Pre-registration BNF Notes PDF

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THE ULTIMATE PRE-REG BNF NOTESIMPORTANT MONITORING DRUGS1. AMIODARONE Treatment of arrhythmias  Loading Dose: 200mg tds for 7 days, then 200mg bd for 7 days then 200mg daily maintenance.  Important side effects: Nausea, Vomiting, Taste disturbance, Pulmonary toxicity, Reversible corneal micro-dep...

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THE ULTIMATE PRE-REG BNF NOTES

IMPORTANT MONITORING DRUGS 1. AMIODARONE  Treatment of arrhythmias  Loading Dose: 200mg tds for 7 days, then 200mg bd for 7 days then 200mg daily maintenance.  Important side 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 – 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 – 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 – used in AF, tachycardias and heart failure.  A positive inotrope – increases the force of myocardial contraction and reduces conductivity within the AV node.  Desired serum concentration: 1-2mcg/L (1.5mcg-3mcg/L indicates toxicity)  Monitoring: Serum electrolytes (especially potassium) and Renal function.  A narrow therapeutic index, 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 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

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3. LITHIUM  Treatment and prophylaxis of mania, bipolar disorder and recurrent depression  A narrow therapeutic index 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 – Risk of lithium toxicity

Lithium and NSAIDs

Excretion of lithium probably reduced by NSAIDs – Risk of lithium toxicity

Lithium and Diuretics

Excretion of lithium reduced by Loop and Thiazide – Sodium depletion

Lithium and Amiodarone

Risk of ventricular arrhythmias

4. METHOTREXATE  Treatment of moderate to severe 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: 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 and a maximum weekly dose of 20mg.  A folate antagonist - treatment with folic acid (5mg) helps to prevent Methotrexate-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) and neuropathic pain.  A narrow therapeutic index. 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

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6. THEOPHYLLINE  A bronchodilator for asthma or COPD  A narrow therapeutic index. 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

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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 4

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 Alli  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. 5

POPULAR DRUG INDICATIONS and FACTS TO KNOW GI, CVS, CNS see separate notes Gastro Intestinal System  Helicobacter pylori Infection o Eradication of H. pylori reduces recurrence of gastric and duodenal ulcers and the risk of re-bleeding. o The presence of H. pylori should be confirmed before starting treatment. 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 o The above regimen eradicates H. pylori in about 85% of cases. BNF page 50

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 (and Alli) – 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 256

 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 disability despite treatment for migraine attacks, cannot take suitable treatments for migraine attacks. BNF page 277

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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 first 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 page 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 440

 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. Sym...