Common Gastrointestinal Drugs

4

DRUGS ACTING ON THE GASTRO INTESTINAL TRACT A. DRUG USED FOR TREATMENT OF PEPTIC ULCER Peptic Ulcer is characterized by various degree of erosion of gut wall. Ulcer develops when aggressive factors out weighs the mucosal resistance to ulceration. Aggressive factors out weighs the mucosal resistance to ulceration.

Pathophysiology may be due to

- Increase in Gastric acid Secretion

- H. pylori infection

- NSAIDS

Pyloric sphincter - control movement of acid stomach content into the duodenum

Viscoid mucous - prevent gastric mucosa from acid stomach content

Cardiac sphincter - prevent reflex into the oesophagus

Factor for opening of cardiac sphincter

- Tight clothing

- Over eating

- Abdominal pressure owing to pregnancy

- Obesity

Common Symptom of PUD

- Epigastric pain which comes 90min - 3hr after eating (main)

- Right upper Quadrant pain

- Abdominal fullness

- Nausea (Vomiting)

Dietary regimen & drug therapy are the corner stone of the treatment

The treatment is aimed at

- Withdrawal of the offending agent such as NSAIDs

- Improve life style (avoid smoking, alcohol, spicy foods, caffeine containing beverage)

- All Stimulants which increase gastric acid secretion

- Relief of pain

- Acceleration of ulcer healing

Pharmacotherapy of peptic Ulcer

1. Antacids 2. H2 - receptor antagonist

3. Proton pump inhibitors

4. Antibiotic, bismuth, antimuscarinic

1. Antacid

-Weak bases and react with acid to form salt with H2O - Act locally in the stomach

MOA: - neutralize the acid in the stomach and indirectly inhibiting activity of pepsin (pepsin is inactive above PH4)AntacidNeuralizing

Salt

SolubilityAdverse

Capacity

Formed of Salt

EffectNaHCa3(systemic) High

Nacl

High

- Systemic alkalosis

- Fluid Retention

CaCa3

Moderate

CaC12

Moderate - Hypercalcemia

- Nephrolithiasis

AlOH)3 High

AlCl3

Moderate- Constipation

- Interfere with the

Bio availability of

many drug.

Mg (OH)2High

MgCl2

Low

- Diarrhea

- Hyper magnesia

Drug Interactions

- Antacid decrease gastric absorption of tetracycline and oral iron products

- With enteric coated products Use

1. To Neutralize meal Stimulated gastric acid secretion

- Usually taken 1 hour after meal

2. Beneficial in healing duodenal ulcer - Often used in conjunction with H2 - receptor antagonist

3. Dyspepsia (epigastric discomfort)

2.Anti-Secretary Drugs

H2-receptor antagonist

MOA: - They competitively inhibit the action of histamine on the H2 - receptor that

trigger parietal cell response to chemical stimulation. These are the most popular drugs for the treatment of peptic ulcer.

They bring about symptomatic relief & ulcer healing A. Cimetidine

- Inhibit stimulated acid secretion (e.g. histamine, insulin)

- Inhibit meal stimulated acid secretion

Use - 1. Prophylaxis of duodenal ulcer

2. Short term treatment of gastric ulcer

Dose: - 400mg po bid

300mg IV Adverse Effect

- Hepatotoxicity

- Diarrhea, Dizziness

- Inhibit P450 enzymes

- Sexual dysfunction (antiandrogenic effect)

Kinetics

- Following oral administration, 80% is absorbed

- Mostly excreted unchanged in urine

B. Ranitidine- 5 times more potent than cimetidine

- Action is more selective and long duration of action

Dose: - 150mg Bid or 300mg at bed time

Advantage

- Doesn't produce sexual dysfunction

- Doesn't interfere with hepatic Metabolism

C. Famotidine - About 40 times more potent than cimetidine

- Well tolerated and posses fewer side effect

- Doesn't interfere with Hepatic drug metabolism

Doses: - 20mg bid or 40mg once a day at bed time

Proton-Pump inhibitor

Parietal cells secrete H+ ions which is accomplished by an enzyme H+, K+- ATPase (serve as a proton pump, exchanging K+ for H+ ions). It is required for HCl secretion

Omeprazole

MOA: - bind to H+-K+ ATPase enzyme and inactivate it

Effect

- More potent than H2 - blocker - Has longer duration of action

- No rebound increase in gastric acid secreation

Dose: 20mg once a day (best if taken before break fast) Adverse effect

- Inhibit drug metabolizing enzyme

- Hyper gastremia- Prolonged complete suppression of the acid barrier to bacteria entry into the body

3. Anti-Muscarinic agent

Pirenzepine

MOA: - M1- receptor antagonist

Effect: - Beneficial in treatment of duodenal ulcer than gastric ulcer

SE: - anticholinergic side effect: dryness, dizziness, headache

4. Mucosal Protective Agent

Bismuth

-Form white precipitate in gastric acid

MOA - PPt (antacid-glyco protien complex) coats the ulcer site - Drug may cause constipation and black stool Carbenoxolone sodium(ulcer healing)MOA - Increase production and viscosity of mucous

S.E. - Aldosterone like effect (hypertension, fluid retention and hypokalemia)

5. Antibiotics-against H.Pylori infection:doxorubicin,ampicillin

B. DRUGS USED AS LAXATIVES (Purgatives,Cathartics)Constipation is difficult to define. In general, it may be defined as infrequent or seemingly incomplete evacuation

Diagnosis: - Clinical

Non - drug treatment:

- Removal of underlying cause

- More fiber diet intake

- Increase fluid intake Phatology; change in diet ,exercise,GI motility

Laxatives: - drug which produce soft formed stool

Purgative: - Produce sever action, watery stool

laxative are not usually recommended for children under 4 years of age

1. Stimulant or irritant Laxative

Castor Oil

- Castor Oil is obtained from seed of ricinus communis

- By itself, it is not irritant

MOA: - when ingested

Castor Oil Pancreatic Ricinoleic acid

Lipase - Ricinoleic acid causes stimulation of small intestine and thereby increases peristalisis

and result in laxative action.

Dose: 5-30ml

- Effect quickly seen in 2-3 hr

CI ; pancreatic disease

Bisacodyl

- Structurally similar to phenolphthalein (color indicator)- Can be used orally or rectally

- Stimulate the large intestine

Dose 10mg in the night

10mg rectally in the morning.

children 5mg rectally in the morning (4yrs)2. Osmotic Laxatives

Salt: - Mg S04, Mg citrate

MOA: - when given orally, not absorbed from GIT. They exert osmotic effect on the GIT there by holding considerable amount of water.

(ses in bulk which exert mechanical effect thereby (ses motility and facilitating evacuation of faces.

- These drug act both in small intestines and large intestines

- Onset of action is fast and hence given before meals (breakfast) in the morning.

- Patient should be advised to take plenty of water

- Small amount of these drug which are absorbed may produce toxic effect especially in

renal insufficiency.

Mg - Market CNS depression

Na - aggravate CHF(congestive heart failure)3. Bulk Laxatives

Lactose

- Non-absorbable disaccharide act by its stomach effect

MOA

1.Natural and Synthetic Polysacharide and cellulose derivative which when administered

Are not absorbed and increase the bulk of indigestible residue.

2. These drug absorb water and swell up, producing mechanical stimulation of evacuation

- Action is mild and stable 12-36hr

4. Lubricant laxative Liquid Paraffin

MOA 1. Oil retard the reabsorption of water from rectal mass in the colon

2. Oil also act as lubricant ,facilitating stool passage

Dose 10ml po every night for 3 days

Glycerin 1 gm rectally at night after moistening with water

C. ANTI-EMETICSNausea refers to the feeling of an imminent desire to vomit

Vomiting; refers to the forceful oral expulsion of gastric content

These are drugs which oppose or counter act nausea and vomiting.

Vomiting may triggered by a variety of stimuli.

Vomiting range from the physiologic state of pregnancy to serious pathology.

CTZ Emetic Substance (ipecac)Pain

VC Pregnancy ( specially multiple pregnancyBad taste

Post Operative Vomiting

Bed Sight

Anticancer Drug

Rotation

Electrolyte Disturbance

VC= Vomiting Center

CTZ= Chemoreceptor trigger zone

The vomiting center has mainly muscarinic receptor

E.g. D2= Dopamine (D2) receptor

H1= Histamine (H1) receptor

Non-drug treatment of N/V

- Correction of the underling cause

- Hydration

1.H1-receptor antagonist

These have little or no effect against vomiting produced by substance acting directly on the CTZ but are effective in motion sickness & against vomiting caused by substances which act locally in the stomach. Promethazine

Therapeutic category: - Anti-emetic, Antihistamine

Use: - Symptomatic treatment of various allergic conditions, antiemetic, motion sickness

pregnancy implication; possible respiratory depression if drug is delivered near time of delivery.

MOA: - compete with histamine for H1-receptor; reduce stimuli to the brainstem reticular

system

SE bradycardia

Dosage: - Adults

Oral - 25mg at bed time - Allergic

IM/IV - 25mg

- antiemetic Oral, IM/IV 12.5 - 25mg every 4-6 hours

motion sickness 25mg 30-60minute before departure.

Administration: - IM is the preferred route of administration

: - Due to the possibility of orthostatic hypotension IV route is not usually

Preferred.

Solution for injection may be diluted in 25-100ml NS or D5W (max one at

25mg/ml) and infused over 15-30minute.

Meclizine

therapeutic category;-antihistamine;antiemetics

Use;- prevention and treatment of motionsickness

SE;- slight to moderate drowsiness

thickening of bronchial secreation

Dosage;-12.5-25mg ,1hr before travel,repeat the dose every 12to 24 hr if needed

2.Muscarinic receptor antagonistHyoscine

Therapeutic category: - Anticholinergic, Antisposmodic

use ;-motionsickness,spasm

hyocine is the most potent agent available for prevention of motion sickness,though it is less useful once sickness occursMOA: - block the action of Acetyl Choline at parasympathetic sites in smooth muscle, Secretary Glands and the CNS; and hence dries secreation, antagonize histamine.

Dietry Consideration: - should be taken before meal or food

Dosage: - adults 10mg 2 tab prn 3.Dopamine antagonist

Metoclopromide

Therapeutic category: - Antiemetic; Dopamine antagonist

MOA: - block the dopamine receptor in chemo receptor trigger zone of the CNS

SE ;- disorder of movement,drowsiness,fatigue

occulogyric crisis(rapid involuntary eye movement)

disorder of menstruation(due to prolactin release)

PK;-half life -4hr

excreation;-urine

Dosage:- Adults:- 10-15mg/dose up to four times a day 30 minute before meal

Children: - 0.1-0.2mg/kg/dose up to four times a day

Administration: - injection solution may be given IM, direct IV push or infusion.

Lower doses (