PHCP Lec Topic 4: Diseases of the GI tract  Tricyclic antidepressants

 Antacids containing calcium carbonate or aluminum

Constipation hydroxide.
- Fewer than three stools per week for women five for  Barium sulfate
men despite a high-residue diet, or a period of more  Calcium channel blockers
than 3 days without a bowel movement, straining at  Clonidine
stool more than 25% of the time and/or two or fewer  Diuretics (non-potassium-sparing)
stools per week, and straining at defecation and less  Ganglionic blockers
than one stool daily with minimal effort.  Iron preparations.
 Muscle blockers (d-tubocurarine, succinylcholine)
Pathophysiology  Nonsteroidal anti-inflammatory agents
- It is not a disease but a symptom of an underlying  Polystyrene sodium sulfonate
disease or problem.
- Causes: Approach to Treatment
o Low fiber diet  Dietary modification
o Inadequate fluid intake  Increase fiber consumption.
o Decreased physical activity.  Adjust bowel habit to adapt a regular schedule.
o Use of drugs that may cause constipation.  Recognize disease that can cause constipation.
 Malignancies must be removed through a surgical
Diseases that may cause Constipation. resection.
 GI disturbance:  Treatment may be a combined pharmacotherapeutic
o Irritable bowel syndrome and non-pharmacotherapeutic approach.
o Diverticulitis
o Upper or lower GI tract diseases Dietary Modification
o Hemorrhoids  Increase fiber to 20-25 grams per day.
o Anal fissures  High fiber content must be continued for 1 month.
o Lymphogranuloma venereum  Abdominal distention and flatus may be experienced
 Diabetes particularly in high bran consumption.
 Hypothyroidism
Pheochromocytoma
 Hypercalcemia
 Enteric Glucagon intake
 Pregnancy
 Cardiac disease
 Neurologic constipation:
o Head trauma.
o CNS tumor
o Spinal cord injury
o Parkinson's
o Psychogenic causes

Types of Laxatives
 Osmotic
o Lactulose
- Not recommended as a first-line agent for
the treatment of constipation because it is
costly and may cause flatulence, nausea, and
abdominal discomfort or bloating.
- Used in pre-surgery.
o Sorbitol
Drug Induced Constipation
- Monosaccharide has been recommended as
 Analgesics
a primary agent in the treatment of
o Inhibitors of prostaglandin synthesis
functional constipation in cognitively intact
o Opiates
patients.
 Anticholinergics
o Magnesium Hydroxide
 Antihistamines
o Polyethylene Glycol
 Antiparkinsonian agents (e.g., benztropine or
- Whole-bowel irrigation
trihexyphenidyl)
 Phenothiazines
 - Typically, 4 L of this solution is administered - Examination for microorganisms, blood, mucus, fat,
over 3 hours to obtain complete evacuation osmolality, pH, electrolyte and mineral concentration,
of the GI tract. and cultures.
- Stool test kits are useful for detecting GI viruses,
 Stimulant particularly rotavirus (Coronavirus).
o Bisacodyl - Direct endoscopic visualization and biopsy of the colon
o Senna and radiographic studies are helpful in neoplastic and
 Stool softener inflammatory conditions.
o Docusate sodium
- Surfactant agent, increase water and
electrolyte secretion in the small and large
bowel and result in a softening of stools
within 1 to 3 days.
 Bulk forming laxatives
o Methylcellulose
o Psyllium
 Lubricating
o Mineral oil
- the only lubricant laxative in routine use and
acts by coating stool and allowing easier
passage.

Diarrhea
- Increased frequency and decreased consistency of fecal
discharge as compared with an individual’s normal
bowel pattern.
- It is often a symptom of a systemic disease.
- Acute Diarrhea is commonly defined as shorter than 14
days’ duration, persistent diarrhea as longer than 14
days’ duration.
o Most cases of acute diarrhea are caused by
infections with viruses, bacteria, or protozoa, and
are generally self-limited.
- Chronic Diarrhea as longer than 30 days’ duration.
- Diarrhea is an imbalance in absorption and secretion of Treatments
water and electrolytes.
- It may be associated with a specific disease of the
gastrointestinal (GI) tract or with a disease outside the
GI tract.
- A change in active ion transport by either decreased
sodium absorption or increased chloride secretion.
- A change in intestinal motility
- An increase in luminal osmolarity
- An increase in tissue hydrostatic pressure
- Occurs when a stimulating substance (e.g., vasoactive
intestinal peptide [VIP], laxatives, or bacterial toxin)
increases secretion or decreases absorption of large  Antisecretory
amounts of water and electrolytes. o Bismuth subsalicylate (ADR: Black stool & tongue)
- Inflammatory diseases of the GI tract can cause o Lactase
exudative diarrhea by discharge of mucus, proteins, or - For people who are lactose intolerant
blood into the gut. o Racecadotril (Hidrasec)
- Acute diarrheal episodes subside within 72 h of onset, - Enkephalinase inhibitor that reduces
whereas chronic diarrhea involves frequent attacks over hypersecretion of water and electrolytes into
extended time periods. the intestinal lumen.
o Abrupt onset of nausea, vomiting, abdominal pain, o Bacterial replacements
headache, fever, chills, and malaise - Bacillus clausii, Lactobacillus acidophilus,
o Bowel movements are frequent and never bloody, Lactobacillus bulgaricus
and diarrhea lasts 12–60 h - Probiotics
 Antimotility
Stool Analysis o Diphenoxylate
- Schedule V
 - Combined with atropine to reduce the ulcer or gastric cancer. Bacterial enzymes (urease,
likelihood of abuse. lipases, and proteases), bacterial adherence, and H.
o Loperamide pylori virulence factors produce gastric mucosal injury.
- Phenylpiperidine derivative that acts on the o HP induces gastric inflammation by altering the
μ(mu) receptor. host inflammatory response and damaging
- No CNS effect. epithelial cells.
- Loading dose, 2 tablets - Nonselective NSAIDs (including aspirin) cause gastric
o Paregoric mucosal damage by two mechanisms:
- Camphorated tincture of opium o (1) a direct or topical irritation of the gastric
o Opium tincture epithelium
o Difenoxin o (2) systemic inhibition of endogenous mucosal PG
- (hindi na mabasa yung nasa ppt) synthesis.
 Adsorbent  COX-2 selective inhibitors have a lower risk of
o Kaolin – pectate mixture ulcers and related GI complications than
- China clay nonselective NSAIDs. Addition of aspirin to a
o Polycarbophil selective COX-2 inhibitor reduces its ulcer-
o Attapulgite/Palygorskite sparing benefit and increases ulcer risk.
- magnesium aluminum phyllosilicate  Use of corticosteroids alone does not
increase risk of ulcer or complications, but
ulcer risk is doubled in corticosteroid users
PHCP Lec Topic 5: Peptic Ulcer Disease taking NSAIDs concurrent.
- Cigarette smoking has been linked to PUD, impaired
Peptic Ulcer Disease ulcer healing, and ulcer recurrence. Risk is proportional
- It refers to ulcerative disorders of the upper to amount smoked per day.
gastrointestinal (GI) tract that require acid and pepsin - Psychological stress has not been shown to cause PUD,
for their formation. but ulcer patients may be adversely affected by
- The three common etiologies include: stressful life events.
o Helicobacter pylori infection - Carbonated beverages, coffee, tea, beer, milk, and
spices may cause dyspepsia but do not appear to
o Non-steroidal anti-inflammatory drug (NSAID) use
increase PUD risk.
o Stress-related mucosal damage (SRMD)
o Ethanol ingestion in high concentrations is
- Benign gastric ulcers, erosions,
associated with acute gastric mucosal damage and
and gastritis can occur anywhere
upper GI bleeding but is not clearly the cause of
in the stomach, although the
ulcers.
antrum and lesser curvature
o Dyspepsia, also known as indigestion, refers
represent the most common
to discomfort or pain that occurs in the upper
locations.
abdomen, often after eating or drinking. It is not a
- Most duodenal ulcers occur in
disease but a symptom.
the first part of the duodenum
- HP – Duodenal; NSAIDs – Gastric
(duodenal bulb)

Clinical Presentation
Pathophysiology
- Abdominal pain is the most frequent PUD symptom.
- Pathophysiology is determined by the balance between
Pain is often epigastric and described as burning but
aggressive factors (gastric acid and pepsin) and
can present as vague discomfort, abdominal fullness, or
protective factors (mucosal defense and repair).
cramping.
o Gastric acid, H. pylori infection, and NSAID use are
- Nocturnal pain may awaken patients from sleep,
independent factors that contribute to disruption
especially between 12 am and 3 am.
of mucosal integrity.
- Pain from duodenal ulcers often occurs 1 to 3 hours
 Increased acid secretion may be involved in
after meals and is usually relieved by food, whereas
duodenal ulcers, but patients with gastric
food may precipitate or accentuate ulcer pain in gastric
ulcer usually have normal or reduced acid
ulcers.
secretion (hypochlorhydria)
o Antacids provide rapid pain relief in most ulcer
- Mucus and bicarbonate secretion, intrinsic epithelial
patient.
cell defense, and mucosal blood flow normally protect
- Heartburn, belching, and bloating often accompany
the gastroduodenal mucosa from noxious endogenous
pain. Nausea, vomiting, and anorexia are more
and exogenous substances. Endogenous prostaglandins
common in gastric than duodenal ulcers and may be
(PGs) facilitate mucosal integrity and repair.
signs of an ulcer-related complication.
o Disruptions in normal mucosal defense and
o Severity of symptoms varies among patients and
healing mechanisms allow acid and pepsin to
may be seasonal, occurring more frequently in
reach the gastric epithelium.
spring or fall.
- HP infection causes gastric mucosal inflammation in all
infected individuals, but only a minority develop an
 o Presence or absence of epigastric pain does not
define an ulcer.
 Ulcer healing does not necessarily render the
patient asymptomatic.
 Absence of pain does not preclude an ulcer
diagnosis, especially in the elderly who may
present with a “silent” ulcer complication.
- Ulcer complications include upper GI bleeding,
perforation into the peritoneal cavity, penetration into
an adjacent structure (eg, pancreas, biliary tract, or
liver), and gastric outlet obstruction.
- Bleeding may be occult or present as melena or
hematemesis. Perforation is associated with sudden,
sharp, severe pain, beginning first in the epigastrium
but quickly spreading over the entire abdomen.
o Symptoms of gastric outlet obstruction typically
occur over several months and include early
satiety, bloating, anorexia, nausea, vomiting, and
weight loss.
Diagnosis
- Physical examination may reveal epigastric tenderness
between the umbilicus and the xiphoid process that
less commonly radiates to the back.
- Routine blood tests are not helpful in establishing a
diagnosis of PUD. Hematocrit, hemoglobin, and stool
guaiac tests are used to detect bleeding.
o Stool guaiac test: test for fecal occult blood.
 Refers to the blood in the feces that is not
visibly apparent.
- Diagnosis of PUD depends on visualizing the ulcer
crater either by upper GI radiography or endoscopy.
o Endoscopy is preferred because it provides a more
accurate diagnosis and permits direct visualization
of the ulcer.
- Diagnosis of H. pylori infection can be made using
endoscopic or non-endoscopic (urea breath test [UBT],
serologic antibody detection, and fecal antigen) tests.
- Testing for HP is only recommended if eradication
therapy is planned. If endoscopy is not planned,
serologic antibody testing is reasonable to determine
HP status.
o The UBT and fecal antigen tests are the preferred
non-endoscopic methods to verify HP eradication
but must be delayed at least 4 weeks after
completion of treatment to avoid confusing
bacterial suppression with eradication.
Treatment
- Overall goals are to relieve ulcer pain, heal the ulcer,
prevent ulcer recurrence, and reduce ulcer-related
complications.
- In H. pylori-positive patients with an active ulcer,
previously documented ulcer, or history of an ulcer
related complication, goals are to eradicate H. pylori,
heal the ulcer, and cure the disease with a cost-effective
drug regimen.
- The primary goal for a patient with an NSAID-induced
ulcer is to heal the ulcer as rapidly as possible.
Pharmacologic Treatment
 PPI based therapy.
o PPI, Clarithromycin, Amoxicillin or Metronidazole.
 Bismuth based quadruple therapy.
o PPI or H2RA, Bismuth subsalicylate (4X/day),
Metronidazole, Tetracycline
 Bismuth-based quadruple therapy is
recommended as an alternative for patients
allergic to penicillin.
 All medications except the PPI should be
taken with meals and at bedtime.
 Non-bismuth quadruple or “concomitant therapy”
o PPI, Clarithromycin, Amoxicillin, Metronidazole
o Non-bismuth quadruple therapy (also called
“concomitant” therapy) contains a PPI, amoxicillin,
clarithromycin, and metronidazole taken together
at standard doses for 10 days.
o Both non-bismuth quadruple therapy and hybrid
therapy have demonstrated higher eradication
rates than traditional triple-therapy.
 Sequential therapy
o PPI (day 1-10), Amoxicillin (day 1-5) Metronidazole
(day 6-10), Clarithromycin (day 6-10)
 In sequential therapy, the antibiotics are administered
in a sequence rather than all together.
o The rationale is to treat initially with antibiotics
that rarely promote resistance (e.g., amoxicillin) to
reduce bacterial load and preexisting resistant
organisms and then to follow with different
antibiotics (e.g., clarithromycin and
metronidazole) to kill any remaining organisms.
o The potential advantages of superior eradication
rates require validation in the United States before
this regimen can be recommended as first-line H.
pylori eradication therapy.
 Hybrid therapy
o PPI (D 1-14), Amoxicillin (D1-14),
Metronidazole(D7-14), Clarithromycin (D7-14)
 Patients with NSAID-induced ulcers should be tested to
determine H. pylori status.
o If H. pylori positive, start treatment with a PPI-
based three-drug regimen.
o If H. pylori negative, discontinue the NSAID and
treat with a standard four-week regimen of a PPI,
 histamine2-receptor antagonist (H2RA), or o Bismuth subsalicylate, a nonprescription
sucralfate PPIs are preferred because they provide formulation of bismuth and salicylate, reduces
more rapid symptom relief and ulcer healing. stool frequency and liquidity in infectious
 If the NSAID must be continued despite ulceration, diarrhea. Bismuth causes black stools.
initiate treatment with a PPI (if H. pylori negative) or a
PPI-based three-drug regimen (if H. pylori positive).
 PPI treatment should be continued for 8 to 12 weeks if Characteristics of Common Causes of Peptic Ulcer Disease
the NSAID must be continued.
 Co-therapy with a PPI or misoprostol or switching to a
selective cyclooxygenase-2 (COX-2) inhibitor is
recommended for patients at risk of developing an
ulcer-related complication.

Medications used to control acidity.

 Antacids:
o Weak bases that neutralize stomach acid by
reacting with protons in the lumen of the gut and
may also stimulate the protective functions of the
gastric mucosa.
o Popular antacids include magnesium hydroxide
(Mg[OH]2) and aluminum hydroxide (Al[OH]3).
Neither of these weak bases is significantly
absorbed from the bowel.
 Magnesium hydroxide has a strong laxative
effect,
 Aluminum hydroxide has a constipating
action.
o These drugs are available as single-ingredient
products and as combined preparations.
 Calcium carbonate and sodium bicarbonate
are also weak bases, but they differ from
aluminum and magnesium hydroxides in
being absorbed from the gut. Because of
their systemic effect.
 H2-receptor antagonists—Cimetidine and other H2
antagonists (ranitidine, famotidine, and nizatidine)
inhibit stomach acid production, especially at night.
o Cimetidine: first H2RA, with antiandrogen effect
o Ranitidine: eight folds more potent than
cimetidine
o Famotidine: Most potent
o Nizatidine: Most bioavailable
 Proton pump inhibitors—Omeprazole and other proton
pump inhibitors (esomeprazole, (dex) lansoprazole,
pantoprazole, and rabeprazole) are lipophilic weak
bases that diffuse into the parietal cell canaliculi, where
they become protonated and concentrated more than
1000-fold.
 They irreversibly inactivate the parietal cell H+/K+
ATPase, the transporter that is primarily responsible for
producing stomach acid.
o Proton pump inhibitors may decrease the oral
bioavailability of vitamin B12 and certain drugs
that require acidity for their gastrointestinal
absorption.
 Colloidal bismuth—Bismuth has multiple actions,
including formation of a protective coating on ulcerated
tissue, stimulation of mucosal protective mechanisms,
direct antimicrobial effects, and sequestration of
enterotoxins.
PHCP Lec Topic 6: Nausea and Vomiting
 Nausea is usually defined as the inclination to vomit or
as a feeling in the throat or epigastric region alerting an
individual that vomiting is imminent.
 Vomiting is defined as the ejection or expulsion of
gastric contents through the mouth, often requiring a
forceful event.
 The three consecutive phases of emesis are nausea,
retching, and vomiting.
o Nausea, the imminent need to vomit, is associated
with gastric stasis.
o Retching is the labored movement of abdominal
and thoracic muscles before vomiting.
o The final phase of emesis is vomiting, the forceful
expulsion of gastric contents due to GI retro
peristalsis.
 Vomiting is triggered by afferent impulses to the
vomiting center, a nucleus of cells in the medulla.
Impulses are received from sensory centers, such as the
Chemoreceptor Trigger Zone (CTZ), cerebral cortex, and
visceral afferents from the pharynx and GI tract.
 When excited, afferent impulses are integrated by the
vomiting center, resulting in efferent impulses to the
salivation center, respiratory center, and the
pharyngeal, gastrointestinal (GI), and abdominal
muscles, leading to vomiting.
Specific Etiologies of Nausea and Vomiting
Clinical Presentation of Nausea and Vomiting

Pharmacologic Treatment
Treatment of simple nausea or vomiting usually requires
minimal therapy.
 Antacids
- Single or combination nonprescription antacid
products, especially those containing magnesium
hydroxide, aluminum hydroxide, and/or calcium
carbonate, may provide sufficient relief from
simple nausea or vomiting, primarily through
gastric acid neutralization. Common antacid
dosage regimens for the relief of nausea and
vomiting include one or more 15 to 30 mL doses
of single- or multiple-agent products.
 Antihistaminic—anticholinergic agents
- Dimenhydrinate (Dramamine)
- Diphenhydramine (Benadryl)
- Hydroxyzine (Vistaril, Atarax)
- Meclizine (Bonine, Antivert)
- Scopolamine (Transderm Scop)
- Trimethobenzamide (Tigan)
- Antiemetic drugs from the antihistaminic-
anticholinergic category may be appropriate in the
treatment of simple nausea and vomiting,
especially associated with motion sickness.
- Adverse reactions that may be apparent with the
use of the antihistaminic anticholinergic agents
primarily include drowsiness or confusion, blurred
vision, dry mouth, urinary retention, and possibly
tachycardia, particularly in elderly patients.
 Benzodiazepines are relatively weak antiemetics and
are primarily used to prevent anxiety or anticipatory
nausea and vomiting. Both alprazolam and lorazepam
are used as adjuncts to other antiemetics in patients
treated with cisplatin-containing regimens.
 Phenothiazines are most useful in patients with simple
nausea and vomiting. Rectal administration is a
reasonable alternative in patients in whom oral or
parenteral administration is not feasible.
- Problems associated with these drugs are
troublesome and potentially dangerous side
effects, including extrapyramidal reactions,
hypersensitivity reactions with possible liver
dysfunction, marrow aplasia, and excessive
sedation.
 Dexamethasone is the most commonly used
corticosteroid in the management of chemotherapy-
induced nausea and vomiting (CINV) and postoperative
nausea and vomiting (PONV), either as a single agent or
in combination with 5- hydroxytryptamine-3 receptor
antagonists (5-HT3-RAs).
- For CINV, dexamethasone is effective in the
prevention of both cisplatin-induced acute emesis
and delayed nausea and vomiting with CINV when
used alone or in combination.
 Metoclopramide is used for its antiemetic properties in
patients with diabetic gastroparesis and with
dexamethasone for prophylaxis of delayed nausea and
vomiting associated with chemotherapy administration.
- MOA: acts as Dopamine 2 receptor antagonist at
the CRTZ
 Oral nabilone (Cesamet) and oral dronabinol (Marinol)
are therapeutic options when CINV is refractory to
other antiemetics; but are not indicated as first-line
agents. These are man-made forms of THC
(tetrahydrocannabinol) from cannabis or commonly
known as marijuana.
Neurokinin 1 Receptor Antagonists
- Substance P is a peptide neurotransmitter with a
preferred receptor is NK1 and is believed to be the
primary mediator of the delayed phase of CINV and one
of two mediators of the acute phase of CINV.
- Aprepitant and fosaprepitant (injectable form of
aprepitant) are NK1 receptor antagonists that are
indicated as part of a multiple drug regimen for
prophylaxis of nausea and vomiting associated with
high-dose cisplatin-based chemotherapy.
- The combination NK1 receptor antagonist/5-HT3-RA
products, netupitant/palonosetron and the NK1
receptor antagonist, rolapitant, are used in patients
receiving moderate to highly emetogenic
chemotherapy as part of a three-drug combination
consisting of an NK1 receptor antagonist,
dexamethasone, and a 5- HT3-RA.
o This combination is now considered the standard
of care for CINV.
5-Hydroxytryptamine-3 Receptor Antagonists
- 5-HT3-RAs (dolasetron, granisetron, ondansetron, and
palonosetron) are used in the management of CINV,
PONV, and radiation-induced nausea and vomiting.
- The most common side effects associated with these
agents are constipation, headache, and asthenia.
Disorders of Balance
 Scopolamine (usually administered as a patch)
scopolamine is effective for the prevention of motion
sickness and is considered first-line for this indication.
Antiemetic Use During Pregnancy
 Initial management of nausea and vomiting of
pregnancy (NVP) often involves dietary changes and/or
lifestyle modifications.
 Pyridoxine (10–25 mg one to four times daily) is
recommended as first-line therapy with or without
doxylamine (12.5–20 mg one to four times daily).
 Patients with persistent NVP or who show signs of
dehydration should receive IV fluid replacement with
thiamine.
 Patients with persistent NVP or who show signs of
dehydration should receive IV fluid replacement with
 thiamine. Ondansetron, promethazine, and
metoclopramide have similar effectiveness for
hyperemesis gravidarum, although ondansetron may be
better tolerated due to less adverse effects.
o Hyperemesis gravidarum:
 Medical term for severe nausea and vomiting
during pregnancy.
 Symptoms may lead to dehydration, weight
loss and electrolyte imbalance.
Antiemetic use in Children
 For children receiving chemotherapy of high or
moderate risk, a corticosteroid (such as
dexamethasone) plus 5-HT3-RAs should be
administered. The best doses or dosing strategy has not
been determined.
 For nausea and vomiting associated with pediatric
gastroenteritis, there is greater emphasis on
rehydration measures than on pharmacologic
intervention.
PHCP Lec Topic 7: Gastro Esophageal Reflux Disease
 GERD is symptoms or complications resulting from
refluxed stomach contents into the esophagus, oral
cavity (including the larynx), or lungs.
 Episodic heartburn that is not frequent or painful
enough to be bothersome is not included in the
definition.
 In some cases, reflux is associated with defective lower
esophageal sphincter (LES) pressure or function.
 Patients may have decreased LES pressure from
spontaneous transient LES relaxations, transient
increases in intraabdominal pressure, or an atonic LES.
 Some foods and medications decrease LES pressure.
Clinical Presentation
 Problems with other normal mucosal defense
mechanisms may contribute to development of GERD:
o Abnormal esophageal anatomy
o Improper esophageal clearance of gastric fluids
o Reduced mucosal resistance to acid.
o Delayed or ineffective gastric emptying
o Inadequate production of epidermal growth
factor,
o Reduced salivary buffering of acid.
 Esophagitis occurs when the esophagus is repeatedly
exposed to refluxed gastric contents for prolonged
periods.
o This can progress to erosion of the squamous
epithelium of the esophagus (erosive
esophagitis).
 Substances that promote esophageal damage upon
reflux into the esophagus include gastric acid, pepsin,
bile acids, and pancreatic enzymes.
 Composition and volume of the refluxate and duration
of exposure are the primary determinants of the
consequences of gastroesophageal reflux.
 An “acid pocket” is thought to be an area of unbuffered
acid in the proximal stomach that accumulates after a
meal and may contribute to GERD symptoms
postprandially.
 GERD patients are predisposed to upward migration of
acid from the acid pocket, which may also be
positioned above the diaphragm in patients with hiatal
hernia, increasing the risk for acid reflux.
 Reflux and heartburn are common in pregnancy
because of hormonal effects on LES tone and increased
intraabdominal pressure from an enlarging uterus.
 Obesity is a risk factor for GERD due to increased intra-
abdominal pressure.
 Transient LES relaxations, an incompetent LES, and
impaired esophageal motility have also been attributed
to obesity.
 Complications from long-term acid reflux include
esophagitis, esophageal strictures, Barrett esophagus,
and esophageal adenocarcinoma.
 Symptom-based GERD (with or without esophageal
tissue injury) typically presents with heartburn, usually
described as a substernal sensation of warmth or
burning rising up from the abdomen that may radiate to
the neck.
o It may be waxing and waning in character and
aggravated by activities that worsen reflux (eg,
recumbent position, bending-over, eating a high-
fat meal).
o Other symptoms are water brash
(hypersalivation), belching, and regurgitation.
o Alarm symptoms that may indicate complications
include dysphagia, odynophagia, bleeding, and
weight loss.
o The absence of tissue injury or erosions is termed
nonerosive reflux disease (NERD)
 Tissue injury–based GERD (with or without esophageal
symptoms) may present with esophagitis, esophageal
strictures, Barrett esophagus, or esophageal carcinoma.
 Alarm symptoms may also be present.
 Extraesophageal symptoms may include chronic cough,
laryngitis, and asthma.
  Clinical history is sufficient to diagnose GERD in patients
with typical symptoms.
 Perform diagnostic tests in patients who do not
respond to therapy or who present with alarm
symptoms. Endoscopy is preferred for assessing
mucosal injury and identifying strictures, Barrett
esophagus and other complications.
 Ambulatory pH monitoring, combined impedance–pH
monitoring, high-resolution esophageal pressure
topography (HREPT), impedance manometry, and an
empiric trial of a proton pump inhibitor may be useful
in some situation.
Treatment
 Therapy is directed toward decreasing acidity of the
refluxate, decreasing the gastric volume available to be
refluxed, improving gastric emptying, increasing LES
pressure, enhancing esophageal acid clearance, and
protecting the esophageal mucosa.
 Treatment is determined by disease severity and
includes the following:
o Lifestyle changes and patient-directed therapy
with antacids and/or nonprescription acid
suppression therapy (histamine 2–receptor
antagonists
o [H2RAs] and/or proton pump inhibitors [PPIs])
o Pharmacologic treatment with prescription-
strength acid suppression therapy
o Anti-reflux surgery
Pharmacologic Therapy
 Antacids and Antacid-Alginic Acid Products
o Antacids provide immediate symptomatic relief for
mild GERD and are often used concurrently with
acid suppression therapies. Patients who require
frequent use for chronic symptoms should receive
prescription-strength acid suppression therapy
instead.
 Short duration, frequent administration, may
cause GI disturbances (diarrhea,
constipation).
 Proton Pump Inhibitors
o PPIs (dexlansoprazole, esomeprazole,
lansoprazole, omeprazole, pantoprazole, and
rabeprazole) block gastric acid secretion by
inhibiting hydrogen potassium adenosine
triphosphatase in gastric parietal cells, resulting in
profound and long lasting antisecretory effects.
o Rapid relief, higher healing rate than H2 receptor
blocker
o Lansoprazole, esomeprazole, and pantoprazole are
available in IV formulations for patients who
cannot take oral medication.
 Histamine 2–Receptor Antagonists
o The H2RAs cimetidine, ranitidine, famotidine, and
nizatidine in divided doses are effective for
treating mild to moderate GERD.
o Low-dose nonprescription H2RAs or standard
doses given twice daily may be beneficial for
symptomatic relief of mild GERD.
o The most common adverse effects include
headache, fatigue, dizziness, and either
constipation or diarrhea. Cimetidine
(gynecomastia) may inhibit the metabolism of
theophylline, warfarin, phenytoin, nifedipine, and
propranolol, among other drugs.
 Promotility Agents
o Promotility agents may be useful adjuncts to acid-
suppression therapy in patients with a known
motility defect (e.g., LES incompetence, decreased
esophageal clearance, delayed gastric emptying).
However, these agents are not as effective as acid
suppression therapy and have undesirable adverse
effects.
 Metoclopramide, a dopamine antagonist,
increases LES pressure in a dose-related
manner and accelerates gastric emptying.
 Bethanechol has limited value because of
side effects (e.g., urinary retention,
abdominal discomfort, nausea, flushing).
 Mucosal Protectants
o Sucralfate (iselpin) is a nonabsorbable aluminum
salt of sucrose octa sulfate.
 It has limited value for treatment of GERD
but may be useful for management of
radiation esophagitis and bile or nonacid
reflux GERD.
Non-Pharmacologic Therapy
 Weight reduction for overweight or obese patients.
 Avoid foods that decrease LES pressure.
 Include protein-rich meals to augment LES pressure.
 Avoid foods with irritant effects on the esophageal
mucosa.
 Eat small meals and avoid eating immediately prior to
sleeping (within 3 hours if possible).
 Stop smoking.
 Avoid alcohol.
 Avoid tight-fitting clothes.
 For mandatory medications that irritate the esophageal
mucosa, take in the upright position with plenty of
liquid or food (if appropriate)
Evaluation of Therapeutic Outcomes
 Monitor frequency and severity of GERD symptoms and
educate patients on symptoms that suggest presence of
complications requiring immediate medical attention,
such as dysphagia.
 Evaluate patients with persistent symptoms for
presence of strictures or other complications.
  Monitor patients for adverse drug effects and the
presence of extraesophageal symptoms such as
laryngitis, asthma, or chest pain. These symptoms
require further diagnostic evaluation.
PHCP Lec Topic 8: Cirrhosis
Liver
- The liver and its companion, the biliary tree and
gallbladder are considered together because of their
anatomic proximity, interrelated function and
overlapping features of some diseases that affects
these organs.
- Functions:
o Maintains metabolic hemostasis.
o Processing dietary lipids, carbohydrates, amino
acids, vitamins,
o Synthesis of serum proteins
o Detoxification and excretion of endogenous
products and xenobiotics.
Clinical Presentation
 Signs and symptoms:
o Asymptomatic
o Hepatomegaly, splenomegaly
o Pruritus, jaundice, palmar erythema, spider
angiomata, hyperpigmentation
o Gynecomastia, reduced libido
o Ascites (water bag), edema, pleural effusion, and
respiratory difficulties
o Malaise, anorexia, and weight loss
o Encephalopathy
Laboratory tests
 Hypoalbuminemia: Serum albumin is produced in the
liver
 Elevated prothrombin time
 Thrombocytopenia – Thrombopoietin is produced by
the liver and kidney.
 Elevated alkaline phosphatase
 Elevated aspartate transaminase (AST), alanine
transaminase (ALT), and
 γ-glutamyl transpeptidase (GGT)
Treatment: General Approaches to Treatment
1. Identifying and eliminating, where possible, the causes
of cirrhosis
2. Assessing the risk for variceal bleeding and beginning
pharmacologic prophylaxis when indicated
3. Evaluating the patient for clinical signs of ascites and
managing with pharmacologic therapy (e.g., diuretics
and paracentesis)
 There’s coagulation disorder in cirrhosis.
4. Monitoring for hepatic encephalopathy: lactulose may
be given to the patient.
5. Monitoring frequently for signs of hepatorenal
syndrome, pulmonary insufficiency, and endocrine
dysfunction
Drug Therapy
 β-Adrenergic Blockade: Mainstay primary prophylaxis
for variceal bleeding
o Reduce portal pressure by reducing portal venous
inflow by:
 Decrease in cardiac output through β1-
adrenergic blockade and a decrease in
splanchnic blood flow through β2-adrenergic
blockade.
 Nonselective B-Blocker should be used -
propranolol or nadolol.
 Somatostatin and Octreotide
o Decrease splanchnic arterial blood flow with a
subsequent decrease in portal inflow through:
o Inhibition of vasodilatory gastrointestinal peptides
including glucagon, vasoactive intestinal peptide,
calcitonin gene-related peptide, and substance P.
o Trans jugular intrahepatic portosystemic shunt
(TIPS) can be used which would connect the portal
vein with the hepatic vein.
 Furosemide and Spironolactone
o To decrease water retention with ascites
 Broad-Spectrum antibiotics
o For Bacterial Peritonitis
o Most common pathogens: E. coli, Klebsiella
pneumoniae, and Streptococcus pneumoniae
o Cefotaxime, Aztreonam, Ofloxacin
Viral Hepatitis
- Refers to the clinically important hepatotropic viruses
responsible for hepatitis A (HAV), hepatitis B (HBV),
delta hepatitis, hepatitis C (HCV), and hepatitis E.
Hepatitis A
- Infectious hepatitis
- Benign
- Self-limiting disease with 15- 50 days incubation period
- HAV does not cause chronic hepatitis.
- Does not have a carrier state.
- Only rarely cause fulminant hepatitis
- Has the largest potential among hepatitis virus to cause
epidemic.
- Spread by ingestion of contaminated water and food
and is shed in the stool for 2- 3 weeks before and 1
week after the onset of jaundice.
- HAV viremia is transient, so blood transmission is rare.
- Small non-enveloped, single stranded RNA
- Humans are the only reservoir.
- Most common transmission is by fecal-oral route.
- 85° Celsius is enough to inactivate the virus.
- Resilient virus
- Can resist denaturation by acid pH 3.0, drying and
temperatures as high as 56C and as low as – 20C.
- Boiling, chlorination and iodination are effective in
destroying the virus.
- Prodrome:
o Mild flulike symptoms
o Anorexia
o Nausea and vomiting
o Fatigue
o Malaise
o Low grade fever
 o Mild headache
o Smokers lose their taste of tobacco.
- Icteric phase:
o Dark urine
o Bilirubinemia
o Pale stool
o Jaundice (70-85%)
o Degree of icterus increases with age.
o Abdominal pain
o Pruritus
o Arthralgia
- Relapsing:
o Uncommon sequelae of acute infection
o More common in elderly patients
o Occur in 3-20% of patients.
- Physical Examination:
o Hepatomegaly is common.
o Jaundice or scleral icterus may occur.
o Fever may be present (up to 40C)
- Person aged 5 – 14 years old are most likely to acquire
acute HAV infection over vaccine.
- High risk:
o Childcare workers
o Low hygiene population
o Foreign travelers
o Food handlers at the point of food preparation are
common source of outbreak. Any food can be
contaminated by HAV.
- Complications:
o Prolonged cholestasis may follow after acute
infection.
 Cholestasis is defined as a decrease in bile
flow due to impaired secretion by
hepatocytes or to obstruction of bile flow
through intra-or extrahepatic bile ducts.
 Protracted period of jaundice greater than 3
months
 Corticosteroids and Ursodeoxycholic acid
may shorten the period of cholestasis.
- Serologic test:
o Anti-hepatitis A virus immunoglobulin M
 Test is positive at the time of onset of
symptoms and is usually accompanied by the
first rise in ALT.
 The result remains positive for 3-6 months
after primary infection and for as long as 12
months in 25% of patients.
 Relapsing Hepatitis: IgM persist for the
duration of the diseases.
o Anti-hepatitis A virus Immunoglobulin G
 Appears soon after IgM and generally persist
for many years.
 Presence of IgG in the absence of IgM
indicates Past infection or vaccination rather
than acute infection. IgG provides protective
immunity.
- Desired outcome:
o Patients would usually recover without clinical
sequelae.
o Goal is to have complete recovery.
o Other goals:
 Reduce complications.
 Reduce transmission.
- General Approach to treatment:
o Prevention and prophylaxis are key to managing
the virus.
o The importance of good hand hygiene cannot be
overemphasized in preventing disease
transmission.
o Immunoglobulins used for pre- and postexposure
prophylaxis and offers passive immunity.
- Vaccines:
o Havrix and Vaqta
o Recommended for children of 12 months of age
up to 18 years.
o Composed of inactivated viruses, 2 doses
o Can be administered with immunoglobulin
injections.
- Immunoglobulin:
o Ig can be given post-exposure.
o If receipt within 2 weeks of infection, it will reduce
infectivity by 85%.
o Used for people who had recent contact with
infected individuals.
- Liver transplantation:
o For chronic relapsing HAV infection
- Post exposure prophylaxis:
o Passive immunization with Gammagard reduces
infection when administered within 15 days of
exposure.
o Recommend for non-immunized close contacts of
those recently diagnosed with acute HAV
infection.
o Acute HAV infection are seen in commercial food
handlers.
- Diet and Activity:
o Patients should avoid alcohol and medications that
may accumulate in the liver.
o Bed rest in acute illness.
o Restricting transmission
o Return to work should probably be delayed for 10
days after onset of jaundice.
- Prevention:
o Hepatitis A vaccine can be used by adults and
children over 1 year and is recommended for
travelers to the developing world.
o Avoid exposure to contaminated water or
untreated tap water – if in doubt, drink bottled
drinks or boil water.
o Ensure meat and seafood has been thoroughly
cooked – do not eat raw shellfish.
o Avoid cream products such as mayonnaise, cheese
or yogurt.
o Practice good hygiene by washing hands
frequently and drying with paper towel.
 o Seroconversion
- Initial or acute phase HBV infection:
o The HBV enters a 4- to 10-week incubation period.
o During which antibodies toward the HBV core are
produced and the virus replicates profusely.
o Active viral replication results in high serum HBV
DNA levels and HBeAg secretion.
o Patients are highly infectious during this time.
- The immunoactive phase:
o Marks a decrease in HBV DNA levels with ongoing
Hepatitis B secretion of HBeAg.
- Worldwide healthcare problem especially in developing o Patients are symptomatic.
areas. o With hepatitis and with increased ALT
- Commonly transmitted via body fluids such as blood, o Lasts a few weeks if acute, years if chronic.
semen and vaginal secretion o As immune system regains control; HBVDNA
- The pathogenesis and clinical manifestations of drops, ALT normalizes, liver inflammation resolves.
hepatitis b are due to the interaction of the virus and - Seroconversion phase:
host immune system, which lead to liver injury and o Development of detectable specific antibodies to
potentially cirrhosis and hepatocellular carcinoma
microorganisms in the blood serum as a result of
(stage 1 liver cancer).
infection or immunization.
- Patients can have either an acute symptomatic disease
 HBeAg is replaced by Anti-HBeAg*
or an asymptomatic disease.
 Subsequent recovery
- Signs and symptoms:
- Can produce:
o Easy fatigability, anxiety, anorexia, and malaise
o Acute hepatitis with recovery clearance of the
o Ascites, jaundice, variceal bleeding, and hepatic
virus
encephalopathy can manifest with liver
o Non progressive chronic hepatitis
decompensation.
o Progressive chronic hepatitis ending with cirrhosis.
o Hepatic encephalopathy is associated with
o Fulminant hepatitis with massive liver necrosis
hyperexcitability, impaired mentation, confusion,
o Asymptomatic carrier obtundation, and eventually coma.
- Can withstand: o Vomiting and seizures
o Extreme temperature - Clinical Presentation Laboratory tests:
o Humidity o Presence of hepatitis B surface antigen for at least
- Mode of transmission: 6 months
o Blood and body fluid o Intermittent elevations of hepatic transaminase
o Body secretions (alanine transaminase and aspartate
 Saliva transaminase) and hepatitis B virus DNA greater
 Semen than 105 copies/mL
 Sweat o Liver biopsies for pathologic classification as
 Tears chronic persistent hepatitis.
 Breastmilk o Chronic active hepatitis, or cirrhosis
 Vertical transmission o Viral attachment of the hepatocyte🡪goes to the
o Sexual transmission is the primary mechanism for nucleus-> attaches to the DNA-> synthesis of RNA.
HBV infection. o HBsAg is the most prominent surface antigen and
- International travel was the most prevalent identifiable is detectable at the onset of clinical symptoms.
risk factor followed by: o Persists even 6 months after
o Injection drug use
o Detection (after 6 months*) means an increased
o Sexual contact
risk for developing chronic states such as cirrhosis,
o or household contact with a hepatitis B Infected hepatic decomposition, hepatocellular carcinoma.
person o High levels of antibodies (IgM antiHBcAg) are
- Three antigens are used to indicate the phase of the detectable during acute infections.
disease: o If there is an infection and if it is proliferating,
o HBsAg – surface antigen of the DNA virus
there should be HBcAg*
o HBcAg – core antigen (no envelope*)  Indicator of active viral replication.
 Can lead to replication.  Means that the person infected can transmit
o HBeAg – secreted by the precore. * the virus.
 Extracelluar form of HBcAg o Patients who respond.
- Three phases using the Absence or presence of HBeAg: - Prevention:
o Acute or initial phase o Vaccine which uses HBsAg
o Immunoactive phase o Recombivax HB and Engerix-B.
 o Twinrix is a combination vaccine for HAV and HBV
in adults.
o Comvax and Pediarix are used for children.
o Prevent or reduce exposure by using latex
condoms and not sharing drug or tattoo needles.
o Health workers should be careful to avoid needle
stick injury.
o HBV immune globulin and vaccine should be given
within 12 hours of birth to infants of HBV positive
mothers.
- Treatment – Desired Outcome:
o HBV infections are not curable*
 Cure is not possible because the HBV
template is integrated into the host genome.
o Goals of therapy are to:
 Increase the chances for seroclearance
 prevent disease progression to cirrhosis and
HCC,
 and to minimize further injury in patients
with ongoing liver damage.
- General Approach to Treatment:
o Response to therapy is monitored by:
 Biochemical (normalization of ALT levels),
 Histologic examination of liver cells from
biopsy
 and virologic response (undetectable serum
HBV DNA levels and loss of HBeAg in HBeAg-
positive patients)
 All chronic HBV patients should be counseled
on preventing disease transmission.
 Sexual and household contacts should be
vaccinated.
 To minimize further liver damage, all chronic
HBV patients should avoid alcohol and be
immunized against HAV.
- Pharmacologic Therapy:
o Because hepatic damage is sustained by ongoing
viral replication, drug therapy aims to suppress
viral replication by either immune mediating or
antiviral agents.
o First-line therapy options
 Interferon (IFN)-α2b
 Lamivudine
 Telbivudine
 Adefovir
 Entecavir
 Pegylated IFN-α2a
Hepatitis C
- HCV is the most common blood-borne pathogen.
- It is approximately five times as common as HIV.
- But nearly 75%may be unidentified.
- It is caused by an RNA virus from the Flaviviridae.
- Risk factors:
o The single largest risk factor for infection is
injection drug use.
o Another is through blood transfusions.
o Chronic hemodialysis
- Pathophysiology:
o Vast majority of cases are chronic hepatitis.
o Damage is due to Cytotoxic T-cell mediated
apoptosis of infected hepatocytes.
o RNA dependent RNA polymerase🡪 enzyme
needed in HCV replication, lacks proofreading
capabilities and generates mutant viruses known
as quasispecies.
- Clinical Presentation:
o HCV RNA is detected 1-2weeks of exposure.
o ALT would rise and indicate hepatic injury and cell
necrosis.
o 85%of acutely infected individuals’ goon to
develop chronic HCV infection.
o Defined as persistently detectable HCV RNA for 6
months or more.
o S/S are similar to previous discussions.
- Treatment - Desired Outcome:
o The primary goal of therapy is to eradicate HCV
infection.
o Resolving the infection prevents the development
of chronic HCV infection sequelae.
- Work Up:
o Rapid antibody test for HCV
o Recombinants immunoblot assay to confirm
infection.
o Polymerase chain reaction
o CBC: thrombocytopenia is common ion patients.
o Thyroid function: low thyroxine is common in 10%
of patients.
o Liver function test.
o Quantitative HCV RNA assay
o Liver biopsy
- General Approach to Treatment:
o Treatment for HCV is necessary because nearly
85% of acutely infected patients develop chronic
infections and are at risk of developing cirrhosis,
and HCC.
o Treatment is indicated for patients previously
untreated who have chronic HCV, circulating HCV
RNA, increased ALT levels.
- Treatment:
o IFN-α and Ribavirin are usually given together.
o No vaccine – there is only a very low prevalence of
the disease.
o NS3/4A protease inhibitor:
 Boseprevir
 Interfere with the ability if the HCV to
replicate by inhibiting key viral enzyme,
NS3/4A serine protease.
  Reversibly binds to the nonstructural
protein 3.
 Must be administered together with
PGN-INF alfa and ribavirin.
 Telaprevir
 Inhibits HCV NS3/4A protease needed
for proteolytic cleavage of the HCV-
encoded polyprotein into mature form.
 For Genotype 1 infection in
combination with peginterferon alfa
and ribavirin
 Specifically intended for patients with
compensated liver disease such as
cirrhosis
o Thrombopoeitin receptor agonists:
 Eltrombopag
 For thrombocytopenia in patients with
hepatitis C to allow initiation and
maintenance of interferon-based
therapy.
 Stimulates bone marrow platelet
production to provide stable platelet
counts to allow therapy with
interferons.
o Antivirals:
 Interferon alfa 2b
 Protein product recombinant therapy
 Ribavirin
 Antiviral nucleoside analogue.
 Not effective when given alone.
- Prevention:
o There is no available vaccine for HCV.
o Avoid risky behavior such as sharing needles or
personal items such as toothbrushes and razors.
PHCP Lec Topic 9: Pancreatitis
Pancreas
- The pancreas is an organ located in the abdomen. It
plays an essential role in converting the food we eat
into fuel for the body's cells.
- Trypsin – Digests proteins
- Chymotrypsin – Digests proteins
- Amylase – Digests Carbohydrates
- The pancreas has two main functions: an exocrine
function that helps in digestion and
an endocrine function that regulates blood sugar such
as insulin and glucagon.
Pancreatitis
- Acute pancreatitis (AP) is an inflammatory disorder of
the pancreas characterized by upper abdominal pain
and pancreatic enzyme elevations.
- Chronic pancreatitis (CP) is a progressive disease
characterized by long-standing pancreatic inflammation
leading to loss of pancreatic exocrine and endocrine
function.
Acute Pancreatitis
- Gallstones and alcohol abuse account for most cases in
the United States. Diabetes mellitus and autoimmune
disorders such as inflammatory bowel disease are also
associated with an increase in acute pancreatitis. A
cause cannot be identified in some patients (idiopathic
pancreatitis).
- AP is initiated by premature activation of trypsinogen to
trypsin within the pancreas, leading to activation of
other digestive enzymes and autodigestion of the gland.
- Activated pancreatic enzymes within the pancreas and
surrounding tissues produce damage and necrosis to
pancreatic tissue, surrounding fat, vascular
endothelium, and adjacent structures. Lipase damages
fat cells, producing noxious substances that cause
further pancreatic and peripancreatic injury.
- Release of cytokines by acinar cells injures those cells
and enhances the inflammatory response. Injured
acinar cells liberate chemoattractant that attract
neutrophils, macrophages, and other cells to the area
of inflammation, causing systemic inflammatory
response syndrome (SIRS). Vascular damage and
ischemia cause release of kinins, which make capillary
walls permeable and promote tissue edema.
- Pancreatic infection may result from increased
intestinal permeability and translocation of colonic
bacteria.
- Local complications in severe AP include acute fluid
collection, pancreatic necrosis, infection, abscess,
pseudocyst formation, and pancreatic ascites.
- Systemic complications include respiratory failure and
cardiovascular, renal, metabolic, hemorrhagic, and CNS
abnormalities.
Drug induced Pancreatitis.
 Well supported Association
o Cimetidine
o Enalapril
o Erythromycin
o Furosemide
o Hydrochlorothiazide
 o Cisplatin
o Tamoxifen
o Sulindac
 Probable Association
o Acetaminophen
o Atorvastatin
o Ifosfamide
o Methyldopa
o Simvastatin
o Oxaliplatin
Pharmacologic Therapy
Clinical Presentation
 The initial presentation ranges from moderate
abdominal discomfort to excruciating pain, shock, and
respiratory distress.
o Abdominal pain occurs in 95% of patients and is
usually epigastric, often radiating to the upper
quadrants or back.
 Onset is usually sudden, and intensity is often described
as “knife-like” or “boring.”
o Pain usually reaches maximum intensity within 30
minutes and may persist for hours or days.
o Nausea and vomiting occur in 85% of patients and
usually follow onset of pain.
 Signs include:
o Epigastric tenderness on palpation with rebound
tenderness and guarding in severe cases.
o The abdominal distention with tympanic sound
and decreased or absent bowel sounds in severe
disease.
o Vital signs may be normal, but hypotension,
tachycardia, and low-grade fever are often
observed, especially with widespread pancreatic
inflammation and necrosis, Dyspnea and
tachypnea are signs of acute respiratory
complications.
o Jaundice and altered mental status may be
present; other signs of alcoholic liver disease may
be present in patients with alcoholic pancreatitis.
Treatment
Chronic Pancreatitis
 IV anti emetics for nausea
 Patients requiring ICU admission should be treated with
antisecretory agents if they are at risk of stress-related
mucosal bleeding.
 Vasodilation from the inflammatory response, vomiting,
and nasogastric suction contribute to hypovolemia and
fluid and electrolyte abnormalities, necessitating
replacement.
 Patients should receive aggressive fluid replacement to
reduce the risks of persistent SIRS and organ failure.
 Different guidelines recommend goal directed IV fluid
with either lactated Ringer’s at an initial rate of 5 to 10
mL/kg/hour or crystalloids at a rate of 250 to 500
mL/hour.
 Parenteral opioid analgesics are used to control
abdominal pain. Parenteral morphine is often used, and
patient-controlled analgesia should be considered in
patients who require frequent opioid dosing (e.g., every
2–3 hours).
 Empiric antimicrobial therapy may be considered in
patients with necrosis who deteriorate or fail to
improve within 7 to 10 days, but not for those without
signs or symptoms.
 Patients with known or suspected infected AP should
receive broad-spectrum antibiotics that cover the range
of enteric aerobic gram-negative bacilli and anaerobic
organisms.
o Imipenem-Cilastatin: now replaced by
Meropenem.
o Fluoroquinolones (Ciprofloxacin, Levofloxacin) plus
Metronidazole (if patient is allergic to penicillin)
 Parenteral histamine2-receptor antagonists and proton
pump inhibitors do not improve the overall outcome of
patients with AP.
- Results from long-standing pancreatic inflammation and
leads to irreversible destruction of pancreatic tissue
with fibrin deposition and loss of exocrine and
endocrine function.
- Chronic ethanol consumption accounts for about two
thirds of cases in Western society. Most of the
remaining cases are idiopathic, and a small percentage
are due to rare causes such as autoimmune, hereditary,
and tropical pancreatitis.
 - The exact pathogenesis is unknown. Activation of
pancreatic stellate cells by toxins, oxidative stress,
and/or inflammatory mediators appears to be the cause
of fibrin deposition.
- Abdominal pain may be caused by abnormal pain
processing in the central nervous system and
sensitization of visceral nerves. This may explain the
hyperalgesia that CP patients often experience with the
need for various methods of pain management.
- Impaired inhibition of somatic and visceral pain
pathways may also cause pain in areas distant to the
pancreas.
Clinical Presentation
 The main features of CP are abdominal pain,
malabsorption with steatorrhea, weight loss, and
diabetes. Jaundice occurs in ~10% of patients.
 Patients typically report deep, penetrating epigastric or
abdominal pain that may radiate to the back. Pain often
occurs with meals and at night and may be associated
with nausea and vomiting.
 Steatorrhea and azotorrhea occur in most patients.
Steatorrhea is often associated with diarrhea and
bloating.
 Weight loss may occur.
 Pancreatic diabetes is a late manifestation commonly
associated with pancreatic calcification.
 Diagnosis is based primarily on clinical presentation and
either imaging or pancreatic function studies.
Noninvasive imaging includes Abdominal ultrasound,
Computed tomography (CT), magnetic resonance
cholangiopancreatography (MRCP). Invasive imaging
includes endoscopic ultrasonography (EUS) and ERCP
 Serum amylase and lipase are usually normal or only
slightly elevated but may be increased in acute
exacerbations.
 Total bilirubin, alkaline phosphatase, and hepatic
transaminases may be elevated with ductal obstruction.
Serum albumin and calcium may be low with
malnutrition.
 Pancreatic function tests include:
o Serum trypsinogen (<20 mg/mL is abnormal)
o Fecal elastase (<200 mcg/g of stool is abnormal)
o Fecal fat estimation (>7 g/day is abnormal; stool
must be collected for 72 hours)
o Secretin stimulation (evaluates duodenal
bicarbonate secretion)
o 13C-mixed triglyceride breath test (not available in
the U.S.)
Goals of Treatment
 Major goals for uncomplicated CP are to relieve
abdominal pain.
 Treat complications of malabsorption and glucose
intolerance and improve quality of life.
 Secondary goals are to delay development of
complications and treat associated disorders such as
depression and malnutrition.
Nonpharmacologic Therapy
 Lifestyle modifications should include abstinence from
alcohol and smoking cessation.
 Advise patients with steatorrhea to eat smaller, more
frequent meals and reduce dietary fat intake.
 Reduction in dietary fat may be needed if symptoms are
uncontrolled with enzyme supplementation.
 Consumption of a low-fat purified amino acid elemental
diet may reduce pain.
 Supplementation with medium-chain triglycerides
should be considered for patients with steatorrhea who
are unable to gain weight.
 Enteral nutrition via a feeding tube is recommended for
patients who cannot consume adequate calories, have
continued weight loss, experience complications, or
require surgery.
 Invasive procedures and surgery are used primarily to
treat uncontrolled pain and the complications of
chronic pancreatitis.
Pharmacologic Therapy
 Pain management should begin with weak opioid
analgesics (e.g., tramadol, codeine) scheduled around
the clock (rather than as needed) to maximize efficacy.
 Administration of short-acting analgesics prior to meals
may decrease postprandial pain.
 Severe pain requires more potent opioids. Unless
contraindicated, oral opioids should be used before
parenteral, transdermal, or other dosage forms.
 Adjuvant agents should be added if patients have
inadequate relief from opioids alone. Pregabalin (75 mg
twice daily initially; maximum 300 mg twice daily) has
the best evidence.
 Selective serotonin reuptake inhibitors (e.g.,
paroxetine), serotonin/norepinephrine reuptake
inhibitors (e.g., duloxetine), and tricyclic
antidepressants can be considered in difficult-to-
manage patients.
 Adding pancreatic enzyme supplements for pain control
(e.g., 4–8 tablets/capsules of a preferred product with
each meal plus a histamine2-receptor antagonist or
proton pump inhibitor) may be considered in select
patients, but no clinical trial data support this approach
for pain management.
 Pancreatic enzyme supplementation and reduction in
dietary fat intake are the primary treatments for
malabsorption due to CP.
 This combination enhances nutritional status and
reduces steatorrhea. The enzyme dose required to
minimize malabsorption is 30,000 to 50,000 units of
lipase administered with each meal.
 The dose may be increased to a maximum of 90,000
units per meal.
  Products containing enteric-coated microspheres or  Most thyroid hormone is transported by Thyroxine
mini-microspheres may be more effective than other Binding Globulin (TBG). Prealbumin and albumin also
dosage forms. serves as carriers.

Mechanism of Action
 T4 and T3 dissociated from thyroid-binding proteins,
entering the cell by the active transport.
 Within the cell, T4 is converted to T3 enters the
nucleus, where T3 binds to a specific T3 protein, a
member of c-erb oncogene family.

Diagnostic Tests

PHCP Lec Topic 10: Hypothyroidism and Hyperthyroidism

Thyroid Physiology
 The normal thyroid
gland secretes sufficient
amounts of the thyroid
hormones and a peptide
(Calcitonin)
 Iodine-Containing
Hormones:
o Triiodothyronine Hyperthyroidism
- It is the clinical syndrome that results when tissues are
(T3) – active, 10x
exposed to high levels of thyroid hormone.
more potent
- Grave’s Disease (most common)
o
- Toxic Uninodular Goiter and Toxic Multinodular Goiter
Tetraiodothyronine/Thyroxine (T4) – Inactive
- Subacute Thyroiditis – viral infxn
 Iodine – main component of thyroid hormone.
- Thyroid Storm – AKA thyrotoxic crisis
o Daily Intake: 150mcg/day
 200 mcg/day - pregnant

Etiology
 The three most common causes of thyrotoxicosis are
associated with hyperfunction of the gland and include
the following:
o Diffuse hyperplasia of the thyroid associated with
Graves’ disease (approximately 85% of cases)
o Hyperfunctional multinodular goiter
o Hyperfunctional thyroid adenoma
Hormone Transport  Graves’ Disease
 After Thyroid-Stimulating Hormone (TSH) stimulation o Results from the action of thyroid-stimulating
of the thyroid gland, T3 and T4 are cleaved from antibodies (TSAb) directed against the
thyroglobulin and released into the circulation. thyrotropinreceptor on the surface of thyroid cell.
 Thyroglobulin – serves as scaffold for thyroid hormone These immunoglobulins bind to the receptor and
synthesis. activate the enzyme adenylate cyclase in the same
 Iodine organification - formation of MIT manner as TSH.
(monoiodotyrosine) and DIT (diiodotyrosine)  Multinodular Goiter
 Proteolysis of thyroglobulin liberates the T3 and T4 in o Follicles with autonomous function coexist with
the blood. normal or even nonfunctioning follicles.
Thyrotoxicosis occurs when autonomous follicles
generate more thyroid hormone than is required.
  Toxic Adenoma o Propylthiouracil – 300-600mg daily
o Autonomous thyroid nodule (toxic adenoma) is a  For pregnant
thyroid mass whose function is independent of o Methimazole – 30-60mg daily
pituitary control. Hyperthyroidism usually occurs o ADR’s:
with larger nodules (>3 cm in diameter)  Pruritic maculopapular rash
 Granulomatous (de Quervain) Thyroiditis  Arthralgia
o Develops after a viral syndrome, but rarely has a  Fever
specific virus been identified in thyroid  Benign transient leukopenia
parenchyma.  Agranulocytosis
 Painless (silent, lymphocytic, or postpartum)  Aplastic anemia
Thyroiditis  Lupus-like syndrome
o Etiology is not fully understood; autoimmunity  GI intolerance
may underlie most cases.  Hepatotoxicity
 Hypoprothrombinemia
Clinical Manifestations  Monitor every 6-12 months after remission.
 Thyroid Storm (Thyrotoxic Crisis)  If relapse occurs, alternate to second course
o Sudden acute exacerbation of all the symptoms, of antithyroid drugs.
presenting life threatening syndrome encountered
during infection, surgery, cessation of anti-thyroid  Iodides
medication, or any form of stress. o MOA: Acutely blocks thyroid hormone release, inh
thyroid hormone biosynthesis by interfering with
Risk Factors intrathyroidal iodide use, and decreases size and
 Older than age 60 vascularity of the gland
 History of thyroid problems o ADR’s:
 Family history of thyroid problems  Hypersensitivity reactions
 Type 1 Diabetes  Salivary gland swelling
 Too much iodine consumption  Iodism
- Metallic taste, burning mouth and
Clinical Manifestations throat, sore teeth and gums, head cold,
 Soft, warm and flushed skin stomach upset, diarrhea.
 Retraction of upper lid – wide stare  Gynecomastia
 Periorbital edema, exophthalmos o Potassium Iodide
 Dec HR, stroke volume, cardiac output, pulse pressure  KISS, 38mg iodide per drop
 Dec inotropic and chronotropic o Lugol Solution
 GI tract hypermotility, diarrhea and malabsorption  6.3mg iodide per drop
 Nervousness, hyperkinesia, emotional lability, agitation o Adjunctive for Graves’ disease for surgery
 Inc erythropoiesis, anemia o Used 3-7 days after RAI treatment so RAI can
 Menstrual irregularities concentrate in the thyroid.

 Adrenergic Blockers
Laboratory and Diagnostic Tests o Propranolol, Nadolol
 Thyroid ultrasound – this test can see if your thyroid  partially block conversion of T4 to T3, small
gland has any nodules. overall effect
 Thyroid scan – this test uses a radioactive substance to o Propranolol
make an image of the thyroid.  20-40mg QID initial dose for most
 Blood tests – measure the amount of thyroid hormone  240-480mg/day in younger and severely toxic
and thyroid stimulating hormone in your blood. patients
o Adjunctive to RAI without compromising RAI
Interventions therapy.
 Goals: Eliminate excess thyroid hormone, minimize o Ameliorate symptoms – palpitations, anxiety,
symptoms, and long-term consequences; and provide tremor and heat intolerance.
individualized therapy based on the type and severity of o No effect on peripheral thyrotoxicosis and protein
disease, patient age and gender, existence of metabolism
nonthyroidal conditions, and response to previous o Contraindications: decompensated heart failure,
therapy sinus bradycardia, MAOI and TCA therapy,
hypoglycemia
Pharmacological Treatment o Side effects: N&V, anxiety, insomnia,
 Thioureas (Thionamides) lightheadedness, bradycardia, hematologic
o MOA: Block thyroid hormone synthesis by disturbances
inhibition of peroxidase enzyme  Radioactive Iodine (RAI)
 o MOA: Concentrates in thyroid and disrupts
hormone synthesis by incorporating into thyroid
hormones and thyroglobulin
o Sodium-Iodide 131 – oral liquid
o DOC for Graves’ disease, toxic autonomous
nodules and toxic multinodular goiters
o Contraindicated to pregnancy.
o Hypothyroidism commonly occurs months-years
after RAI.
o Acute Side effects:
 Mild thyroidal tenderness
 Dysphagia
Interventions
 Surgical Removal of the glans (Thyroidectomy)
o >80g, severe ophthalmopathy
o PTU/methimazole is given until px is biochemically
euthyroid.
o Iodides for 1-14 days before surgery
o Propranolol – several weeks pre-op and 7-10 days
post-op (maintain 90bpm)
Hypothyroidism
- The inability of the thyroid gland to supply sufficient
thyroid hormone.
- A syndrome resulting from deficiency of thyroid
hormones and is manifested largely by a reversible
slowing down of all body functions.
- Conditions: cretinism (children), Myxedema(adult)
Pathophysiology
 Hypothyroidism can be
caused by permanent loss
or atrophy of functional
thyroid tissue (primary
hypothyroidism);
insufficient stimulation of a
normal thyroid gland as a
result of hypothalamic or
pituitary disease
(secondary
hypothyroidism, often accompanied by compensatory
thyroid gland enlargement); or a defect in the TSH
molecule.
Etiology
 Primary Hypothyroidism
o Accounts for the vast majority of cases and may be
accompanied by an enlargement in the size of the
thyroid gland (goiter).
o Congenital Hypothyroidism
 Most often result of endemic iodine
deficiency in the diet, inborn errors of thyroid
metabolism (dyshormonogenetic goiter),
where in any one of the multiple steps
leading to thyroid hormone synthesis may be
defective:
 Iodide transport into thyrocytes
 Organification of iodine (binding of
iodine to tyrosine residues of the
storage protein, thyroglobulin)
 Iodothyrosine coupling to form
hormonally active T3 and T4

o Autoimmune Hypothyroidism
 Vast majority of patients have primary
hypothyroidism.
 Due to thyroid gland failure from
chronic autoimmune thyroiditis
(Hashimoto’s disease/Hashimoto’s
Thyroiditis)
 Defects in suppressor T-lymphocyte function
 Lead to survival of random mutating
clones of helper T-lymphocytes directed
against antigens on the thyroid
membrane – interaction leads to B-
lymphocyte stimulation of thyroid
antibody production.
 Circulating autoantibodies
 Including anti-microsomal, antithyroid
peroxidase, and antithyroglobulin
antibodies, are found in this disorder,
and the thyroid is typically enlarged
(goitrous)
o Iatrogenic Hypothyroidism
 This can be caused by either surgical or
radiation induced ablation.
 A large resection of the gland (total
thyroidectomy) for the treatment of
hyperthyroidism or a primary neoplasm.
 Ablated by radiation, whether in the
form of radioiodine administered for
the treatment of hyperthyroidism, or
exogenous irradiation, such as external
radiation therapy to the neck.
 Drugs given intentionally to decrease
thyroid secretion (e.g., methimazole
and propylthiouracil) can also cause
acquired hypothyroidism, as can agents
used to treat non-thyroid conditions
(e.g., lithium, p-aminosalicylic acid).
 Secondary or Central Hypothyroidism
o Uncommon pituitary failure - deficiencies of TSH
or, far more uncommonly, TRH.
o Due to destruction of thyrotrophs by pituitary
tumors, surgical therapy, external pituitary
radiation, postpartum pituitary necrosis (Sheehan
syndrome), trauma and infiltrative processes of
the pituitary (metastatic tumors)
 Cretinism
o Develops in infancy or early childhood.
o Maternal T3 and T4 cross the placenta and are
critical for fetal brain development.
 If there is maternal thyroid deficiency before
the development of the fetal thyroid gland,
mental retardation is severe. In contrast,
maternal thyroid hormone deficiency later in
pregnancy, after the fetal thyroid has become
 functional, does not affect normal brain  Rifampin, CBZ, Phenytoin – increase
development. nondeiodinative T4 clearance.
 Myxedema  Amiodarone – block conversion of T4 to T3
o Hypothyroidism developing in the older child or  Thyroid Preparations
adult. o Desiccated Thyroid Preparations
 Former DOC of hypothyroidism
 Unstable because animal origin (pig thyroid
gland)
 Antigenic
o Fixed Ratio (Liotrix®) Preparations
 4:1 (synthetic T4:T3)
 Very expensive, requires multiple monitoring.
 4x more potent than L-thyroxine; short t1/2
o Liothyronine (Synthetic R3)
 Uniform potency
Risk Factors  High incidence of cardiac AE
 Risk for developing increases with age.
 More common in women than men
 Increases during pregnancy, after delivery and around
menopause.
 Common in whites and Asians
 With another autoimmune disorder
 Past treatment with radioactive iodine
 Thyroid surgery
 Down syndrome or turner syndrome

Clinical Manifestations
 Pale, cool, puffy, yellowish skin, face and hands.
 Dry and brittle hair and nails
 Dropping of eyelids, periorbital edemia, loos of
temporal aspects of eyebrows
 Inc peripheral vascular resistance
 Dec HR, stroke volume, cardiac output, pulse pressure
 Dec appetite, dec frequency of bowel movement
 Lethargy, fatigue, slow mental processes
 Neuropathies, weak and muscle cramps
 Dec erythropoiesis, anemia
 Menorrhagia

Interventions
 Goals: Restore thyroid hormone concentrations,
provide symptomatic relief, prevent neurologic deficits
in newborns and children, and reverse the biochemical
abnormalities

Pharmacological Treatment
 Levothyroxine (L-thyroxine, T4)
o DOC thyroid hormone replacement and
suppressive therapy
o DOC for pregnant women
 50mcg daily, long standing disease and older
patient’s w/o cardiac disease
 25mcg/day, older patients w/ cardiac disease
– titrated 25mcg at monthly intervals
 125mcg/day, ave maintenance dose for
adults
o Drug Interactions:
 Cholestyramine, CaCO3, sucralfate, Al(OH)3,
FeSO4, soybean formula and dietary
supplements, espresso coffee –impair GI
absorption