Download Trichiuris trichiura

Drugs and the Symptoms of
Diarrhea and Constipation
Antidiarrheal Agents
Opium Poppy (Papaver somniferum)
• the most infamous flower in history
• wars have been fought over it
• used medically and recreationally since 5000 B.C.
Poppy Plant
Alkaloids in the poppy plant
• isoquinolines – no CNS effect
• phenanthrenes – CNS effect
1. morphine – central sedating & relaxing effect
2. codeine – central sedating & relaxing effect
3. thebaine – stimulant
Opioids and Opiates
• Opiates - refer to alkaloids extracted
from poppy pods and their semisynthetic counterparts which bind to the
opioid receptors
> Natural Opiates:
morphine, codiene and thebaine
> Semi-synthetic Opiates:
heroin and naloxone
Opioids and Opiates
• Opioid - blanket term used for any drug
which binds to the opioid receptors in the
CNS.
Synthetic Opioids:
methadone, pethidine (Demerol),
loperamide
Opiates and Opioids
MOA:
 increase colonic phase segmenting activity
> prolongs transit time of fecal mass → allows
more time for absorption of water and
electrolytes from the intestinal lumen
 decrease mass colonic movements
 decrease the gastrocolic reflex
Disadvantage:
dependence when used for prolonged
periods
Opiates and Opioids
Adverse Effects:
loperamide and diphenoxylate
– may precipitate toxic megacolon in
patients with
 active inflammatory bowel disease or
 acute colitis due to bacteria, amoebae,
schistosomes, or ischemia
Loperamide
 also inhibits gastrointestinal secretion
 40% of dose exhibits first pass hepatic
metabolism
 does not cross BBB
 no potential for addiction
 no analgesic properties
Diphenoxylate
 combined with a small amount of atropine
sulfate
 no analgesic properties
 high doses cross BBB → can lead to
dependence
Anticholinergics
Primary effect:
to relieve cramps by reducing contractile
activity.
The effect on diarrhea is negligible.
Kaolin and pectin
- adsorbents
- only few studies demonstrate efficacy
Kaolin
- a hydrated magnesium aluminum silicate
- practically insoluble in water & inorganic
solvents
Activated charcoal
no controlled studies to confirm efficacy
Cholestyramine
mechanism: binds bile acids and the toxins of
Clostridium difficile
may be effective for antibiotic-induced
pseudomembranous colitis
Oral Rehydration Therapy
• The Lancet (1978):
ORT is "potentially the most important
medical discovery of the 20th century".
Pharmacological Considerations in Oral
Rehydration Treatment
1. Physiological disturbances in diarrhea
2. Physiological criteria for ORS solutions
3. Physiological basis of ORS solutions
Physiologic disturbances in diarrhea
1. loss of body water – mild, moderate,
severe dehydration
2. sodium osmolalilty disturbance – isotonic,
hypotonic, hypertonic dehydration
3. other electrolyte disturbances –
hypokalemia, hypocalcemia,
hypomagnesemia
4. acid-base disturbance – metabolic
acidosis
WHO ORS Solution
Approximate Electrolyte Content
Hydrite
Glucolyte New
Total Osmolality
280
280
Glucose (mmol/L)
55
100
Na (mmol/L)
90
60
75
K (mmol/L)
20
20
HCO3 (mmol/L)
30
-Citrate (mmol/L)
-10
Flavor
available available
A 1-liter preparation of ORT solution
contains:
• sodium chloride (NaCl) - 2.6g
• trisodium citrate dehydrate - 2.9g
• potassium chloride (KCl) - 1.5g
• anhydrous glucose - 13.5g
Advantages of the New ORS:
• lower osmolarity
• improves the efficacy of ORS
• reduces the need for unscheduled
intravenous infusions
• lowers stool volume
• causes less vomiting compared with
standard ORS
1.
2.
3.
4.
5.
The Former ORS:
total osmolality: 280-300 mosm/L (isosmotic
with plasma)
glucose – approx 20 grams (111 mmol/L)
Na concentration – close to plasma conc
*ideal Na:glucose conc ratio = 1:1 to 1:4
potassium – 20 mmol/L is well tolerated
bicarbonate or citrate: must have optimal
conc for correcting base deficit acidosis
*bicarbonate – 30-48 mmol/L
citrate – 10 mmol/L
Physiologic basis of ORS
Sodium absorption can be “turned on” by the
presence of certain products of digestion.
This responsiveness is maintained even in
the presence of bacterial toxins.
Glucose and other carrier-mediated sodium
absorption remain intact.
Citrate and potassium are absorbed
independently.
Citrate also enhances sodium and chloride
absorption.
ORT Today:
• World production: 500 million sachets
of ORT/year
• Part of the UNICEF Child Survival
Revolution Program for the Third
World:
Growth Monitoring
ORT
Breastfeeding
Immunization
Zinc
• reduces severity and duration of
diarrhea
 reduces stool output and frequency
 reduces need for hospitalization
• prevents subsequent episodes of
diarrhea
• Treatment Dose of Elemental Zinc: (14
days)
 20 mg/kg/day children 6 mos & above
 10 mg/kg/day infants below 6 mos
Magnesium
• Severe diarrhea causes an isotonic loss
of fluid from the body's extracellular
compartment.
 very little magnesium is in ECF
compartment, very little is lost in
diarrhea → there is no need to
replace it.
A 45 year old previously street sweeper is
brought to the ER with 6 episodes of profuse
watery stools and 4 episodes of vomiting of
whitish liquid within the last 5 hours. She has
not urinated for the last 5 hours. She was
weak, with sunken eyeballs and poor turgor.
Her bladder is not distended. PR = 107/min,
RR = 31/min, BP = 80/50, T = 37.6oC. Initial
IV fluid replacement should include:
A. glucose, Na, and Cl
B. glucose
C. glucose, Na, Cl, and bicarbonate
D. glucose, Na, K, Cl, and bicarbonate
A 45 year old previously street sweeper is
brought to the ER with 6 episodes of profuse
watery stools and 4 episodes of vomiting of
whitish liquid within the last 5 hours. She has
not urinated for the last 5 hours. She was
weak, with sunken eyeballs and poor turgor.
Her bladder is not distended. PR = 107/min,
RR = 31/min, BP = 80/50, T = 37.6oC. Initial
IV fluid replacement should include:
A. glucose, Na, and Cl
B. glucose
C. glucose, Na, Cl, and bicarbonate
D. glucose, Na, K, Cl, and bicarbonate
A 45 year old previously street sweeper is
brought to the ER with 6 episodes of profuse
watery stools and 4 episodes of vomiting of
whitish liquid within the last 5 hours. She has
not urinated for the last 5 hours. She was
weak, with sunken eyeballs and poor turgor.
Her bladder is not distended. PR = 107/min,
RR = 31/min, BP = 80/50, T = 37.6oC. Initial
IV fluid replacement should include:
A. glucose, Na, and Cl
B. glucose
C. glucose, Na, Cl, and bicarbonate
D. glucose, Na, K, Cl, and bicarbonate
Nora, a nursing student, interviewed patients
in a depressed area. She suddenly
developed profuse watery diarrhea and
vomiting. She just overheard at the radio that
there is an outbreak of Vibrio cholera in that
same area. She recalled that she drank tap
water during her interview. At the ER, she
continued to have profuse diarrhea. The most
important immediate management is:
A. Tetracycline C. Ciprofloxacin
B. Loperamide D. Fluid & electrolyte
replacement
Nora, a nursing student, interviewed patients
in a depressed area. She suddenly
developed profuse watery diarrhea and
vomiting. She just overheard at the radio that
there is an outbreak of Vibrio cholera in that
same area. She recalled that she drank tap
water during her interview. At the ER, she
continued to have profuse diarrhea. The most
important immediate management is:
A. Tetracycline
C. Ciprofloxacin
B. Loperamide
D. Fluid & electrolyte
replacement
Nora, a nursing student, interviewed patients
in a depressed area. She suddenly
developed profuse watery diarrhea and
vomiting. She just overheard at the radio that
there is an outbreak of Vibrio cholera in that
same area. She recalled that she drank tap
water during her interview. At the ER, she
continued to have profuse diarrhea. The most
important immediate management is:
A. Tetracycline
C. Ciprofloxacin
B. Loperamide
D. Fluid & electrolyte
replacement
Antibiotics in Acute Diarrhea - only for the
following:
a. Vibrio cholerae
b. Shigella
c. Amoebic dysentery
d. Giardia lamblia
Antibiotics in Acute Diarrhea - only for the
following:
a. Vibrio cholerae
Tetracycline
Ciprofloxacin
Chloramphenicol
Furazolidone
Cotrimoxazole
Erythromycin - preferred for children
Antibiotics in Acute Diarrhea - only for the
following:
b. Shigella
Cotrimoxazole
Ampicillin
Ciprofloxacin
Ceftriaxone
Antibiotics in Acute Diarrhea - only for the
following:
c. Amoebic dysentery
Metronidazole
d. Giardia lamblia
Metronidazole;
Furazolidone palatable for children
Paromomycin for pregnant patients
Tetracycline
Tetracyclines
A. Conventional Tetracyclines
1. Oxytetracycline (Terramycin)
2. Tetracycline
B. Second Generation
1. Doxycycline (Vibramycin, Doxin)
2. Minocycline (Minocin)
Spectrum of antibacterial activity: broad
Classification Based on Spectrum of Activity
• Broad
Aminopenicillins
Chloramphenicol
Tetracyclines
First and Second Generation
Cephalosporins
Imipenem
Spectrum of antibacterial activity: broad
Pharmacokinetics:
1. incomplete but adequate absorption from
GIT
2. absorption impaired by presence of food,
milk, divalent and trivalent ions (calcium,
iron, aluminum)
3. widely distributed to all tissues and fluids
4. limited penetration into CNS; crosses
placental barrier
5. bound and stored in many tissues
including dentine and enamel of
unerupted teeth
6. metabolized to varying degrees
7. mainly renal excretion; doxycycline
excreted in feces
Indications:
1. primary uses: drug of choice for
Mycoplasma, Chlamydia, Rickettsia,
and Vibrios
2. secondary use: syphilis, respiratory
infections, leptospirosis, acne
3. sclerosant solution for pleurodesis
Adverse effects:
1. GIT disturbances
2. photosensitivity – especially
Demeclocycline (not listed in MIMS)
3. hepatotoxicity – especially if given in high
doses to pregnant patients with impaired
liver function (may lead to hepatic
necrosis)
Classification Based on
Toxic and Adverse Effect Potential
• Hepatotoxicity
Rifampicin
Pyrazinamide
Isoniazid
Tetracycline
Erythromycin estolate
Enamel dysplasia
4. nephrotoxicity
a. Fanconi-like syndrome –
especially due to out-of-date or
deteriorated tetracyclines due to
the degradation product
(ahydroepitetracycline)
b. nephrogenic diabetes insipidus
5. bone and dentine tissue defects
6. superinfection
7. hypersensitivity reaction
8. vestibular toxicity – vertigo (dosedependent, reversible); noted with
Minocycline
Resistance:
widespread; plasmid-mediated
Ciprofloxacin
Quinolones
MOA: inhibits
• DNA gyrase (toposiomerase II)
• and topoisomerase IV
Mode of action: bactericidal
Quinolones
Antimicrobial spectrum: broad.
• Excellent activity against gram negative
bacilli (E. coli, Klebsiella, Campylobacter,
Enterobacter, P. mirabilis, Pseudomonas,
Salmonella, and Shigella)
• Good activity vs. staph except methicillinresistant strains
*Poor activity against anaerobes and strep
Pharmacokinetics:
1. well absorbed from the GIT
2. >50% bioavailability following oral
intake
3. food delays absorption
4. high lipid solubility
5. high concentration in most tissues
6. renal excretion
Adverse effects:
1. GIT – nausea, vomiting, diarrhea
(most common)
2. CNS – headache, restlessness
3. skin – rashes, photosensitivity
4. arthropathy
Contraindications: not for use in children less
than 18 (cause cartilage erosions in young
animals)
• Resistance:
point mutation in binding region of
the target enzymes:
primarily DNA gyrase (topoisomerase II)
secondarily topoisomerase IV
Macrolides
Macrolides
MOA: binds to the p-site of the 50s ribosomal
subunit to inhibit bacterial protein synthesis
Mode of action: primarily bacteriostatic
Spectrum of antibacterial activity: gram
positive aerobic bacteria; some gram
negative aerobes
Pharmacokinetics:
1. instability at acid pH
2. hydrolysis of esters a prerequisite
for absorption
3. absorption mainly from the
duodenum, impeded by food
4. good distribution
Pharmacokinetics:
5. good intracellular concentration
6. poor concentration in the CNS even in the
presence of inflammation
7. excretion: bile and feces (Erythromycin),
liver and kidneys (Clarithromycin), or
slowly in urine
unchanged (Azithromycin)
Indications:
1. as drug of first choice (Campylobacter,
Mycoplasma, or Legionella)
2. as alternative drug to Penicillins,
Tetracyclines, etc.
3. as adjunct in treatment
Chloramphenicol
Chloramphenicol
Spectrum:
broad
usually bacteriostatic
Chloramphenicol
Pharmacokinetics:
1. well absorbed orally
2. very well distributed in tissues,
including the CNS
3. metabolized in the liver by
conjugation with glucoronic acid
(inactivated by a hepatic
glucoronosyltransferase)
4. major route of excretion is by tubular
secretion
Aplastic anemia
Adverse effects:
1. hematologic
a. bone marrow depression –
aplastic anemia
b. simple anemia
2. Gray baby syndrome – in neonates;
characterized by cyanosis and
cardiovascular collapse
3. hypersensitivity reaction
4. gastrointestinal tract effects
Other Indications:
topical ophthalmic antibiotic
pneumococcal pneumonia
•
•
•
•
Furazolidone
An effective drug for giardiasis,
although metronidazole is still
the drug of choice
Can be used for children
Cure rate is 80-90%
Adult dose:
100 mg 4 times a day for 7 days
Co-Trimoxazole
(Trimethoprim
and Sulfamethoxazole)
Sulfonamides
MOA: inhibits folic acid synthesis by
competitive inhibition of dihydropteroate
synthetase
Pharmacokinetics:
1. rapid & complete absorption from GIT
2. variable protein binding
3. good distribution
4. metabolism in the liver
5. renal excretion
Clinical uses:
1. uncomplicated UTI
2. malaria (Fansidar, Metakelfin)
3. toxoplasmosis
4. Pneumocystis carinii (Cotrimoxazole)
Adverse effects:
1. hematologic (agranulocytosis,
hemolytic anemia)
2. GIT
3. hypersensitivity reaction – skin rashes,
drug fever, Steven-Johnson syndrome,
vasculitis
4. renal – crystalluria
Contraindications:
1. infants less than 2 months old
2. pregnant and lactating mothers
Diaminopyrimidines
MOA: inhibits folic acid synthesis by
selective inhibition of bacterial
dihydrofolate reductase
Cotrimoxazole exhibits a 2-step inhibition in
the synthesis of folic acid
PABA
dihydropteroate synthesis   Sulfonamides
dihydrofolic acid
dihydrofolate reductase   Trimethoprim
tetrahydrofolic acid

purines

DNA
Adverse effects:
1. GIT – nausea, vomiting
2. hypersensitivity reactions
3. antifolate effects (megaloblastosis,
granucytopenia, thrombocytopenia)
Ampicillin
•
•
•
•
•
Beta-Lactam Antimicrobials
Penicillins
Cephalosporins
Beta-Lactamase Inhibitors
Monobactams
Carbapenems
Penicillins
Semi-Synthetic Penicillins
2. Aminopenicillins/Broad spectrum
penicillins
a. Ampicillin
b. Amoxicillin
c. Bacampicillin
Ceftriaxone
•
•
•
•
•
Beta-Lactam Antimicrobials
Penicillins
Cephalosporins
Beta-Lactamase Inhibitors
Monobactams
Carbapenems
Third Generation
a. Cefotaxime (Claforan)
b. Cefoperzaone (Cefobis)
c. Ceftriaxone (Rocephin)
d. Ceftazidime (Fortum)
e. Cefametet (Globocef)
f. Cefixime (Tergecef)
Metronidazole
Nitroimidazoles
MOA: involves interference with DNA by a
metabolite in which the nitro group of
Metronidazole has been reduced
E. Histolytica
Cyst and trophozoite
Giardia lamblia
Gas gangrene
(Anaerobic)
Paromomycin
Aminoglycosides
Spectrum: intermediate
For aerobic and facultative gram-negative
bacteria
> effective only against aerobes
> transport into bacteria is oxygendependent
Aminoglycosides
Pharmacokinetics:
1. not absorbed from the GIT
2. low protein binding
3. does not penetrate the CNS
4. high concentration in the renal cortex
and inner ear
Which of the following is LEAST effective in
Shigella dysentery?
A. cotrimoxazole
C. Amoxicillin
B. ampicillin
D. none of the above
Which of the following is LEAST effective in
Shigella dysentery?
A. cotrimoxazole
C. amoxicillin
B. ampicillin
D. none of the above
Amoebicidal Agents
Classification
Tissue/Extraintestinal Amoebicides
a. Chloroquine palmitate
b. Emetine hydrochloride & Dehydroemetine –
not available
Luminal Amoebicides
a. Dichloroacetanides
1. Diloxanide furoate
(Furamide)
2. Etofamide (Kitnos)
b. Antibiotics
1. Paromomycin
2. Erythromycin
3. Tetracycline
Classification
Luminal/Intestinal Amoebicides
c. Haloginated hydroxyquinolines – not
available
Both Tissue and Luminal Amoebicides
a. Metronidazole
b. Tinidazole (Fasigyn)
c. Secnidazole (Flagentyl)
1.
2.
3.
4.
Clinical Spectrum of Amoebiasis
asymptomatic intestinal infection
mild to moderate intestinal infection
(nondysenteric colitis) – several semiformed mucoid, bloody stools passed
severe intestinal dysentery (dysenteric
colitis) – increased number of semiformed liquid stools, blood streaked;
patient may become prostrate and
toxic with fever up to 40o C
extraintestinal amoebiasis – most
common site is the liver
Gross specimen, amoebiasis
Tissue Amoebicides
act on bowel, liver, and extraintestinal tissues
do not eradicate cysts
a. Emetine
MOA: inhibits protein synthesis (inhibits
movement of ribosome along mRNA)
Kinetics: poorly absorbed
Indications: amoebic abcess, symptomatic
relief of amoebic dysentery
Most impt adverse reaction: cardiac effect (on
SA node)
Tissue Amoebicides
b. Dehydroemetine
analog of emetine
same amoebicidal properties but less
toxic
Tissue Amoebicides
c. Chloroquine
antimalarial
MOA: forms a complex with DNA: prevents
replication and transcription to mRNA
effective for hepatic amoebiasis, liver abcess,
in moderate to severe intestinal amoebiasis
to eradicate trophozoites
Tissue Amoebicides
c. Chloroquine
antimalarial
Contraindicated in pregnancy, psoriasis,
porphyria
Adverse effects are dose-related nausea,
vomiting, diarrhea, pruritus, headache,
retinopathy
Luminal Amoebicides
poorly absorbed, reaches high concentration
in bowel
activity limited to cysts and trophozoite close
to the mucosa
a. Amides
Diloxanide furoate
MOA:
unknown, directly amoebicidal
Kinetics:
rapidly and significantly absorbed
from GIT
the unabsorbed drug is the active
anti-amoebic
a. Amides
Diloxanide furoate
Indication:
drug of choice for asymptomatic
infection
used with other drugs in mild
intestinal infection
a. Amides
Diloxanide furoate
Contraindications:
children below 2 years
pregnancy
Adverse reactions:
flatulence
nausea,vomiting, abdominal cramps
pruritus
tingling sensation
a. Amides
Etofamide
Mode of action:
directly amoebicidal
No known dangerous influence on
organogenesis and pregnancy
Tetracycline
• indirect action
• interferes with enteric flora essential for the
well-being of the amoeba
• used in combination
Erythromycin
• directly amoebicidal
Paromomycin
• directly amoebicidal, affecting ribosomal
protein synthesis
• has no extraluminal activity
Both Tissue and Luminal Amoebicides
Nitroimidazoles (Metronidazole)
Indication:
• for all forms of amoebiasis
Drug interactions:
• with alcohol (disulfiram-like)
• with warfarin (metabolism inhibited)
A 4 year old boy that has diarrhea and
malnutrition was noted to have a mixed
parasitic infection of Ascaris, Capillaria
philippinensis, and Trichiuris trichiura.
The single agent that is effective for this
patient is:
A. pyrantel pamoate C. diethylcarbamazine
B. mebendazole
D.. metronidazole
Metronidazole and alcohol taken together will
cause:
A. inhibition of alcohol dehydrogenase by
metronidazole
B. severe nausea and vomiting
C. disulfiram-like effects
D. all of the above
metronidazole
disulfiram
A 4 year old boy that has diarrhea and
malnutrition was noted to have a mixed
parasitic infection of Ascaris, Capillaria
philippinensis, and Trichiuris trichiura.
The single agent that is effective for this
patient is:
A. pyrantel pamoate C. diethylcarbamazine
B. mebendazole
D. metronidazole
Antiparasitic
Agents
Mebendazole and Albendazole
(Benzimidazoles)
• MOA: inhibit microtubule polymerization
by binding to beta-tubulin →
immobilization
→ death
Mebendazole and Albendazole
(Benzimidazoles)
Pharmacokinetics - Mebendazole:
• poorly and erratically absorbed
• rapid first-pass hepatic metabolism
(both cause low systemic
bioavailabilitry)
• 95% bound to proteins
• excreted in the bile and in the urine
*mebendazole is the active drug
form and not its metabolites
Mebendazole and Albendazole
(Benzimidazoles)
Pharmacokinetics - Albendazole:
• variably and erratically absorbed
• absorption enhanced by a fatty meal
• metabolized to albendazole sulfoxide
which has potent antihelminthic activity
• 70% bound to plasma proteins
• excreted through urine
Mebendazole and Albendazole
(Benzimidazoles)
• Indications:
both drugs effective for Enterobius,
Ascaris, Trichiuris, and hookworms
albendazole is more effective agaiinst
hydatid cysts
Mebendazole and Albendazole
(Benzimidazoles)
Adverse Effects:
• allergic reactions
• alopecia
• reversible neutropenia agranulocytosis
• hypospermia
• teratogenic in exp’tal animals
*Albendazole has lesser ADRs
Mebendazole and Albendazole
(Benzimidazoles)
Contraindications
• pregnant patients
• children below 2 years old
* Albendazole is contraindicated in
hepatic cirrhosis
Pyrantel pamoate
MOA:
depolarizing
neuromuscular
blocking agent
 releases Ach and
inhibits cholinesterase
 induces marked, persistent
activation of nicotinic receptors
 spastic paralysis of worms
Pyrantel pamoate
Pharmacokinetics:
• poorly absorbed from the GIT
(hence, its selective action on
the GIT nematodes)
• excreted in urine and feces
Pyrantel pamoate
Indications:
• hookworms
• pinworms
• Ascaris
*Ineffective against Trichiuris
Pyrantel pamoate
Adverse effects:
• transient and mild GIT upset
• headache
• dizziness
• rash
• fever
Pyrantel pamoate
Drug interaction:
Pyrantel + Piperazine = antagonism
Contraindications:
• pregnancy
• children less than 2 years old
Oxantel pamoate
effective against Trichiuris
Oxantel-pyrantel combination (Quantrel)
is available in a fixed dose of each drug
Piperazine citrate
MOA:
blocks the response of Ascaris muscle to
acetylcholine, causing flaccid paralysis
of Nematodes
Pharmacokinetics:
• absorbed rapidly from the GIT
• 20% excreted unchanged in the urine
Indications:
• Enterobius
• Ascaris
Drug interaction with pyrantel:
antagonism
Levamisole
(also an imidazole derivative)
• as efficacious as Piperazine
• also an immunomodulant
Levamisole
Indications:
• Ascariasis
• more often used as imunomodulant
Adverse effects:
• mild and transient – headache,
nausea and vomiting, abdominal
pain, weakness, dizziness, and rash
Diethylcarbamazine citrate
• used mainly in lymphatic filariasis and
loaisis
Pharmacokinetics:
• readily absorbed in the GIT, skin, and
conjunctiva
• widely distributed
• excreted in urine
Diethylcarbamazine citrate
Adverse effects:
• nausea, vomiting, headache, drowsiness
• allergic reactions arise from the death of
the filariae or microfilariae
Precaution:
• adjust doses in renal failure
Schistosoma japonicum
Praziquantel
MOA:
increases cell membrane permeability to
calcium resulting in marked contraction,
followed by paralysis of worm
musculature
Praziquantel
Pharmacokinetics:
• rapidly and almost completely
• absorbed from the GIT
• peak serum concentration is reached in
1-2 hours; penetrates the BBB
• first pass metabolism in liver
• excretion: renal
Praziquantel
Adverse effects:
• most common – malaise, headache,
dizziness, anorexia
• others – drowsiness, nausea, vomiting,
abdominal pain, low grade fever, pruritus
Contraindication:
• ocular cysticercosis
• children under 4 years old
• pregnant and lactating mothers
Niclosamide
MOA:
• inhibits oxidative phosphorylation
Pharmacokinetics:
• minimally absorbed following oral
administration
Niclosamide
Adverse effects:
• mild and transient nausea, vomiting,
diarrhea, abdominal discomfort;
Contraindications/precautions:
• consumption of alcohol
• children below 2 years old
• pregnancy
Niridazole
MOA:
not established
Pharmacokinetics:
• absorbed slowly
• peak serum concentration attained in 6
hours
• mainly excreted in the urine, some in feces
Niridazole
Adverse effects:
• GIT – nausea, vomiting, diarrhea, abdominal
pain
• headache, dizziness
• myalgia
• hematologic and neuropsychiatric effects
Review:
TABULATION OF THE
DIFFERENT ANTIHELMINTHIC
AGENTS & THEIR CHIEF
INDICATIONS
(Didactic Study Guide)
A 4 year old boy that has diarrhea and
malnutrition was noted to have a mixed
parasitic infection of Ascaris, Capillaria
philippinensis, and Trichiuris trichiura.
The single agent that is effective for this
patient is:
A. pyrantel pamoate C. diethylcarbamazine
B. mebendazole
D. metronidazole
DRUGS OF CHOICE & ALTERNATE DRUGS
Ascaris lumbricoides
• Pyrantel pamoate, Mebendazole
• Piperazine citrate
Trichiuris trichiura (whipworm)
• Mebendazole
*Updated from: Handbook of Pediatric
Infectious Diseases, 2004, a PPS
Publication
DRUGS OF CHOICE & ALTERNATE DRUGS
Necator americanus & Ancylostoma duodenale
• Mebendazole
• Pyrantel pamoate
Enterobius vermicularis (pinworm)
• Pyrantel pamoate
• Mebendazole
*Updated from: Handbook of Pediatric
Infectious Diseases, 2004, a PPS Publication
DRUGS OF CHOICE & ALTERNATE DRUGS
Strongyloides stercoralis
• Albendazole
• Thiabendazole
Schistosoma japonicum
• Praziquantel
*Updated from: Handbook of Pediatric
Infectious Diseases, 2004, a PPS
Publication
DRUGS OF CHOICE & ALTERNATE DRUGS
Taenia saginata & Taenia solium
• Niclosamide
• Praziquantel
• Paromomycin
Cysticercosis
• Praziquantel
*Updated from: Handbook of Pediatric
Infectious Diseases, 2004, a PPS Publication
DRUGS OF CHOICE & ALTERNATE DRUGS
Wuchereria bancrofti & Brugia malayi
• Diethylcarbamazine citrate
Capillaria philippinensis
• Mebendazole
Paragonimus westermani
• Praziquantel
• Bithionol
*Updated from: Handbook of Pediatric
Infectious Diseases, 2004, a PPS Publication
DRUGS USED
IN THE TREATMENT OF
CHRONIC INFLAMMATORY
BOWEL DISEASE
A. Preparations Available
1. Salicylates
a. 5-aminosalicylic acid/
Mesalazine (Salofalk)
2. Corticosteroids
3. Immunosuppressives
a. Azathioprine
b. Mercaptopurine
Drug Prototype: Mesalazine
MOA:
1. affects multiple sites in the arachidonic
acid pathway, critical in the
pathogenesis of inflammation
2. more importantly, it inhibits leukotriene
formation
3. also a free radical scavenger
Drug Prototype: Mesalazine
Pharmacokinetics:
• formulated for 5-ASA to be delivered to the
distal segments of the small bowel or colon
Adverse effects:
• upper GIT irritation
• systemic salicylate toxicity
Indication:
• only for the treatment of active colitis
DRUGS AND OTHER CHEMICAL
CAUSES OF DIARRHEA
Drugs Associated with Diarrhea
•
•
•
•
•
•
Acarbose
Alcohol – due to enterocyte injury
Antacids – magnesium salts
Antibiotics (most common)
Anticoagulants
Antihypertensives – especially
propranolol
Drugs Associated with Diarrhea
• Antimetabolites – especially colchicine
• Cardiovascular drugs – especially
digoxin
• Cholestyramine
• Cholinergics
• Cimetidine
• Cytotoxic Agents – especiall 5-FU plus
interferon or leucovorin
Drugs Associated with Diarrhea
•
•
•
•
•
•
Domperidone
HIV medications – especially nelfinavir
Lactose-containing pharmaceuticals
Lactulose
Metoclopromide
Misoprostol
Drugs Associated with Diarrhea
•
•
•
•
•
•
•
•
Misoprostol
NSAIDs – especially naproxen
Orlistat
Potassium supplements
Prostaglandins
SSRIs – especially paroxetine
Sulfasalazine
Ticlopidine
Other frequently incriminated drugs:
• bronchodilators
• laxatives [e.g., senna, cascara,
bisacodyl, ricinoleic acid (castor oil)]
• prostaglandins, prokinetic agents - may
produce hypermotility with resultant
diarrhea
• sorbitol containing agents – osmotic
diarrhea
Acute diarrhea, often associated with
systemic compromise, can follow ingestion
of toxins including:
• organophosphate insecticides
• amanita and other mushrooms
• arsenic, and
• preformed environmental toxins in
seafoods, like ciguatera and scombroid.
Osmotic Causes
Osmotic diarrhea occurs when ingested,
poorly absorbable, osmotically active
solutes draw enough fluid lumenward to
exceed the resorptive capacity of the
colon.
Some causes of osmotic diarrhea:
• Osmotic laxatives Ingestion of
magnesium-containing antacids, health
supplements, or laxatives
• Carbohydrate malabsorption
Carbohydrate malabsorption due to
acquired or congenital defects in brushborder disaccharidases and other
enzymes
> Lactulose - causes diarrhea on this
basis
Cathartics, Laxatives,
and Enemas
Definition:
Agents which promote and/or ease
defecation by accelerating the passage of feces
through the colon,
by influencing the consistency and
amount of stool,
and by facilitating its rectal elimination.
a. Cathartics – produce prompt fluid
evacuation
b. Laxatives – promote soft formed
stools over a protracted
period
c. Enemas – cause
fragmentation, liquefaction,
or lubrication of feces and
fluid distension of bowels
with reflex elimination
A 55-year old post-myocardial infarction
patient was given a maintenance dose of the
liquid preparation of sodium picosulfate
beginning his third hospital day. Why?
A. because he did not defecate for 3 days
B. the summer heat will induce constipation
C. to prevent straining
A 55-year old post-myocardial infarction
patient was given a maintenance dose of the
liquid preparation of sodium picosulfate
beginning his third hospital day. Why?
A. because he did not defecate for 3 days
B. the summer heat will induce constipation
C. to prevent straining
A 55-year old post-myocardial infarction
patient was given a maintenance dose of the
liquid preparation of sodium picosulfate
beginning his third hospital day. Why?
A. because he did not defecate for 3 days
B. the summer heat will induce constipation
C. to prevent straining
Mechanism of action of Contact Cathartics:
not established but in general, they
produce a net intraluminal accumulation of
fluid and electrolytes
Disadvantages:
a. potential fluid and electrolyte losses
b. dependence, habituation, and tolerance
in prolonged use
Indications of laxatives and cathartics:
1. to ease pain of fecal elimination in patients
with episiotomy, painful thrombosed
hemorrhoids, or perianal abcess
2. to ease elimination and reduce excessive
straining and intraabdominal pressure in
hernias, anorectal stenosis, cerebral and
coronary artery disorders
Indications of laxatives and cathartics:
3. to relieve constipation in pregnancy and
puerperium
4. in geriatric patients with poor eating habits
and with poor abdominal and perineal
muscle tone
5. children with congenital or acquired
megacolon
Indications of laxatives and cathartics
6. altered bowel motility (e.g., intake of
cholinergics, narcotics)
7. to prevent absorption of ammonia and
other neurotoxins in patients with hepatic
encephalopathy
8. preparation of bowel for surgery and
for radiologic, proctoscopic, and
colonoscopic procedures
Indications of laxatives and cathartics:
9. to obtain fresh stools for parasitologic
examinations
10. to accelerate excretion of various
parasites, including nematodes, after
helminthic treatment
11. to hasten excretion of poisonous
substances
12. to modify effluent in patients with an
ileostomy or colostomy
CATHARTICS AND LAXATIVES
Classification based on mechanism of action:
1. Bulk-formers:
a. Bran
b. Agar
2. Contact catarthics/ Irritant/Stimulant Laxatives and
Cathartics
a. Standard Senna concentrate (Senokot)
b. Diphenylmethane derivatives
1] Bisacodyl (Dulcolax)
2] Na picosulfate (Laxoberal)
c. Castor oil
3. Saline cathartics - Magnesium salts
a. Mg sulfate (Epson salts)
c. Mg carbonate
b. Mg hydroxide (Milk of magnesia)
4. Lubricants
a. Mineral oil (liquid petrolatum)
b. Glycerin
Indications for enemas:
1. to relieve impaction
2. to empty rectum and colon prior to
radiologic or endoscopic procedures
3. to cleanse large bowel prior to surgery or
delivery
4. for patients with fecal incontinence or
colostomy
5. to establish rectal reflex in constipated
patients
In general,
laxatives should be
avoided in children
Some time ago, at the Seattle Olympics, nine
athletes, all mentally or physically challenged,
were standing on the start line for the 100 m
race.
The gun fired and the race began. Not
everyone was running, but everyone wanted
to participate and win.
They ran in threes, a boy tripped and
fell, did a few somersaults and started
crying.
The other eight heard him crying.
They slowed down and looked behind
them.
They stopped and came back… All of
them…
A girl with Down’s Syndrome sat down
next to him, hugged him and asked,
“Feeling better now?”
Then, all nine walked shoulder to shoulder
to the finish line.
The whole crowd stood up and applauded.
And the applause lasted a very long time…
People who witnessed this still talk about
it. Why?
Because deep down inside us, we all know
that the most important thing in life is
much more than winning for ourselves.
The most important thing in this life
is to help others to win. Even if that
means slowing down and changing
our own race.
A candle loses nothing if it is
used to light another one.”
May the Season of Hope 
 bring Love and Peace to Everyone! 