DRUGS ACTING ON THE GIT

DRUGS ACTING ON THE GIT
By: Zenaw T.(B.Pharm, MSc in pharmacology)
3/25/2021 ZENAW T.(B.Pharm, MSc in pharmacology) 1

DRUGS USED FOR CONTROL OF GASTRIC ACIDITY
Regulation of acid secretion
• Functionally, the gastric mucosa is divided into three areas of

secretion.
• Cardiac gland area- secretes mucus and pepsinogen.
• parietal gland area- secretes hydrogen ions, pepsinogen,

and bicarbonate.
• pyloric gland area in the antrum secretes gastrin and

mucus.

• The parietal cells secrete H+ in response to gastrin,
cholinergic, and histamine stimulation
• Gastrin (a stimulatory hormone)
 A peptide hormone synthesized in endocrine cells
 Its main action is stimulation of the secretion of acid by the

parietal cells
• Ach and Gastrin activate release of Histamine from

enterochromaffin-like cells (ECL) which stimulates H2 Rs on
parietal cells (the main pathway of proton pump activation)

• Histamine stimulation stimulate H+–K+ pump.
• The mucosal cytoprotection is provided by mucus and

bicarbonate secretion
• Locally produced prostaglandins (E2 & I2) inhibit acid secretion

and stimulate both mucus and bicarbonate secretion
• The principal pathological conditions in which gastric acid

secretion needs to be reduced include:
• Peptic ulcer
• Reflex esophagitis-in w/c gastric juice causes damage to

the esophagus
• Causes – Infection with gram-negative, H. pylori
- Increase HCl secretion
- Inadequate mucosal defense.
- stressful condition and foreign substances

including drugs

• Therapy of peptic ulcer and reflex esophagitis aims to
↓ the secretion of gastric acid with
o H2-receptor antagonists or
o Proton pump inhibitors
Neutralize secreted acid with antacids
Killing the bacteria

Secretion of H+ by parietal cells –Acid secretion
Regulators
of
Acid secretion
Ach
Histamine
Gastrin
ENS
cells
Fig: Targets of treating PUD
Interactions among an enterochromaffin-like (ECL) (secretes

histamine), a ganglion cell of the enteric nervous system (ENS), a Cholecystokinin receptor
parietal cell (secretes acid), and a superficial epithelial cell 2 (CCK2); EP3 receptor.
(secretes mucus and bicarbonate)
Treatment of peptic ulcer
 Eradicating the H. pylori infection
 Reducing secretion of gastric acid with the use of proton

pump inhibitors or H2-receptor antagonists
 Providing agents that protect the gastric mucosa from

damage such as misoprostol and sucralfate
 Neutralizing gastric acid with nonabsorbable antacids

Drugs used forb PUD and GERD
Antimicrobials
H2-receptor antagonists
Proton pump inhibitors
Prostaglandins
Antacids

A) Antacids
• Are weak bases that react with gastric acid to form H2O
& salts there by diminishing gastric acidity
• Less effective for gastric ulcers
• Antacids differ each other by
Onset and duration of action
Systemic effects
Special application
1. Magnesium hydroxide
• Insoluble powder reacts with HCl to form MgCl2+ H2O

and neutralizes gastric acid
Cont…
• rapidly acting
• Adverse effects
 Magnesium acts as osmotic laxative and causes

diarrhea
 Mg may accumulate to high level in patients with renal

impairmentCNS toxicity (encephalopathies)
2. Aluminum hydroxide
• Forms AlCl3 in the stomach & increases stomach PH
• Can relax gastric smooth muscle, delays gastric

emptying and causes constipation
Cont…
• Has long duration of action
• Serum phosphate levels also may become depressed

because of phosphate binding within the gut.
• Combinations of Mg2+ and Al3+ hydroxides provide

a relatively balanced and sustained neutralizing capacity;
(justify)
• Aluminum hydroxide + Magnesium hydroxide
• Calcium carbonate + Magnesium carbonate

Contd…
• Aluminum hydroxide causes constipation
• Magnesium hydroxide causes diarrhea
• The binding of phosphate by aluminum-containing
antacids can lead to hypophosphatemia
• Sodium bicarbonate
◦ Can cause systemic alkalosis
◦ Liberates CO2, causing belching and flatulence
◦ The sodium content of antacids can be an important
consideration in patients with hypertension or congestive
heart failure

Cont…
Use of antacids
• Dyspepsia
• Symptomatic relief of peptic ulcer
• Adjuncts for healing peptic ulcer (with H2-receptor

blockers and antimuscarinics)

Drug interaction of antacids.
• affect absorption, bioavailability and renal elimination in many
drugs
E.g. TTC (Al+3 Mg+2) form complex with the drug which is not
absorbable
• Al (OH)3  absorption of digitalis, oral anticoagulants,
ketoconazole & atropine
• alkalinize the urine
 ↑ excretion of acidic drugs
  excretion of basic drugs
– Food delays stomach emptying allowing more time for the

antacid to react

H2 – RECEPTOR ANTAGONISTS
• Includes
o Cimetidine, Ranitidine, Famotidine, Nizatidine
• MOA: bind to the H2-receptors on the cell membranes of

parietal cells and prevent histamine induced stimulation of
gastric acid secretion.
• Have differences in their relative potency,
• Used for healing 70 to 85% of duodenal ulcers with 4 to 6

weeks of therapy

Cont…
• After prolonged use, down-regulation of receptor production

occurs, resulting in tolerance to these agents.
• Especially effective at inhibiting nocturnal acid secretion.
 Night time-only dosing can be used.
a.Cimetidine
• Therapeutic uses:- Gastric & Duodenal ulcers & Gastro

esophageal reflex disease (heart burn)-low doses of H2-
antagonist

Adverse effects:-
 CNS: headache, dizziness
 Endocrine effects: Altered lactation, galactorhea in females;
gyneacomastia and impotence in males due to prolactin
stimulating & antiandrogenic effect
• Drug interaction:
 Cimetidine inhibits liver microsomal enzyme so slows
metabolism of many drugs for example:-Warfarin, Diazepam,
phenytoin, theophylline & Imipramine
 ↓ed efficacy of PPIs
 Drugs such as ketoconazole, which depend on an acidic medium
for gastric absorption, may not be efficiently absorbed if taken
with H2 blockers

b. RANTIDINE
• Similar to Cimetidine
• But differ in that rantidine
Is more potent than Cimetidine
Produce fewer adverse effects
Causes fewer drug interactions
c. FAMOTIDINE AND NIZATIDINE
• Very similar to ranitidine
• No anti-androgenic effect
• Do not suppress the metabolism of other drugs
Note: Potency of famotidine

3/25/2021
>ranitidine>cimetidine
ZENAW T.(B.Pharm, MSc in pharmacology) 19
PROTON PUMP INHIBITORS
• Includes
– Omeprazole ,Lansoprazole ,esomeprazole,Pantoprazole

,Rabeprazole
Mechanism of action
These are substituted benzimidazole prodrugs, which
accumulate on the luminal side of parietal cells’ secretory
canaliculi.
 They become activated by acid transport and then

bind covalently to the actual H+ –K+ ATPase enzymes
3/25/2021 (proton pumps); irreversibly

ZENAW blocking them.
T.(B.Pharm, MSc in pharmacology) 20
Pharmacokinetics
 The prodrugs are unstable in the presence of acid and

therefore must be administered as
Enteric-coated drugs
Powdered drug combined with sodium bicarbonate

(omeprazole)
 These drugs ideally should be given about 30 minutes before

meals.
 Rate of absorption may be reduced by food.

 PPIs are prodrugs with an acid-resistant enteric coating to
protect them from premature degradation by gastric acid
 The coating is removed in the duodenum, and the prodrug
is absorbed and transported to parietal cells
 There, it is converted to the active form, which forms a
stable covalent bond with H+/K+-ATPase
 It takes about 18 hours for the enzyme to be resynthesized
 At standard doses, all PPIs inhibit both basal and stimulated
gastric acid secretion by ~90%.
 Approved for the treatment of GERD and have gained
favor over H2 antagonists
 PPIs reduce the risk of bleeding from an ulcer caused by
aspirin and other NSAIDs
3/25/2021
Used with antimicrobial regimens
ZENAW T.(B.Pharm, to eradicate H.pylori 22
MSc in pharmacology)
Omeprazole
Therapeutic uses
• Gastric and duodenal ulcers
• Severe gastroesophageal reflux
• NSAIDs-induced Pus
• Pathologic hypersecretory syndromes such as Z-E

syndromes
• As one component of therapy for Helicobacter pylori

infection

Adverse effects
• Headache, diarrhea, rashes, dizziness, mental confusion, etc
• Hypergastrinemia due to the marked reduction in acid

secretion.
Precautions and contraindications

• Should be used in caution in
Patients with liver d/se
Women who are pregnant or breast feeding

MUCOSAL PROTECTIVE AGENTS
1. SUCRALFATE
• is an aluminum hydroxide–sulfated sucrose complex that is

only minimally absorbed from the GI tract.
MOA
• Form complex gels with mucus
• ↓ degradation of mucus by pepsin
• Limit diffusion of H+
• Other effects are a direct reduction in pepsin activity and a

slight rise in tissue prostaglandin levels.
Therapeutic use
• Frequently used for prophylaxis of stress-induced gastritis in
patients in intensive care units.
• Treatment of duodenal ulcers
Adverse
• Constipation =main side effect.
• Less common- dry mouth, nausea, vomiting, headache, rashes
• Has no systemic side effects

Drug interaction
• Sucralfate requires acidic pH to be activated
• Should not be administered with
H2-blockers, PPIs and non-buffer antacids
• It reduces the absorption of a no. of other drugs
– e.g. theophylline, TTC, digoxin, amitriptyline

BISMUTH COMPOUNDS
• Includes- bismuth subsalicylates, bismuth subcitrate
MOA
• Proposed mechanisms include
Formation of a protective coating over the ulcer base
↑ secretion of HCO3 and PGs
Suppressing the growth of H. pylori
Therapeutic uses
• Provide a physical barrier over the surface of the ulcer

Adverse effects
• Generally well tolerated
• Nausea & vomiting
• Blackening of the tongue & feces.
• Should be given with caution for patients with renal impairment

PROSTAGLANDIN ANALOGUE
• MISOPROSTOL
MOA
• It inhibits gastric acid secretion
• Maintains or increases secretion of mucus & bicarbonate
• ↑ mucosal b/d flow by promoting vasodilation
Therapeutic use
• Prevent NSAIDs-induced ulcers.
• Promote the healing of ulcers
Adverse effects
• Diahrraoea, abdominal
3/25/2021 cramps,
ZENAW T.(B.Pharm, dysmenorrhea
MSc in pharmacology) 30
Drugs against H. pylori induced PUD
• For patients with peptic ulcer disease who are infected with
H.pylori
• Successful eradication is possible with combinations of

antimicrobial drugs and antisecretory
 Initial treatment (triple therapy for about 14 days)
• Amoxicillin lg p.o. bid
• Clarithromycin 500mg p.o. bid
• Omeprazole 20mg p.o. bid (40mg once daily)

Cont…
• Alternative
– Amoxicillin lg p.o bid
– Metronidazole 500mg p.o bid
– Omeprazole 20mg bid
 Quadraple therapy for 14 days
• Metronidazole (250mg tid) + bismuth cpd (120mg qid)
+ TTC (500mg qid) + Anti H2 or proton pump
inhibitor

EMETICS & ANTEMETICS
 Vomiting is the ejection/expulsion of gastric content through

the mouth.
 Are protective reflexes that prevent further absorption from

the GIT.
 Etiology
 GI, Neurologic, metabolic, drug, pregnancy, irritant

food/drug, noxious odors

Structures involved in regulation of emesis
 Central emesis center (medulla)
 Afferent impulses
Chemoreceptor trigger zone (CTZ)
• Receptors: Serotonin (5-HT3), Dopamine (D2), and

Opioids
Cerebral cortex
Vestibular system:- rich in M1 and H1 receptors
Visceral afferents from pharynx and GIT: rich in 5-HT3

receptor
 Efferent impulses to
Salivation center
Respiratory center
Pharyngeal, GI and abdominal muscles
• The main neurotransmitters evolved in the control of

vomiting are: -
– Acetycholine
– Histamine
– 5-HT – 5HT3 in CTZ
– Dopamine – D2 in CTZ
Antiemetics
• Used for Motion sickness, Morning sickness & Vomiting

caused by GI disorders, various drugs and diseases. The
drugs include
 Antihistamines
 Anticholinergics
 Canabinoids
 Centrally acting Dopamine antagonists
 5-HT3 Receptor Antagonists

1. ANTIHISTAMINES
• Include- dimenhydrinate, Diphenhydramine, Meclizine

and Promethazine
• Block peripheral stimulation of the emetic center.
• Are most effective in motion sickness
• However, not effective against substances that directly on the

CTZ.
• Promethazine is effective for treating motion sickness

2.MUSCARINIC RECEPTOR ANTAGONISTS
• Hyoscine (scopolamine) is the most commonly

employed for antiemetic effects
• Principally for prophylaxis and treatment of motion

sickness.
• Their GI effects(ed motility, secretion and spasm) tend to

reduce enteric stimulation of the vomiting center
• Use of antihistamine and anticholinergic drugs is limited by

sedation, dizziness, confusion, dry mouth, cycloplegia, and
urinary retention.

3.PHENOTHIAZINES DERIVATIVES
• Chlorpromazine, prochlorperazine, trifluperazine,

triethylperazine
• Act at the CTZ by inhibiting dopaminergic transmission.
• For vomiting caused by
– radiation sickness, uremia, liver disease and migraine
– For cancer chemotherapy and toxin induced vomiting.
• Not effective in motion sickness.
• SE: - Sedation, hypotension, extrapyramidal

symptoms

METOCLOPROMIDE
MOA
• Blocks dopamine D2 receptors in the CTZ
• Increase upper GI motility by increasing the action of Ach
• Well absorbed by all routes
Therapeutic uses
• Antiemetic for vomiting induced by drug, disease
• Effective against the highly emetogenic drugs e.g. cisplatin
• Reflex oesophagitis

S/E
• Drowsiness, fatigue, insomnia, and altered motor

coordination.
• Galactorrhea & menstruation disorder
• Contraindicated for persons with a history of seizures and

hypersensitivity
5-HT ANTAGONISTS
• Odansetron, Tropisetron, Granisetron

• Antagonists of 5-HT3 receptors which are found peripherally
on vagal nerve terminals and centrally in the CTZ.
DRUG THERAPY FOR CONSTIPATION
• Constipation is defined as the infrequent passage of

stool.
 Causes
Lack of dietary fiber, drugs, hormonal

disturbances, neurogenic disorders, and systemic
illnesses.
In most cases no specific cause is found.
Laxatives and purgatives (Cathartics):-
• Are drugs which promote evacuation of the bowel

 Laxatives cause the evacuation of formed fecal material from the
rectum while
 Cathartics cause evacuation of unformed, usually watery fecal
material from the entire colon.
• Cathartics and purgatives imply strong effect
• Clinically indicated for
To relieve constipation
Prevent straining
Empty the bowel in preparation for bowel
surgery or diagnostic procedures.
C/I to laxative use
Undiagnosed abdominal pain, or vomiting
In the presence of obstruction of the bowel
The laxatives include:
1. Bulk forming laxatives
• Are substances that are largely unabsorbed from the intestine
• When water is added, these substances swell and become jel like
which increase the bulk of the fecal mass that stimulates peristalsis
and defecation. Eg. Psyllium, methylcellulose
• DOC in chronic constipation
• Because their use results in increased water content in the

feces, the patient should be advised to drink adequate amounts
of water; otherwise dehydration may result.

2.Osmotic laxatives
• Cause osmotically mediated water retention, which then
stimulates peristalsis
• Laxatives containing Mg cations and phosphate anions are called

saline laxatives
 Use
• To correct temporary constipation
• Used as adjuncts in the treatment of poisoning to hasten removal of

some poisons from the GI tract.
Adverse reaction
• Cause dehydration of the body and electrolyte disturbances

3. STIMULANT LAXATIVES
• Act on the mucosa of the intestine to stimulate peristalsis

either by irritation or by exciting reflexes in the
myenteric plexuses.
• All act in the lumen of the GI tract and are inactive if given
parenterally.
• Eg. Castor oil, Bisacodyl, Cascara sagrada and glycerine

i. Bisacodyl
• Is an irritant/stimulant laxative
• Available as an enteric coated tablet
• To avoid gastric irritation, patients should swallow

tablet with out chewing.
ii. Castor oil
• Is a test less oil that is hydrolyzed in the gut to yield ricinoleic

acid, the active purging agent
• This hydrolysis requires bile
• Given as a laxative before radiography in biliary

obstruction
DRUGS USEFUL FOR TREATING DIARRHEA
• Diarrhea is the frequent passage of liquid feces
Causes
– Infection- mostly virus, but also bacteria’s
– Chemical irritants
– Inflammation of the bowel
– Excessive parasympathetic activity
Mgt is directed at
– Diagnosis and treatment of the underlying causes,
– Replacement of lost water and salt
– Relief of cramping,
3/25/2021 ZENAW Reducing the passage of unformed stools
ANTI DIARRHEAS AGENTS
 Oral rehydration therapy therefore is a

cornerstone for patients with acute illnesses
resulting in significant diarrhoea.
Q. what are the components of ORS? The reason

of combining glucose in the preparation?
Pharmacotherapy of diarrhea should be reserved

for patients with significant or persistent
symptoms.
• Anti diarrheas agents can be
• Specific agents
– Anti-infective
– Drugs for malabsorption syndrome
• Non-specific agents
Act on or with in the bowel to provide symptomatic

relief
Not influence the actual causes

1. Antimotility Agents
a. OPIOIDS
• Well known antidiarrheal
• Limited use CNS effects and potential for addiction
• Increase colonic phasic segmenting activity through
inhibition of presynaptic cholinergic nerves in the
submucosal and myenteric plexuses Increased colonic
transit time and fecal water absorption.

Cont’d
Loperamide
a Non prescription opoid agonist
Meperidine analog
• Does not cross the blood-brain barrier
• has no analgesic properties or potential for

addiction.
• Adverse effects associated with its use include abdominal

pain and distention, constipation, dry mouth,
hypersensitivity, and nausea and vomiting.

Cont’d
B. anticholinergic
• Rarely used alone in treating diarrhea
• But may be used as adjuncts in combination with

adsorbents
• Can relieve cramping associated with diarrhea

2.Adsorbents
• Includes
o Pectin, Kaolin, Charcoal
• They adsorb intestinal toxins or microorganisms or

coat intestinal mucosa
• May be useful in acute diarrhea but are seldom used on

a chronic basis.
• The adsorbents are generally safe, but they may interfere

with the absorption of some drugs from the GI tract.
• Should not be taken within 2 hours of other medications

(which they may bind).
DRUGS AFFECTING THE
RESPIRATORY SYSTEM

Physiology of respiration
• Respiration is a process of exchange of oxygen and carbon

dioxide b/n the atmosphere and the cells of the human body.
• Autonomic pathways innervate the airways
o Parasympathetic innervations
M3 R are found on bronchial smooth muscle and

glands
 Mediate bronchoconstriction and mucus secretions
Stimulation of the vagus causes bronchoconstriction

Cont’d
o Sympathetic
β-adrenoceptors are abundantly expressed on

human airway smooth muscle
β-agonists relax bronchial smooth muscle
• The common Respiratory disorders
Asthma
Cough
rhinitis

BRONCHIAL ASTHMA
• Is a chronic reversible airway obstruction characterized by
cough, shortness of breath, chest tightness, wheezing
and rapid respiration
• Symptoms are produced by reversible narrowing of the airway,

which increases resistance to airflow and consequently reduces
the efficiency of movement of air to and from the alveoli.
• In addition to airway obstruction, cardinal features of asthma

include inflammation and hyper-reactivity of the airway

• Factors that contribute to airway obstruction in asthma
 Contraction of the smooth muscle that surrounds the

airways
 Excessive secretion of mucus and in some, secretion of

thick mucus that adheres to the walls of the airways
 Edema of the respiratory mucosa.
Airway Inflammation
• Antigens, such as pollen, sensitize individuals by eliciting the

production of antibodies of the IgE type.
• Antibodies attach Antigens to the surface of mast cells and

basophils.
• If the individual is re-exposed to the same antigen days to
months later, the resulting antigen–antibody reaction on lung
mast cells triggers the release of histamine and the cysteinyl
leukotrienes, that produce bronchoconstriction, mucus
secretion, and pulmonary edema.
• Mast cells also release a variety of chemotactic mediators,

such as leukotriene B 4 and cytokines.
• These agents recruit and activate additional inflammatory

cells, particularly eosinophils and alveolar macrophages,
both of which are also rich sources of leukotrienes and
cytokines.
• Ultimately, repeated exposure to antigen establishes a chronic
inflammatory state in the asthmatic airway.
Mediators of Bronchial Asthma
– Histamine
– peptides (kinins)
– Arachidonic acid derivatives (prostaglandins)
– leukotriens and platelet activating factors

TREATMENT STRATEGY
• Overall objectives of therapy are to return lung function to as
near normal as possible and to prevent acute exacerbations
of the disease.
• Primary classes of antiasthma drugs are bronchodilators

and anti-inflammatory agents.
• Bronchodilators are used both in maintenance therapy and as

needed to reverse acute attacks
• Based on the underlying Pathophysiology of the disease, anti-

inflammatory therapy must be used in conjunction with
Bronchodilators in all but the mildest asthmatics.
The drugs are classified into
1. Bronchodilators- are often referred to as relievers
– Β2-adrenergic agonists
– Methylxanthines
– Muscarinic antagonists
– Leukotrienes modifiers
2. anti-inflammatory- are also called controllers
– Glucocorticoids
3. mast cell stabilizers e.g. Cromolyn sodium

fig-Mechanism of bronchodilators
1.BETA2 (β2)- ADRENOCEPTOR AGONISTS
• Includes:
 Non- selective β agonist:-epinephrine, isoproterenol
 the selective β2-adrenoceptors, including Albuterol

(Ventolin, Salbutamol), terbutaline, and salmeterol
• This class of agents has become the mainstay of modern

bronchodilator therapy
• agents are used both as needed to reverse acute episodes of

bronchospasm and prophylactically to maintain airway
patency over the long term.
MOA
• Stimulation of 2-receptor on bronchial smooth muscle cells
activates adenylate cyclase consequently increasing cytosolic
cAMP  bronchial relaxation
• Stimulation of 2- receptor in inflammatory cells increases
intracellular cyclic AMP, activating a signaling cascade that
inhibits the release of inflammatory mediators and cytokines.

Classified as
• SABA e.g. Salbutamol, terbutaline, metaproteranol
 used for symptomatic relief of asthma
 Terbutaline and albuterol are administered either orally or by inhalation
 maximum effect occurs within 30 minutes and duration of action3-5

hrs
 Effective in prevention of exercise-induced asthma

• LABA e.g. Salmetrol, Formetrol
o Higher lipophilicityresponsible for the extended effect
o Used for maintenance tt of asthma
o Taken regularly
o Used in adjunctive therapy in patients whose asthma is inadequately

controlled by glucocorticoids
o Salmeterol is given by inhalation only
 Its long duration of action makes salmeterol

particularly suitable for prophylactic use, such as in
preventing nocturnal symptoms of asthma
 Not used to reverse acute symptoms.

Adverse effects
• Inhaled drugs have relatively few side effects
• muscle tremor, which results from a direct stimulation

of β2 –adrenoceptors in skeletal muscle.
• β2-Agonists also cause tachycardia and palpitations in

some patients.
Oral Therapy with β- Agonists
• Not generally recommended for routine use due to

adverse effects
• Situations where oral therapy is used
 In children (< 5 yrs) who can not manipulate

metered-dose inhalers (albuterol or metaproterenol
syrups)
 In some severe asthma exacerbations, aerosols can

worsen cough and wheezing by causing local irritation

2.Methylxanthines
• The three important methylxanthines are theophylline,

theobromine, and caffeine from beverages of tea,
cocoa, & coffee, respectively
• Theophylline: Not frequently used nowadays due to the

greater effectiveness of β2-agonists and glucocorticoids. Its
lower cost is the main reason behind its use in some
settings.
• Aminophylline: theophylline-ethylenediamine complex is the

drug preparation in the treatment of asthma.

MOA
• Inhibits PDE enzyme, thus causing increased cytosolic

levels of cAMP
Cardiac stimulation
Smooth muscle relaxation
Decreased release of inflammatory mediators from

mast cells
• Adenosine receptor blocker
Blockade of adenosine mediated bronchoconstriction

Pharmacological effects of methylxanthines
• CNS- Alertness, deferral of fatigue, nervousness, insomnia,
Convulsion and death at very high doses
• CVS  Direct +ve inotropic and chronotropic effect
• GIT  Stimulation of secretion of both gastric acid and

digestive enzymes
• KidneyWeak diuretics
• Smooth Muscle  Bronchodilation: the major therapeutic

action in asthma.
• Skeletal MuscleStrengthen the contractions of isolated

skeletal muscle like diaphragm. They improve airflow in
patients with dyspnea
3/25/2021 ZENAWor hypoxia
Cont’d
Clinical uses: anti asthmatic in patients who do not

respond to β2 agonists in acute condition
– Nowadays has less prominent role primarily because

of the modest benefits it affords, its narrow
therapeutic window, and the required monitoring of
drug levels
Adverse effects
• It has a narrow therapeutic window and produces side

effects that can be severe, even life threatening
• GI: anorexia, nausea, vomiting, abdominal discomfort

• CNS effects-stimulant effect causing nervousness, tremor,
insomnia, anxiety
• CVS-Positive inotropic and chronotropic effects, vasodilation in

most blood vessels
• Theophylline should be used with caution in patients with

myocardial disease, liver disease, and acute myocardial
infarction.
• Drug interaction
– Drug that decrease theophlline levels
o Phenobarbitone, phenytoin, rifampicin,
– Drug that increase theophylline levels: Erythromycin,

3.ANTICHOLINERGICS
• Anticholinergic agents are less effective than β2-agonist
• Ipratropium bromide is a quaternary amine derivative that is

used via inhalation in the treatment of COPD and to a lesser
extent, asthma with albuterol.
Adverse Effects
• Ipratropium is virtually devoid of the CNS side effects
associated with atropine.
• The most prevalent peripheral side effects are dry mouth,

headache, dizziness, nausea.
GLUCOCORTICOIDS
MOA
• The anti-inflammatory effects of glucocorticoids in

asthma include
Decrease synthesis and release of inflammatory

mediators (esp. that of cytokines)
Decrease infiltration and activity of inflammatory cells
Reduces bronchial hyper-reactivity
Up-regulation of -adrenoceptor number  increase

responsiveness to β2-agonist

• Preparation
 Oral
• Prednisolone
• Methyl prednisolone
 Inhalational
• Beclomethasone
• Dexamethasone
• Triamicinolone
• Flunisolide
• Fluticasone
 Injectable :-Hydrocortisone
Cont’d
Clinical use of corticosteroids
• Inhaled corticosteroids are used for maintenance

treatment of asthma as prophylactic therapy
• Inhaled corticosteroids are not effective for relief
of acute episodes of severe bronchospasm
• Systemic corticosteroids are used for the short-term
treatment of asthma exacerbations that do not respond
to β2- agonists and aerosol corticosteroids.

Cont’d
• Because of the side effects produced by systemically
administered corticosteroids, they should not be used for
maintenance therapy unless all other treatment options
have been exhausted.
Adverse Effects and Contraindications
• Systemic administration of the corticosteroids
Adrenal suppression, cushingoid changes, growth

retardation, cataracts, osteoporosis, CNS effects and
behavioral disturbances, and increased susceptibility
3/25/2021 to infection. ZENAW T.(B.Pharm, MSc in pharmacology) 82

Cont’d
• Inhaled corticosteroids
o Generally well tolerated
o Are either poorly absorbed or rapidly metabolized and

inactivated and thus have greatly diminished systemic
effects relative to oral agents.
o The most frequent side effects are local and include oral
candidiasis, dysphonia, sore throat and throat irritation,
and coughing.
o Special delivery systems (e.g., devices with spacers) can

minimize these side effects.
CROMOLYN SODIUM AND NEDOCROMIL
• Are Chromones
• Both administered by inhalation and have very good safety

profiles, making them particularly useful in treating children
• MOA: The exact MOA in asthma is not known
 Inhibiting mediator release from mast cells, suppressing the

activating effects of chemotactic peptides on human
neutrophils, eosinophils, and monocytes, inhibiting
parasympathetic and cough reflexes and inhibiting leukocyte
trafficking in asthmatic airways.
• . 3/25/2021 ZENAW T.(B.Pharm, MSc in pharmacology) 84

Clinical Use
• Cromolyn sodium and nedocromil sodium are used for the

prophylactic treatment of mild to moderate asthma and
should not be used for the control of acute bronchospasm.
Adverse effects
• Generally well tolerated
• Include transient bronchospasm, cough or wheezing,

laryngeal edema, joint swelling and pain, angioedema,
headache, rash, and nausea.

Severe acute asthma (status asthmaticus)
• Is a medical emergency requiring hospitalization.
• Treatment includes
– oxygen (in high concentration, usually 60%),
– inhalation of salbutamol given by nebuliser
– IV hydrocortisone followed by a course of oral

prednisolone .
• Additional measures occasionally used include
– nebulised ipratropium,
– intravenous salbutamol or aminophylline , and

3/25/2021
antibiotics (if bacterial infection is present).
ZENAW T.(B.Pharm, MSc in pharmacology) 86
Cough
• Cough is a useful physiological mechanism
 clear the respiratory passages of foreign material and

excess secretions (useful/productive cough)
The cough reflex
• Involves the central and peripheral nervous systems, as well as
the smooth muscle of the bronchial tree.
• Irritation of the bronchial mucosa ⇒ Bronchoconstriction ⇒
Stimulates cough receptors (stretch receptor) in
tracheobronchial passages ⇒Afferent fibers of the vagus nerve
⇒ cough centers in the CNS (medulla)

Treatment approaches
• Two approaches of t/t
– Specific t/t: treat the cause (bacteria, virus…)
– Non-specific t/t: to relieve symptoms
• Include: -expectorants and mucolytics
-demulcents
-Antitussive

Expectorants
• Stimulate the production of respiratory secretions
• Facilitate removal of mucus by increasing volume and

decreasing viscosity of bronchial secretion
E.g. Guaifenesine, iodide,NH4Cl products
Guaifenesine
• is the only OTC expectorant recognized as safe and effective by

the FDA.
• S/E-diarrhea, drowsiness, nausea or vomiting and stomach pain
note: NH4Cl should be avoided in pts with renal, hepatic and

heart
3/25/2021
diseases ZENAW T.(B.Pharm, MSc in pharmacology) 89
MUCOLYTIC AGENTS
• React directly with mucus to make it more watery
• Acetylcysteinemost common and effective
Decrease the viscosity of mucus
Adverse reactionsburning sensation and nausea
Have unpleasant odor

• Antitussives-suppress cough
• Used to treat dry, non productive cough
• Two major groups
1. Opioid antitussive-Codeine and hydrocodone
• Act within the CNS to elevate the cough threshold
• Effective and less addiction liability

• Decrease secretions in the bronchioles
2. Non-opioid antitussive
a. DEXTROMETORPHAN
• As effective as codeine
• Act within the CNS
• Used as active ingredients in most antitussive non-
prescription preparations
b. DIPHENHYDRAMINE
• Antihistamine with the ability to suppress cough
• Has sedative and anticholinergic properties
• N.B. Cough suppressants and expectorants should not be
combined. Why?

Drugs Used to Treat Allergic Rhinitis
• Rhinitis is an inflammation of the mucous membranes of the
nose and is characterized by sneezing, itchy nose/eyes, watery
rhinorrhea, and nasal congestion.
• An attack may be precipitated by inhalation of an allergen

(such as dust, pollen, or animal dander).
• The foreign material interacts with mast cells coated with IgE
generated in response to a previous allergen exposure

• The mast cells release mediators, such as histamine,
leukotrienes, and chemotactic factors, that promote
bronchiolar spasm and mucosal thickening from edema
and cellular infiltration.
• Combinations of oral antihistamines with

decongestants are the first-line therapies for allergic
rhinitis.
A. Antihistamines (H1-receptor blockers)
e.g. Diphenhydramine, Chlorpheniramine, and Loratadine
B. alpha1-Adrenergic agonists
Short-acting agonists such as phenylephrine, and Longer-
acting oxymetazoline constrict dilated arterioles in the nasal
mucosa and reduce airway resistance
C. others
Corticosteroids- Beclomethasone, budesonide, fluticasone,
flunisolide, and triamcinolone, are effective when administered
as nasal sprays
• Topical steroids may be more effective than systemic

antihistamines in relieving the nasal symptoms of both allergic
and nonallergic rhinitis.
Cromolyn
• Intranasal cromolyn may be useful for prophylaxis when

administered before contact with an allergen, at least 1 to 2
weeks prior to allergen exposure.

DRUGS ACTING ON THE GIT

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DRUGS ACTING ON THE GIT

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DRUGS ACTING ON THE GIT

By: Zenaw T.(B.Pharm, MSc in pharmacology)

3/25/2021 ZENAW T.(B.Pharm, MSc in pharmacology) 1

Regulation of acid secretion

• Functionally, the gastric mucosa is divided into three areas of

• Cardiac gland area- secretes mucus and pepsinogen.

• parietal gland area- secretes hydrogen ions, pepsinogen,

• pyloric gland area in the antrum secretes gastrin and

3/25/2021 ZENAW T.(B.Pharm, MSc in pharmacology) 2

• Gastrin (a stimulatory hormone)

 A peptide hormone synthesized in endocrine cells

 Its main action is stimulation of the secretion of acid by the

• Ach and Gastrin activate release of Histamine from

3/25/2021 ZENAW T.(B.Pharm, MSc in pharmacology) 3

• The mucosal cytoprotection is provided by mucus and

• Locally produced prostaglandins (E2 & I2) inhibit acid secretion

• The principal pathological conditions in which gastric acid

• Reflex esophagitis-in w/c gastric juice causes damage to

- Increase HCl secretion

- Inadequate mucosal defense.

- stressful condition and foreign substances

3/25/2021 ZENAW T.(B.Pharm, MSc in pharmacology) 5

↓ the secretion of gastric acid with

o Proton pump inhibitors

Neutralize secreted acid with antacids

Killing the bacteria

3/25/2021 ZENAW T.(B.Pharm, MSc in pharmacology) 6

Fig: Targets of treating PUD

Interactions among an enterochromaffin-like (ECL) (secretes

 Reducing secretion of gastric acid with the use of proton

 Providing agents that protect the gastric mucosa from

 Neutralizing gastric acid with nonabsorbable antacids

3/25/2021 ZENAW T.(B.Pharm, MSc in pharmacology) 8

3/25/2021 ZENAW T.(B.Pharm, MSc in pharmacology) 9

• Less effective for gastric ulcers

• Antacids differ each other by

Onset and duration of action

• Insoluble powder reacts with HCl to form MgCl2+ H2O

 Magnesium acts as osmotic laxative and causes

 Mg may accumulate to high level in patients with renal

• Forms AlCl3 in the stomach & increases stomach PH

• Can relax gastric smooth muscle, delays gastric

• Serum phosphate levels also may become depressed

• Combinations of Mg2+ and Al3+ hydroxides provide

• Aluminum hydroxide + Magnesium hydroxide

• Calcium carbonate + Magnesium carbonate

3/25/2021 ZENAW T.(B.Pharm, MSc in pharmacology) 12

3/25/2021 ZENAW T.(B.Pharm, MSc in pharmacology) 13

• Symptomatic relief of peptic ulcer

• Adjuncts for healing peptic ulcer (with H2-receptor

3/25/2021 ZENAW T.(B.Pharm, MSc in pharmacology) 14

– Food delays stomach emptying allowing more time for the

3/25/2021 ZENAW T.(B.Pharm, MSc in pharmacology) 15

o Cimetidine, Ranitidine, Famotidine, Nizatidine

• MOA: bind to the H2-receptors on the cell membranes of

• Have differences in their relative potency,

• Used for healing 70 to 85% of duodenal ulcers with 4 to 6

3/25/2021 ZENAW T.(B.Pharm, MSc in pharmacology) 16

• After prolonged use, down-regulation of receptor production

• Especially effective at inhibiting nocturnal acid secretion.

 Night time-only dosing can be used.

• Therapeutic uses:- Gastric & Duodenal ulcers & Gastro

3/25/2021 ZENAW T.(B.Pharm, MSc in pharmacology) 17