Download Norfloxacin 400 mg or ciprofloxacin 500 mg orally

The Important Aspect of
Infectious Diseases in Adults
Department of Pharmacology & Therapy
Faculty of Medicine
Universitas Gadah Mada
Yogyakarta
Normal Microbial Flora of the Digestive System
• Mouth
• 1 ml saliva = millions of bacteria
• Stomach and small intestine
• Few organisms due to HCl and rapid
movement of food
• Large intestine
• 100 billion bacteria per gram of feces
• 40 % of fecal mass is microbial cell material
• Lactobacillus, Bacteriodes, Enterobacter,
E. coli. Proteus spp.
Bacterial Diseases of Lower G.I.
• Infections
• Pathogens enters G.I.
Tract and multiples
• Bacteria may penetrate
the intestinal mucosa or
may pass to other
systemic organs
• Delay in appearance of
symptoms while pathogen
increases in number or
invades tissue
• Usually a fever
• Intoxications
• Ingestion of a
preformed toxin
• Sudden onset of
symptoms ( few
hours )
• Fever not always
present
Drugs for diarrhea
OPIATES AND THEIR DERIVATIVES
Opiates and opioid derivatives (a) delay the transit of intraluminal
contents or (b) increase gut capacity, prolonging contact and
absorption.
Enkephalins, endogenous opioid substances, regulate fluid movement
across the mucosa by stimulating absorptive processes. Limitations
to the use of opiates include an addiction potential (a real concern
with long-term use) and worsening of diarrhea in selected infectious
diarrhea.
Most opiates act through peripheral and central mechanisms
with the exception of loperamide, which acts only peripherally.
Loperamide is antisecretory; it inhibits the calcium-binding protein
calmodulin, controlling chloride secretion. Loperamide, available as
2-mg capsules or 1 mg/5 mL solution (both are nonprescription
products), is suggested for managing acute and chronic diarrhea
The usual adult dose is initially 4 mg orally, followed by
2 mg after each loose stool, up to 16 mg/day.
Used correctly, this agent has rare side effects such as
dizziness and constipation.
If the diarrhea is concurrent with a high fever or bloody
stool, the patient should be referred to a physician.
Also, diarrhea lasting 48 hours beyond initiating
loperamide warrants medical attention. Loperamide
can also be used in traveler’s diarrhea. It is
comparable to bismuth subsalicylate for treatment of
this disorder.
Diphenoxylate is available as 2.5-mg tablets
and as a 2.5 mg/5 mL solution. A small amount of
atropine (0.025 mg) is included to discourage abuse.
In adults, when taken as 2.5 to 5 mg three or four times
daily, not to exceed a 20-mg total daily dose,
diphenoxylate
is rarely toxic. Some patients may complain of
atropinism (blurred vision, dry mouth, and urinary
hesitancy). Like loperamide, it should not be used in
patients at risk of bacterial enteritis with Escherichia
coli, Shigella, or Salmonella.
Difenoxin, a diphenoxylate derivative, is also
combined with atropine and has the same uses,
precautions, and side effects. Marketed as 1-mg
tablet, the adult dosage is 2 mg initially followed by 1
mg after each loose stool, not to exceed 8 mg/day.
ADSORBENTS
Adsorbents are used for symptomatic relief. These
products, many not requiring a prescription, are
nontoxic, but their effectiveness remains unproven.
Adsorbents are nonspecific in their action; they adsorb
nutrients, toxins, drugs, and digestive juices.
Coadministration with other drugs reduces their
bioavailability. The Food and Drug Administration overthe-counter review panel recommends only
polycarbophil as an effective adsorbent.
Polycarbophil absorbs 60 times its weight in water and
can be used to treat both diarrhea and constipation. It is
a nonprescription product and is sold as 500-mg
chewable tablets. This hydrophilic nonabsorbable
product is safe and may be taken four times daily, up to
6 g/day in adults.
Bacterial Diseases of
Lower G.I.
• Diarrhea – infections and intoxications
• Blood or mucus - dysentery
• Abdominal cramps, nausea and vomiting
• Defense mechanism to rid body of harmful
material
• Gastroenteritis
• Inflammation of stomach or intestinal
mucosa
Escherichia Gastroenteritis
• 1. ETEC - enterotoxigenic E. coli
• Not invasive
• Enterotoxin – watery diarrhea
• 2. EIEC - enteroinvasive E. coli
• Invades intestinal wall
• Inflammation, fever & Shigella-like dysentery
• 3. EHEC - enterhemorrhagic E. coli
• E. coli
• Found in intestines of animals, especially cattle
• Hemorrhagic colitis – inflammation of colon with
bleeding
• HUS – Hemolytic Uremic Syndrome
• Blood in urine leading to kidney failure (kidneys effected
by toxin)
Enterotoxigenic E. coli
First line:
Norfloxacin 400 mg or ciprofloxacin 500
mg orally twice daily × 3 days
Alternatives:
Trimethoprim-sulfamethoxazole DS tablet
every 12 hours
Shigellosis (Bacillary Dysentery)
• Bacterial infection - Shigella sp. Gram (-),
facultative, rods
•
•
•
•
Shigella sonnei
Shigella dysenteriae
Shigella flexneri
Shigella boydii
Incubation period:
• 12 hours to 2 weeks
• Usually fever
• Mild case of Shigellosis
• Traveler’s Diarrhea
Invasive (Dysentery-Like) Diarrhea
Shigella species
First line:
Trimethoprim-sulfamethoxazole DS twice daily × 3–5
days
Alternatives:
Ofloxacin 300 mg, norfloxacin 400 mg, or ciprofloxacin
500 mg twice daily × 3 days, or nalidixic acid 1 g/day ×5
days; azithromycin
500 mg orally × 1, then 250 mg orally daily
× 4 days.
Salmonellosis
(Salmonella Gastroenteritis)
• Bacterial Infection – Salmonella sp.
• Salmonella
• Gram (-), facultative, non-spore forming rods
• Found in G.I. Tract of humans and many animals
• All are considered pathogenic
• Taxonomy
• Use serotype rather than species
• Over 2000 serotypes (50 common in U.S.)
• Salmonella arizonae
Salmonella brazil
• Salmonella atlanta
Salmonella pakistan
• Salmonella berlin
Salmonella california
Salmonellosis
• Incubation time 12 – 36 hours
• Bacteria invade the intestinal
mucosa and multiply
• May pass thru mucosa into
lymphatic or circulatory system and
become systemic
• Fever, abdominal pain, cramps and
diarrhea
Salmonellosis
• 1 billion Salmonella per gram of
feces
• Mortality rate < 1 %
• Higher in infants and elderly
• Recovery in a few days
• Some may shed bacteria in feces for 6
months
Salmonellosis
• Contamination
• Meats, poultry, eggs, pet reptiles
(turtles)
• Undercooked or Raw Eggs
Salmonella
Nontyphoidal
First line:
Trimethoprim-sulfamethoxazole DS twice daily; ofloxacin
300 mg, norfloxacin 400 mg, or ciprofloxacin 500 mg
twice daily × 5 days; or ceftriaxone 2 g IV daily or
cefotaxime 2 g IV three times daily × 5 days
Alternatives:
Azithromycin 1000 mg orally × 1 day, followed by
500 mg orally once daily × 6 days
Typhoid Fever
• Salmonella typhi - most virulent
Salmonella
• Only found in humans (feces)
• Systemic disease
• Spreads thru body, found in blood,
urine, feces
Enteric fever
First line:
Ciprofloxacin 500 mg orally twice daily × 3–14 days
(ofloxacin and perfloxacin equally efficacious)
Alternatives:
Azithromycin 1000 mg orally × 1 day, followed by
500 mg daily × 5 days; or cefixime, cefotaxime,
and cefuroxime; or chloramphenicol 500 mg four
times daily orally or IV × 14 days
Campylobacter
First line
Erythromycin 500 mg orally twice daily × 5 days;
azithromycin 1000 mg orally × 1 day, followed by
500 mg daily or clarithromycin 500 mg orally twice
daily
Alternative:
Ciprofloxacin 500 mg or norfloxacin 400 mg orally
twice daily × 5 days
Cholera
• Vibrio cholerae - Gram (-)
• Endemic in Asia and India
• Cholera toxin
• Secretion of Cl- leads to H2O loss and
diarrhea
• 12 – 20 liters of fluid per day ( 3 – 5
gallons)
Enterotoxigenic (Cholera-Like) Diarrhea
Vibrio cholerae
First line agents
Doxycline 300 mg oral single dose;
tetracycline 500 mg orally four times daily × 3 days;
trimethoprimsulfamethoxazole tablet twice daily × 3
days; norfloxacin 400 mg orally twice daily × 3 days;
ciprofloxacin 500 mg orally twice daily × 3 days or 1 g
orally single dose
Alternatives agents
50 mg/kg IV every 6 hours,
erythromycin 250–500 mg PO every 6–8 hours,
and furazolidone
C. Difficile
First line:
Metronidazole 250 mg four times daily to 500 mg three
times daily × 10 days
Alternatives:
Vancomycin 125 mg orally four times daily × 10
days; bacitracin 20,000–25,000 units four times
daily × 7–10 days
Traveler’s Diarrhea
Prophylaxis
Norfloxacin 400 mg or ciprofloxacin 500 mg orally
daily (in Asia, Africa, and South America);
trimethoprim-sulfamethoxaxole DS tablet orally daily
(in Mexico)
Treatment
Norfloxacin 400 mg or ciprofloxacin 500 mg orally
twice daily × 3 days, or trimethoprim-sulfamethoxazole
tablet orally twice daily × 3 days (in Mexico), or
azithromycin 500 mg orally once daily × 3 days (only
in areas of high prevalence of quiniolone-resistant
Campylobacter species, such as Thailand)
Food Poisoning from
Seafood
• Vibrio parahaemolytica
• Found in salt H2O estuaries
• Associated with poisoning from
•
•
•
•
Raw oysters
Shell fish
Shrimp
crabs
ANTIMOTILITY AGENTS
Agents that inhibit peristalsis such as diphenoxylate
and loperamide are contraindicated in most toxinmediated diarrheal illnesses (enterohemorrhagic
E. coli, pseudomembranous colitis, shigellosis).
Slowing of fecal transit time is thought to result in
extended toxin-associated damage. On the other
hand, in traveler’s diarrhea, a combination
of appropriate antibiotics and loperamide controls
symptoms within 10 hours.
Rotavirus Infection
Oral fluid and electrolyte replacement is the
cornerstone of treatment. Oral Lactobacillus therapy
may reduce the duration of diarrhea and of viral
excretion.
There is no role for antibiotics in acute infection.
Bismuth subsalicylate, although shown to decrease the
duration of diarrhea and stool output, is not
recommended for routine use because of the selflimiting nature of the disease and the risk of
bismuth subsalicylate overdose.
Antimotility agents are not recommended because they
have not been shown to decrease the duration
or volume of diarrhea.
Staphylococcal Food Poisoning
(Staphylococcal intoxication)
• Ingesting an enterotoxin by Staph. aureus
• Staphylococci
•
•
•
•
High resistance to heat
Resistant to drying out
Resistant to high osmotic pressures
Resistant to high salt conc.
• Found in nasal passages and hands
• Contaminate food
* 1 million bacteria per gram of food to produce enough enterotoxin to cause
illness
Most reliable method of preventing
Staphylococcal intoxication:
• Adequate refrigeration during storage to prevent
toxin production
• Toxin
• Triggers vomiting reflex center of brain
• Abdominal cramps & diarrhea
• Recovery usually complete in 24 hours.
• Mortality rate – 0 % in healthy people
Treatment: Supportive
Peptic Ulcers
• Helicobacter pylori – microaerophilic
spiral
• 30% - 50 % of normal pop. are infected,
but only 15% of those develop ulcers
•
• H2O + urea
urease
ammonia + CO2
• Urea Breath Test
• Swallow radio-active urea
• If positive, patient will exhale radio-active CO2
within 30 minutes
Therapy of Helicobacter pylori Infection
Triple therapy × 14 days: [Proton pump inhibitor + clarithromycin 500 mg
+ (metronidazole 500 mg or amoxicillin 1 g)] twice a day. (Tetracycline
500 mg can be substituted for amoxicillin or metronidazole.)
Quadruple therapy × 14 days: Proton pump inhibitor twice a day +
metronidazole 500 mg three times daily + (bismuth subsalicylate 525 mg
+ tetracycline 500 mg four times daily)
or
H2 receptor antagonist twice a day + (bismuth subsalicylate 525 mg +
metronidazole 250 mg + tetracycline 500 mg) four times daily
Dosages:
Proton pump inhibitors:
Omeprazole: 20 mg
Lansoprazole: 30 mg
Rabeprazole: 20 mg
Pantoprazole: 40 mg
Esomeprazole: 40 mg
H2 receptor antagonists:
Cimetidine: 400 mg
Famotidine: 20 mg
Nizatidine: 150 mg
Ranitidine: 150 mg
Farmakologi Obat Pada
Infeksi Hati dan Empedu
Eti Nurwening Sholikhah
Bagian Farmakologi dan Terapi
Fakultas Kedokteran
Universitas Gadah Mada
Hepatitis
• Inflammation of the liver
• Viral Hepatitis
• 5 different viruses
•
•
•
•
•
Hepatitis A
Hepatitis B
Hepatitis C
Hepatitis D
Hepatitis E
Hepatitis A (Infectious Hepatitis)
• HAVss RNA no envelope
• Enters via oral route, multiplies in G.I. Tract spreads
to liver
• Virus is shed in feces
• HAV is resistant to normal chlorine disinfectants used
for water
• HAV can survive several days on surfaces (cutting
boards)
• 50% of infections are subclinical
• Symptoms
• Nausea
• Fever
diarrhea
chills
abdominal discomfort
jaundice
• Recovery results in lifelong Immunity
The ultimate goal in treating acute viral hepatitis is
to return the individual to the previous state of
health.
Intermediate goals while the individual is acutely
symptomatic and infectious include decreasing
morbidity and acute mortality, normalizing
aminotransferases (to stop hepatic inflammation),
stopping viral replication in the host, and ultimately
eradicating the virus.
Pharmacologic agents offer no clear benefit in the
treatment of patients infected with HAV.
Corticosteroids have been used in patients with acute
HAV when cholestatic hepatitis or fulminant hepatic
failure is evident.
Hepatitis B (Serum Hepatitis)
• HBVds DNA envelope
• Transmitted by blood, semen, saliva, breast milk
• 50% cases asymptomatic
• Symptoms
• Loss of appetite fever joint pains jaundice
• 10% become chronic carriers of HBV
• Chronic carriers are 200 times more likely to
develop liver cancer
• HBV Vaccination is required
Numerous pharmacologic agents with varying modes of
action are in clinical development. Three agents are
currently approved for use in the United States by the
Food and Drug Administration and include interferon-α2b
(IFN-α2b), lamivudine, and adefovir
Dipivoxil.
No drug therapy is recommended for patients with
normal ALT values because this group responds poorly to
therapy.
Lamivudine therapy should be used for exacerbations
because it has a rapid onset of effect. In contrast,
IFN-α2b onset of action may not be rapid enough to
prevent hepatic decompensation.
Interferons
IFN-α2b is currently the only interferon approved
by the FDA for management of chronic HBV.
As compared to a placebo response of 12% to 17%, 33%
to 37% of patients respond to IFN-α2b therapy by losing
HBeAg and HBV DNA.42 Even though most of these
patients will maintain a long-term response, the low
overall response rates combined with the adverse
effects and need for subcutaneous dosing make IFNα2b a less-than-ideal agent.
Pretreatment predictors of response to IFN-α2b include
low viral load (HBV DNA <200 copies/mL) and high ALT
(>100). For this subset of chronic HBV patients, an IFNα2b regimen is a rational option, although these same
parameters
Lamivudine
Lamivudine (Epivir-HBV, 3TC) is a nucleoside analog that
competitively inhibits viral reverse transcriptase and
terminates proviral DNA chain extension. Because it does
not affect host response, it suppresses viral replication
but does not directly eliminate the virus from the
hepatocytes.
Its efficacy is also not associated with, or dependent
upon, the flare response seen with interferon.
Like IFN-α2b though, lamivudine
demonstrates higher response rates in patients with
elevated transaminases (ALT >100) and lower viral loads
Adefovir Dipivoxil
Adefovir is a nucleotide analog of deoxyadenosine
monophosphate that is active against retroviruses (like
HIV), herpes viruses, and hepadnaviruses. Adefovir
dipivoxil 10 mg by mouth once daily for 48 weeks has
been approved for use in adult patients with chronic
HBV who are either treatment na¨ıve or have lamivudineresistant HBV.
This agent is also active against HIV but requires higher
(125mg daily) doses for treatment. Consequently, the use
of adefovir in HBV patients coinfected with HIV may
induce antiretroviral resistance.
Hepatitis C (Non A, Non B
Hepatitis)
• HCVss RNA envelope
The pharmacologic management of acute HCV is confounded by
limitations in the ability to recognize the infection in mainly
asymptomatic patients.
Trials evaluating the role of interferon therapy included small
sample sizes and used heterogeneous end-points to evaluate
outcomes.
Despite these limitations, SVRs in the range of 83% to 100% have
been reported with IFN-α monotherapy in small uncontrolled trials,
suggesting the potential advantages of early therapy.
However, the timing, type of regimen, and duration of therapy
remain undefined.
The management of treatment-na¨ıve patients with chronicHCVis
betterdefined with recent large randomized controlled trials
comparing pegylated interferon plus ribavirin to interferon and
ribavirin
Acute Cholecystitis
Primary agents:
First-generation cephalosporin
Alternative:
Aminoglycoside plus ampicillin if severe infection
Cholangitis
Primary agent:
Aminoglycoside with ampicillin with or without
clindamycin or metronidazole
Alternative:
Use vancomycin instead of ampicillin if patient is
allergic to penicillin