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Chemotherapy V
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Fluoroquinolones (FQ)
Quinolone antimicrobials having one or more
fluorine substitutions
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Classification
I generation FQ
Norfloxacin
Ciprofloxacin
Ofloxacin
Pefloxacin
II generation FQ
Lomefloxacin
Levofloxacin
Sparfloxacin
Gatifloxacin
Moxifloxacin
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Pcokinetics of FQs
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Therapeutic applications of FQs
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Uses of FQS
Gonorrhoea
Chancroid
Bacterial gastroenteritis caused by Shigella,
Salmonella and Campy. Jejuni Typhoid
Bone & soft tissue infection
Tuberculosis
Gram (-) septecemia Meningitis
Conjunctivitis
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Adverse effects
Headache
Dizziness
Nephrotoxicity
Diarrhea
Nausea
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Drug interactions
Plasma concentration oftheophylline, caffine
and warfarin are increased by ciprofloxacin
NSAIDS may enhance the CNS toxicity of FQs
seizures are reported
Antacids may decrease the absorption of FQS
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Anti tubercular drugs
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Tuberculosis
Mycobacteria are slender, rod-shaped bacteriawith lipid-rich cell walls
that stain poorly with the Gram stain,
but once stained, the walls cannot be easilydecolorized by treatment with acidified organicsolvents.
Hence, they are termed acid-fast.
The most widely encountered mycobacterialinfection is tuberculosis
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Anti TB drugs
I line drugs
Isoniazid (H)
Rifampin (R)
Pyrazinamide(Z) Ethambutol (E)
Streptomycin (S)
II line drugs
Cycloserine
Kanamycin
Amikacin Capreomycin
Ethionamide
PAS
Ciprofloxacin Clarithromycin
Azithromycin
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Isoniazid
antibacterial activity ofisoniazid is limited to
mycobacteria.
readily absorbed from the gastrointestinal
tract and is widely distributed throughout the
tissues and body fluids, including the CSF
Metabolism largely involves acetylation
excreted in the urine partly as unchanged drug
and partly in the acetylated form
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Rifampin
one of the most active antituberculosis agents
also effective against most Gram-positive
bacteria as well as many Gram-negative
species
Rifampicin is given orally and is widely
distributed in the tissues and body fluids
excreted partly in the urine and partly in the
bile
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Rifampin
Induced hepatic microsomal enzyme which
increase the degradation of self as wells as
many other drugs like warfarin,
glucocorticoids, narcotic analgesics, oral
antidiabetic drugs, dapsone and oestrogen
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Ethambutol
Ethambutol has no effect on organisms other
than mycobacteria
Ethambutol is given orally and is well
absorbed
it is taken up by erythrocytes and slowly
released
partly metabolized and is excreted in the urine
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Pyrizinamide
Pyrazinamide is inactive at neutral pH but
tuberculostatic at acid pH
well absorbed after oral administration and is
widely distributed penetrating well into the
meninges
excreted through the kidney, mainly by
glomerular filtration
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Streptomycin
First clinically useful drug against TB
Administered as i.m. inj., distributed only
extracellularly
Not metabolized and excreted unchanged in
urine via glomerular filtration
May cause ototoxicity, nephrotoxicity and pain
at injection site
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Adverse effects I line anti TB drugs
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Capreomycin
Peptide antibiotic given by intramuscular
injection
May cause kidney damage and injury to the
eighth nerve, with consequent deafness and
ataxia
Should not be given at the same time as
streptomycin
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Cycloserine
Broad-spectrum antibiotic that inhibits the
growth of many bacteria, including coliforms
and mycobacteria
Rapidly absorbed orally, distributed
throughout the tissues and body fluids, and
reaches CSF
Mostly eliminated in active form in the urine
Adverse effects: headache and irritability to
depression, convulsions and psychotic states
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Therapy of TB: DOTS
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Drugs used to treat leprosy
Paucibacillary leprosy
Characterised by one to five numb patches
is mainly tuberculoid type
Treated for 6 months with dapsone and rifampicin
Multibacillaryleprosy
Characterised by more than five numb skin
patches
is mainly lepromatous type
and is treated for at least 2 years with rifampicin,
dapsone and clofazimine
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Dapsone
Dapsone is chemically related to the
sulfonamides
Dapsone is absorbed orally and widely
distributed
There is enterohepatic recycling of the drug,
but some is acetylated and excreted in the
urine
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Dapsone
May cause haemolysis of red cells
methaemoglobinaemia, anorexia, nausea and
vomiting, fever, allergic dermatitis and
neuropathy
May also cause lepra reactions
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Clofazimine
Clofazimine is a dye of complex structure
has anti-inflammatory activity and is useful in
patients in whom dapson causes
inflammatory side effects
Skin and urine can develop a reddish colour
and the lesions a blue-black discoloration
Nausea, giddiness, headache and
gastrointestinal disturbances
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Anti malarial drugs
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Introduction
Malaria is an acute infectious disease caused
by four species of the protozoal genus
Plasmodium
P. falciparum, P. vivax, P. malariae & P. ovale
Parasite is transmitted to humans through the
bite of a female Anopheles mosquito
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Chloroquine
Well absorbed orally
High affinity for melanin, nuclear chromatin &
retina
Partly metabolized by liver and slowly
excreted in urine
Side effects: nausea, vomiting, anorexia,
itching, epigastric pain, difficulty in
accommodation and headache
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Chloroquine
Parenteral administration can cause
hypotension, cardiac depression, arrhythmias
and CNS toxicity
Prolonged use may cause loss of vision
Loss of hearing, rashes photoallergy, mental
disturbance and graying of hair
Should not be co administered with other
antiarrhythmics (mefloquine, amiodarone,
etc)
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Mefloquine
Developed to deal chloroquine resistant P.
falciparum
Oral absorption is slow, high plasma protein
binding
Extensive metabolism in liver and primarily
secreted in bile
Adverse effects: dizziness, nausea, vomiting,
diarrhoea, abdominal pain and sinus
bradycardia
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Mefloquine
Neuropsychiatric reactions (disturbed sense of
balance, ataxia, errors in operating machinery,
strange dreams, anxiety, hellucination and
rarely convulsions)
Rarely, Hematological, hepatic and cutaneous
toxicity
Interactions: Halofantrine or quinidine can
cause QTc lengthening or cardiac arrests
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Quinine
Levo rotatory alkaloid from cinchona bark
Rapidly & completely absorbed orally
Large fraction is metabolized in liver and
excreted in urine
Adverse effects: Cinchonism (ringing in ears,
nausea, vomiting, headache, mental
confusion, vertigo, difficulty in hearing and
visual defects)
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Pyrimethamine
Slow absorption & concentrated in organs like
liver, spleen, kidney & lungs
Metabolized & excreted in urine
Adverse effects: Nausea, rashes,
megaloblastic anemia and granulocytopenia
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Primaquine
Readily absorbed after oral ingestion
Oxidized in liver & excreted in urine
Adverse effects: Haemolysis,
methemoglobinemia, tachypnoea & cyanosis
Should be avoided during pregnancy because
fetus is G-6-PD deficient
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Artemisinin derivatives
Artesunate and arteether
Adverse effects: nausea, vomiting, abdominal
pain, itching & drug fever
Interactions: Concurrent administration of
artemisinin compounds with terfenadine,
astemizole, antiarrhythmics, TCA &
phenothiazine may increase the risk of cardiac
conduction defects
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