 months of age. Ciprofloxacin is licensed for pseudomonal infections in cystic fibrosis (for children above 5 years old) and for treatment and prophylaxis of inhalational anthrax. BNF page 377
Quinolones and Convulsions - CSM have warned that quinolones m ay indice convulsions in patients with or without a history of convulsions. Taking NSAIDs at the same time may also induce them. Therefore should also be used with caution in epileptics BNF p age 377 Amphotericin B – The CSM have advised that anaphylaxis occurs rarely with any intravenous amphotericin product and a test dose is advisable before the first infusion. The patient should be carefully observed for at least 30 minutes after the test dose. Prophylatic antipyretics and hydrocortisone should only be used in patients who have previously experienced acute adverse reactions (in whom continued treatment with amphotericin is essential). BNF page 386
Itraconazole - Rare reports of heart failure have been reported. CSM advise caution when
prescribing itraconazole to patients at high risk of heart failure. Those at risk include Patients receiving high doses and long courses, older patients and those with cardiac disease and patients receiving treatment with negative inotropic drugs e.g.. calcium channel blockers. BNF page 383 Ketoconazole – Associated with fatal hepatotoxicity. The CSM advise that prescribers should weigh the potential benefits of ketoconazole treatment against the risk of liver damage and should carefully monitor patients both clinically and biochemically. It should not be used by mouth for superficial fungal infections. The risk of this greater if given for longer than 10 days. BNF page 385
Mefloquine (Lariam) – CSM have advised that travellers should be informed about adverse reactions to mefloquine (nausea, vomiting, diarrhoea, abdominal pain, dizziness, loss of balance, headache, and sleep disorders) and if these occur, medical advice should be sought on alternative antimalarials before the next dose is due. The PIL should always be provided when dispensing mefloquine. BNF p age 416-417
Endocrine System Carbimazole (antithyroid drug) - Doctors are reminded of the importance of recognising bone
marrow suppression induced by Carbimazole and the need to stop treatment promptly. a. Patients should be asked to report symptoms and signs suggestive of infection, especially sore throat. b. A white blood cell count should be performed if there is any clinical evidence of infection . c. Carbimazole should be stopped promptly of there is clinical or laboratory evidence of neutropenia. BNF page 449
Steroids - CSM advice on chickenpox, withdrawal, pregnancy and breast feeding see BNF p age 453-455 HRT - BNF page 458 Desmopressin (posterior pituitary hormone for diabetes) can cause hyponatraemic convulsions (low sodium in blood, occurs in dehydration). Patients being treated for primary nocturnal enuresis should be warned to avoid fluid overload (including swimming) and stop taking desmopressin during episodes of vomiting and diarrhoea. BNF p age 475-476
Gynaecology Medroxyprogesterone acetate (Depo-Provera) be used only when other methods of
contraception are inappropriate. In all women, benefits of using medroxyprogesterone acetate beyond 2 years should be evaluated against risks (as reduction in bone mineral density has been reported). In women with risk factors for osteoporosis a method of contraception other than medroxyprogesterone acetate should be considered. BNF page 510
Spermicidal contraceptives - Products such as petroleum jelly (Vaseline), baby oil, oil based vaginal and rectal preparations are likely to damage condoms and contraceptive diaphragms made from latex rubber, and may render them less effective as a barrier method of contraception and as a protection from sexually transmitted diseases (including HIV). BNF page 512
Co-Cyprindiol (Dianette) - Venous thromboembolism occurs more frequently in women taking co-cyprindiol than those taking a low-dose combined oral contraceptive. The CSM has reminded prescribers that co-cyprindiol is licensed for use in women with severe acne which has not responded to oral antibacterials and for moderately severe hirsutism; it should not be used solely for contraception. It is contra-indicated in those with a personal or close family history of venous thromboembolism. Women with severe acne or hirsutism may have an inherently increased risk of cardiovascular disease. BNF pag e 742
Cytotoxic drugs Guidelines on handling cytotoxic drugs:
1. 2. 3. 4. 5. 6.
Trained personnel should reconstitute cytotoxics Reconstitution should be carried out in designated areas Protective clothing (including gloves) should be worn The eyes should be protected and means of first aid should be specified Pregnant staff should not handle cytotoxics Adequate care should be taken in the disposal of waste material, including syringes, containers, and absorbent material. BNF pag e 527
Tacrolimus (prophylaxis of organ rejection) - Cardiomyopathy has been reported in children given tacrolimus after transplantation. Patients should be monitored carefully. BNF pag e 569 Tamoxifen is linked with a small risk of endometrial cancer but patients can be told that the benefits far outweigh the risks. A 20mg dose daily substantially increases survival in early breast cancer. Also note tamoxifen is linked with endometrial changes and thromboembolism (report any sudden breathlessness or pain in the calf of one leg) BNF p age 582-583
Nutrition Thiamine IV - reports potentially serious allergic adverse reactions.
BNF pag e 628
Musculoskeletal and Joint diseases: NSAIDs and GI side effects - See BNF p age 642-644 NSAIDs and asthma - Any degree of worsening of asthma may be related to the ingestion of
NSAIDs either prescribed or (in the case of ibuprofen and others) purchased over the counter. B N F page 644
Azapropazone (NSAID for pain and inflammation in rheumatic disease) CSM has restricted its use to rheumatoid arthritis, ankylosing spondylitis (inflammation of synovial joints in the backbone) and acute gout only where other NSAIDs have been tried and failed. It is CI in patients with history of peptic ulceration and the maximum daily dose is now reduced to 600mg for RA and ankylosing spondylitis in patients over 60 years and those with renal impairment. Not in B NF 62
Tiaprofenic acid (NSAID for pain and inflammation in rheumatic disease) - has had reports of severe cystitis. Tiaprofenic acid should not be given to patients with urinary-tract disorders and should be stopped if urinary symptoms develop. Patients should be advised to stop taking tiaprofenic acid and to report to their doctor promptly if they develop urinary-tract symptoms (such as increased frequency, nocturia, urgency, pain and urinating, or blood in urine). BNF page 652
Methotrexate - Blood count, liver toxicity, pulmonary toxicity, with aspirin and other NSAIDs. See BNF p age 658-659 Baclofen (skeletal muscle relaxant – for severe spasticity e.g. multiple sclerosis) The CSM have advised that serious side effects can occur on abrupt withdrawal. To minimise risk, discontinue by gradual dose reduction over at least 1 to 2 weeks (longer if symptoms occur). BNF page 672
Nutrition Co-cyprindiol – Venous thromboembolism occurs more frequently in women taking co-cyprindiol
than those taking low-dose combined oral contraceptive. Reserved for women with severe acne or hirsutism. BNF page 742
KEY COUNSELLING POINTS – ON DRUGS Gastro-Intestinal System Antacids - a. They are best taken when symptoms occur or are expected, usually between meals or at bedtime. b. They should preferably not be taken at the same time as other drugs since they may impair absorption. c. Antacids can damage enteric coatings on tablets. d. The words ‘low Na+’ added after some preparations indicates a sodium content of less than 1mmol per tablet or 10ml dose. This is directed for people with hypertension. BNF p age 44-46 Ispaghula - Preparations that swell in contact with liquid should always be carefully swallowed with water and should not be taken immediately before going to bed. BNF
page 68
Liquid Paraffin should not be taken immediately before going to bed. BNF
page 71
Cardiovascular system Nitrate Tolerance - Patients on long acting nitrates can rapidly develop tolerance (reduce therapeutic effect). Reducing the nitrate concentration in the blood for 4 to 8 hours each day usually maintains effectiveness e.g. by giving twice daily preparations after 8 hours then after 16 hours. BNF page 125 Glyceryl Trinitrate Sublingual Tablets – GTN tablets should be supplied in glass containers of not more than 100 tablets, closed with a foil-lined cap, and containing no cotton wool wadding (i.e. the original container). They should be discarded after 8 weeks. They should be placed under the tongue to dissolve. Dosing is ‘when required’. BNF page 125 GTN spray – Spray one to two doses under the tongue then close mouth. This should relieve the pain within a minute or so. If no improvement after 5 minutes then use it again. If no improvement, then use again after 5 more minutes. Then if no improvement despite using the spray 3 times within 15 minutes, call an ambulance.
Respiratory System Salbutamol inhalation - Advise patients not to exceed the stated dose. If a previously effective dose of inhaled salbutamol fails to provide at least 3 hours relief, a doctor’s advice should be obtained as soon as possible. BNF page 180 CFC-free inhalers - Patients receiving CFC-free inhalers should be reassured about their efficacy and counselled that aerosol may feel and taste different. BNF page 187 Ipratropium - Acute angle-closure glaucoma reported with nebulised Ipratropium, particularly when given with nebulised salbutamol (and possibly other beta 2 agonists). Care is needed to protect patient’s eyes from nebulised drug or from drug powder. BNF page 182 Corticosteroid Inhalers - The risk of oral candidiasis can be reduced by rinsing the mouth with water after using the inhaler or by using a spacer device. BNF page 187
Central Nervous System Patients taking MAOIs (including Linezolid) should avoid large amounts of Tyramine rich foods as it can cause a hypertensive crisis. An early warning symptom may be a throbbing headache. The danger of interaction persists for up to 2 weeks after treatment with MAOIs is discontinued. Tyramine rich foods include mature cheese, pickled herring, broad bean pods, Bovril, Oxo, Marmite or any similar meat or yeast extracts, undistilled alcohol beverages, and fermented soya bean products. Patients also need to avoid stale or ‘going off’ foods and stick to eating fresh foods. Alcoholic drinks need to be avoided (including drinks with low alcohol content). Note that no tyramine at all can cause hypotension. BNF p age 240-241
Epileptic Medication summarised – Carbamazepine and Oxcarbazepine linked with Blood, Hepatic and Skin disorders reported (Patients and their carers need to be able to recognise signs of blood, liver, or skin disorders). Ethosuximide linked with Blood disorders. Lamotrigine linked with Blood and Skin reactions. Phenytoin linked with Blood and Skin disorders. Topiramate linked with Myopia with secondary angleclosure glaucoma. Sodium Valproate linked with Liver toxicity, Blood or Hepatic disorders and Pancreatitis (Patients need to know how to recognise signs of pancreatitis – abdominal pain, nausea and vomiting). Vigabatrin linked with visual field defects. B N F section 4.8.1
Parkinson’s disease – Excessive daytime sleepiness and sudden onset of sleep can occur with co-careldopa, co-beneldopa, and dopamine receptor agonists. Patients starting treatment should be warned of the possibility of these effects and the need to exercise caution when driving or operating machinery. Patients, who have suffered excessive sedation or sudden onset of sleep, should refrain f rom driving or operating machinery until the effects have stopped. BNF page 302 Disulfiram (treatment of alcohol dependence) – Patients should be aware of unpredictable and occasionally severe nature disulfiram -alcohol interactions. Reactions can occur within 10 minutes and last several hours which may require oxygen therapy. Patients should not ingest alcohol at all and should be warned of possible presence of alcohol in liquid medicines, remedies, tonics, foods and even toiletries (alcohol should be avoided at least one week after therapy has stopped). BNF page 315
Infection Malaria prophylaxis - Travellers need to be warned about the importance of avoiding mosquito bites and importance of taking prophylaxis regularly and importance of immediate visit to doctor if ill within one year and especially within 3 months of return. BNF p age 410-419
Endocrine System Insulin: A. Wash hands before using a blood glucose monitor. B. Beware of problems with absorption as a hot climate or exercise can increase the absorption of insulin and a cold climate or cool skin can reduce it. Absorption is most rapid from the abdomen and slowest from the thigh. C. Avoid diabetic foods as a healthy diet is more important. Diabetic foods substitute sorbitol for glucose and are there for the occasional treat. D. Check feet daily and wear appropriate footwear. Do not treat any foot conditions yourself – consult a chiropodist or doctor. E. Be aware of retinopathy. F. Sick day rules: Common illness can upset diabetic control. Consult urgent medical help immediately if vomiting, drowsiness or deep rapid breathing occurs. Do not stop taking insulin or oral hypoglycaemics. Test blood glucose every 2 to 4 hours. Drink plenty of fluids to prevent dehydration. If not able to eat then take Lucozade or sugar containing drinks. G. Travelling with Insulin: use a cool bag for carrying the insulin. On long haul flights, inject before eating and carry extra carbohydrates. Test more regularly. Acarbose - Tablets should be chewed with first mouthful of food or swallowed whole with a little liquid immediately before food. To counteract possible hypoglycaemia, patients receiving insulin or a sulphonylurea as well as acarbose need to carry glucose (but not sucrose – acarbose interferes with sucrose absorption). BNF page
440
Alendronic acid (osteoporosis) - Tablets should be swallowed whole with plenty of water while sitting or standing; to be taken on an empty stomach at least 30 minutes before breakfast (or another oral medicine); patient should stand or sit upright for at least 30 minutes after taking tablet. Also, patients should stop taking tablets and seek medical attention if they develop symptoms of oesophageal irritation such as Dysphagia, new or worsening heartburn, pain on swallowing or retr osternal pain. BNF p age 480-481
D i d r o n e l P MO (osteoporosis) – Avoid food for at least 2 hours before and after oral
treatment, particularly calcium containing products such as milk; al so avoid iron, mineral supplements and antacids. BNF page 482 Risedronate (osteoporosis) - Tablets should be swallowed whole with plenty of water while sitting or standing; to be taken on an empty stomach at least 30 minutes before breakfast (or another oral medicine); patient should stand or sit upright for at least 30 minutes after taking tablet. Granules should be stirred into a glass of water and after dissolution complete taken immediately. BNF page 483
Gynaecology Oral contraceptives – see indications section Prazosin (urinary retention)- First dose effect – where the first dose may cause collapse due to hypotensive effect (therefore should be taken on retiring to bed). Patient should be warned to lie down if symptoms such as dizziness, fatigue or sweating develop, and to remain lying down until they are abate completely. BNF
page 516
Drugs Affecting Immune Response Ciclosporin (potent immunosuppressant e.g. for organ transplantation – brand Neoral) – Total daily dose should be taken in 2 divided doses. Avoid grapefruit or grapefruit juice for one hour before dose. For oral solution - Mix the solution with orange juice (or squash) or apple juice (to improve taste) or with water immediately before taking (and rinse with more to ensure total dose). Do not m ix with grapefruit juice. Keep the medicine measure away from other liquids (including water) BNF page
566-568
Skin Isotretinoin (oral retinoid for severe acne) – Warn patient to avoid wax epilation (risk of epidermal stripping), dermabrasion, and laser skin treatment (risk of scarring) during treatment and for at least 6 months after stopping; patient should avoid exposure to UV light (including sunlight) and use sunscreen and emollient (including lip balm) preparations from the start of treatment. Take tablets with or after food. B N F
pag e 742-743
COUNSELLING and IMPORTANT POINTS ON ANTIBIOTICS Penicillin
V, Flucloxacillin, Ampicillin - Label 9: regular Intervals and complete the course.
Label 23: an hour before food or on an empty stomach. Amoxicillin - Unlike Ampicillin, absorption is not affected b y the presence of food. Label 9: regular Intervals and complete the course. Cephalosporins (Cefaclor, Cefalexin) - Label 9: regular Intervals and complete the course. Tetracycline, Oxytetracycline - Label 7: Do not take milk, indigestion remedies, or medicines containing iron or zinc at the same time of day as this medicine (prevents absorption of the antibiotic and should be taken 2-3 hours apart) Label 9: regular Intervals and complete the course. Label 23: an hour before food or on an empty stomach. Doxycycline - Label 6: Do not take indigestion remedies or medicines containing iron or zinc at the same time of day as this medicine. Label 9: regular Intervals and complete the course. Label 11:
Avoid exposure of skin to direct sunlight or sun lamps. Label 27: With plenty of water. C: Capsules should be swallowed whole with plenty of fluid during meals while sitting or standing. Lymecycline - Label 6: Do not take indigestion remedies or medicines containing iron or zinc at the same time of day as this medicine. Label 9: regular Intervals and complete the course. Minocycline - Label 6: Do not take indigestion remedies or medicines containing iron or zinc at the same time of day as this medicine. Label 9: regular Intervals and complete the course. C: Tablets or capsules should be swallowed whole with plenty of fluid during m eals while sitting or standing. Erythromycin - Label 5: Do not take indigestion remedies at the same time of day as this medicine.(should be taken 2-4 hours apart) Label 9: regular Intervals and complete the course. Label 25: swallowed whole, not chewed. Clindamycin - Label 9: regular Intervals and complete the course. Label 27: with plenty of water. C: Patients should discontinue immediately and contact the doctor if diarrhoea develops; capsules should be swallowed with a glass of water. Trimethoprim - Label 9: regular Intervals and complete the course. C: Watch out for signs of blood dyscrasias i.e. sore throat. Rifampicin - Label 8: Do not stop taking this medicine except on your doctor’s advice. Label 14: This medicine may colour the urine. Label 22: Half to one hour before food. C: Watch out for signs of liver toxicity i.e. nausea, vomiting, malaise, jaundice. Metronidazole - Label 4: Warning. Avoid alcoholic drink. Label 9: regular Intervals and complete the course. Label 21: with or after food. Label 25: swallowed whole, not chewed. Label 27: with plenty of water. Ciprofloxacin - Label 7: Do not take milk, indigestion remedies, or medicines containing iron or zinc at the same time of day as this medicine. Label 9: regular Intervals and complete the course. Label 25: swallowed whole, not chewed. C: Driving – may impair performance of skilled tasks e.g. driving. Effects are enhanced by alcohol. Nitrofurantoin - Label 9: regular Intervals and complete the course. Label 14: This medicine may colour the urine. Label 21: with or after food.
DRUGS THAT REQUIRE COUNSELLING ON REPORTING SORE THROAT – RISK OF BLOOD DYSCRASIAS Patients or their carers need to be able to recognise signs of blood dyscrasias such as agranulocytosis so that they know when to seek immediate medical at tention. Symptoms include sore throat, fever, malaise, rash, mouth ulcers, bruising or bleeding:
Aminosalicylates (e.g. Mesalazine, Sulfasalazine) Full blood count should be performed and the drug stopped immediately if there is suspicion of a blood dyscrasias.
Mirtazapine Carbamazepine Ethosuximide Phenytoin Sodium valproate Co-trimoxazole Trimethoprim Carbimazole Gold (Drug for rheumatic disease) Penicillamine (Drug for rheumatic disease) Methotrexate Azathioprine (transplant recipient) Bone marrow suppression – patients should be warned to report any signs or symptoms of bone marrow suppression e.g. inexplicable bruising, bleeding or infection.
HEPATOTOXIC DRUGS
Labetalol – Severe hepatocellular damage reported after both short-term and longterm treatment. Appropriate lab testing needed at first sign of symptom of liver dysfunction. If lab evidence of damage present; or jaundice, labetalol should be stopped and not restarted. BNF page 102 Sodium Valproate – reported usually in the first 6 months and usually with multiple antiepileptic therapies. Monitoring for liver function is important. BNF page 295 Rifampicin and Isoniazid – patients and their carers need to know how to recognise signs of liver disorders and should be advised to discontinue treatment and seek immediate medical attention if symptoms such as persistent nausea, vomiting, malaise or jaundice. BNF page 372 & 373 Itraconazole - patients should be told how to recognise signs of liver disorder and advised to seek prompt medical attention if symptoms such as anorexia, nausea, vomiting, fatigue, abdominal pain, jaundice or dark urine develop. BNF page 383 Pioglitazole - rare reports of liver dysfunction reported. BNF Page 442 Cyproterone (Prostate cancer treatment) - Direct hepatic toxicity; including jaundice, hepatitis and hepatic failure have been reported. BNF Page 586 Leflunomide (rheumatoid arthritis) BNF Page 658 Methotrexate BNF Page 659 Halothane for anaesthesia has had reports of severe hepatotoxicity. BNF Page 795
RENAL FUNCTION
Reduced renal excretion of a drug or its metabolites can cause toxicity. Therefore the dose may need to be adjusted. Renal function is measured by GFR (Glomerular Filtration Rate) or it can be expressed by CCL (Creatinine Clearance). In the Open Book Exam, calculations will involve Creatinine Clearance values to be determined using the formula. This value can then be used to decide whether the dose needs to be adjusted or whether the patient should avoid the medication in the question – Prescribing in Renal Impairment – BNF Pag e 17-18
DRUGS WITH WARNING CARDS
Lithium Warfarin MAOI’s Steroids
DRUGS WHERE THE SAME BRAND NEEDS TO BE PRESCRIBED Different drug versions of e.g. modified release preparations may not have the same clinical effect. To avoid confusion between different formulations, the same brand should be specified by the prescriber.
Lithium Theophylline and Aminophylline Diltiazem and Nifedipine
DRUGS WITH DRIVING WARNINGS
Epilepsy - Patients suffering from epilepsy may drive a motor vehicle provided they have been seizure free for one year. If subject to having attacks only while asleep, they should have had no awake attacks within 3 years. BNF p age 283 Diabetes - Drivers need to notify the DVLA of their condition. Driving is not permitted when hypoglycaemic episodes occur. Drivers should check t heir blood glucose levels before driving and at 2 hour intervals on long journeys. If hypoglycaemia occurs – stop the vehicle in a safe place, switch off the ignition, eat or drink a suitable source of sugar and wait until recovery before continuing journey. This may take 15 minutes or longer which should preferably be confirmed by checking bloodglucose concentration. BNF page 427
DRUGS AND SURGERY
D r u g s n o r m a l l y N O T S TO P P ED b e f o r e s u r g e r y : BNF pag e 675
Antiepileptics Antiparkinsoniun drugs Antipsychotics and Anxiolytics Bronchodilators Cardiovascular drugs - Potassium sparing diuretics may need to be stopped on morning of surgery because hyperkalaemia may develop if renal perfusion is impaired or if there is tissue damage. ACE inhibitors and Angiotensin II antagonists can be associated with severe hypotension after induction of anaesthesia and therefore may need to be discontinued 24 hours before surgery. Beta blockers shouldn’t be stopped suddenly and can be continued. Drugs for dependence Glaucoma drugs Immunosuppressants Progestogen only contraceptives - All are suitable before and after surgery even for surgery that involves prolonged immobilisation of the lower limb. Thyroid or antithyroid drugs
O t h er S u r g e r y P o i n t s o n D r u g s
Antidepressants - Lithium Should be stopped 24 hours before major surgery. Normal dose can be continued for minor surgery. MAOI should not be withdrawn suddenly as there is risk of withdrawal symptoms. Gradual withdrawal is advised and they should be stopped 2 weeks before the surgery. TCA do not need to be stopped before surgery but there is a risk of arrhythmias and hypotension, therefore the anaesthetist should be informed if they are not stopped. Aspirin or Oral anticoagulant - Needs to stop because increased risk of bleeding. It may need to be replaced by heparin therapy to prevent blood clotting. Combined hormonal contraceptives – Should be stopped 4 weeks before major elective surgery and all surgery to the legs or surgery which involves prolonged immobilisation of the lower limb. Can be recommended again 2 weeks after full mobilisation. If the COC cannot be stopped (e.g. trauma surgery) then heparin and graduated compression hosiery is advised. These recommendations do not apply for minor surgery. (Stop HRT 4 to 6 weeks before surgery and restart full mobilisation) BNF page 460 Diabetes - Give an injection of the patient’s usual insulin on the night before operation. Early on the day of the operation, give an infusion of glucose with potassium and insulin on a sliding scale. Once the patient begins to eat, start SC insulin before breakfast and stop IV insulin 30 minutes later. BNF page 429
D r u g s t o h e l p w i t h t h e s u r g e ry :
H2 receptor antagonist (1 to 2 hours before surgery) or a Proton pump inhibitor such as Omeprazole (12 hours before surgery) may be used before surgery to increase the pH and reduce the volume of gastric fluid to prevent acid aspiration from general anaesthetics. Antimuscarinic drugs like hyoscine reduce saliva secretion to prevent lung congestion. Benzodiazepines - Relief of anxiety, sedation and amnesia. Antibiotics may be given for prophylaxis of infection depending of the likely organisms which could cause infection. Post-operatively - Pain Relief, Heparin to prevent DVT, Nausea and vomiting management. Driving - IV benzodiazepines and short general anaesthetics can extend risks for at least 24 hours after administration.
PREGNANCY Foods to Avoid:
Soft and blue veined cheeses All types of pâté (and any liver products) Raw eggs, partially raw eggs – e.g. homemade mayonnaise .
Raw meat
Fish - shark, swordfish, marlin
Social Drugs: Alcohol - 1st and 2nd trimesters - Regular daily intake is teratogenic (foetal alcohol syndrome) and rd may cause growth restriction; occasional single drinks are probably safe. In the 3 trimester
withdrawal syndrome may occur in babies of alcoholic mothers.
Smoking - Can cause vasoconstriction, hypoxia, low birth weight, premature birth or perinatal birth. Caffeine - Limit intake to 2 cups per day. A high intake can possibly increase miscarriage and stillbirth rate.
Gastro Intestinal System Misoprostol (for NSAID-induced ulcers) - Should not be used in women of childbearing age
unless the patient requires NSAID therapy and is at a high risk of complications from NSAID-induced ulceration. In such patients, it is advised that misoprostol should only be used if the patient takes effective contraceptive measures and has been advised of the risks if pregnant. Misoprostol in all trimesters must be avoided. It is a potent uterine stimulant (has been used to induce abortion) and may be teratogenic.
Omeprazole is the only PPI that is not known to be harmful. H2 antagonists should be avoided unless essential. Loperamide – Should be avoided. Oral Rehydration Salt preparations can be used to replace lost fluid.
Simple antacids – are appropriate for pregnant women e.g. Gaviscon. Avoid those with high content of sodium as a high salt content can cause a rise in blood pressure.
Bulk forming laxatives – are appropriate for pregnant women e.g. Fybogel. Osmotic laxatives – Lactulose is not known to be harmful. Macrogols should be avoided unless essential as no information is available.
Stimulant laxatives – Avoid as no information available. Haemorrhoid treatments - Local therapies are appropriate but avoid steroids.
Cardiovascular System Hypertension – Methyldopa is a centrally acting antihypertensive and is the treatment of choice
for hypertension in pregnancy and also pre-eclampsia. Pre-eclampsia is pregnancy induced hypertension which can cause hypertensive crisis.
Heparin - Do not cross placenta but LMWH preferred. i.e enoxaparin not known to be harmful. Warfarin - Teratogenic; should not be given in the first trimester. (Congenital malformations, Fetal and neonatal haemorrhage).
Statins - should be avoided as a decreased synthesis of cholesterol possibly affects fetal development. Congenital abnormalities have been reported.
Respiratory System Inhaled bronchodilators - Safe in pregnancy Inhaled corticosteroids - Benefit of treatment in asthma, outweighs risk. Risk of intra-uterine
growth restriction on prolonged or repeated systemic treatment. Corticosteroid cover may be required by the mother during labour. Monitor closely if fluid retention occurs.
Central Nervous System Epilepsy - Benefit of treatment outweighs risk to foetus. Risk of teratogenicity is greater if more
than one drug is used. Adequate folate supplements are advised for women before and during pregnancy to counteract the risk of neural tube defects. Regular monitoring of serum levels is important. Prophylactic vitamin K can help stop bleeding complications on delivery. Routine injection of vitamin K at birth effectively counteracts any antiepileptic associated risk of neonatal haemorrhage. Breastfeeding is acceptable with almost all antiepileptic drugs taken in normal doses. BNF page 247
Analgesics - Paracetamol is safe in pregnancy although advise ‘when required’ use only. Ibuprofen and Aspirin are contraindicated in pregnancy.
Opioid analgesics are contraindicated in the 3rd trimester because they depress neonatal respiration. Can lead to withdrawal effects in neonates of dependent mothers, gastric stasis and risk of inhalation pneumonia in the mother during labour. Morning sickness – Promethazine (antihistamine) may be required for short term treatment as first line therapy. Prochlorperazine or metoclopramide may be considered second line therapy.
Infections: Penicillins, Cephalosporins, Erythromycin, Clindamycin are NOT known to be harmful in pregnancy. Tetracyclines - 1st Trimester animal studies show effects on skeletal development. In 2nd and 3rd trimester dental discolouration and maternal hepatotoxicity found with large parenteral doses. Aminoglycosides can cause auditory or vestibular nerve damage. The risk is greatest with
streptomycin. It is probably very small with gentamycin and tobramycin, but avoid unless essential. If nd rd given, serum aminoglycoside concentration monitoring is essential. Risk in the 2 and 3 trimester.
Macrolides (except erythromycin) Manufacturer advises use only if potential benefit outweighs risk. Co-trimoxazole has teratogenic (developmental abnormalities of the foetus) risk in the 1st rd trimester because Trimethoprim is a folate antagonist. In the 3 trimester, there is risk of neonatal haemolysis and methaemoglobinaemia (presence of methaemoglobin in the blood which cannot bind to oxygen and therefore cannot transport it round the body). Trimethoprim = teratogenic.
Rifampicin - 1st trimester very high doses show to be teratogenic in animal studies. 3rd trimester there is risk of neonatal bleeding being increased.
Metronidazole - Manufacturer advises avoidance of high-dose regimens. Quinolones - Avoid in all trimesters due to arthropathy (joint disorders) in animal studies. Nitrofurantoin - May produce neonatal haemolysis in the 3rd trimester.
Endocrine System Oral antidiabetic drugs - Avoid as can cause neonatal hypoglycaemia. Insulins are substituted
during pregnancy in all diabetics. If oral drugs are used then they should be stopped at least 2 days before delivery.
Finasteride - Avoid in all trimesters as can cause feminisation of the male foetus. Finasteride is excreted in semen and use of a condom is recommended if sexual partner is pregnant or likely to
become pregnant. Women of child bearing age should avoid handling crushed or broken tablets. BNF page 401
Gynaecology Combined oral contraceptive – can be started 3 weeks after child birth (risk of thrombosis if
started earlier)
Progestogen only contraceptive – start at any time after 3 weeks of child birth (increased risk of breakthrough bleeding if started earlier).
Cystitis – A suspected UTI should be referred. Sodium bicarbonate and sodium citrate are not advised for pregnancy due to their high sodium content. Potassium citrate can be used.
Musculoskeletal and Joint diseases Methotrexate – avoid (teratogenic; fertility may be reduced during therapy but this may be
reversible). Manufacturer advises effective contraception use during and for at least 3 months after treatment has been stropped for both men and women.
BREASTFEEDING
Bromocriptine (dopamine receptor agonist) suppresses lactation Combined oral contraceptive is not recommended in breast feeding because oestrogens have adverse effects on lactation – The progestogen only pill is preferred.
Metronidazole - produces a bitter metallic milk taste. Aspirin - Avoid as can cause Reye’s syndrome. Lithium - Avoid as can cause toxicity in infant.
POPULAR CONTRAINDICATIONS
Tetracyclines are contraindicated in children under 12 years old and pregnant because deposition of tetracyclines in growing bone and t eeth (by binding to calcium) causes staining (yellow/grey) and occasionally dental hypoplasia, which could be permanent. Quinolones can cause joint disorders in children and should therefore not be recommended. Aspirin is contraindicated in children under 16 years old.- Reye’s syndrome NSAIDs are contraindicated in patients with history of sensitivity to aspirin. Salicylate salt products (Bonjela, Bonjela cool) – not suitable for under 16 years of age due to Reye’s syndrome. (New Law)
HOSPITAL PHARMACY and KEY PARAMETERS Blood Pressure Normal Blood Pressure Value: 120/80 High Blood Pressure (Hypertension in a non-diabetic patient): 140/90 or above High Blood Pressure (Hypertension in diabetic patient): 130/80 or above Normal Pulse: 60 to 80 beats per minute INR: International Normalised Ratio is the method of expressing the time it takes for blood to clot. Target INR values usually range between 2 and 3.5 for medical conditions such as DVT, Atrial fibrillation etc. So an I NR which is very high (possibility of bleeding) would mean that the Warfarin dose needs to be reduced. For an INR which is lower than the target set by the clinic, the Warfarin dose would need to be increased (possibility of coagulation).
Blood Glucose: Normal Blood Glucose Range: 4 to 9mmol/litre Normal Range Before Meals: 4 to 7mmol/litre Normal Range After meals: < 9mmol/litre Considered HIGH if Fasting Blood Glucose >7mmol/litre Cholesterol Desirable Lipid Profile (Targets): Total Cholesterol: < 5mmol/L LDL Cholesterol: < 3mmol/L Serum Triglycerides: < 1.7mmol/L HDL Cholesterol: > 1.0mmol/L Alcohol Units: A large Glass of wine (250ml) = 3 units A standard Glass of wine (175ml) = 2 units A small Glass of wine (100ml) = 1 unit Half a pint of 3.5% beer, lager, cider = 1 unit A single shot of 40% spirit (25ml) = 1 unit A single measure of whiskey = 1 unit A standard measure Port, Sherry (50ml) = 1 unit BMI: BMI less than 18.5 – underweight BMI between 18.5 and 24.9 – normal weight BMI between 25.0 and 29.9 – overweight BMI 30.0 or above – obese Electrolytes: Sodium: 136 – 146mmol/L Potassium: 3.5 – 5.1mmol/L Calcium: 2.15 – 2.5mmol/L Magnesium: 0.7 – 1.0mmol/L Urea: 2.5 – 6.4mmol/L Creatinine clearance (CCL) Men: 97 – 140ml/min, Women: 85 – 125ml/min Hospital Abbreviations:
PC = Presenting Complaint PMH = Patient Medical History SH = Social History DHx = Drug History O/E = On Examination CVS = Blood Pressure and Pulse R/S = Respiratory system GIT = Gut
Hospital Charts
Patient Details Allergies section Drugs for ‘once only’ or ‘pre-anaesthetic medication’ MEDICATIONS SECTION -
Drug and strength Date Route (PO, top, inh, sc, iv, im) Time of day Dose according to the time of day (denoted by x indicates that a dose is given) Additional instructions (e.g. pc – after food)
‘As required’ medicines e.g. paracetamol Intravenous and subcutaneous infusions
KEY TABLES FOR OPEN BOOK Palliative Care Table on Page 20 – Equivalent doses of morphine sulphate and diamorphine hydrochloride.
Gastro-Intestinal System Table on Page 50 - Recommended regimens for H. pylori eradication in adults.
Cardiovascular System Page 105 – Hypertension thresholds and targets for treatment Page 147 – Target INRs Page 147 – What to do if there is a haemorrhage (INR too high)
Respiratory System Table on Page 174-175 – Management of chronic and acute asthma Table on Page 200 – Dose of intramuscular injection of adrenaline (epinephrine) for anaphylactic shock Page 203-204 – Long-term Oxygen therapy and when it should be considered
Central Nervous System Page 210 – Equivalent doses to Diazepam 5mg Table on Page 221 - Equivalent doses of oral antipsychotics Table on Page 230 - Equivalent doses of depot antipsychotics
Infections Table on Page 326 - Notifiable Diseases. Doctors need to notify the Proper Office when
attending a patient suspected of suffering from any of the diseases listed in the table.
Table on Page 328 to 336 - Summary of antibacterial therapy. Gives you specific infectious diseases and their specific antibiotic treatment.
Table on Page 337 to 338- Summary of antibacterial prophylaxis. Gives you specific infectious diseases and their specific proph ylactic treatments.
Endocrine System Table on Page 451 – Equivalent anti-inflammatory doses of corticosteroids.
Lists equivalent doses of other corticosteroids for anti-inflammatory treatment compared with prednisolone 5mg.
Table on Page 459 - HRT Risk Table. Lists the risks of cancers and other medical conditions when taking HRT.
Nutrition Table on Page 589 – Iron content of different iron salts Page 603 – G6PD deficiency Table on Page 606 – Electrolyte concentrations for intravenous fluids Table on Page 615 – Proprietary Infusion Fluids for Parenteral Feeding Tables on Page 640 – Drugs which are unsafe in acute porphyrias
Skin Table on Page 722 – Suitable quantities of corticosteroid preparations to be prescribed for specific areas of the body. For an adult single daily application for 2
weeks.
Page 723 – Topical corticosteroid preparation potencies. Table on Page 755 – Suitable quantities of parasiticidal preparations. For an adult single application.
DRUGS LIKELY TO BE ABUSED Codeine Linctus Kaolin and Morphine Gees Linctus Do-Do Chesteze Laxatives (Senna, Bisacodyl) Antihistamines for temporary sleeplessness Solvents
G6PD DEFICIENCY Glucose 6-phosphate dehydrogenase deficiency can lead to acute haemolytic anaemia which can occur from taking certain drugs. Ingestion of fava beans (especially raw) and broad beans can also cause the deficiency. Notes for prescribing drugs to patients with G6PD deficiency: G6PD deficiency is heterogeneous; a drug found safe in one individual with the deficiency may not be equally safe in another individual. Manufacturers do not routinely test drugs for their effects on G6PD deficient individuals. The risk and severity of haemolysis is almost always dose-related.
Drugs with definite risk of haemolysis in most G6PD deficient individuals: Dapsone Methylene blue Nitrofurantoin Primaquine Quinolones Sulphonamides
Drugs with possible risk of haemolysis in most G6PD deficient individuals:
Aspirin Chloroquine Menadione Quinine
