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Antibiotics for TB and Leprosy

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Name first line antibiotcs
Isoniazid, Rifampin, Pyrazinamide, Ethambul & Streptomycin.
Name second line antibiotics.
Para-aminosalicycic acid, capreomycin sulfate, cycloserine, ethionamide, kanamycin, amikacin, & quinolones(ciprofloxacin & olfloxacin)



How does Isoniazid work and what are it's effects?

Oral/IN/IV, penetrates into fluids & tissues, metabolized in liver by acetylation, excreted in urine with pyrodoxine (vitamin B6) ? Interferes w/the production of the mycolic acid component of cell wall in TB.
Effects – Hepatotoxicity increases the chance of hepatitis (chances increase w/age and alcohol). Also B6 deficiency.Pellagra(peripheral neuritis, rash and anemia)




What does Rifampin cause?
All body fluids like urine & saliva turn bright red-orange; not harmful.

How does Rifampin work?
Oral/IV, penetrates, metabolized via microsomal oxidase system(increasing it's own metabolism),& excreted via liver. Stops the DNA- dependent RNA polymerase.

Besides TB and leprosy, what other disease is Rifampin given to?
Meningitis
To what diseases is Rifampin second line for?
Legionella Pneumophila & Ehrlichia
What antibiotic cannot be given for more than 2 months and why?

Pyrazinamide because it causes hepatotoxic & gout(arthritis of the [big] toes)
How does pyrazinamide work through the body?
It is unknown.
How is Ethambul different from the other first line drugs?
It's bacteriostatic which means it stops the disease but wont't kill it.
Pharmokinetics of Ethambul.
Oral, can cross blood/brain barrier & renal excretion.
Ethambul can be used for kids?
False
What are the effects of Ethambul?
Decreased visual acuity, color vision loss, and loss of central vision(central scotoma)
What is the mechanism of action of Streptomycin?
Binds to 30S ribosomal subunit and prevents protein synthesis.

What is Streptomycin?
Aminoglycoside
What are the effects of Streptomycin?
Vestibular & Ototoxic(ears & nerves)
How are second line drugs used?
When multidrug resistant Mycobacterium Tuberculosis appears
What are the symptoms of Active TB?
fever, cough,& night sweats (2 months)
What is the 6 month regimen of Active TB?
2 months of isoniazid, rifampin & prazinamide; followed by 4 months of isoniazid & rifampin
What is the 9 month regimen of Active TB?
9 months of isoniazid and rifampin.
What does PPD stand for?
purified protein derivative
What does it mean when a person has ppd?
They have a latent Mycobacterium Tuberculosis that develop a reactivation tuberculosis
What is the two treatments for PPD reactors and why do they differ?
Isoniazid alone for 6-12 months (prophylactic therapy).Rifampin & Pyrazinamide for 2 months has a high rate of non-compliance
What must be taken into account before treating PPD Reactors?
Risk of developing isoniazid-induced liver injury VS. Risk of developing reactivation TB
Who has a higher risk of developing Isoniazid Hepatitis?
Alcohol consumers & people over the age of 35
What percentage do 20 years or younger people have of developing isoniazid hepatitis?
No percentage just very rare
What percentage do people 20-34 years of have of developing Isoniazid Hepatitis?
less than .3 percent
What percentage do people 35- 49 years of age have of developing Isoniazid Hepatitis?
less than 1.2 percent
What percentage of people over the age of 50 have a risk of developing Isoniazid Hepatitis?
2.3 percent
What increases a persons chance of having reactivation TB?
PPD conversion, fibrotic scars on chest XR, exposure to someone with active TB and being immunosuppressed
What is another name for the PPD test?
Tuberculin Test
How does the PPD test work?
A tuberculin reaction is classified as positive based on the diameter of the induration in conjunction with certain patient-specific risk factors.
What is a normal PPD test?
15 millimeters
Who are the people who are at the greatest risk of Reactivation TB?
People with a PPD test lower than 5mm, people with HIV, fibrotic changes in the XR & people who come in close contacts with people with TB.
If the PPD test is negative who should still be treated and for how long?
Kids for three months.
Who is at moderate risk of Reactivation TB?
People with a PPD less than 10 mm, peoplw who with medical conditions that lower their immune system(diabetes & renal failure),people with recent skin conversion w/in 2 years & people who inject drugs.
What people are at at lesser risk of Reactivation TB?
People 35 and under with a PPD less than 10, homeless, prisoners, nursing homes and foreign born with a prevalence of TB.
What people have been exposed to Isoniazid Resistant organisims?
People from Africa, Asia and South America; homeless or others
What should be done is Isoniazid resistance is suspected?
4 or more first line drugs should be used; Never add just a single drug always add two.

What happens in hepatotoxicity?
Enzymes that are injured leave the liver and into the blood
How do all TB antibiotics work?
All penetrate into most tissue and reach caseous granulomas (infected area)
What are some symptoms of TB antibiotics? Name 5
Nausea,vomiting, abdominal pain, loss of appetite, diarrhea, feeling tired or weak, jaundice & hepatomegaly
What is used to treat Leprosy?
Sulfones which are Dapsone & Sulfoxone.
What is the mechanism of action of Sulfones?
Block dihydrofolic acid(DFH) synthesis, precursor to tetrahydrofolic acid(TH4);therefore killing bacteria
What are the effects of Sulfones?
Skin rash, drug fever & agranulocytosis(infection vulnerability)
What two other drugs are used for leprosy?
Rifampin & Clofazimine
What is the mechanism of action of Clofazimine?
It binds to DNA and is anti inflammitory for leprosy reactions?
What are the effects of Clofazimine?
Since it's a red compound it turns the body parts where there's leprosy lesions tan, black and/or red.
How many people develop Leprosy reactions?
50%, 1/2, half
What causes these reactions in leprosy?
It's an immune mediated response to the increase in dead organisms due to the treatment.
During what time does type 1 leprosy reaction occur?
During the 1st year of treatment
What is the name of type 2 leprosy reaction?
Erythema Nodosum Leprosum
What are the symptoms of type 1 leprosy reaction?
Skin lesions swell, accumulate fluid, ulcerate and neuropathy
(sensory or motor nerve loss)
What is the treatment for type 1 reaction leprosy?
Prednisone or Clofazimine
What is type 2 leprosy reaction?

A painful nodular rash erupts in a previously normal area of skin, along with high fever, neuropathy, orchitis, arthritis, iritis & lymphadenopathy.
What three drugs can be used for type 2 leprosy reaction?
Prednisone or Clofazimine but most of the time THALIDOMIDE
What diseases is type 2 leprosy reaction associated with?
Borderline Leproatous & Lepromatous Leprosy
What two drugs should pregnant women avoid?
Pyrazinamide & Streptomycin
Which drug for leprosy develops a quick resistance?
Sulfones
Pyrazinamide is related to _________.
Nicotinamide
What type of bacterium is TB & Leprosy?
Mycobacterium
Why is Thalidomide accepted in the U.S?
It has a potent teratogen

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