Farmakologi

Saluran Cerna

Tri Widywati
Dep. Farmakologi & Terapeutik,
Fakultas Kedokteran
Universitas Sumatera Utara
April 2011, KBK Blok 6
 Acid-Related Pathophysiology
The stomach secretes:
• Hydrochloric acid (HCl)
• Bicarbonate
• Pepsinogen
– Pepsin breaks down proteins (proteolytic)
• Intrinsic factor
• Mucus
– Provide a protective mucous coat
– Protect against self-digestion by HCl
• Prostaglandins
 Drugs used in dyspepsia
• Anti-acid agents • Prokinetic Agents
– Antacids / Alginates – Cisapride - withdrawn
– H2A’s – Metoclopramide /
– PPI’s Domperidone

• Mucosal Protectants • Helicobacter Pylori Agents,

– Misoprostol/Prostaglandin Antibiotics - H pylori
– (Sucralfate) – Amoxycillin
– (Bismuth) – Clarithromycin
– Metronidazole
 Mechanism of anti-hyperacidity
Gastric phase Parietal Cell Cephalic phase
Food in Gaster Nervus Vagus

HCl
Asetilcholine
Cl¯

I
G-cell

PP
K+

H+
Gastrin
H+ ECL-cell
H+

Histamine
 Antacids: General
• Neutralize acid
• Prevent/treat PUD, GERD, Esophagitis,
heartburn, gastritis, GI Bleeding and stress
ulcers.
• Separate administration from other drugs
by 1 to 2 hours
• For treating of PUD, 1 &3 hours after
meals and at bedtime
 Antacids: Mechanism of Action
• Promote 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
overproduction of acid
• Antacids DO neutralize the acid once it’s in
the stomach
 Antacids
• Used alone or in • OTC formulations
combination available as:
• Aluminum salts – Capsules and tablets
• Magnesium salts
– Powders
• Calcium salts
– Chewable tablets
• Sodium – Suspensions
bicarbonate – Effervescent granules
and tablets
 Magnesium Hydroxide/
Aluminum Hydroxide
• Treatment of PUD pain and to promote
healing
• Neutralizes gastric acid and inactivating
pepsin
• Magnesium Hydroxide
– Contraindicated with impaired renal function
– the failing kidney cannot excrete extra
magnesium, resulting in accumulation
• Aluminum Hydroxide gel (Amphogel)
– Choice for clients with chronic renal failure
– Aluminum does not accumulate
 Antacids: Calcium Salts
• May cause constipation
• Their use may result in kidney stones
• Long duration of acid action may cause
increased gastric acid secretion
(hyperacidity rebound)
• Often advertised as an extra source of
dietary calcium
 Antacids: Sodium Bicarbonate
• Highly soluble
• Buffers the acidic properties of HCl
• Quick onset, but short duration
• May cause metabolic alkalosis
• Sodium content may cause problems in
patients with CHF, hypertension, or renal
insufficiency
 Antacid-Drug Interactions
• Adsorption of other drugs to antacids
– Reduces the ability of the other drug to be absorbed into the
body
• Chelation
– Chemical binding, or inactivation, of another drug
– Produces insoluble complexes
– Result: reduced drug absorption
• Increased stomach pH
– Increased absorption of basic drugs
– Decreased absorption of acidic drugs
• Increased urinary pH
– Increased excretion of acidic drugs
– Decreased excretion of basic drugs
 Patient Teaching: Antacids
• Magnesium may cause diarrhea
• Calcium or aluminum may cause constipation
• Renal patients should not take products
containing Magnesium
• Take 1-2 hours ā or after other medications
• 1 & 3 hours PC and HS
• Antacids may cause premature dissolving of
enteric-coated medications, resulting in stomach
upset
Histamine Receptor Antagonists
• Ex. Cimetidine, ranitidine, famotidine,
nizatidine
• Prevention & treatment of PUD,
Esophagitis, GI bleeding, stress ulcers,
and Zollinger-Ellison Syndrome
• May alter the effects of other drugs
 H2 Antagonists:
Mechanism of Action
• Block histamine (H2) at the receptors of
acid-producing parietal cells
• Production of hydrogen ions is reduced,
resulting in decreased production of HCl
– Inhibit secretion of gastric acid
– Suppressed acid secretion in the stomach
 Famotidine
• With or without food
• Preferred over cimetidine
• Does not inhibit the cytochrome p450
system
• Renal impairment monitor creatinine
 H2 Antagonists: Side Effects
• Overall, less than 3% incidence of side
effects
• Cimetidine may induce impotence and
gynecomastia
• May see:
– Headaches, lethargy, confusion, diarrhea,
urticaria, sweating, flushing, other effects
 H2 Antagonists:
Drug Interactions
• cimetidine
– Binds with P-450 microsomal oxidase
system in the liver, resulting in inhibited
oxidation of many drugs and increased
drug levels
– All H2 antagonists may inhibit the
absorption of drugs that require an
acidic GI environment for absorption
 Teaching: Histamine Receptor
Antagonists
• OTC, do not take longer than 2 weeks
• Take with or without food
• Do not take an antacid for approx 1 hour
before or after taking one of these drugs
• SMOKING has been shown to decrease
the effectiveness of H2 blockers
 Proton Pump Inhibitor (PPI)
• The parietal cells release positive
hydrogen ions (protons) during HCl
production
• This process is called the “proton pump”
• H2 blockers and antihistamines do not
stop the action of this pump
• Mechanism of Action of PPI:
– Prevent the movement of hydrogen ions from
the parietal cell into the stomach
– Result: achlorhydria - ALL gastric acid
secretion is blocked
 Proton Pump Inhibitors
• Strong inhibitors of gastric acid secretion
• Bind to the gastric proton pump and
prevent “pumping” or release of gastric
acid (24 hr action)
• Indicated in PUD, Gastritis, GERD, &
Zollinder-Ellison syndrome
• Faster relief and healing than H2RA’s
 Proton Pump Inhibitors
• Total inhibition of gastric acid secretion
– lansoprazole (Prevacid)
– omeprazole (Prilosec)*
– rabeprazole (Aciphex)
– pantoprazole (Protonix)
• available for parenteral administration
– esomeprazole (Nexium)

*The first in this new class of drugs

 Teaching: Proton Pump Inhibitors

Instruct the patient taking omeprazole:

• It should be taken before meals
• The capsule should be swallowed whole, not crushed,
opened, or chewed
• It may be given with antacids
• Emphasize that the treatment will be short term
– Take the medication for the full course prescribed
(4-8 weeks)
• Polymorphism in drug metabolism, then wide
interindividual variability of its efficacy
 Sulcrafate (Carafate)
• Cytoprotective agent
– Used for stress ulcers, erosions, PUD
• Attracted to and binds to the base of ulcers and
erosions, forming a protective barrier over these areas
– Protects these areas from pepsin, which normally breaks
down proteins (making ulcers worse)
• It requires an acid pH to activate
• May cause constipation, nausea, and dry mouth
• May impair absorption of other drugs, especially
tetracycline
– Binds with phosphate; may be used in chronic renal failure
to reduce phosphate levels
– Do not administer with other medications
 Teaching: Sulcrafate
• Give approximately 2 hours before or after
other drugs
• Take on an empty stomach before meals
and @ HS
 Misoprostol (Cytotec)
• Synthetic prostaglandin analog
• Prostaglandins
– Protect gastric mucosa from injury by
enhancing local production of mucus or
bicarbonate
– Promote local cell regeneration
– Help to maintain mucosal blood flow
 misoprostol
• Used for prevention of NSAID-induced
gastric ulcers
• Doses that are therapeutic enough to treat
duodenal ulcers often produce abdominal
cramps, diarrhea
• Do not give to women of childbearing
years unless a reliable method of birth
control can be DOCUMENTED
 Antiflatulents
• used to relieve the painful symptoms
associated with gas
• several agents are used to bind or alter
intestinal gas and are often added to
antacid combination products
• OTC antiflatulents
– Activated charcoal
– Simethicone
 Simethicone
• May be mixed in antacid formulation or given
alone
• Causes gas bubbles to coalesce
– Alters elasticity of mucus-coated bubbles, causing them to
break
– Used often, but there are limited data to support effectiveness
• Aids in the passage of gas through the GI
• Give after meal and @ HS
• Shake liquid preparations thoroughly
 Activated Charcoal
Absorbent Agent
• Used in emergency treatment of certain
poisons
• If told to give both this and ipecac syrup to
treat the poisoning, do not give this
medicine until after vomiting and the
vomiting has stopped. This usually takes
about 30 minutes.
• Activated charcoal will cause stool to turn
black
 Syrup of Ipecac
Emetic
• Use in emergency to induce vomiting
• Do not give to unconscious victim
• Give 1 dose if vomiting does not occur,
may give second dose but no more
• Do not give if ingestion of petroleum
based products has occurred
 ANTI EMETIC
Useful vomiting : as a protective mechanism for
eliminitating irritant or harmful substances from the
upper GIT; symptom; side effect

Emesis : controlled by the vomiting centre in the medulla

Vomiting centre dose not initiate, but rather it coordinates
the act of emesis on receiving stimuli from various sources

Chemoreceptor Trigger Zone (CTZ) : sensitive to the

action of drugs and other chemicals
Vestibular system
Periphery : distension or irritation of the gut, MCI,
biliary or renal stone
Cortical centre
 Two centres : Emetic centre (EC) & Chemoreceptor trigger zone (CTZ)
Both near the floor of the fourth ventricle, close to the vital centre
EC is within the BBB, CTZ outside in the area postrema  they are connected together
 Classification of antiemesis drugs

Antagonis dopamin (D2): der. procainamide (metoclopramide);

der. benzimidazole (domperidon);
der. phenotiazine (chlorpromazine);
der. Butyrophenone ( haloperidol, droperidol)

Antagonis 5-HT3 : granisetron, ondansetron, tropisetron

Antikolinergik : scopolamie, antihistamine (siklizin, meklizin,

sinarizin, prometazin, dimenhidrinat)

Other agents
Kortikosteroida : dexamethason
Benzodiazepin : lorazepam
Canabinoid : mariyuana, THC
 Medications to Alleviate
Nausea/Vomiting
• Antimuscarinics
– Scopolamine-patch
– Antihistamines
• Promethazine
• Benadryl-can be given IV
– Phenothiazines
• Compazine-given IM
– These classes have anitcholinergic effects
– Common contraindications with these classes:
• Do not give to client with glaucoma, BPH (urinary retention),
pyloric/bladder neck obstruction, biliary obstruction
• Common side effects:
– Dry mouth, constipation, hypotension, sedative effects
 Promethazine
• PO, IM, Rectal, IV
• Inhibits the CTZ in the medulla,
• Give 30-60 minutes ā radiation, chemo,
etc
• Will cause drowsiness
 Medications to Alleviate
Nausea/Vomiting
• 5-HT receptors-antagonists to serotonin
receptors
– Work peripherally and centrally to reduce
vomiting
– Used for Chemotherapy/radiation, migraine
induced vomiting
• ondansetron (Zofran),
• granisetron (Kytril),
• dolasetron (Anzemet)
 prokinetics
• Metoclopramide and Domperidone
– Antiemetics
– Act on Dopamine receptors
– Enhance release of acetylcholine
– Increased gastric emptying (prokinetics)
– Side effects of Metoclopramide:
hallucinations, tremors, dyskinesias, anxiety,
restlessness, insomnia
Thankyou