TREATMENT OF PEPTIC ULCER

          TREATMENT OF PEPTIC ULCER 

Peptic ulcer was one of the most common gastric disease. After introducing drugs like proton pump inhibitors , antacids ,etc number of peptic ulcer cases have gone down drastically . 

Before learning about the drugs for treatment of peptic ulcer one must have a thorough knowledge about the physiology of peptic ulcer formation.

Peptic ulcer occurs due to imbalance between  DEFENSIVE FACTORS AND AGGRAVATING FACTORS

DEFENSIVE FACTORS                   

1. MUCUS                                     
2. BICARBONATE                        
3. MUCOSAL BLOOD FLOW 

AGGRAVATING FACTORS

1. GASTRIC ACID 
2. NSAID'S 
3. CORTICOSTEOIDS
4. HELICOBACTER PYLORI
5. ALCOHOL
6. SMOKING    
   
   Due to the imbalance, patient initially suffers through gastritis ie. inflammation of gastric mucosa due to gastric irritation by aggravating factors (alcohol,NSAID's,etc) .                 

       If this gastritis persists it will lead to peptic ulcer .
       This can be acute or chronic 

Next we will see about gastric acid synthesis and regulation which is very important to understand the mechanism of action of drugs .

Parietal cell is responsible for secretion of gastric acid.
Parietal cell is stimulated by number of factors :

1. When a person thinks about food , gastric acid gets secreted . it is because of stimulation in brain which transmits impulses via vagus nerve which in turn stimulates the M 1 receptor on the Enteric nervous system (ENS) . ENS will secrete Ach which will act on M 3 receptor of gastric mucosa . (REFER ABOVE DIAGRAM)
2. When food reaches the stomach G CELL gets stimulated . G cell produce gastrin , which will act on CCK-B receptor on parietal cell . thus secreting gastric acid .(DIAGRAM)
3. Histamines are released from Entero chromatoffin like cell -2 present in the sub mucosa . Released histamine will act on H2 receptor of parietal cell. ECL -2 secretes histamine throughout the day thus responsible for basal gastric acid secretion .(DIAGRAM)

Thus we saw about the physiology of gastric acid secretion . Next we will move on to the treatment of peptic ulcer .

DRUGS USED IN PEPTIC ULCER 

1. ANTACIDS 
2. PROTON PUMP INHIBITORS
3. H2 RECEPTOR ANTAGONISTS
4. ANTICHOLINERGICS M 1 BLOCKERS
5. DRUGS INCREASING PROTECTIVE FACTORS
6. ULCER PROTECTIVE DRUGS 
7. ULCER HEALING DRUGS 
8. ANTI HELICOBACTER DRUGS  

1)ANTACIDS

MECHANISM OF ACTION : These drugs are weak bases , they neutralize the gastric acid .
                                             
DRUGS: Sodium bicarbonate , Aluminium hydroxide , magnesium hydroxide , MEGALDRATE , Magnesium tricilicate .

PHARMACOKINETICS: 

1. All antacids are taken orally 
2. Only Sodium bicarbonate is absorbed systemically .
3. Sodium bicarbonate is faster acting but has short period of action
4. Other antacids are not absorbed . 
5. Other antacids have slower onset of action but have longer period of action  

USE: 

1. They give prompt pain relief in Peptic ulcer 
2. Treatment for Hypophosphatemia.

ADVERSE EFFECTS:

1. Sodium bicarbonate uses bleching and gastric distention due to the release of CO2
2. Aluminium hydroxide causes constipation 
3. Magnesium hydroxide causes diarrhoea .
   THUS combination of magnesium and aluminium hydroxide is used . It is called as MEGALDRATE .

 2)PROTON PUMP INHIBITORS 

MECHANISM : These drugs by irreversibly inhibiting H+K+ATPase in parietal cells . Thus meal stimulated and basal acid output is decreased .

DRUGS : Omeprazole , Pantoprazole , Lansoprazole , Rabeprazole

PHARMACOKINETICS :

1. These drugs taken orally and I.V
2. These are PRODRUGS.
3. They are converted to active form SULFENAMIDE (not sulphonamide which is an antibiotic. ) in Parietal cells .
4. They are metabolized in liver 
5. They are excreted in Urine

USE :

1. Peptic ulcer 
2. GERD
3. Zollinger-Ellison diesease
4. Lansoprazole is given in pregnancy 

ADVERSE EFFECTS :

1. Decrease Vit-B 12 absorption 
2. Decrease Ca absorption 
3. Decrease iron absorption 
4. Diarrhoea 

3)H2 RECEPTOR ANTAGONIST : 

MECHANISM: These drugs competitively inhibit H2 receptor in parietal cell , thus inhibits gastric acid secretion

Ach and Gastrin also acts partially by releasing histamine . Action of these agents are also decreased partially by these drugs .

DRUGS : Cimetidine , Ranitidine , Famotidine , Roxatidine

PHARMACOKINETICS :

1. Taken orally 
2. Systemic absorption of the drug happens
3. They are excreted unchanged in urine 
4. It crosses placenta 
5. Potency and Longer action ---- Cimetidine < Ranitidine < Famotidine < Roxatidine 

USES:

1. Peptic ulcer diesease
2. Drug of choice for stress induced ulcer 
3. GERD
4. Zollinger-Ellison Syndrome 
5. Prophylaxis of aspiration pneumonia  

ADVERSE EFFECTS :

1. Headache
2. Diarrhoea 
3. Cimetidine has anti-androgenic effect 
4. Cimetidine is an enzyme inducer 

ANTICHOLINERGIC DRUGS:

PIRENZEPINE AND TELENZEPINE are selective M1 blockers .

Thus used in peptic ulcer disease . 

DRUGS INCREASING PROTECTIVE FACTORS :

Prostaglandin E and Prostaglandin I2 play an important role in secretion of protective factors and inhibition of gastric acid secretion .

Thus Prostaglandin analogue can be given in peptic ulcer disease .

Prostaglandin E analogue called Misoprostol is the commoly used drug .

ULCER PROTECTIVE AGENTS :

MECHANISM: These drugs form a coating over the gastric mucosa and thus protect from the exposure of acid .

DRUGS:

1. SUCRALFATE 
2. COLLOIDAL BISMUTH SUBCITRATE

These drugs should not be given with antacids because these drugs are active only in acidic medium . Antacids creates a basic pH in stomach .

ULCER HEALING DRUGS :

CARBENOXOLONE is the drug for healing of ulcer .

ANTI HELICOBACTER PYLORI DRUGS :

Commonly used regimen for treatment of H.pylori is TRIPLE DRUG THERAPY .
TRIPLE DRUG THERAPY is
PROTON PUMP INHIBITOR (Lanoprazole 30mg or pantoprazole 40 mg ) + AMOXICILLIN 1000 mg + CLARYTHROMYCIN 500 mg twice daily for 2 weeks .

HERE ENDS THE TOPIC . IF ANYONE HAS DOUBTS OR HAS EXTRA POINTS TO ADD TO THIS BLOG  PLEASE DO COMMENT.