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PHARM XL PHARMACY PRE-REGISTRATION EXAM TRAINING 2015 Key Notes Booklet 1 PharmXL 2015 © BNF Chapter 1 – Gastro-Intestinal System Dyspepsia  Too much acid  Upper abdo pain, early satiety, bloating and nausea  Can occur from gastric and duodenal ulcers  Urgent endoscopic investigation needed if A...

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PHARM XL PHARMACY PRE-REG PRE-REGISTRATION ISTRATION EXAM TRAINING 2015 Key Notes Booklet 1 PharmXL 2015 ©

BNF Chapter 1 – Gastro-Intestinal System Dyspepsia  Too much acid  Upper abdo pain, early satiety, bloating and nausea  Can occur from gastric and duodenal ulcers  Urgent endoscopic investigation needed if Alarm Symptoms: - Bleeding - Dysphagia - Recurrent vomiting - Weight loss - Over 55 where unexplained dyspepsia has not resolved  Advise patient about lifestyle changes  Uninvestigated dyspepsia – if symptoms persist, PPI for up to 4 weeks given - If still unresponsive, test for H.Pylori Gastro-Oesophageal Reflux Disease (GORD)  Heartburn, acid regurgitation, sometimes dysphagia, oesophageal inflammation, ulceration  Lifestyle changes: o Avoid excess alcohol and aggravating foods (excess fats) o Weight reduction o Smoking cessation o Raise head of the bed Mild GORD  Antacids  Alginate antacids form ‘raft’ to reduce reflux and protect oesophageal musosa  PPI more effective than H2 – reduce gastric output  Histamine H2 antagonists – reduce gastric output and can promote healing of NSAID ulcers Severe GORD  PPI, then reassess after 4-6 weeks

Then titrate down to minimum effective dose or substitute treatment with H2 antagonist Pregnancy GORD  Dietary and lifestyle changes  Antacid or alginate can be used  If ineffective then ranitidine can be prescribed – omeprazole only in severe or complicated cases Children GORD  Common in infancy, symptoms resolve between 12-18months without treatment  Change frequency and volume of feed  Feed thickener can be used  Older children – lifestyle changes as above followed by alginate Antacids and Simeticone  Antacids usually contain Al or Mg compounds  Antacids given between meals and at bedtime QDS or more – 10ml TDS/QDS promotes ulcer healing  Al and Mg antacids – relatively insoluble and long acting if retained in stomach - Mg antacids have laxative effects - Al antacids can be constipating - Antacids with both Al and Mg reduce these effects  Bismuth containing antacids not recommended (except chelates) – absorbed bismuth can be neurotoxic  Ca containing antacids can cause rebound acid secretion, prolonged high doses cause hypercalcaemia and alkylosis  Simeticone (activated dimethicone) – antifoaming agent to relieve flatulence and hiccups in palliative care  Sodium bicarbonate present in some preparations – not suitable for pts with high BP/salt restricted diets (hepatic problems)  Antacids can damage e/c on some MR tabs and can alter pharmaceutical properties 

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Antispasmodics  Antimuscarinics reduce intestinal motility – common use in IBS and travel sickness  Side effects: - Constipation - Transient bradycardia (then tachycardia and palpitations) - Reduced bronchial secretions - Dilation of pupils - Dry mouth and dryness of skin  Common: Hyoscine Butylbromide (Buscopan)  Alverine, Mebeverine, and Peppermint oil – direct relaxants of intestinal smooth muscle – common use in IBS Motility Stimulants  Metoclopramide and Domperidone – Dopamine receptor antagonists  Stimulate gastric emptying and enhance oesophageal sphincter contraction Helicobacter Pylori infection  Nearly all duodenal and most gastric ulcers that are not associated with NSAID use, are due to H.pylori  Eradication of H.pylori reduces recurrence of ulcers and risk of rebleeding  Also causes regression of most localised gastric mucosa associated lymphoid tissue (MALT) lymphomas  After H.pylori presence confirmed, treatment with acid inhibition and antibacterial is effective  1 week triple therapy – PPI, Clarithromycin, and either Amoxicillin or Metronidazole o If pt has used metronidazole or macrolide, amoxicillin preferred o Normally 85% effective in eradicating H.pylori o Treatment failure often means antibiotic resistance or poor compliance o Two week therapy increases eradication rate but more adverse effects  2 week dual therapy – PPI and a single antibacterial have low eradication rates and not recommended

In eradication failure: PPI plus tripotassium dictratobismuthate, plus tetracycline plus metronidazole 13  C-Urea test kits used for diagnosis of H.pylori infection NSAID associated ulcers  GI bleeding and ulcers can occur with NSAID use, if ulcer occurs NSAID should be withdrawn  High risk pts – over 65, history of peptic ulcer disease, co-morbidity (CV, diabetes, renal or hepatic)  PPI used for protection against bleeding and ulcers with NSAIDs - Provides most rapid healing - Alternatively H2 antagonist or Misoprostol given H2 receptor antagonists  Heal gastric and duodenal ulcers – reduce gastric output as result of H2 receptor blockade  Can promote healing of NSAID associated ulcers (particularly duodenal)  Can mask symptoms of gastric cancer – care required in patients presenting with alarm features, rule out gastric malignancy before treatment  Side effects - Diarrhoea - Headache and dizziness - Rash (erythema multiforme & toxic epidermal necrolysis)  Interaction: Cimetidine slows oxidative hepatic drug metabolim by binding to Cytochrome P450  Should be avoided on pts stabilised on warfarin, phenytoin and theophylline (or aminophylline)  Ranitidine, Famotidine and Nizatidine do not have this interaction with Cyp Prostaglandin Analogues  Misoprostol – synthetic prostaglandin analogue  Anti-secretory, promotes healing of gastric & duodenal ulcers  Can prevent NSAID associated ulcers – useful in elderly/frail who cannot withdraw NSAID use 

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Should not be used in women of child bearing age unless pregnancy has been excluded o Avoid in pregnancy – potent uterine stimulant, induces abortion, teratogenic risk in first trimester o Should only be used if pt takes effective contraceptive measures and is advised of risk of taking misoprostol if pregnant Proton Pump Inhibitors (PPIs)  Inhibit gastric acid secretion – block hydrogen-potassium adenosine triphosphate enzyme system (proton pump of gastric parietal cell  Effective short term for gastric & duodenal ulcers and used in combo with antibacterials for H.pylori eradication  Can mask symptoms of gastric cancer – care needed if alarm symptoms present  Pts at risk of osteoporosis should have adequate intake of Calcium and Vit D  Serum Mg concentrations should be measured in long term use  Side effects: GI disturbances, nausea, vomiting, abdo-pain, headache - By decreasing gastric acidity – can increase risk of GI infections including C.diff infection - Can increase risk of fractures in elderly at high doses for over a year and rebound acidity can occur after stopping prolonged treatment Acute Diarrhoea  Priority is reversal of fluid and electrolyte loss – important in infants and elderly  Antimotility drugs relieve symptoms – used in treatment of acute symptoms in adults (not recommended in children)  Antispasmodics used to treat cramp but are not primary treatment Inflammatory Bowel Disease (IBD)  Includes ulcerative colitis and Crohns disease 1. Aminosalicylates (mesalazine, olsalazine, sulfasalazine) 2. Corticosteroids (hydrocortisone, beclometasone, budesonide and prednisolone) 

3. Unresponsive/Chronic Crohns – azathioprine, mercaptopurine or methotrexate can be used (unlicensed)  Infliximab and Adalimumab licenced for management of severe Crohns and severe ulcerative colitis in pts who have not had benefit from corticosteroid or drug that affects immune system  Corticosteroids not suitable for maintenance therapy due to side effects  Folic acid given to reduce possibility of methotrexate toxicity – given on different day to MTX Adjunct treatment  Attention should be paid to diet – high fibre or low residue diets should be used  Antimotility drugs (codeine/loperamide) may cause paralytic ileus or megacolon in active ulcerative colitus – treating inflammation is better option  Colestyramine – binds unabsorbed salts, can improve diarrhoea Aminosalicylates  Sulfasalazine – 5-ASA and sulfapyridine (carrier to colonic site, but causes s/e)  Newer – mesalazine, balsalazide and olsalazine (s/e of sulfapyridine are mainly avoided)  5-ASA (5-aminosalicylic acid) can cause blood disorders - Pts should report any unexplained bleeding, bruising purpura, sore throat, fever or malaise - Blood count should be performed and drug stopped immediately if suspicion of blood dyscrasia  Renal function should be monitored before starting, at 3 months of treatment and then annually during treatment with aminosalicylate Laxatives  Before starting laxatives – important to ensure no underlying disease  Bowel habit varies considerably from patient to patient  Excess laxative use can cause hypokalaemia  Useful in drug induced constipation, expulsion of parasites after anthelmintic treatment and to clear alimentary tract before surgery 4

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Infants Intake of fluids/juice containing sorbitol (prune, pear, apple) may be sufficient to soften stool  Lactulose can be used to soften stool  Diet should be reviewed to ensure adequate intake of fibre and fluid  Chronic constipation – may need to exceed licensed doses Pregnancy  Dietary lifestyle changes first line  Moderate doses of poorly absorbed laxatives can be used  Bulk forming or laculose can be used Bulk-forming laxatives  Increase faecal mass – stimulates peristalsis  Full effect takes some days to develop  Adequate fluid intake should be maintained to avoid intestinal obstruction  Unprocessed wheat bran taken with food or juice is an effective bulk forming preparation  Common: ispaghula husk (Fybogel), methylcellulose (Celevac) 

Stimulant laxatives  Increase intestinal motility and often cause abdo cramp  Should be avoided in intestinal obstruction  Excessive use can cause diarrhoea and hypokalaemia  Common: bisacodyl, sodium picosulfate, senna and docusate sodium  Dantron – not commonly used due to potential carcinogenicity  Glycerol suppositories act as stimulant due to mildly irritant action of glycerol Faecal softeners  Liquid paraffin used but can cause anal seepage of paraffin and irritation after prolonged use  Docusate sodium has softening properties – useful in haemorrhoids and anal fissure  Enemas containing arachis oil (ground nut oil/peanut) oil lubricate and soften impacted faeces and promote bowel movement

Osmotic laxatives  Increase amount of water in large bowel – draw fluid into bowel or retain fluid already in the bowel  Lactulose – semi-synthetic disaccharide which is not absorbed from GI tract o Produces an osmotic diarrhoea of low faecal ph o Discourages proliferation of ammonia producing organisms – useful in treatment of hepatic encephalopathy  Macrogols – inert polymers of ethylene glycol, impound fluid in the bowel o Giving fluid with macrogols can reduce dehydrating effect sometimes seen with osmotic laxatives  Mg salts useful where rapid bowel evacuation is required  Mg hydroxide products are commonly abused but satisfactory for occasional use  Na salts should be avoided as can give rise to Na and water retention  Common: Lactulose, Macrogols (Movicol) Opioid antagonist  Methylnaltrexone – used for treatment of opioid induced constipation in palliative care  Should be used as adjunct to existing laxative therapy  Does not alter central analgesic effect of opioids Stoma care  EC or MR preparations unsuitable – may not be sufficient release of active ingredient 1. Laxatives: bulk forming laxatives should be used, or a small dose as possible of senna 2. Antidiarrhoeals: loperamide, codeine phosphate 3. Antacids: constipation or diarrhoea from Al or Mg products may be increased in these pts 4. Diuretics: should be used in caution – can become excessively dehydrated and K depletion can occur (give K sparing diuretic) 5. Digoxin: pts are susceptible to hypokalaemia when on digoxin and K supplements advised 6. Potassium: liquid formulations preferred to MR formulations 5

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Analgesics: opioids may lead to troublesome constipation in stoma pts, Paracetamol preferred, anti-inflammatory analgesic may cause gastric irritation and bleeding 8. Iron preparations: oral route may cause loose stools and sore skin, intra muscular route should be used  Care of stoma advised – cleaning, deodorants, sealants etc. 7.

BNF Chapter 2 Notes – Cardiovascular System Positive Inotropic drugs increase force of contraction Cardiac Glycosides  Digoxin – increases force of myocardial contraction and reduces conductivity in atrio-ventricular node - Useful in controlling atrial fibrillation and flutter - Management of AF – dose of digoxin should be determined by the ventricular rate at rest, should not fall persistently below 60 BPM  Response to digoxin can take some time, even hours by IV route  Has long half-life and maintenance doses normally OD – higher doses may need to split to avoid nausea  Hypokalaemia predisposes pt to digitalis toxicity – managed by giving potassium sparing diuretic or K supplements  In toxicity – digoxin specific antibody fragments available to reverse lifethreatening overdosage Diuretics Thiazide and related diuretics  Relieve oedema from CHF and reduce BP in lower doses  Moderately potent diuretics – inhibit Na reabsorption at beginning of DCT  Act within 1-2hrs of oral administration with duration of action of 12-24hrs  Given in morning normally – so diuresis doesn’t interfere with sleep

In hypertension, low dose thiazide (eg. bendro 2.5) will give maximal BP lowering effect, high doses cause more changes in plasma electrolytes and ions o Bendroflumethiazide – used for mild or moderate HF and hypertension o Chlortalidone – thiazide related compound, longer duration than thiazides, given alternate days to control oedema o Indapamide – chemically related to chlortalidone, can lower BP with less metabolic disturbance and less aggravation of diabetes mellitus Contra-indications  Thiazides & related diuretics should be avoided in hypokalaemia, hyponatraemia, hypercalcaemia and addison’s disease  Used in caution in pts with hepatic impairment and avoided in severe liver disease Loop Diuretics  Inhibit reabsorption from acending limb of Loop of Henle  Used in pulmonary oedema from left ventricular failure and in CHF  Diuretic resistant oedema can usually be treated with a loop diuretic  Can be added to anti-hypertensive to achieve better control of BP  Furosemide and Bumetanide act within 1hr of oral admin, similar in activity Contra-indications  Avoid in severe hypokalaemia, severe hyponatraemia and renal failure from nephrotoxic drugs  Hypokalaemia induced by loop diuretics can cause hepatic encephalopathy and coma – K sparing diuretics can be used to prevent this Potassium-sparing diuretics  Amiloride and triamterene are weak diuretics on their own  However cause retention of K and are therefore given with thiazide or loop diuretics – more effective alternative to K supplements  K supplements must not be given when pt also taking K-sparing diuretics  Use of a K-sparing diuretic with an ACEi or ATII antagonist can also cause severe hyperkalaemia 

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Combination treatments available, if compliance is a problem – coamilozide, co-amilofruse

Aldosterone antagonists  Spironolactone potentiates thiazide or loop diuretics by antagonising aldosterone  Used in treatment of oedema and ascites caused by cirrhosis of liver  Eplerenone used as adjunct in LV dysfunction and HF after myocardial infarction  K supplements must not be given with aldosterone antagonists Drugs for arrhythmias  Verapamil – acts on supraventricular arrhythmias  Amiodarone – acts on supraventricular and ventricular arrhythmias  Lidocaine – acts on ventricular arrhythmias  Vaughn Williams classification o I – membrane stabilising: Lidocaine o II – beta-blockers o III – amiodarone, sotalol (also class II) o IV – CCBs Beta-adrenoreceptor blocking drugs  Block beta-adrenoreceptors in heart, peripheral vasculature, bronchi, pancreas and liver  Intrinsic sympathomimetic activity (ISA) – capacity of beta blockers to stimulate as well as block adrenergic receptors  Oxprenalol, Pindolol, Acebutolol and Celiprolol have intrinsic activity and cause less bradycardia and less coldness of extremities  More water soluble beta blockers – less moves into the brain and therefore less sleep disturbance and less nightmares - Eg. Atenolol, Celiprolol, Nadolol and Sotalol - Water soluble beta blockers excreted by kidneys, dosage reduction often needed in renal impairment

Have short duration of action – need to be given bd or tds, but MR formulation available (od)  Some beta blockers have longer duration of action and are given od – Atenolol, Bisporolol, Carvedilol, Celiprolol and Nadalol  Beta blockers can precipitate bronchospasm – usually avoided in pts with asthma - If asthma is well controlled, a cardioselective beta blocker can be used at a low dose - Atenolol, bisoprolol, metoprolol and nebivolol are cardioselective but not cardiospecific  Beta blockers associated with fatigue, coldness of ectremeties, sleep disturbances and nightmares  Can affect carbohydrate metabolism and affect metabolic responses to hypoglycaemia – can mask symptoms such as tachycardia Pregnancy  Should be avoided in pregnancy, may cause intra-uterine growth restriction, neonatal hypoglycaemia and bradycardia  Latetalol not known to be harmful in maternal hypertension – except in first trimester  Infants should be monitored if being breastfed – possible toxicity due to beta-blockade Use in Hypertension  Reduce CO, alter baroreceptor reflex sensitivity and block peripheral adrenoreceptors  Some B-blockers depress plasma renin secretion Use in Angina  Reduce cardiac work – improve exercise tolerance and relieve symptoms of angina  Sudden withdrawal can lead to angina exacerbation, gradual reduction in dose preferred  Risk of precipitating heart failure (HF) when B-blockers and Verapamil (CCB) used together 

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Use in Myocardial Infarction  Can sometimes reduce recurrence rate of MI  However not suitable in all conditions  Sudden cessation of B-blocker can cause rebound worsening of MI Use in Arrhythmias  Attenuate effects of sympathetic system on automacity and conductivity in the heart  Can be used in conjunction with digoxin to control ventricular response in atrial fibrillation  Also useful in management of supraventricular tachycardias Use in Heart Failure  Can produce benefit in HF by blocking sympathetic activity Other uses  Can also be used in anxiety, palpitation, tremor and tachycardia  Prophylaxis of migraine  Betaxolol, carteolol, levobunolol and timolol used topically in glaucoma (eyedrops) Side Effects  BBC Loses Viewers In Rochdale – Bradycardia, Brochoconstriction, Claudication, Vivid dreams & nightmares, negative Inotropic action, Reduced sensitivity to hypoglycaemia Contraindications  ABCDE – Asthma, heart Block, Cardiac failure, Diabetes mellitus (hypoglycaemic shock), Extremities (occlusivearterial disease) Hypertension and HF  Lowering raised BP reduces risk of stroke and coronary events, HF and renal failure  Possible causes of hypertension (eg. renal, endocrine), contributory factors, risk factors and presence of complications should be established  Patients should be given advice on lifestyle changes – as can play key role in precipitating high BP - Smoking cessation - Weight reduction

- Reduce excessive alcohol and caffeine - Reduce dietary salt - Reduce total and unsaturated fat - Increase exercise - Increase fruit and vegetable intake Thresholds and targets for treatment  Target for patients under 80 = 140/90 (clinic) or 135/85 (ambulatory or home)  Patients with 140/90mmHg or higher should be offered measurement in ambulatory position or home BP reading to confirm diagnosis and stage of hypertension Stage 1 hypertension  BP 140/90 or higher and ambulatory/home average 135/85 or higher  Treat pts under 80 and target organ damage – LV hypertrophy, CKD, retinopathy, diabetes, CV disease  Give lifestyle changes for patients under 40 with no target organ damage Stage 2 hy...