View large version
Embed image
Lifestyle Modifications For GORD Head of bed elevation , (6-8 inches) is important for individuals with nocturnal or laryngeal symptoms. Dietary modification should be kept sensible to ensure compliance. Patients should avoid potent reflux inducers such as fatty foods, chocolate, peppermint, and excessive alcohol, which may reduce LOS pressure. Patients should avoid acid inducers eg cola/ orange juice. Patients should stay standing after meals. Advise patiets to avoid tight fitting garments , which reduces reflux by decrea - ing the stress on a weak sphincter. Obesity is a risk factor for GERD, erosive esophagitis, and esophageal adenocarci - noma so weight loss should be suggested. Promotion of salivation by either chewing gum or use of oral lozenges is useful. Restrict smoking (this diminishes salivation and decreases LOS pressure). Only weight loss and head of bed elevation have supportive evidence. The adverse effects of H2 antagonists Gynecomastia and impotence occurs with cimetidine specifically in a dose- and time-dependent fashion. Gynecomastia and impotence rarely seen if treatment is limited to normal doses for 8 weeks or less. Immune and hematopoietic effects is implicated in idiosyncratic cases of myelosuppression, thrombocytopoenia, neutropoenia, anaemia, and pancytopoenia. Haemolytic anaemia is possible. Polymyositis and interstitial nephritis can occur with cimetidine. Immune complex rashes can occur with ranitidine. Fever can occur with both cimetidine and ranitidine. CNS symptoms such as confusion, restlessness, somnolence, agitation, headaches, and dizziness and, with prolonged therapy, hallucinations, focal twitching, seizures, unresponsiveness, and apnoea can occur Mental status changes appear to be most common in elderly patients on ITU with comorbid renal or hepatic dysfunction -usually associated with cimetidine. Ranitidine may cause headaches. Hepatic dysfunction can occur with an occasional transient aminotransferase rises. Patients can rarely get a hepatitis with eosinophilia. Cardiac effects can occur as H2 receptors are present in the heart. Possible risk factors for cardiac events include rapid intravenous infusion, high dose, and conditions that would delay drug clearance and underlying cardiac disease. A mild increase in serum creatinine has been observed with cimetidine (competes with creatinine for excretion). Patients can very rarely get immune mediated interstitial nephritis. Prostaglandins They are u sed for prevention of NSAID-induced gastric ulcer. They are contraindicated in fertile women not on contraception. They selectively reduce the ability of the parietal cell to generate cyclic AMP in response to histamine. Prostaglandins also enhance mucosal defense mechanisms. Histamine
Acetylcholine
Gastrin
Cl-
H+
H-K-ATPase pump
cysteine
Parietal Cell
Vagal postganglionic neurons
Muscarinic M3 receptors
Antral G-cells
Enterochromaf - fin-like (ECL) cells
+
P P I p r o d r u g Active PPI HCl
sulfhydryl
Metabolised by P450 ( CYP2C19)
Delayed metabolisers (Mutation homozy - gotes- 5% caucasians) Intermediate metabolisers (Wild type heterozy - gotes) Rapid metabolisers (Wild type homozy - gotes)
Clinical efficacy of PPI decreases Induction of CYP1A, another P450 isoenzyme, may occur in CYP2C19 deficient or saturated individuals, making them suscepti - ble to interference with theophylline metabo - lism If this metabolic pathway becomes saturated, the isoenzyme may become a major target for interactions with many drugs, including warfarin, diazepam, clopidogrel and phenytoin. CYP3A4-mediated metabolism also may be activated under such conditions and may become the principal route of drug elimination. Bioavailability Peak serum conc after 1-2hrs Availability reduced by antacids but not food
Renal excretion T he dose of all the H2RAs is generally reduced by 50 % in patients with moderate to severe renal failure Hepatic excretion The bioavailability of cimetidine, famotidine, and ranitidine is reduced 30 - 60 % by 1st pass hepatic metabolism. Dose adjustment needed if given iv
GORD Treatment 1 H2 Antagonists H2 antagonists are ineffective for severe esophagitis and have no dose-response curve. The different H2 receptor antagonists have equivalent efficacy at equivalent doses. If symptoms continue after 6 weeks treatment with H2 antagonists, the treatment should be changed to another medication.
Written by Dr Sebastian Zeki
