Treatment of Gastroesophageal Reflux Disease (GERD) PDF

█ TREATMENT OF GASTROESOPHAGEAL REFLUX DISEASE (GERD) Definition: reflux of gastric contents into the esophagus due to incompetent lower esophageal sphincter (LES). Heartburn and chest pain are the major complain which may be misdiagnosed of angina pectoris. ▌Non-drug therapy = life style modifica...

█ TREATMENT OF GASTROESOPHAGEAL REFLUX DISEASE (GERD) Definition: reflux of gastric contents into the esophagus due to incompetent lower esophageal sphincter (LES). Heartburn and chest pain are the major complain which may be misdiagnosed of angina pectoris. ▌Non-drug therapy = life style modification Drugs ↑ LES pressure:  Head of bed elevation: because most damage to  Metoclopramide the esophagus occurs at night when HCl can  Domperidone  Bethanechol remain in contact with the mucosa for long period.  Erythromycin  Weight reduction.  Avoid: Drugs ↓ LES pressure: – Stress, Smoking, Spices, alcohol.  Anticholinergic – Ulcerogenic drugs e.g. NSAIDs. drugs  Nitrates ▌Drug therapy  Decreasing HCl secretion: H2 blockers and proton pump inhibitors.  Prokinetic drugs.  Antacids and antacid combinations: (Gaviscon). ▌Surgical treatment: if medical therapy failed. █ PROKINETIC DRUGS Definition: they are drugs that increase upper GIT motility and enhance gastric emptying. They include: Dopamine antagonists: e.g. Metoclopramide and Domperidone. Serotonin (5-HT4) agonists: e.g. Mosapride Cholinomimetic agents: e.g. Bethanechol. Macrolide antibiotics: e.g. Erythromycin 1. Metoclopramide Mechanism and pharmacological effects  Metoclopramide ↑ LES tone and enhances gastric emptying and upper GIT motility through:  Blocking of dopamine (D) receptors (central & peripheral) leading to decrease the inhibitory action of dopamine on the GIT motility.  Enhances cholinergic transmission in the upper GIT. 259   N N.B. Metoclopramide has no e effect on small s intesttinal or collonic motility.  Anttiemetic action: a du ue to bloc ckade of D2 recepttors in thee chemoreceptor trigg ger zone of o the medu ulla (CTZ).. Therap peutic use es  Gasstroesoph hageal reflux: to enh hance gastric emptyinng and ↑ LLES pressu ure.  Disorders off gastric emptying: e e.g. diabetic gastro oparesis aand postop perative gasstric retentiion.  Beffore small bowel en ndoscopy (20 mg given by slo ow i.v.i.): to o enhance e gastric eva acuation an nd peristalttic movem ment. Also to t prevent vomiting.  Beffore emerrgency su urgery and d labor to evacuate the stom mach and prevent asp piration of gastric g con ntents duri ng anestheesia.  Tre eatment off nausea anda vomitiing of vario ous causes. Advers se effects – Sed dation (the most commmon adve erse effect)). – Extrapyramid s (e.g. dys dal effects ystonia andd dyskines sia): (especcially in old age) due e to blocka ade of D2 in n the basall ganglia. – Hyp perprolacttinemia du ue to blockkade of D2 in the pitu uitary gland d. Drug in nteraction ns – Antticholinerg pine) antag gic drugs (e.g. atrop gonize its prokinetic p action. – Oth her dopamine blo ockers (e e.g. antips sychotic drugs) ad dministere ed with mettoclopramiide may prrecipitate a acute extra apyramidal effects. 2. Dom mperidon ne Mecha anism and pharmac cological e effects  It blocks periipheral D2 receptorss leading to ↓ the inhibitory acction of do opamine on G GIT motilityy. It does NOT N crosss BBB so itt has no CNS C side efffects.  Anttiemetic efffect less than t meto clopramide. Therap peutic use es  Thee same usees as meto oclopramid de.  To counteracct nausea a and vo omiting caused by y levoodopa an nd bromocriptine d during tre eatment off Parrkinson’s disease because b it blocks D2 2 receptors s in th he CTZ ressponsible for f vomiting g but does s not blockk D2 receptors in i the basaal ganglia re esponsible e for parkins sonism. 260 Adversse effectss: there is growing g at domperidone may ↑ QT interrval and evvidence tha predisp pose to seriious arrhyth hmia and sudden dea ath. M Metoclopra amide D Domperido one Dopam mine recepttor blockad de C Central and d periphera al P Peripheral only o Choline ergic transsmission In ncrease N No effect Antiem metic effect S Strong W Weaker Extra-p pyramidal side s effects P Present N No Hyperp prolactinem mia S Significant M Minimal 3. Betthanechol Bethannechol stim mulates mu uscarinic MM3 in the smooth s ms of the GGIT and my yenteric plexus.. It was ussed in the past for tthe treatmment of GE ERD and g gastroparesis, but now, it is rarely used for this indicatio on due to multiple m cholinergic sside effects s. 4. Mac crolide an ntibiotics s: erythro omycin Macrolide antibiootics such as erythro omycin dirrectly stimulate mottilin receptors on GIT sm mooth mu uscle and promote e the onset of a migrating motor co omplex. Intravenous erythhromycin (33 mg/kg) iss beneficia al in some patients w with gastrop paresis; howeve er, tolerance rapidly y developss. It may beb used in n patients with acutee upper GIT hemmorrhage to promote e gastric e emptying of o blood be efore endosscopy. █ ANT TACIDS AN ND ANTAC CID-ALGIN NIC ACID PRODUC CTS Gavisc con: (algin nic acid + Mg-trisilica M ate + Al-hy ydroxide + NaHCOO3): Alginic acid in prresence off saliva an nd NaHCO O3 forms a highly vviscous fo oamy soluttion of Na--alginate that t floats on the gastric co ontents as s a raft an nd prevents gastric reflux. █ H2 B BLOCKER RS AND PP PIS  PPIs are moree effectivee than H2 blockers foor the treattment of G GERD.  Oncce-daily do osing of PPPIs provide es effective e symptom m relief and d tissue he ealing in 85––90% of paatients; up to 15% off patients require r twice-daily doosing. 261