UNIT-II
Chemotherapy:-
Q. General principles of chemotherapy:
Ans:
1) Duration of drug administration:
⦁ Insufficient dose can develop resistance.
⦁ intermediate dose may not cure infection.
⦁ Optimize dose should be used for therapy.
2) Continue therapy:
⦁ Acute infection treated for 5-10 days.
⦁ After cure, the therapy must be continued to avoid reinfection.
3) Test for cure:
⦁ After therapy symptoms may disappear before pathogen eliminates.
4) Prophylactic chemotherapy: Used to avoid surgical site infections.
Sulfonamides and Cotrimoxazole:-
1) Sulfonamides:
⦁ It is used to treat a wide variety of bacterial infections
⦁ Used to treat infections in middle ear, urine, respiratory, and intestinal infections.
⦁ It is also used to prevent and treat a certain type of pneumonia.
Mechanism of action:-
⦁ Stops bacteria from making dihydrofolic acid and trimethoprim
⦁ Prevents the formation of tetrahydrofolic acid.
⦁ (Sulphamethizole,Sulfisoxazole,Sulphamethizine,Sulfacetamide) are sulfonamides,
⦁ (Write more by own language)
2) Cotrimoxazole:
⦁ It is an antibiotic mainly used in the treatment of bladder infections.
⦁ It also is used to treat traveler's diarrhea.
⦁ Used in combination with other drugs to treat certain types of pneumonia.
Mechanism of action:-
⦁ It works by stopping the growth of bacteria.
⦁ Eliminates bacteria that cause urinary tract infections.
(Write more by own language)
Antibiotics:- Penicillins, cephalosporins, chloramphenicol, macrolides, quinolones and fluoroquinolins, tetracycline and aminoglycosides.
(i) Penicillin :-
1) Historical background:-
⦁ Alexander Fleming discovered the first antibiotic penicillin .
⦁ Penicillin is derived from the Penicillium mould .
⦁ Penicillin is a group of antibiotics that used to treat different types of gram positive and gram negative bacterial infections.
2) Nomenclature :-
⦁ Sulfur atom at 1st position and nitrogen atom at 4th position then called 1-thia-4aza-bicyclo(3.2.0) -heptane's.
⦁ Sulfur atom at 4st position and nitrogen atom at 1st position then called 1-aza-4-thia-bicyclo(3.2.0) -heptane's.
3) Steriochemistry:-
⦁ The penicillin molecule contains three chiral carbon atoms at C-3, C-5 and C-6
⦁ All natural and synthetic penicillins have the same absolute configuration
⦁ The absolute stereochemistry of the penicillins is designated as 35: 5R: 6R.
4) Mechanism of action:-
It destroys bacteria by inhibiting the enzyme- transpeptidase responsible for the formation of the cell wall and cross-linking in the bacterial cells.
5) Chemical Degradation:
The Penicillins gets degraded under the acidic and basic conditions as well as in the presence of β-lactamases.
6) Uses :-
respiratory tract infections, fever, ear, skin, gum, mouth, and throat infections.
(ii) Cephalosporins:-
⦁ used to treat wide range of infections from gram-positive and gram-negative bacteria.
⦁ used to treat Skin infection, resistant bacteria, meningitis, and other infections.
Mechanism of Action:-
⦁ It destroys bacteria by inhibiting the enzyme- transpeptidase responsible for the formation of the cell wall and cross-linking in the bacterial cells
⦁ Activation of Autolytic enzymes: Autolysins or Murein Hydrolases
Uses:-
⦁ used as antibiotics.
⦁ Alternative to Penicillins
⦁ Gonorrhoea
⦁ Typhoid fever
⦁ Meningitis
(iii) Chloramphenicol:-
⦁ It is an antibiotic.
⦁ is a semi-synthetic broad-spectrum antibiotic.
⦁ It is mainly used to treat eye infections (such as conjunctivitis) and ear infections.
⦁ It comes as eye drops and eye ointment.
Mechanism of action:-
Inhibit the protein synthesis by binding with ribosomes.
Absorption:-
Rapidly and completely absorbed from gastrointestinal tract following oral administration (bioavailability 80%)
Side effects :-
⦁ nausea
⦁ vomiting
⦁ loss of appetite
⦁ diarrhea
⦁ abdominal pain.
Macrolide: Erythromycin, Clarithromycin, Azithromycin.
(i) Erythromycin:-
⦁ is an antibiotic used for the treatment bacterial infections.
⦁ it belongs to a group macrolide antibiotics.
⦁ Slows the growth or kills bacteria by reducing the production of important proteins needed by the bacteria to live.
Mechanism of action:-
Inhibit Protein synthesis by binding to the 23S ribosomal RNA molecule .
Uses:-
Used in respiratory tract, ear, nose, throat, lungs, and skin infections.
Side effects :-
⦁ nausea
⦁ vomiting
⦁ loss of appetite
⦁ diarrhea
⦁ abdominal pain.
(Write Same for Clarithromycin, Azithromycin and include Pharmacokinetics ,Pharmacodynamics and Excretion through Urine etc.)
(iv) Quinolones:-
Nalidixic Acid:
⦁ It is an antibacterial agent.
⦁ Used in urinary tract infection caused by gram-negative microorganisms.
⦁ Prevents the bacterial cells from dividing and repairing and kills them.
Mechanism of action:-
⦁ It stops the action of a bacterial enzyme DNA-gyrase
⦁ and kills bacteria.
Uses :-
⦁ used in urinary tract infection.
⦁ used to treat many bacterial infections.
⦁ also used in infection of tonsils, sinus, nose, throat, female genital organ, skin & soft tissues and lungs.
Tetracyclines:- Tetracycline,Oxytetracycline, Chlortetracycline, Minocycline, Doxycycline.
Tetracycline:-
⦁ Tetracycline is used to treat a wide variety of infections.
⦁ It is an antibiotic that works by stopping the growth of bacteria.
⦁ This antibiotic treats only bacterial infections.
Mechanism of action:-
⦁ These are protein synthesis inhibitors.
⦁ They inhibit the initiation of translation.
⦁ They inhibit the binding of aminoacyl-tRNA to the mRNA translation complex.
Uses:-
⦁ Used to treat infections caused by pneumonia and other respiratory tract infections.
⦁ sexually transmitted infections.
⦁ certain infections of skin, eye, lymphatic, intestinal, genital and urinary systems; and certain other infections that are spread by ticks, lice, mites, and infected animals.
(Write Same for Oxytetracycline, Chlortetracycline, Minocycline, Doxycycline.)
Aminoglycosides:- Streptomycin, Neomycin, Kanamycin
1. Streptomycin:-
⦁ it is the first aminoglycoside antibiotic the used in treatment of tuberculosis.
⦁ It inhibits bacterial growth by inhibiting protein synthesis.
⦁ it binds to the 16S rRNA of the bacterial ribosome
⦁ interfere with the binding of formylmethionyl-tRNA .
⦁ It is chemically stable and rapidly bactericidal and have broad spectrum.
2. Neomycin:-
⦁ Most potent aminoglycoside.
⦁ is used to prevent or treat skin infections caused by bacteria. It is not effective against fungal or viral infections.
⦁ Neomycin comes in cream and ointment that is applied to the skin.
Side effect:-
⦁ irritation
⦁ burning
⦁ redness
⦁ rash
⦁ itching
⦁ hearing difficulty
⦁ decreased urination
3. Kanamycin:-
⦁ Kanamycin is made up of 3 rings.
⦁ Ring II is sugar group and ring I and III are non-sugar group.
⦁ Kanamycin B is a more potent antibiotic than kanamycin A or C.
⦁ is used to treat serious bacterial infections in many different parts of the body.
Mechanism:-
⦁ It bind to 30S proteins and 16S rRNA.
⦁ Specifically Kanamycin binds to four nucleotides of 16S rRNA and a single amino acid of protein S12.
⦁ So incorrect amino acids are inserted into the polypeptide.
Clinical Uses:-
⦁ gram-negative infection
⦁ skin, bone or soft tissue infection
⦁ urinary tract infection
⦁ Sepsis
⦁ severe intra-abdominal infections
⦁ Severe pelvic inflammatory disease
⦁ Endocarditis
⦁ Mycobacterium infection
(fluoroquinolins point not Written )
---------------------------------------------END OF UNIT 2 -------------------------------------------