Dr. RAGHU PRASADA M SMBBS,MDASSISTANT PROFESSORDEPT. OF PHARMACOLOGYSSIMS & RC.

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DRUGS NEUTRALISE GASTRIC ACID (ANTACIDS)SYSTEMIC ANTACIDS-SODIUM BICARBONATENONSYSTEMIC ANTACIDSBUFFER TYPE- ALUMINIUM HYDROXIDE, MAGNESIUMTRISILICATE, MAGALDRATENON- BUFFER TYPE- MAGNESIUM HYDROXIDE

CALCIUM CARBONATEMISCELLANEOUS- ALGINATES, SIMETHICONE

DRUGS WHICH REDUCE GASTRIC ACID SECRETIONH2 RECEPTOR ANTAGONISTS- CIMETIDINE,RANITIDINE, NIZATIDINE, ROXATIDINEPROTON PUMP INHIBITORS- OMEPRAZOLEPANTOPROZOLE, RABEPRAZOLEANTICHOLINERGICS-PROPATHELINE, OXYPHENONIUM,PIRENZEPINE, TELENZEPINEPROSTAGLANDIN ANALOGUES-MISOPROSTOL,ENPROSTIL,

MUCOSAL PROTECTIVES SUCRALFATE, COLLOIDAL BISMUTH SUBCITRATE,

RANITIDINE BISMUTH CITRATEULCER HEALING DRUGS-CARBENOXOLONEANTI-HELICOBACTER PYLORI DRUGS-AMOXICILLIN,CLARITHROMYCIN, TETRACYCLINE, METRONIDAZOLE,RANITIDINE BISMUTH CITRATE

Promote the gastric mucosal defense mechanisms: Secretion of:

-Mucus: Protective barrier against HCl.-Bicarbonate: Helps buffer acidic properties of HCl.-Prostaglandins: Prevent activation of proton pump.Antacids DO NOT prevent the over-production ofacid.Antacids NEUTRALIZE the acid once it’s in thestomach.

Reduction of pain associated with acid-relateddisorders.Raising gastric pH from 1.3 to 1.6 neutralizes 50%of gastric acid.Raising gastric pH point from 1.3 to 2.3 neutralizes90% of the gastric acid.

Sodium Bicarbonate:Highly soluble.Quick onset, but short duration.Raises gastric ph 7.4 rebound acidityHcl+ NaHco3 co2+ Nacl co2belchingUnreacted alkali cause metabolic alkalosis.

NaclNa load HTN, CCFSodium content may cause problems in patientswith hypertension or renal insufficiency.

Can heal duodenal ulcerlonger duration

Poorly absorbed, do not disturb systemic acid balance

Magnesium salts:Forms: carbonate hydroxide, oxide, trisilicate.

Commonly cause a laxative effect. Usually used with the other agents to counteract this

effect. Dangerous when used with renal failure-the Failing

kidney cannot excrete magnesium, resulting inaccumulation.

Example :combination products such as aluminium &magnesium.

Aluminum hydroxide, magnesium trisilicate andmagaldrate salts:

Raise gastric PH to 3-4pepsin activity is inhibited around4

They neutralise gastric HCL to form magnesium chlorideand aluminium chloride react with bicarbonates Aland Mg carbonate

Bicarbonate not available for systemic absorptionNacl formed in this process account for chloride loss

Forms: carbonate, hydroxide, phosphate. Have constipating effects. Often used with magnesium to counteract constipation.

Example: aluminum carbonate

Calcium carbonate and magnesium hydroxidePowerful, fast actingCaCo3 Cacl2 CACo3+Cl. Stearate+NaclMay cause constipation.Serum calciummay result in kidney stones.Long duration of acid action may cause increase ofgastric acid secretion (hyperacidity bound)Often advertised as an extra source of dietary calcium.

Simethicone: Silicon polymer and water repellant Decrease surface tension thereby reduce bubble

formation - added to prevent reflux Foaming agent, prevents hiccups and reduces

flatulence Used topically for bed soresSodium Alginates: hydrophobic colloidal carbohydrate

from brown sea weedForm a layer of foam on top of gastric contents &reduce refluxOxethazaine: Surface anaesthetic

Minimal and depend on the compound used: Aluminum and Calcium:-Constipation

Magnesium:-DiarrheaCalcium carbonate: Produce gas and belching;often combined with simethicone.

Cimetidine, Ranitidine, Famotidine, NizatidineReversible competitive inhibitors of H2 receptorHighly selective, no action on H1 or H3 receptorsAll phases of gastric acid secretionVery effective in inhibiting nocturnal acid secretion(as it depends largely on Histamine )Modest impact on meal stimulated acid secretion(as it depends on gastrin, acetylcholine andhistamine)Volume of pepsin content and IF are also reducedVolume reduced by 60 – 70% - anti ulcerogeniceffect

All drugs are absorbed orally adequatelyBioavailability upto 80 %Absorption is not interfered by presence of foodCan cross placental barrier and reaches milkPoor CNS penetration2/3rd of the drugs are excreted unchanged in bileand urine

Preparations: available as tablets, injections

Duodenal ulcer – 70 to 90%Gastric Ulcer – 50 to 75% (NSAID ulcers)Stress ulcer and gastritisGERDZollinger-Ellison syndromeProphylaxis of aspiration pneumoniaUrticaria

Overall, less than 3% incidence of side effects.Cimetedine may induce impotence andgynecomastia.

Drug Interactions:Cimetedine: Binds with P-450 microsomal oxidasesystem in the liver, resulting in inhibited oxidation ofmany drugs and increased drug levels.

All H2 antagonists may inhibit the absorption ofdrugs that require an acidic GI environment forabsorption.

Smoking has been shown to decrease theeffectiveness of H2 blockers.Assess for allergies and impaired renal or liverfunction.

Use with caution in patients who are confused,disoriented or elderly.

Taken one hour before or after antacids. Ranitidine may be given intravenously.

Substituted Benzimidazole derivativesLansoprazole, Omeprazole, Rabeprazole

Pantoprazole, EsomeprazoleMechanism of action:The parietal cells release positive hydrogen ions

(protons) during HCl productionProton PumpProtonated within canaliculus henderson-hasselbatch trapping

PPI(prodrugs) active entity is SULFENAMIDEforms covalent disulfide bond with H/K-ATP aseIrreversible inactivation

Irreversibly bind to H+/K+ ATPase enzyme preventsthe movement of hydrogen ions from the parietalcell into the stomach Achlorhydria gastric acidsecretion is blocked

In order to return to normal acid secretion, theparietal cell must synthesize new H+/K+ ATPase.

ME-TOO DRUGS PRO-DRUGS SUICIDAL INHIBITORS HIT AND RUN DRUGS

Proglumide

Oral acid resistant formulations release the drugin the intestine parietal cell canaliculi

They irreversibly inactivate the proton pumpmolecule – but half life only 1-2 Hrs

Still action persists for 24 Hrs to 48 hrs after a singledose – irreversible inhibition of PPI

New PP synthesis takes time (24 to 48 hoursuppression of acid secretion, despite the muchshorter plasma half-lives of the parent compounds)

Action lasts for 4-5 days

Given 30 minutes to 1 hour before food intakebecause an acidic pH in the parietal cell acidcanaliculi is required for drug activation, and foodstimulates acid production

Concomitant use of other antisecretory drugs - H2receptor antagonists – reduces action

Highly protein bound and rapidly Metabolized by theliver by CYP2C19 and CYP3A4 – dose reductionnecessary in severe hepatic failure

Excreted in Kidneys minimally (no dose reductionneeded in renal failure and elderly)

Therapeutic uses: GERD maintenance therapy. Erosive esophagitis Short-term treatment of active duodenal and begin

gastric ulcers. Zollinger-Ellison syndrome. Treatment of H.Pylori-induced ulcers.

The most common are GIT troubles in the form ofnausea, abdominal pain, constipation, flatulence,and diarrhea

Subacute myopathy, arthralgias, headaches, and skinrashes

Prolonged use: Leucopenia and hepatic dysfunction Vitamin B12 deficiency->6-8wks Hypergastrinemia which may predispose to

rebound hypersecretion of gastric acid May promote the growth of gastrointestinal

tumors (carcinoid tumors )

Assess for allergies and history of liver disease.Drug interaction- Decrease gastric acidity decrease absorption of

digoxin and ketoconazole Inhibit CYP 2Cincrease serum levels of diazepam,

phenytoin, and warfarin.

Quaternary drugs-Propantheline, Oxyphenonium MOA-Muscarinic receptor inhibitiondecrease

gastrointestinal motility and secretion Adjuncts in the management of peptic ulcer disease

and Zollinger-Ellison syndrome, Refractory to standard therapies.S/E- blurred vision, dry mouthPirenzepine Telenzapine-- Prevent recurrences

Inhibit cAMPInhibits secretion of gastric acid andstimulate secretion of mucus and bicarbonate.Dilate blood vessel of mucous membrane.Prevention of gastric ulcers induced by NSAIDs.Less effective than H2-receptor antagonists for acutetreatment of peptic ulcers.S/E-diarrhoea, colic painProduces uterine contractions and is contraindicatedduring pregnancy.

SucralfateIn water or acidic solutions it forms a viscous,

tenacious paste that binds selectively to ulcers orerosions for up to 6 hours.

Also stimulates prostaglandin release and mucus andbicarbonate output.

Inhibit H.PyloriNeeds acid environment; affectsabsorption of other drugs

Colloidal bismuth subcitrateBismuth coats ulcers and erosions protecting themfrom acid and pepsin and bicarbonate production

Binds to an ulcer crater, coating it and protecting itfrom acid and pepsin Inhibits the activity of pepsinIncreases mucous secretionIncrease prostaglandin synthesisHelps to eradicate H. pylori

Endoscopy Barium meal – contrast x-

ray Biopsy – bacteria &

malignancy H.Pylori: Endoscopy cytology Biopsy – Special stains Urease Breath test.

MARSHALL AND WARREN

Is a bacteria that causes chronic inflammation of the innerlining of the stomach. Produce enzymes (tissue damage), inflammation – ulcer. Duodenal ulcer - Gastric ulcer Risk factor for esophagus and stomach cancers. Eradication is important to prevent recurrence

of ulcer.

No HP No ulcer

NEW TESTAMENT

Eradication Of H Pylori

Triple Therapy

The BEST among all the Triple therapy regimen is:Omeprazole / Lansoprazole - 20 / 30 mg bdClarithromycin - 500 mg bdAmoxicillin / Metronidazole - 1gm / 500 mg bd

Given for 14 days followed by P.P.I for 4 – 6 weeks

Short regimens for 7 – 10 days not very effective

Ranitidine Bismuth citrate - 400 mg bdTetracycline - 500 mg bdClarithromycin / Metronidazole - 500 mg bd

Omeprazole - 20mg OD

Bismuth subsalicylate – 2 tab qid

Metronidazole - 250 mg qid

Tetracycline - 500 mg qid

Uses

Duodenal ulcer and peptic ulcer

MALT type lymphoma

Non-ulcer dyspepsia