SYSTEMIC PHARMACOLOGY II

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 It is an acute, diarrheal illness caused by intestinal infection that
occurs when bacterium Vibrio cholerae is ingested.

 Cholera spread across the world from its original reservoir in the
Ganges delta in India.

 According to WHO (2017), cholera cases in

Yemen hit the half MILLION mark with nearly
2000 people DIED since the outbreak in April
2017.

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 Gram negative

 Slightly curved

 Comma shaped

 Polar flagellum (actively motile)

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 Cholera is not a contagious disease.

 The bacterium can only be transmitted by:

› Drinking contaminated water

› Eating raw or undercooked foods

 Carriers: houseflies and other insects

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Symptoms usually start suddenly, half a day to five days after ingestion of the bacteria.

 Mild to severe diarrhea (pale, milky stool appearance)

 Nausea and vomiting

 Dehydration

 Lethargy

 Muscle cramps

 Having dry skin and mouth with extreme thirst

 Lead to death if left untreated.

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Oral rehydration salts
•Up to 80% of cases can be
treated through this.

Antimicrobial Therapy
•Example: Tetracycline,
doxycyclin, ciprofloxacin
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 Most of the mild and moderate cases of cholera
can be successfully treated with ORS

 ORS is a sodium and glucose solution which is

prepared by diluting with 250 ml of cool, boiled
water.

 ORS does not stop the diarrhea, but it replaces

the fluids and electrolytes (salts) lost. Thus, it can
treat and prevent further dehydration.
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 ORS work because sodium/glucose co-transport proteins on the villi
of the intestinal lumen transport sodium and glucose from intestine
into the cells.

 As osmolarity of the cells increases (due to influx of sodium and

glucose molecules), water is reabsorbed back from intestine into the
body.

 Thus, ORS reverse the electrolyte imbalances and rehydrating the

patient
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 Dosage

› Adult: 4 times of 250 ml (for first 2 hours); max: 12 times x

250ml/day

› Children: 3 times of 250 ml (for first 2 hours); max: 6 times daily

 Side effects: Hypernatremia, nausea, vomiting,

hyperkalemia, oedema

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 WHO only recommends treatment with antibiotics for severely ill

cholera patients.

 Example: Doxycycline, azithromycin, tetracycline, ciprofloxacin, and

erythromycin

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 Doxycycline has bacteriostatic activity against a broad range of gram
+ve and gram -ve bacteria.

MOA:

 It inhibits bacterial protein synthesis by binding to 30s ribosomes subunits.

Thus, preventing the bacteria to reproduce.
Side effects:

 GI effects (nausea, vomiting), photosensitivity,

hypersensitivity reactions.

Dosage: 300 mg daily for 3 days 11

Pharmacokinetics of Doxycycline:

 Absorption: Readily and almost completely absorbed from the GI

tract. Food and milk products may decrease absorption.

 Distribution: Widely distributed in body tissues and fluids, excellent

penetration into the liver and kidneys. Moderate penetration into CSF.

 Metabolism: Partially inactivated in GI tract by chelation formation.

 Excretion: Through urine and faeces.

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 Doxycycline can also be used for conditions
indicated:
› Syphilis (oral) - Treponema pallidum

› Uncomplicated gonorrhoea (oral)- Neisseria gonorrhoeae

› Prophylaxis of typhus fever (oral)- Rickettsia

› Lyme disease (oral)- Borrelia burgdorferi

› Respiratory tract infections (oral)- Mycoplasma pneumoniae

› Relapsing fever (oral)- Borrelia recurrentis

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 Azithromycin is a semisynthetic azalide antibiotic.
 It has relatively broad but shallow antibacterial activity. It inhibits some
gram +ve bacteria, some gram -ve bacteria, and many atypical
bacteria.
Side effects
 GI disturbances (nausea, vomiting), mild rash, problems with hearing,
decrease sense of taste or smell, dizziness, tired feeling, sleep problems
(insomnia) and vaginal itching or discharge.
Dosage: 1g as a single dose
Half life: 68 hour
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Mechanism of action

 Azithromycin works by interfering with bacterial protein synthesis.

 It binds to the 50s subunit of bacterial ribosome and thus inhibiting

translation of mRNA.

 Therefore, prevent the bacteria from growing.

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Pharmacokinetics:

 Absorption: Rapidly absorbed from the GI tract. Reduced by food.

 Distribution: Widely distributed especially in tissue except CSF.

 Metabolism: Undergo hepatic metabolism via demethylation.

 Excretion: Through bile (as unchanged drug and inactive metabolites)

and urine.

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 Azithromycin can also be used for conditions indicated:

› Acute bacterial sinusitis- H. influenzae, M. catarrhalis, or S. pneumoniae

› Pharyngitis or tonsillitis- S. pyogenes

› Trachoma or Urethritis - C. trachomatis

› Genital ulcer disease (in men)- H. ducreyi

› Gonorrhea- in combination with ceftriaxone

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 http://www.mayoclinic.org/diseases-conditions/cholera/symptoms-
causes/dxc-20311185

 http://www.who.int/cholera/prevention_control/Antibiotics_for_chol
erahttp://www.who.int/mediacentre/factsheets/fs107/en/

 http://www.webmd.com/a-to-z-guides/cholera-faq#1

 http://www.who.int/mediacentre/news/releases/2017/cholera-
yemen-https://www.cdc.gov/cholera/general/index.html

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