Chemotherapy V

Fluoroquinolones (FQ)
Quinolone antimicrobials having one or more fluorine substitutions

Classification
I generation FQ Norfloxacin Ciprofloxacin Ofloxacin Pefloxacin II generation FQ Lomefloxacin Levofloxacin Sparfloxacin Gatifloxacin Moxifloxacin

Pcokinetics of FQs

Therapeutic applications of FQs

Uses of FQS
Gonorrhoea Chancroid Bacterial gastroenteritis caused by Shigella, Salmonella and Campy. Jejuni Typhoid Bone & soft tissue infection Tuberculosis Gram (-) septecemia Meningitis Conjunctivitis

Adverse effects
Headache

Diarrhea Dizziness

Nausea Nephrotoxicity

Drug interactions
Plasma concentration of theophylline, 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

Anti tubercular drugs

Tuberculosis
Mycobacteria are slender, rod-shaped bacteria with lipid-rich cell walls that stain poorly with the Gram stain, but once stained, the walls cannot be easily decolorized by treatment with acidified organic solvents. Hence, they are termed acid-fast. The most widely encountered mycobacterial infection is tuberculosis

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

Isoniazid
antibacterial activity of isoniazid 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

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

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

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

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

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

Adverse effects I line anti TB drugs

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

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

Therapy of TB: DOTS

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

Multibacillary leprosy
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

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

Dapsone
May cause haemolysis of red cells methaemoglobinaemia, anorexia, nausea and vomiting, fever, allergic dermatitis and neuropathy May also cause lepra reactions

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

Anti malarial drugs

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

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

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)

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

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

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)

Pyrimethamine
Slow absorption & concentrated in organs like liver, spleen, kidney & lungs Metabolized & excreted in urine Adverse effects: Nausea, rashes, megaloblastic anemia and granulocytopenia

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

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