Transcript Digestive Drug Agents

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Antacids
Histamine 2 blockers
Proton pump inhibitors (PPI)
Anti-diarroheal drugs
Laxatives
Anti-emetics
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Peptic ulcer occurs in that part of the
gastrointestinal tract which is exposed to
gastric acid and pepsin.
The etiology of peptic ulcer is not clearly
known. It results probably due to an imbalance
between the aggressive (acid, pepsin, bile, and
H.pylori) and defensive ( gastric mucus,
bicarbonate secretion, prostaglandins, and
nitric oxide )
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H2-blockers: Cimetidine, ranitidine,
Famotidine, and roxitidine
Proton pump inhibitors: Omeprazole,
lansoprazole, pantoprazole, rabeprazole,
Esomeprazole.
Anticholinergic: Pirenzepine, propantheline,
oxyphenonium.
Prostaglandin analogue: misoprostol
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Neutralization of gastric acid
systemic: sodium bicarbonate and sodium
citrate
Nonsystemic: mg hydroxide, magnesium
trisilicate, aluminum hydroxide gel, and
calcium carbonate
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Ulcer protective's: Sucralfate, and bismuth
subsalicyte.
Anti-h-pylori drugs: amoxicillin,
Clarithromycin, Metronidazole, Tinidazole,
and tetracycline.
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Antacids have been used for centuries in the
treatment of patients with acid related
disorders.
They were the principle of anti-ulcer treatment
until the availability of histamine 2 blockers in
the late of 1970s.
The ancient Greece used crushed coral (calcium
carbonate)in the first century to treat patients
of dyspepsia
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These are basic substances which neutralize
gastric acid and raise PH of gastric contents.
Antacids donot decrease acid production,
rather agents that raise the antral PH to greater
than 4.
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It is water soluble but the duration of action is
short.
It is potent neutralizer, Ph may rise above 7.
It is absorbed systematically, large doses will
induce alkalosis
Produces carbon dioxide in stomach,
distention, discomfort, belching, risk of ulcer
perforation.
Increases sodium load, may worsen edema and
CHF.
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However antacids are extensively used,
especially on OTC market.
In addition many antacids contain simethicone
which reduces gas and bloating.
Basically there are three forms of antacids:
Aluminum antacid
Calcium antacid
Magnesium antacid
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The OTC antacid formulations are available:
Capsules
Tablets
Powders
Chewable tablets
Suspension
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Antacids originally believed to work by
neutralization of gastric acidity.
They donot nothing for prevent over production
of acid.
They do this by stimulating:
Mucus
Prostaglandin
Bicarbonate secretion
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The primarily drug effect of antacids is the
reduction of the symptoms associated with
various acid related disorders such as peptic
ulcer disease and hyperacidity.
The ability of antacids to reduce the pain
associated with acid related disorders is
thought to be result, inhibition of protein
digesting ability of pepsin.
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Mg results diarrhea
Al & Ca can result constipation.
Rebound hyperacidity
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The amount of antacid necessary to neutralize
hydrochloric acid depends on the:
Patient
Condition been treated
Buffering capacity of the preparation used.
Adult dosage is 5-10ml 3-4 times a day, Hs.
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Calcium carbonate neutralization will produce
gas and possible belching, for this reason it
may be combined with an anti-flatulent type of
drug such as simethicone.
Calcium containing products have a long
duration of acid action, which can cause
hyperacidity rebound.
Calcium carbonate is available 1-2 tabs Prn.
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Mg containing antacids commonly cause a
laxative effect and frequent administration of
these antacids alone often cannot be tolerated.
Administration of Mg containing antacids is
dangerous in patients with renal failure,
because of failing of kidney cannot excrete
extra Mg and accumulation may occur.
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Histamine -2 blockers reduce Hcl but donot
abolish stimulated acid secretion.
They have become the most popular drugs for
the treatment of many acid related disorders.
These can be attributed by their:
Efficacy
Safety profile
Patient acceptance
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Cimetidine
Famotidine
Nizatidine
Ranitidine
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They have ability of blocking parietal cells.
They reduce the amount of Hcl in the parietal
cells.
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Confusion
Lethargy
Headache
Abdominal cramp
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In 1977 Cimetidine was the first agent in this
class to be released in the market.
Cimetidine comes available 200, 300, 400,
800mg tablets, 300mg/ml, 200mg/ml,
150mg/ml parentral injection.
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PPI is introduced for the treatment of acid
related disorders.
The enzyme H+/K+ ATPase is the final
common step in acid Secretory processes.
PPI drugs are:
Omeprazole 20mg
Lanzomeprazole 30mg
Esomeprazole 40mg
Pantoprazole 20, 10mg
Rapiprazole 20mg
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PPI irreversible binds to H+/K+ATPase. The
binding of this enzyme prevents the movement
of hydrogen ions out of the parietal cell into the
stomach, there by blocking all gastric acid
secretion.
PPI makes the patient achlorhydric.
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Headache
Dizziness
Vomiting
Nausea
Rash
Fatigue
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Omeprazole is a prodrug.
Omeprazole is degraded at low PH and must
be given in granules.
Omeprazole inhibits cytochrome P450 system,
decreasing metabolism of Warfarin, diazepam,
Carbamazepine, and phenytoin and enhancing
the effect of these drugs.
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Omeprazole is currently approved only for the
acute treatment of severe gastrointestinal reflux
disease un responsive to:
Antacids
Antiflatulents
H2-blockers
Adult dosage is 20mg/day for 4-8 weeks.
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Sucralfate: it is compound of aluminum and
sucrose which coats the base of the ulcer
protecting it from pepsin and acid allowing it
to heal.
Dosage is 1gm 1 hour before each meal.
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It protects the ulcer by causing coagulation at
the base of the ulcer. It has also anti H. pylori
action.
It should not be combined with antacids.
The tongue and the stool may appear black
after taking dosage 120gm 1 hour before meals
and at the bed time.
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Prostaglandins exert some protective effect on
the gastric mucosa and this is why NSAIDs
which inhibits prostaglandin synthesis can
cause peptic ulceration.
One of the prostaglandin preparation
misoprostol reduces the risk of gastric ulcers in
patients who are taking NSAIDS, especially in
elderly patients having history of ulcers.
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For helicobacter pylori associated ulcers, there
are two therapeutic goals:
Heal the ulcer
Eradication of the organism
The best treatment regimen is for a 10-14 days
of Triple Drug regimen.
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The regimen consists of:
PPI, E.g omeprazole 20mg BD
Clarithromycin 500mg BD
Metronidazole 400mg BD
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For treatment of aspirin or other NSAIDS
induced ulcers the best treatment is to give a
proton pump inhibitor, which provides prompt
healing of the ulcer.
PPI are also useful in bleeding ulcers as they
raise the gastric PH. It is observed that intra
gastric PH above 6 may enhance coagulation
and platelet aggregation.
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ID/CC: A 22 year old female presents to the ER
with severe abdominal colic and a history of
profuse watery diarrhea of several days duration.
HPI: She also complains dizziness and desire to
lose weight, that she has been taken by magnesium
sulfate.
PE: Hypotension, lethargy.
Labs: Hypokalemia
Discussion:
Treatment:
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Diarrhea is defined as the abnormal frequent
passage of loose stools.
Diarrhea is the abnormal passage of stools with
increased frequency, fluidity and weight.
Diarrhea is divided into:
Acute diarrhea
Chronic diarrhea
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Acute Diarrhea
Bacterial
Drug induced
Viral
Nutritional
Protozoal
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Chronic Diarrhea
Tumors
Diabetes mellitus
Hyperthyroidism
Addison's disease
Irritable bowl syndrome
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Electrolytes
Bulk agents
Absorbents
Anti-inflammatory
Opioids
Intestinal flora modifiers
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Bismuth subsalicte is a pregnancy category C
agent.
It should be used with caution in children and
teenagers who have or are recovering from
chicken pox or flu because of attendance risk of
Reyes syndrome.
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Bismuth subsalicyte have two harmless sideeffects:
Darkening of the stool
Darkening of the tongue
It is available in a OTC drug.
Available 262 mg chewable tablet and 262
mg/15ml suspension.
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Attapulgite has replaced the use of kaolinpectin in this preparation.
Kaolin is a naturally hydrated aluminum
compound that is now rarely used as an antidiarrheal agents.
How ever pectin which is extracted from the
apples or citrus fruit and is used in many
combination products.
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The original kaopectate contained 980mg/5ml
of kaolin and 21.7 mg/5ml of pectin.
Attapulgite is an OTC agent.
It is a pregnancy category C agent.
Available 300mg chewable tablet and
600mg/15ml solution.
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Lomotil is a synthetic opiate agonist that is
structurally related to meperidine.
It has little or no analgesic activity.
It is classified in a pregnancy category C agent.
Available as 2.5mg/5ml + 0.025mg/5ml
atropine solution, and 2.5mg + 0.025mg,
diphenoxylate and atropine respectively.
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Loperamide is a synthetic anti-diarrheal that
similar to diphenoxylate.
Decreases the number of stools and water
content.
It is the only opiate anti-diarrheal agent that is
available as an OTC medication.
Loperamide is a pregnancy category B agent.
Available 1mg tab, 1mg/5ml oral.
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Lactobacillus acidophilus is an acid producing
bacteria prepared in a concentrated oral
administration.
Has been used for more than 75 years in the
treatment of uncomplicated diarrhea,
particularly that caused by antibiotic treatment
that destroys normal florae.
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It is an OTC medication.
Available 1g powder, 1g tablet, and 1g
capsules.
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Laxatives are used for the treatment of
constipation, which is defined as a condition of
abnormally infrequent and difficult passage of
feces through the lower GIT.
Constipation is not a disease but it is a
symptom of disease.
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Pregnancy
Hypothyroidism
Hypokalemia
Parkinsons disease
Iron supplements
Anti-cholinergics
Poor fluid intake
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Lack of exercise
Anxiety
Stress
AL-antacids
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Bulk-forming agents
Methylcellulose
Psyllium
Polycarbophil
Stool Softeners- Emollient
Docusate salts
Mineral oil
Glycerin
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Hyperosmotic
Lactulose
Sorbitol
Saline
Mg sulphate
Mg phosphate
Mg citrate
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Stimulant
Castor oil
Anthraquinones
Diphenylmethane Derivatives
Bisacodyl
Laxocodyl
Phenolphthalein
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Chloride channel activator
Lubiprostone: stimulate the chloride channel 2
in the intestine by increasing the secretion.
Opiod receptor antagonist
Methylnaltrexone
Alvimopan
5HT4 receptor antagonist
Tegaserod
Cisapride
Prucalopride
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Decreased absorption of vitamins
Nutrient malabsorption
Gastric irritation
Skin rash
Mg toxicity
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Methylcellulose is a synthetic bulk forming
laxative that attracts water into intestine,
absorbs excess water into stool and stimulating
intestines.
Contraindicated in patients who have shown
Hypersensitivity
Hepatitis
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It is a pregnancy category C agent.
It is an OTC medication.
Available 105mg, 364mg powder and 500mg
tablets.
Adult dosage is 1 tabs, 1-3 times per day.
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Mineral oil is the only lubricant laxative in the
emollient category.
Prevent water from escaping the stool and
lubricating the intestines.
It is a mixture of liquid hydrocarbons derived
from petroleum.
It is classified in a pregnancy category C agent.
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Mineral oil agents are available as enemas or as
suspensions, 1.4, 2.75, 4.75mg/5ml.
Adult dosage is 15-45ml as a single daily dose.
Peadtric dose is 5-15ml per day.
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It is a disaccharide sugar containing one
molecule of galactose and one molecule of
fructose.
It is a synthetic derivative of the natural sugar
lactose, which is not digested in the stomach or
absorbed in the small intestine.
Lactulose is classified pregnancy category C
agent.
Available 3.33g/5ml oral or rectal solution.
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Glycerin promotes bowel movements by
increasing osmotic pressure.
It is very mild laxative, commonly used in
children.
It is classified pregnancy category C agent.
Available 4ml per applicator rectal solution.
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It is classified pregnancy category B agents.
Magnesium salts are:
Mg saline
Mg citrate
Milk magnesia
Epsom salts
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Cautiously given to all patients with renal
insufficiency because they can be absorbed
systematically causing hypermagnesimia.
Available as magnesium hydroxide 77.5mg/ml
suspension and milk of magnesia 300-500mg
tablets.
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ID/CC: A 22 year old female presents to the ER
with severe abdominal colic and a history of
profuse watery diarrhea of several days
duration.
HPI: She also complains of dizziness and a
desire to lose weight (direct questioning
discloses that she has been taking magnesium
sulphate intermittently).
PE: Hypotension, no fever, and lethargic.
Labs: Hypokalemia, hyponatremia,
hyperchloremia.
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Treatment: Discontinue laxatives and offer
counseling. Give IV glucose and electrolytes to
restore fluid balance.
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Discussion: Laxative abuse remains a common
way people attempt to lose weight; abuse is
also common among psychiatric patients.
Laxatives can interfere with the absorption of
several medications such as tetracycline and
calcium supplements. Continued abuse may
lead to melanosis coli, colonic neuronal
degeneration and the lazy intestine syndrome.
Patients with chronic constipation abuse
laxatives to the point of being dependant on
them for evacuation.
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Nausea and vomiting are the two
gastrointestinal disorders that can be not only
extremely unpleasant but also lead to other
more serious complications if not treated
promptly.
Vomiting which is also known emesis, is the
forcible emptying or expulsion of gastric and
occasionally intestinal contents through the
mouth.
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There is variety of stimuli that can induce
nausea and vomiting and these are:
Foul odors
Foul tastes
Irritation of stomach
Irritation of the stomach
Certain drugs
Anti-cholinergics
1. Scopolamine
2. Hyocine
3. Hyoscyamine
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Antihistamines
1. Meclizine
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Neuroleptic agents
1. Metoclopramide
2. Domperidone
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Serotonin blockers
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Tetrahydrocannabinoid (THC)
1. Dronabinol
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These drugs blocks:
Acetylcholine
Histamine
Dopamine
Serotonin
Stimulation of THC.
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Scopolamine is the primary anti-cholinergic
drug used as an anti-emetic.
It has potent effects on the vestibular nuclei,
which are located in the inner ear and represent
the area of the brain that controls balance.
Works by blocking ACH, correcting and
imbalance between the two neurotransmitters
ACH and nor-epinephrine.
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This makes the scopolamine one of the most
commonly used drugs for the treatment and
prevention of motion sickness.
It is classified pregnancy category C agent.
Available as 0.3, 0.4, 1 mg/ml parentral.
Scopolamine hydrobromide salt that is used for
ophthalmic purposes.
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It is a pregnancy category B agent.
Most commonly treated disorders are:
Dizziness
Vertigo
Nausea
Vomiting
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Contraindicated by:
Hypersensitivity
Shock
Lactation
Available as 12.5, 25, 50mg tablets and 15,25,
50mg capsules.
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It is classified in a pregnancy category C agent.
Contraindicated by:
Hypersensitivity
Coma
Seizure
Bone marrow depression
Available as 2.5, 5, 25mg suppository and
5mg/5ml solution, 5mg/ml injection.
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Metoclopramide is the oldest and most
commonly used drug in the anti-emetic drugs.
It is available by prescription.
Classified pregnancy category B agent.
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Available as 5mg, 10mg/5ml oral solution, 5,
10mg tablets and 5mg/ml injection.
Contraindicated by:
Breast cancer
Seizure
Hypersensitivity
GI obstruction
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Dronabinol is the only currently available THC.
Approved by FDA in 1985 for the treatment of
nausea and vomiting related to cancer
chemotherapy.
It is a pregnancy category C agent.
Available in 2.5, 5, 10mg capsules.
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ID/CC: A 6 year old boy is brought by his
parents to the emergency room in a comatose
state.
HPI: The child had been suffering from
chickenpox and had been given bismuth
subsalicyte by the family physician for
diarrhoe.
PE: Fever, comatose
Labs: Marked hypoglycemia, increased blood
ammonia concentration.
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Pathology: severe cerebral edema, acute
hepatic necrosis.
Imaging: CT scan reveals generalized cerebral
edema.
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Discussion: although the cause of the highly lethal
reyes syndrome is unknown, epidemiologic
evidence strongly links this disorder with
outbreaks of viral diseases especially influenza B
and chickenpox.
Treatment: speacific therapy not available.
Supportive measures include lactulose to control
hyperammonia, fresh frozen plasma to replenish
clotting factors, mannitol or dexamethasone to
lower increased intracranial pressure and
mechanical ventilation. Exchange transfusion,
dialysis.
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ID/CC: A 39 year old male presents to his
family doctor because of increasing
embarrassment and concern over breast
enlargement.
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HPI: The patient has a long history of burning
epigastric pain on awakening in the mornings
and between meals that decreases with food
and antacids (peptic ulcer disease), for which
he has been taken Cimetidine. Directed
questioning reveals that he has also been
suffering from hallucinations and impotence.
Imaging: CXR: normal
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Discussion: All the H2 blockers are well
tolerated, although Cimetidine is associated
with several side effects, particularly reversible
gynecomastia. H2 blockers produce an increase
in serum prolactin levels (especially ranitidine)
and alter estrogen metabolism in men. Other
side effects include headache, confusion, low
sperm counts, and hematologic abnormalities.
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Treatment: Switch to other histamine receptor
antagonists such as ranitidine or famotidine.
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ID/CC: A 64 year old male with metastatic
lung cancer is seen with complaints of severe
bone pain and anorexia.
HPI: He spends most of his time in bed because
of profound weakness and chronic nausea.
PE: Mild fever (38 degree), tachycardia,
underweight (45kg), and sunken eyes.
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Discussion: Anorexia syndrome is
characterized by progressive weight loss,
lipolysis, loss of muscle mass, anorexia,
diarrhea and fever.
Some drugs that have proven effective in
improving appetite include megestrol acetate
and dronabinol. Megestrol acetate is a synthetic
progesterone that stimulates the appetite,
resulting in weight gain and recovery of
muscle mass.
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It is relatively non-toxic. Side effects are rare
and include altered menses with unpredictable
bleeding and mild edema. Dronabinol a
synthetic THC is the active component in
marijuana and is used to treat nausea and
vomiting associated with cancer chemotherapy
as well as to stimulate appetite. Side effects are
due mainly to the pyschoactive effects of the
drug and include dizziness, ataxia,
hallucinations, tachycardia, hypertension, URI
symptoms.
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Treatment: Treat with megestrol acetate or
Dronabinol to increase the appetite, adequate
palliatative pain medications.
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