Indirect: increased vagal activity, slows SA node discharge Direct: shortens action potential and refractory period↑force, contraction, CO Effects are dangerously enhanced with hypokalaemia | heart failure, Atrial fibrillation | arrhythmias, cardiac conduction disorder, cerebral impairment, diarrhoea, dizziness, eosinophilia, nausea, skin reactions, vision disorders, vomiting | | | anti-thrombotic drugs - antiplatelet drugs | aspirin, clopidogrel, tirofiban, prasugrel, ticagrelor (meant to be first-line but can cause dyspnea) | arterial thrombosis, angina, acute MI, CVA/TIA | haemorrhage anywhere, GI bleeding, peptic ulcer, asthma | anti-thrombotic drugs | | anti-thrombotic drugs - anticoagulants | heparin, warfarin, LMWH (e.g., enoxaparin), rivaroxaban, dabigatran | venous thrombosis, DVT, PE, NSTEMI, atrial fibrillation | haemorrhage anywhere warfarin→ skin necrosis | anti-thrombotic drugs | | anti-thrombotic drugs - fibrinolytic drugs (used principally to open occluded arteries in patients with MI/stroke) | - streptokinase

• tPA (acts on plasminogen → plasmin → breaks down fibrin) | STEMI, PE, CVA | haemorrhage | anti-thrombotic drugs | | anti-thrombotic drugs - Direct Oral Anti-coagulants (doac)/ noac (novel anticoag..) | rivaroxaban, apixaban, | patients with hip/knee replacements and arterial fibrillation | | | | anti-arrhythmic drugs - ventricular tachycardia | amiodarone | | | | | -       Class I = voltage activated Na+ channels inhibit Na+ channels which increase length of time for action potential threshold to be reached, decreases peak value. (prevents beginning) | Flecainide | Rhythm Control | | Anti-arrhythmic drugs | | -  Class II = β-blockers inhibit sympathetic system, which slows down action potentials coming through SA. | Propanalol | Rate Control | | Anti-arrhythmic drugs | | -  Class III = voltage activated K+ channels blocks K+ channels. slows down repolarisation and increases refractory period (point where channels won’t open) | Amiodarone, sotalol | Rhythm Control | | Anti-arrhythmic drugs | | -       Class IV = CCB calcium causes contraction, ccb’s inhibit contraction of the heart → slow down conduction between myocytes. | Verapamil | Rate Control | | Anti-arrhythmic drugs | | heart failure drugs | ACE inhibitors, ARBs, beta-blockers, mineralocorticoid antagonists, neprilysin inhibitors, SGLT2 inhibitors | | | | | neprilysin inhibitor | sacubitril, valsartan | Sacubitril/valsartan is a replacement for ACE inhibitors and ARBs in patients with HFrEF who remain symptomatic | | |

2. Latent – 3 months RI or 6 months I
3. If affects CNS – 2 months RIPE, 10 months RI | isozionid | TB | neuropathy | | | | pyrazinamide | TB | gout | | | | ethambutol | TB | colour blindness | |

| Omeprazole + clarithromycin and amoxicillin OR metronidazole | | | | | Proton Pump Inhibitor (PPI)

•omeprazole •lansoprazole (-PRAZOLEs) | • PUD • Dyspepsia and GORD (Antacids, PPI, H2 antag…) • Eradication of H. pylori infection (Omeprazole + clarithromycin and amoxicillin OR metronidazole) • Zollinger-Ellison syndrome | • Irreversibly inhibit parietal cell (proton pump) leads to $\downarrow$ HCl secretion | • osteoporosis - maintain adequate calcium + vitamin D

• Can mask symptoms of gastric cancer - malignancy to be ruled out in 'red flags' patients | • Diarrhoea (especially lansoprazole) • headache • abdominal pain • nausea • fatigue • dizziness • Increased stomach pH reduces defenses against infection via the GI tract | | Antacids

****•gaviscon •mucogel •peptac | • Symptom relief in GORD • Short term relief in dyspepsia | • Antacids reduce the symptoms of excessive gastric acid secretion by buffering HCl | • intestinal obstruction • excessive water loss (fever, diarrhoea) | • diarrhoea • constipation | | H2 receptor antagonists

•ranitidine, cimetidine, famotidine, nizatidine | • PUD • Dyspepsia and GORD (Antacids, PPI, H2 antag…) | • competitive antagonists to H2 receptors on parietal cells | • Can mask symptoms of gastric cancer - malignancy to be ruled out in 'red flags' patients | • generally safe • side effects less common than PPI • bowel disturbance • headachea • dizziness | | Misoprostol | • Prophylaxis of NSAID-induced peptic ulcer | • Prostaglandin analogue (prostaglandin E1) | • cautions in conditions which predispose diarrhoea (e.g. IBD) **** | • abdominal pain • diarrhoea • Induce labour | | Antimuscarinic drugs

hyoscine butylbromide scopolamine | • M1 receptors in brain - motion sickness • M3 receptors in GI tract - reduce muscle spasm in IBS | • Competitive antagonists of muscarinic ACh receptors – opposes parasympathetic division of the ANS | • acute MI • arrhythmias • congestive heart failure | • dry mouth • tachycardia • constipation • urinary retention | | Antimotility drugs

• loperamide • codeine phosphate | • Sym…atic relief of acute diarrhoea (usually gastritis) • Sym…atic relief of diarrhoea associated with IBS | • Agonists of μ opioid receptors • $\uparrow$ tone and rhythmic constrictions of intestine • constrict smooth muscle sphincters inhibit peristalsis | • acute UC, acute bloody diarrhoea and C. diff colitis | • Constipation • abdominal cramping and flatulence | | Aminosalicylates

• sulphasalazine • mesalizine • balsalazide | • Mesalazine and balsalazide are first line treatments of mild/moderate UC

1. 5ASA (sulphasalazine or mesalazine) - maintenance
2. Corticosteroids (prednisone)
3. Immunosuppression (azathioprine)
4. Anti-TNF (infliximab) | • 5-ASA acts as anti-inflammatory and immunosuppressant • Mesalazine is 5-ASA • Balsalazide is 5-ASA precursor **** | • blood clotting abnormalities **** | • GI upset, headaches | | Bulk forming laxatives

• e.g. ispaghula husk | • Mild chronic diarrhoea associated with diverticular disease or IBS | • Hydrophilic agents - water is attracted into the stool, increasing bulk and stimulating peristalsis slow acting | • Ensure adequate fluid intake should be maintained to avoid oesophageal or intestinal obstruction | • Abdominal distension, flatulence • Rarely may cause faecal impaction and GI obstruction | | Osmotic laxatives

• lactulose, macrogols, phosphate or citrate enemas | • Bowel preparation before endoscopy or surgery Hepatic encephalopathy | • Osmotically active agents - water is attracted into the stool, increasing bulk and stimulating peristalsis fast acting |
• Caution lactulose in lactose intolerance | • Abdominal cramps • nausea • flatulence • diarrhoea • Phosphate enemas cause irritation and electrolyte disturbances, caution in HF and ascites | | stimulant laxative • senna, bisacodyl | • ALL LAXATIVES: Constipation and faecal impaction | • Increase electrolyte and thus water secretion from the colonic mucosa • Colonic content is increased, stimulating peristalsis | • ALL LAXATIVES CONTRAINDICATED IN BOWEL OBSTRUCTION | • Abdominal cramps • diarrhoea | | Dopamine D2 receptor antagonist

• metoclopramide, domperidone | • FOR ALL- Antiemetic (nausea and vomiting)

• Treatment of GORD as an add on in patients who do not respond to PPIs and/or H2 receptor antagonists | • Antagonists at D2 receptors in chemoreceptor trigger zone of the medulla

• Also relax stomach + lower oesophageal sphincter and disrupt gastroduodenal coordination | • GI haemorrhage, obstruction, or perforation | • diarrhoea | | Histamine H1 receptor antagonists

• cyclizine, cinnarizine | • motion sickness, vertigo and post-operative N+V | • Competitive antagonist of H1 receptors in the vomiting centre and elsewhere in the CNS | • epilepsy | • drowsiness and sedation • Dry mouth | | Phenothiazines

• procloperazine | • vertigo and sometimes in chemotherapy-induced N+V | • Anti-emetic - involves competitive antagonism of D2, H1 and M1 receptors in the vomiting centre, vestibular system and peripherally in the gut Main indications | • CVD | • drowsiness • postural hypertension | | 5-HT3 receptor antagonists

• ondansetron | • chemotherapy and also post-op N+V | • antagonists at 5-HT3 receptors in the chemoreceptor trigger zone, nucleus tractus solitarius and in the GI tract | • congenital long QT syndrome adenotonsillar surgery | • constipation • Diarrhoea and headaches | | Neurokinin-1 receptor antagonists

• fosaprepitant and aprepitant | • N+V associated with chemotherapy | • antagonists at NK1 receptors in the GI tract and the chemoreceptor trigger zone, blocking the effects of substance P (which evokes vomiting) | • acute porphyrias | • Constipation and headache | | Bile acid sequestrants • e.g. colveselam, colestipol, colestramine **** | • Hyperlipidaemia • Cholestatic jaundice • Bile acid diarrhoea **** | • not absorbed by gut - bind to bile acids, preventing reabsorption • excretion of bile salts • lowers LDL

**** | • interfere fat-soluble vitamins absorption (vitamin supplements if treatment long) • Reduced absorption of some drugs (e.g. thiazide diuretics) | • GI tract irritation (diarrhoea) • Large doses needed (unpalatable, inconvenient) | | Ursodeoxycholic acid | • Primary Biliary Cholangitis

• Biliary colic 1)Painkillers 2)Low fat diet, weight loss if obese 3)Recurrent episodes of pain, consider cholecystectomy- ?unfit for surgery- ursodeoxycholic acid | • inhibits cholesterol absorption in intestine and secretion of cholesterol into bile, decreasing biliary cholesterol saturation.

• increases bile acid flow and promotes the secretion of bile acids. | • acute pancreatitis | • painful urination • cloudy urine | | Terlipressin | • oesophageal varices bleeding | • vasoconstriction | | • increased blood pressure • abdominal pain • nausea • diarrhea • headache | | propranolol | • prophylaxis of oesophageal varices | • non selective beta blocker | • diabetes • bradycardia | • asthma, fatigue, heart failure (can worsen in SHORT term), cold peripheries, impotence | | CREON (aka pancrelipase and pancreatin) | chronic pancreatitis (exocrine pancreatic insufficiency) | replaces 3 main pancreatic enzymes made after eating (amylase, lipase, and protease) | CF if <15yrs | abdo cramps messed up sugar levels | | Octreotide | Carcinoid syndrome | Somatostatin analogues | caution in diabetes | alopecia cholecystitis | | Vancomycin | severe C. Difficile moderate=(metronidazole) | antibiotic | | |