FOR BDS/MBBS-GIT PHARMACOLOGY FULL TOPICS

2. Drugs for Peptic Ulcer and Gastroesophageal Reflux Disease
Antiemetic, Prokinetic and Digestant Drugs
Drugs for Constipation and Diarrhoea

4.  Too frequent, often too precipitate passage of poorly formed stools
 WHO defined:- 3 or more loose or watery stools in a 24 hrs. period
 ↑frequency of stool + consistency (watery stool)
 Occurs due to passage of excess water & Electrolytes in faces
 Dehydration-most common cause of death in diarrhea
Cause:-
 ↓ electrolyte and water absorption
 ↑ secretion by intestinal mucosa
 ↑ luminal osmotic load
 Inflammation of mucosa and exudation into lumen

6. Diarrhoea
Infective
gastroenteritis
Irritable bowel
syndrome
Inflammatory
Bowel Disease
Ulcerative colitis Crohn’s
disease
Acute chronic
diarrhoea
Mild Moderate
Secretory
Diarrhoea
Constipation
dominant IBS
Diarrhoea
dominant IBS
Villous
adenoma

7. Type
s
1.acute
Diarrhoea-
2.chronic
diarrhoea-
Persist for more
than 2 weeks
Mild Moderate
5-7%
Body water loss
7-10%
Body water loss

8.  Bacterial:-
Vibrio cholera
Enterotoxigenic E.coli(ETEC)
Clostridium perfringens, Clostridium difficile
Salmonella
Shigella
Campylobacter jejuni
Y. Enterocolitis
 Viral:-
Rotavirus-
CMV
Infectious agents

9.  Absorption:-
 Inhibition of Na+K+ ATPase and structural damage to mucosal cell by Rota virus
causes diarrhoea by reducing absorption
 Secretion:-
 Excess of bile acids also cause diarrhoea by activating adenylyl cyclase
 Prostaglandins, Intracellular Ca++ also stimulate secretory process
 Cholera toxin, Enterotoxigenic E. coli(ETEC) , Staph aureus, Salmonella
stimulate adenylyl cyclase- increasing secretion
 GI motility:-↓segmentation + ↑peristalsis
-:Pathophysiology:-

11. Treatment should always be directed according to underlying cause.
-most diarrhea-self limiting
Rehydration therapy
Drug therapy
I.V. Oral
# severe
fluid loss >10% BW
Oral rehydration therapy

12.  The recommended composition of i.v. fluid
Composition:-
Nacl-5gm (85mM)
Kcl-1gm (13mM) in 1L of water or 5%
NaHCO3-4gm (48mM) glucose solution.
 Volume equivalent to 10% BW should be infused over 2-4 hours
Dhaka Fluid:-

13.  ORS therapy is the core of management of acute diarrhoea(mild-5-7%
BW/moderate-7.5-10% BW)
 A mixture of salts and water
 Purpose:-
 To correct water electrolyte deficient
 To prevent dehydration
 Reduce mortality
 Advantages:-
Simplest, safest, least expensive life saving method
ORS-Therapy

14.  Improved form of ORS with addition of certain actively transported amino
acids like alanine, glycine
 Glucose is replace with boiled rice powder
 Advantages:-
 enhanced absorption
 decrease frequency of diarrhoea
 less chance of osmotic diarrhoea in high dose also
# it has been found to reduce stool volume compared to WHO-ORS in cholera

15.  Mainly in children below 5 yr. age
 Zn+ORS-↓severity of acute diarrhoea
 Zn supplement cont. for 10-14days
 Mechanism:-
1. ↓fluid secretion in intestine by inhibiting cAMP dependent Cl-
transport
2. improve immune response
and help regeneration
of intestinal epithelium
Roll of Zinc in diarrhoea

16. Diarrhoea patients
 Watery Stool Without mucus or blood
 Frequent vomiting,
 Periumbilical cramps,
 No fever
Causative organism:- (non-invasive enterotoxigenic bacteria)
include
 Cholera,
 ETEC,
 Salmonella enteritidis,
 Staph. aureus,
 Bacillus cereus
 Rota virus
ORS and not Antimicrobials
 Watery Stool + mucus / blood
 No vomiting,
 Abdominal cramps
 Mild dehydration with fever
Causative organism:- (entero-invasive
organisms) include
 Shigella,
 Enteropathogenic E. coli (EPEC),
 Campy jejuni,
 Salmonella typhimurium,
 Yersinia enterocolitica,
 E. histolytica,
 Clostridium difficile
Antimicrobials
Non-invasive diarrhoea Invasive diarrhoea
Infective gastroenteritis

17. DRUGS FOR DIARRHOEA
Specific antimicrobial
drugs
Non-Specific antimicrobial
drugs
Probiotics
Norfloxacin
Ciprofloxacin
Ofloxacin
Rifaximin
Cotrimoxazolc
Tetracycline
Erythromycin
Metronidazole
.
Lactobacillus sp.
Bifidobacterium bifidum
Strep. faecalis
Enterococcus sp.
Saccharomyces b
Absorbants Anti-motility
Drugs
Anti-secretory
agents
Ispaghula
Methylcellulose Racecadotril
Bismuth subsalisylate
Anticholinergics
Octerotides
Codeine
Diphenoxylate
Loperamide

18. Causative
organism/Disease
Antimicrobial Agents
Cholera ORS, Tetracycline, Co-trimoxazole
Campylobacter Norfloxacin, other fluroquinolones
Clostridium difficile Metronidazole, Vancomycin
Amoebiasis/giardiasis Metronidazole
Yersinia enterocolitica Cotrimoxazole, Ciprofloxacin
Rotavirus Non-antimicrobial therapy
Salmonella food poisoning ORT, Infant/elderly-ciprofloxacin/azithromycin
Travellers diarrhoea Norfloxacin, cotrimoxazole, doxycycline
Specific Antimicrobial drugs

19. WHO:- “Live micro-organisms which when administered in adequate amounts
confer a health benefit on the host”
 Microbial cell preparations, Live cultures or lyophillised powder
E.g.-Lactobacillus sp, Bifidobacterium bifidum, Strep.faecalis, Enterococcus sp.,
Saccharomyces b
 Advantages:-
1. Restore and maintain healthy gut flora
2. Recolonization of the gut by non-pathogenic mostly lactic acid forming
bacteria
 Use:-Acute infectious diarrhoea, Antibiotic-associated diarrhoea,Travellers
diarrhoea, ulcerative colitis, relief in bloating and flatulence
#curd/yogurt is an abundant source of lactic acid producing organisms, which can
serve as probiotics.
Probiotics

20. Absorbed Water & ↑ stool bulk
Modify consistency & frequency of stool
No action on water electrolytes loss
Eg.- Ispaghula , Psyllium, methylcellulose
USE:-
Irritable bowel syndrome
During ileostomy
Colostomy diarrhea
Bile salt induced diarrhea-Cholestyramine

21. Racecadotril
Bismuth subsalicylate
Anti-cholinergic
Octreotide
Racecadotril
Racecadotril
Prodrug Converted
Thiorphan
+
δ-Opioid receptor
(secretary) agonist
↓Mucosal cAMP
Prevent degradation of
Endogenous enkephalins ↓ intestinal hyperhypersecretion
Enkephalinase inhibitors

22.  Use:- Acute secretary diarrhoeas
 Use In children
 SE:- Nausea, Vomiting, flatulence, Drowsiness
Bismuth Subsalicylate
Anti-secretory
Anti-inflammatory
Anti microbial effects(H. pylori)
Action:- ↓ PG synthesis in intestinal mucosa
↓Cl- secretion
use:- Traveller’s diarrhoea (prophylaxis)

23.  Antispasmodic actions
 ↓ bowel motility and secretion
 Used in drug induced diarrhoea
 Provide some symptomatic relief in dysenteries
 They may beneficial in drug induced diarrhoeas
 Atropine- used in nervous(stress induced) & drug induced diarrhoea
Anti- cholinergics

24.  Synthetic octapeptide analogue of Somatostatin
 Longer acting-t1/2-90min
 Action-
 Potent anti- secretory & antimotility action on the gut.
 It Suppresses hormone (gastrin, cck, glucagon secretin, pancreatic polypeptide, vasoactive
intestinal peptide, and 5-HT) which enhance intestinal mucosal secretion
Use:-
 control diarrhoea in carcinoid
 Refractory diarrhoea in AIDS pt.(S.C.)
 higher doses diarrhoea due to vagotomy or dumping syndrome
 pancreatic fistula
SE:-nausea, abdominal pain, flatulence
Octreotide

25. Anti-motility drugs
These are opioid drugs acting through μ-receptor(enteric neuronal network)
Only symptomatic relief in diarrhoea
 Opioid receptor Action:-
 δ receptor action- secretion
 μ receptor action- propulsive movement
Advantages:-
↑ tone & segmenting activity of the bowel
↓propulsive movement & intestinal secretion
No tolerance develops to constipating action
Anti- motility drugs not to be given in infective diarrheas

26.  Codeine-Prominent constipating action at 60 mg TDS
 MOA:-μ-receptor agonist-↓Peristalsis
 Central effect
 Side effects: nausea, vomiting, dizziness
 Not been used due to abuse potential
Codeine

27.  synthetic opioid, chemically related to pethidine
 Most prominent antidiarrheal agent
 Produced opioid dependence
 Atropine is added in sub pharmacological dose to discourage abuse (dryness of
mouth-unpleasant which masks the euphoria produce by Diphenoxylate)
 (2.5 mg diphenoxylate + 0.025 mg atropine)-FDC
 The anticholinergic properties of atropine may contribute to the antidiarrheal
action
 Contraindication:-
 below 6 year of age- respiratory depression, paralytic ileus and toxic megacolon
in children
Diphenoxylate

28.  Semisynthetic opioid analogue
 Major peripheral μ-opioid action+ Weak anti- cholinergic property
 Most effective, suitable antimotility antidiarrheal agents
 Acts on μ-opioid receptor on circular+ longitudinal muscle fibers-inhibit
propulsive movement
 Advantage:-
1) As antimotility agent-40 time more potent than morphine
2) Poor CNS penetration-no abuse liability
3) Longer duration of action (12hr)
4) ↑anal sphincter tone, antisecretory property
5) interaction with calmodulin receptor-inhibition
Loperamide

29.  USE:-traveler diarrhoea
 Adverse effects:- abdominal cramps and rashes
 Contraindicated:-
 Children age < 4 yrs.:- paralytic ileus occur
 Infective diarrhea- delays clearance of pathogen by producing constipation
may also produced disastrous symptoms

30.  US-FDA approve minimally absorbed oral rifamycin
 Active against-E. coli
 It is as effective as ciprofloxacin
 Less side effect due to poor absorption
 Used-
1.empiric treatment of “travellers diarrhoea”
2.hepatic encephalopathy
3.IBS, before & after gut surgery
Side effect:- flatulence, abdominal pain, defecation urgency and headache
Rifaximin

31. Inflammatory bowel disease
Group of Auto-immune disease in which intestine becomes inflamed
Occurs due to imbalance b/w pro-inflammatory & anti-inflammatory cytokines
major 2 types 1. Crohn’s disease 2.Ulcerative colitis
Drugs
5-amino salicylic acid
compound
Sulfasalazine
Mesalazine
Balsalazide
Olsalazine
Glucocorticoids
Prednisolone
Hydrocortisone
(enema)
Immunosuppressants
Azathioprine
Methotrexate
Cyclosporine
TNF inhibitor
infliximab

32. Pharmacotherapy of Constipation

33. Too infrequent passage of stool that may be due to decrease motility of
colon or due to difficulty in evacuation
 low stool frequency alone is not the sole criterion for the diagnosis of
constipation.
 Many constipated patients have a normal frequency of defecation but complain of
excessive straining
 hard stools,
 lower abdominal fullness, or a sense of incomplete evacuation
Introduction

34. General measures:-
Adequate fluid intake
High fiber contents in diet
Regular exercise
Regulation of bowel habit
Avoid drug causing constipation are best to avoid constipation
According to intensity of action:-
Laxatives Purgatives
Milder action
Soft stool formation
Stronger Action
More fluid evacuation

35. Drugs to treat constipation
Bulk purgatives Osmotic
purgatives
Stimulant
Or
Irritant
purgatives
Fecal
softeners
(lubricants)
Stool wetting
agents
Dietary fibers
Natural plant products & semi
synthetic hydrophilic colloids
Synthetic non absorbed resins

36. Increase volume of non-absorbable solid residue
E.g.-
1.Dietary fibers-
Undigested polysaccharide vegetables, fruits, grains, bran, pectin,
2. Natural plant products & semi synthetic hydrophilic colloids
Psyllium seed, methyl cellulose, carboxymethyl cellulose(CMC),
Ispaghula
3.Synthetic non absorbed resins:- calcium polycarbophil
Bulk Purgatives

37. Mechanism:-
↑ Bulk of intestinal content by water absorption
↑ Mechanical pressure on the wall of intestine
(mechanical distension)
Stimulate of stretch receptors
↑peristalsis
(Promote defecation)

38. Caution:- large amount of water to be taken along with bulk purgatives
to avoid intestinal obstruction
USES:-
Irritable bowel syndrome-
 Functional bowel disorder associated by characteristic clusters of symptoms in
the absence of detectable structural abnormalities in GIT motility
Contraindication:-
Megacolon ,
Megarectum ,
gut ulceration
Side effect:-
Abdominal discomfort ,flatulance

39. Dietary fibers
 Consists of –unabsorbable cell wall +(cellulose, gums, pectin's)
 Residual product of flour industry
 Facilitates colonic transit-absorbs water & ↑H20 content of stool in intestine
 Support bacterial growth –contribute to faecal mass
 Certain DF (gums,pectins,lignins )-binds bile acid & promote there excretion in
faeces
 USES-
 Functional constipation
 Constipation-(irrespective of improving straining of stools)

40. -:Ispaghula:-
Obtain from seed of Plantago ovata
MOA:-
They contain natural colloidal mucilage which forms a gelatinous mass
by absorbing water
Largey fermented in colon – increase bacterial mass & softens the
faeces
Dose:- Ispaghula hask(3-8g)+ water (OD/BID)
Should not swallowed dry- cause esophageal impaction

41. Methylcellulose
Semi-synthetic, colloidal hydrophilic derivatives of cellulose
Largely unfermented in colon
4-6 gm/day is satisfactory
Generous amount of water must be taken with all bulk forming agents

42. Drugs ↑ water content in large intestine
Most powerful & rapidly acting purgative
-:Types:-
Organic purgatives:-
Lactulose:-
semi-synthetic disaccharide of fructose & lactose
Neither digested nor absorbed in small intestine-retains water
Osmotic purgative
Organic purgatives
(sugars)
Non-Organic purgatives /
Saline purgatives

43. MOA:-
Lactulose
↓
After fermentation by colonic bacteria convert to Lactic acid & acetic
acid
↓
Reduces luminal pH in the colon
↓
NH3 NH4
+ (unabsorbed)
↓
Blood ammonia level decrease

44. USES:-
Liver cirrhosis/Hepatic coma:- ↓ NH3 Absorption by converting into
NH4
+(Ammonium ion)
Hepatic encephalopathy
Constipation in children & pregnancy
Non-Organic purgatives /Saline purgatives
Salts of Mg,Na,K
E.g.-MgS04-epson’s salts
MgO-(milk of magnesia)
Sodium phosphate

45. Mechanism:-
Osmotic purgatives are given orally, early morning on empty stomach with plenty of water
↓
Acts on the small & large intestines(within 1-3 hr)
↓
Not absorbed in the gut
↓
Draw fluid into the lumen by osmotic activity
↓
Distend the bowel
↓
Stimulate peristalsis
↓
Evacuation of watery stools in 1-3 hrs

46. • They should be avoided in young children & pt with renal failure-as
they may cause CNS & cardiac depressant
• Sodium phosphate- commonly used in colonoscopy
• Can also be used as enema
• Should be avoided in cardiac pt.
Polyethylene glycol-
Used to evacuate the bowel prior to surgical, Radiological and endoscopic
procedure

47. Stimulant or Irritant purgatives
 Acts via direct stimulation of enteric nervous system
 Leading to peristalsis & purgation
 Also ↑PG and cAMP levels but Na+,K+-ATPase activity in the intestinal mucosa
 Site of action-colon
 They cause evacuation –semi fluid stools
 SE:- upon chronic use-atonic colon
 Large doses may cause loss of fluid & electrolytes
 contraindicated- pregnancy(reflex stimulation of uterus)
E.g.-Bisacodyl, anthraquinone derivatives, castor oil

48. Bisacodyl Anthraquinone derivatives
Available- rectal n tab form
Oral absorption-poor
Preferred-at bed time(Effect seen
after-6-8hrs of admist.)
Uses:-
Constipation & empty the bowel before
endoscopy,surgery,radiological
investigation
SE:-local irritation,
Inflammation
Senna & cascara
Preferred-at bed time(Effect seen
after-6-8hrs of admist.)
Acts locally & induce purgation
Contraindicated in-lactating mother
as they secret by milk
SE:- skin rashes, black pigmentation
of colonic mucosa, discoloration of urine

49. Fecal softeners (lubricants)
Or Stool wetting agents
Non-absorbed drugs that soften the feces-promoting defecation
1. Surfactants- ↓ surface tension of faces
Commonly prescribed-hospitalized pt to minimized straining
e.g.-Docudate-sodium dioctyl sulfosuccinate/Enema
2.Glycerin(suppository)- given twice after surgey to avoid any damage to
the surgery.
Preferred- children
Mineral oil-(liquid paraffin) good for radiology preparation

50. CHOICE & USES OF PURGATIVES
1.Functional constipation-
a. Spastic Constipation(Irritable bowel)- dietary fibers
b. Atonic constipation –Bulk purgatives
2. Bedridden pt-bulk purgatives
3.To avoid straining at stools-bulk purgatives ,luctolose
4.Preparation of bowel for surgery, colonoscopy-bisacodyl

51. Emetics & Anti emetics
• Vomiting:- it is a complex series of protective reflex that help to remove toxic
substances from the gastrointestinal tract (GIT)
• It is the forceful expulsion of the contents of the stomach and upper intestinal
tract through the mouth
• Nausea:- the feeling of vomiting (↓gastric tone & peristalsis)
• Vomiting center-Reticular formation in medulla
• Stimulation of this center occur from cerebellum, cerebral cortex, CTZ, Nucleus
tractus solitarius(NTS)
• CTZ-unprotected by BBB
• Neurotransmitter:-involve in control of vomiting are acetylcholine (ACh),
histamine,5-hydroxytryptamine (5-HT) and dopamine

52. Medulla
Vomiting center
Stimulation
Chemoreceptor trigger
zone(CTZ)-Area
postrema
Cerebellum
Nucleus tractus solitarius
cortex
Smell, pain, sight,
psychogenic stimuli,
Past memory, Fear
+
+
Inner ear (Motion)
Ototoxic drugs like
Aminoglycosides
+ +
Drug induced vomiting (
Cytotoxic drug, opioids,
Cardiac glycosides,
Radiation,
Chemotherapy
Bacterial & viral infection)
+
+
+
GI irritation(Pharyngeal
gagging)
Pragnancy (oestrogen) +
M1,H1 receptor
H1,D2,5-HT3,M1,CB1,μ receptor
H1,D2,5-HT3,M1,NK1-receptor
CB1-Cannabinoid 1 receptor
NK1-Neurokinin1 receptor
μ-opioid receptor

53. Emetics:-
• Drugs that cause vomiting-emetics
• Uses:-
 Acute case of poisoning
Alcohol intoxication
Removal of foreign bodies from oesophagus
• Contraindication of emetics:-
In poisoning of any corrosive (danger of perforation)
CNS stimulant (precipitation of convulsion)
Kerosene poisoning (Aspiration pneumonia due to low viscosity)
Morphine or phenothiazine overdose (emetics are ineffective)
In unconscious pt.(laryngeal reflex impaired.)

54. • Apomorphine:-
• Semisynthetic derivatives of morphine
• Acts as dopaminergic agonist on CTZ
• Induce vomiting (within 5-10min) after administered I.M./S.C.
• Ipecacuanha:-
• Obtained from root of plant Ipecacuanha
• Contains emetine which is used as syrup
• Produce CTZ stimulation & gastric mucosal irritation
• Household remedy:- Mustard oil, strong salt solution can be use in emergency
• They act through stimulation of receptor in stomach
Drug induced vomiting:-
Anti-cancer drug, Apomorphine, chloroquine, quinine, Diltizem, ergot
derivatives, tetracycline, metronidazole

55. Anti-Emetics:-

56. Anti-cholinergic
• Drugs:- Hyoscine (Scopolamine),dicyclomine
• Used as transdermal patch in motion sickness
• Not effective-chemotherapy induced vomiting
• SE:-tachycardia, blurred vision, constipation, urinary retention
• Dicyclomine-effective in morning sickness + motion sickness
• Safe to use in pregnancy
• Anti-spasmodic action-use for colicky pain
• MOA:- Central anti-cholinergic, peripheral antimuscarinic & sedative properties
• USES:- effective against morning sickness, postoperative vomiting, motion
sickness, morning sickness, Meniere's disease
H1-Antihistaminics

57. • They are less effective→ substance induce vomiting by acting directly on CTZ
• Cyclizine, Meclizine→ (long acting) use for sea sickness
• Cinnarizine → Anti-vertigo drug. Additional action. i.e. inhibit influx of Ca++
from endolymph into the vestibular sensory cells which mediate labyrinthine
reflex.
• Morning sickness in pregnancy-(Doxylamine+VitB6) safe drug
• In motion sickness→ should be given half to one hour before journey
• These should be avoided in first trimester of pregnancy to avoid any foetal
damage
5-HT3 Receptor Antagonists
Drugs:- Ondansetron, granisetron, dolasetron and palonosetron.
MOA:- block the depolarizing action of 5-HT3 receptors or vagal afferents in
GIT as well as in CTZ & NTC
It blocks emetogenic impulses both of central & peripheral origin

58. • Advantage:- highly effective(DOC) for anti-cancer drug induced vomiting such
as cisplatin
• Disadvantage:- not effective for motion sickness
• Ondansetron:- prototype drug with short duration of action
• 5HT3 receptor Antagonist
• Pharmacokinetics:-
• Absorption-orally with BA of 70% (due to First pass metabolism)
• Distribution- through out the body
• Metabolism-(hepatic metabolism + glucuronide conjugation)
• Excretion-urine
Uses:-
Chemotherapy(cisplatin) induce vomiting-I.V. infusion
Post operative vomiting

59. • SE:- constipation, headache, rashes, hypotension
• Neuroleptics (D2-receptor Antagonist):-
• Antiemetic effect → blockade of D2-receptors in the CTZ
• D2 blocked in gut →↑gut motility
• Drugs:-phenothiazines, haloperidol
• Advantages:- antipsychotic action+ potent Anti-emetic action
• Disadvantages:-
Not effective → Motion sickness (Muscarinic & Histaminic receptors involve)
Cause Extra pyramidal side effect (EPS)
Prochlorperazine:-D2 blocking phenothiazine
Antivertigo and antiemetic actions- labyrinthine suppressant
Effective-Orally + i.v. preparation

60. Prokinetic Agents:-
• Agents which ↑propulsive gastric motility in coordinated manner to promote
gastric emptying
• Metoclopramide:-
• Prokinetic action due to 5-HT4 Agonist activity in GIT (Peripheral action)
• Central action→D2 blocked in CTZ
• Cumulative effect result in-↑↑gastric and duodenal emptying
• The effects of metoclopramide on the upper GI tract are:
1.↑tone of lower oesophageal sphincter (LES).
2. ↑tone and amplitude of antral contractions.
3. Relaxation of pyloric sphincter.
4. ↑peristalsis of small intestine.
Thus, it promotes forward movement of contents in the upper GIT.

61. Metoclopramide
5-HT4 agonism D2-antagonism 5-HT3 antagonism
↑↑ACh secretion from the myenteric motor neurons
Peristalsis
 Pharmacokinetics:-
 Absorption:-well absorbed orally
 Distribution- cross “BBB”-produce EPS (not seen with domperidone)
 Plasma t1/2-4-6hr.
 Metabolism-sulfation & glucuronide conjugation in liver
 Excretion-urine

62. • USES:-
Vomiting due to
drug induced, Radiation induced,
Post operative, Toxins induced
Post operative paralytic ileus, diabetic gastroparesis
GERD- but less effective than PPI or H2 blockers
Emergency surgery-as pt. May not be empty stomach (before GA)
SE:- sedation, drowsiness, dizziness and diarrhoea, EPS
Long-term use →gynaecomastia, galactorrhoea and menstrual irregularity
Interaction:-
Metoclopramide ×Diazepam- ↑absorption of diazepam(Toxicity)
Metoclopramide ×Digoxin-↓absorption of Digoxin (therapeutic failure)
Metoclopramide ×levodopa- interfering anti-parkinsonian effect(due to D2 blocked action )

63. Domperidone:-
• Similar anti-emetic action of metoclopramide
• Don’t cross “BBB”-No EPS →preferred in children
• Prokinetic action→due to blocked of D2 receptor
• less potent and less efficacious than metoclopramide
• Pharmacokinetics:-
• Absorption-orally effective but low BA (High first-pass metabolism)
• Distribution- Cant cross BBB
• Plasma t1/2-7-8hr
• Metabolism-liver
• Excretion- urine
• USES:-
• Vomiting in children
• levodopa induced vomiting in Parkinson pt.
• Drug induce vomiting-mild-moderate case

64. • Not effective→ sever vomiting, Morning sickness
• SE:-
• Hyperprolactinaemia-D2 blocked action (Pituitary devoid of BBB)
• Dryness of mouth,
• diarrhoea, headache,
• skin rashes, galactorrhoea and menstrual irregularities
• Dose-adult-10-40mg children-0.3-0.6mg/kg(TDS)
Mosapride:-5-HT4 agonist
Neurokinin-1 receptor blockers:- Aprepitant
These are substance-P antagonist that acts by blocking neurokinin-1 receptor
DOC-delayed chemotherapy induce nausea & vomiting
Use for PO nausea & vomiting

65. Adjuvant Antiemetics
• Glucocorticoids:-
• Dexamethasone, betamethasone and methylprednisolone are used as adjuvant
antiemetics.
• USES:-
Anticancer drug-induced vomiting:- in combination with ondansetron or
metoclopramide due to anti-inflammatory action by blocking PG synthesis
Benzodiazepines:- (sedative, amnesic and antianxiety effects)
Lorazepam and alprazolam are used to control psychogenic and anticipatory
vomiting.

66. Question paper:-
Q1. Write short notes on:- (2.5M)
 Metoclopramide (2.5M)
 Prokinetic Agents(3M/2.5M)
 Antiemetics-(3M)
 Ondansetron (3M)
Q2.Discuss the pharmacological basis of :-
Ondansetron in vomiting (3M)
Metoclopramide as prokinetic agent(3M)
Domperidone as antiemetic(3M)
Q3.Discuss treatment of:- Vomiting (3M)

67. DRUGS USED IN PEPTIC ULCER

68. • Acid peptic disease → includes
Peptic ulcer
GERD-gastroesophageal reflex disease
Zollinger-Ellison syndrome (ZE-syndrome)-pathological hypersecretory states
induced by gastrin secreting tumour
Ulcer→ occur in any part of GIT due to imbalance between aggressive(acid,
pepsin, and H.pylori infection) & defensive mucosal factor (gastric mucosa,
bicarbonates, prostaglandins)
Peptic ulcer- stomach & duodenum expose to acid(HCl) & pepsin
Factors affecting HCL secretion
Factor ↑Acid secretion
 Acetylcholine
 Histamine
 Gastrin
Factor ↓Acid secretion
 PGE2
 somatostatin

69. • Mucosal barrier:-
• Consist of →mucous & bicarbonate (HCO3-) secreted by neck cells of gastric
gland & surface of mucosal cells
• Function:-
Protection of GI-tract from infective, chemical, physical agents
It encloses the gastric juice in stomach (impermeable porcelain vase)
HCO3- is trapped in mucous gel together help in maintaining the pH gradient
of
Luminal side-pH (1-2)
Surface of epithelial cells-pH(6-7)
• PGs→ stimulate mucous+HCO3 secretion & also ↑mucosal BF
• Epithelial protection also involve though tight junction that serve as a physical
barrier
• HCL(gastric acid)→secreted from gastric parietal cells due to stimulation of
proton pump (H+/K+ ATPase pump)

70. • Physiology of Gastric secretion:-
• The stomach secretes -2–3 L of gastric juice/day.
• The chief or peptic cells secrete pepsinogen,
• Pepsinogen pepsin
• Parietal or oxyntic cells secrete acid and intrinsic factor (IF).
• Regulation of gastric acid secretion:-
• Receptor mediated binding of Ach(M3), histamine(H2), gastrin(CCK2) in the
activation of protein kinase→ stimulate proton pump to secrete H+ ions in
exchange for K+ into the lumen of stomach
• A Cl- channel couple chloride efflux to the release of H+
• In contrast receptor binding of PG E2 & somatostatin diminish gastric acid
production
Gastric acid

72.  Classification of drugs used in peptic ulcer:-
Reduction of gastric acid
secretion
H2 Antihistaminics
• Cimetidine,
• Ranitidine,
• Famotidine,
• Roxatidine
Proton pump
inhibitors(PPI)
• Omeprazole,
• Esomeprazole,
• Lansoprazole,
• Pantoprazole,
• Rabeprazole
Anticholinergic drugs
• Pirenzepine,
• Telenzepine
• Propantheline
Prostaglandin analogues:
• Misoprostol
Systemic
• Sodium bicarbonate,
• Sodium citrate
Non-systemic
• Magnesium hydroxide,
• Magnesium trisilicate,
• Aluminum hydroxide,
• Calcium carbonate.
• Sucralfate
• Colloidal bismuth
subcitrate (CBS).
• Amoxicillin,
• Tetracycline,
• Clarithromycin,
• Metronidazole,
• Tinidazole
Neutralization of Gastric acid(Antacids)
Ulcer protectives
Anti-H. Pylori drugs

73. • Gastric Anti-secretory Drugs:-
• H2 Receptor Blocker(Anti-Histaminics):-
• Drugs:-Cimetidine, Ranitidine, Famotidine, Roxatidine
Cimetidine is the prototype drug and was the first H2-blocker to be used in clinical
practice
MOA:-Competitively block H2 receptor on parietal cells→↓Acid production
↓Nocturnal acid secretion (histamine mediated) more effectively than acid
secretion stimulated by gastrin,Ach-most effective for duodenal ulcer
Famotidine-higher dose-blocks Non-Competitively
PPI Preferred over H2 blockers due to Side effect & potency
Pharmacokinetics:-
All absorbed orally-food doesn’t interfere with absorption
Lowest BA-Famotidine(40%) & highest BA-Nizatidine(>90%)
Cimetidine-Cross BBB produces CNS side effects especially in elderly patients

74. T1/2-1.5-4hr. Duration of Acting-6-12hr.
Excretion →urine
Cimetidine→not use due to First pass metabolism & antiandrogenic effect
Anti-androgenic effect-
reversible gynecomastia in male→↑prolactin release (higher dose)
Menstrual irregularities and galactorrhoea in women
Cimetidine× Phenytoin, digoxin, theophylline, warfarin, propranolol
(Cimetidine -enzyme inhibitor of Cytochrome-P450-may cause toxicity)
Famotidine-Most potent + longest Acting drug
less Side effect(Anti-androgenic effect) & less drug interaction
USES:-
Duodenal ulcer, gastric ulcer, stress induce ulcer, ZE syndrome, GERD

75. Proton pump inhibitors:-
Drugs:-Omeprazole, Esomeprazole, Lansoprazole, Pantoprazole, Rabeprazole
Irreversible inhibit H+K+ATPase pump(proton pump) plays an important role in
the final step of gastric acid secretion
Omeprazole is the prototype drug
MOA:- PPI(Prodrug)
↓
Activated in Acidic medium in canaliculi of parietal cells into sulfenamide
↓
Active form react with sulfhydryl group(-SH) in H+K+ATPase
↓↓
Irreversible inhibit proton pump
(Inhibit gastric acid secretion)

76. • Pharmacokinetics:-
• Absorption:-PPI→ degraded in Acidic pH of stomach (except-Pantoprazole)
• ↓BA-when taken with food (should be taken empty stomach/Enteric coated
gelatine capsule)
• Omeprazole+NaHCo3→combination therapy (↑pH of stomach→ prevent
degradation)
• Distribution-Highly bound to plasma protein
• They hv shorter t1/2-1-2hr but action last for more than 24hr.due to irreversible
inhibition (hit & run drug)
• Metabolism-sulfation by liver cytochrome-P-450(CYP3A4,CYP2C19)
• Excretion-urine
• Lansoprazole→ most potent, safe in pregnancy
• Pantoprazole, esomeprazole, lansoprazole→ can be given I.V. route
• Rabeprazole→ fastest onset of Action

77.  USES:-
1. Peptic ulcer:-
PPI →Preferred over H2-blockers due to rapid onset of action & ulcer healing.
omeprazole is 20 mg and lansoprazole is 30 mg once daily.
Duodenal ulcers- require 4-weeks therapy and gastric ulcers require 6–8-weeks
therapy for healing.
In acute bleeding ulcers-I.V. PPIs are preferred. (Pantoprazole)
H. pylori-associated ulcers:- triple & quadruple therapy (Lansoprazole)
Stress ulcers (Curling ulcer):- Prophylactic use of oral omeprazole /i.v.PPI
NSAID-induced ulcers:- PPIs are more effective
2. GERD-DOC-PPI(Esomeprazole most effective)
3. Zollinger–Ellison syndrome (Z–E syndrome):- PPI →DOC for Higher doses
of PPIs are needed for healing of ulcers. Surgery is the definitive treatment.

78. • SE:-
Uncommon-safe drug in short term use
Long term therapy-
Sever hypocholorhydria
Hypergastrinemia-include gastric hyperplasia
↓absorption of Vit-B12
Risk of hip fracture-↓Ca++ absorption
Interaction:-
• Omeprazole × Diazepam, phenytoin, warfarin→
• PPI inhibit metabolism (CYP2C19) leading to ↑plasma levels (interaction rare
with pantoprazole, rabeprazole)

79. Anti-cholinergic:-
• Drugs:- Pirenzepine,Telenzepine
• MOA:- Inhibit M1 receptor in intramural ganglia, histamine secreting cells,
gastric parietal cells
• ↓acid secretion at dose→that have minimal effect on heart, eye, bladder
• Oral efficacy equal to anti-histaminic(cimetidine) action in healing gastric &
duodenal ulcer
• SE:-dry mouth, blurring of vision
• Low efficacy
• side effects
Not commonly use
 Prostaglandin analogues:- Drug-Misoprostol-PGE1 Analogue orally effective
 Action-
 Inhibit Acid secretion
 Promote ↑HCO3 secretion

80. Cytoprotective action-
Reinforce mucus layer by ↑phospholipid content of surface epithelium &
↑mucosal BF
• USES-
• NSAID-induced gastric and duodenal ulcers→ Producing cytoprotective
• SE:-Nausea, diarrhea, abdominal cramp, dysmenorrhea
• Contraindication-
• Pregnancy-promote abortion (Abortifacients)
• Weak bases that neutralize GA (They don’t ↓ Acid production )
• ↑pH of gastric contents (optimum peptic activity between pH 2-4)
• Major role→ to provide prompt relief from ulcer pain
Neutralization of Gastric acid (Antacids)

81. An ideal antacid:-
 should be insoluble and capable of neutralizing acid.
should not liberate CO2
should be nonabsorbable
should not disturb the acid–base balance of the body
Types:- Systemic(absorbed from GIT),Local (poorly absorbed)
Systemic antacids:-
Sodium bicarbonate (NaHCO3):-
Water soluble short acting rapidly neutralizes gastric acid
Disadvantages :-
Highly Water soluble & rapidly dissolve from gut
pH raise above 7 cause alkalosis & CO2 accumulation in stomach
Release CO2 cause belching & gastric distension(perforation of ulcer can occur)

82. Contraindicated in chronic cardiac failure pt.→↑Na+ load cause water retention
Sodium citrate:- Action similar to NaHCO3 but no CO2 production
Use to treat systemic acidosis
Local Antacids:-
• Drugs:- Magnesium hydroxide, Magnesium trisilicate, Aluminum hydroxide, Calcium
carbonate
• Insoluble in water are poorly absorbed.
• formed chloride salt in stomach which react with bicarbonate
• HCO3¯ is not available for absorption, hence, there is no systemic alkalosis -no acid
base disturbance
• Combination of antacids produces various beneficial effects.
• 1. Aluminum salts cause constipation and magnesium salts cause diarrhea; so
combination of these two can counteract the adverse effects of each other.
• 2. Magnesium hydroxide has a rapid onset of action, but aluminum hydroxide acts
slowly—the combined product produces rapid and sustained effect.
• 3. Dose of individual antacid is reduced; hence systemic toxicity is minimized.

83. • SE of antacids:-
• 1. NaHCO3-cause systemic alkalosis and sodium overload.
• 2. Magnesium hydroxide- cause diarrhoea.
• 3. Aluminium hydroxide may produce constipation and phosphate depletion.
• 4. Calcium carbonate may produce hypercalcaemia and hypercalciuria.
• 5. Acid rebound can occur
• Drug interactions:-
• Antacids × iron, tetracyclines, fluoroquinolones, ketoconazole
(Antacids ↓ absorption of those drug by forming complex)
• These drugs forms a cover over ulcer surface
• Drugs- Sucralfate, Colloidal bismuth subcitrate (CBS)
Ulcer Protectives

84. • Sucralfate:-
• It is a complex of aluminium hydroxide and sulphated sucrose.
• MOA:-
• In the acidic environment of the stomach (pH <4)
Sucralfate
undergoes polymerization to form a sticky gel
Which bind to protein & glycoprotein in the ulcer
Form a protective coating which acts as barrier to acid, pepsin & bile salt
(Ulcer protecting action)
Cytoprotective effect by→↑PG release, ↑mucus & HCO3- secretion (↑mucosal defence)
Acidic medium (pH-4)
Stomach

85. • Sucralfate × Antacids-(for action acidic medium require)
• Sucralfate × digoxin, tetracyclines, ketoconazole, fluoroquinolones→
sucralfate↓absorption of these drugs (to be taken 2hr after the consumption of
these drugs )
• Minimal absorption-orally
• Should be given empty stomach & 1hr before meal
• Contraindication-Chronic renal insufficiency- Al toxicity occur
• SE:-constipation, Nausea
• Colloidal bismuth subcitrate (CBS):-
Most commonly used oral bismuth preparations
MOA:-
React with protein in the base of the ulcer and protect it from peptic digestion.
Stimulate the secretion of PGE2, mucus and bicarbonate.
Effective against H. pylori along with tetracycline, metronidazole etc.

86. • SE:-Nausea, vomiting, blackening of the tongue and stools
• H.Pylori infection:-
• Helicobacter pylori, a gram-negative, helical rod-shaped bacteria, is associated
with gastritis, duodenal ulcer, gastric ulcer and gastric carcinoma
• Bacteria Residing in deeper portion of mucus gel between mucus layer &
epithelium
• H.pylori produced urease which convert urea → NH3
• Developing countries-80% population infected
• Transmission occur→ contaminated water & food
• Diagnosis-biopsy urease test
• Single Antibiotic regimen → ineffective
• The objectives of combination therapy:-
• To prevent or delay the development of resistant organism.(relapse)
• Promote rapid ulcer healing→by eradicating H.pylori infection

87. Triple Therapy:- (for 2 weeks)
Lansoprazole-30mg BD
Any 2 of –
1.Amoxycillin-1000mg BD
2.Clarithromycin-500mg BD
3.Metronidazole-400mg
BD/Tinidazole-500mg BD
H.Pylori Regimens
Quadruple therapy:- (for 2 weeks)
1.Omeprazole-20mg BD
2.Colloidal bismuth subcitrate-120mg QID
3.Tetracycline-500mg QID
4.Metronidazole-400mg TDS

88. Question paper
• Q1. Write Drug treatment of: - H. Pyroli infection
• Q2. Write short notes on:- (2.5M)
 Omeprazole (2.5M)
 Proton pump inhibitors (5M)
• Q3. Briefly describe drug treatment of any:- Peptic ulcer
• 4.Discuss the following: -Therapeutic use of Clarithromycin in peptic ulcer (3M)
• 5.Describe the following: - Proton pump inhibitors (2.5 M)
• 6.Discuss the pharmacological basis of the use of: (5M)
 Omeprazole in peptic ulcer
 Sucralfate in peptic ulcer
 Antacids in GERD
 7. Classify drugs used for treatment of peptic ulcer. Discuss mechanism of action, uses and
adverse effects of proton pump inhibitors