Call Girls Service Jaipur {8445551418} ❤️VVIP BHAWNA Call Girl in Jaipur Raja...
principals and therapeutics of antimicrobials
1. Dr. V.K. GUPTA
Division of Medicine
Principles and therapeutics of antimicrobialsPrinciples and therapeutics of antimicrobials
2. Antibiotic
Is a chemical substance produced by a microorganism
that inhibits the growth or kills other microorganisms
Antimicrobial agent
Is a chemical substance derived from a biological source
or produced by chemical synthesis that kills or inhibits
the growth of microorganisms
Antibiotic
3. Sources of Antibiotics
• Natural - Mainly fungal sources
Benzylpenicillin and Gentamicin are natural antibiotics
• Semi-synthetic - Chemically-altered natural compound
Ampicillin and Amikacin are semi-synthetic antibiotics
• Synthetic - Chemically designed in the lab
Moxifloxacin and Norfloxacin are synthetic antibiotics
• There is an inverse relationship between toxicity and
effectiveness as you move from natural to synthetic
antibiotics
4. Role of Antibiotics
To inhibit multiplication
Antibiotics have bactericidal / bacteriostatic effect
Minimal Inhibitory Concentration = MIC
MIC = lowest concentration of antibiotic that inhibits
growth
(Riviere 2009)
5. Role of Antibiotics
• To destroy the bacterial population
• Minimal Bactericidal Concentration = MBC
• MBC = lowest concentration of antibiotic that kills
bacteria
• Antibiotics have a bactericidal effect
(Riviere
2009)
6. Mechanisms of Action
Antibiotics operate by inhibiting crucial life
sustaining processes in the organism: the synthesis
of cell wall material ,DNA, RNA, ribosome's and
proteins.
Target
The target of the antibiotic should be selective to
minimize toxicity for host but all antibiotics are
toxic to some degree
(Riviere 2009)
7. Ideal Antibiotics
Selective target – target unique
Narrow spectrum – does not kill normal flora
High therapeutic index – ratio of toxic level to
therapeutic level
Few adverse reactions – toxicity, allergy
Various routes of administration – IV, IM, oral
Good absorption from site of injection
Good distribution to site of infection
Emergence of resistance is slow
( Goodman & Gilman's 2006)
8. (A) Based on spectrum of activity
Narrow spectrum
Active against either gram-negative or gram-
positive bacteria e.g. penicillin,
streptomycin, erythromycin
Broad-spectrum
Active against both gram-positive and gram-
negative bacteria e.g. tetracycline &
chloramphenicol
(Riviere 2009)
Classification of antibiotics
9. (B)Based on effects of AB
(a)Bacteriostatics
inhibit bacterial growth.
The body requires an effective innate and acquired immune
system in the case of bacteriostatic antibiotics.
For immuno-compromised patients bacteriostatic
antibiotics usually not effective.
Antimetabolites and inhibitors of protein synthesis (except
aminoglycoside antibiotics) are usually bacteriostatic
(Riviere 2009)
10. (b) Bactericidal
Antibiotic kills bacteria.
Inhibitors of cell wall synthesis and agents
affecting cell membrane permeability are
bactericidal
(Riviere 2009)
11. (C) Based on mode of action
A. Antibacterial agents that inhibit the cell wall
synthesis
B. Antibacterial agents that alter the function of
the cytoplasmic membrane
C. Antibacterial agents that inhibit the protein
synthesis
D. Antibacterials that inhibit the nucleic acid
synthesis
( Goodman & Gilman's 2006)
12. 1. Cause misreading of mRNA code and affect
permeability e.g. streptomycin & gentamicin
2. Inhibit DNA gyrase e.g. fluoroquinolones
3. Interfere with DNA function e.g. Rifampin
4. Interfere with DNA synthesis e.g. acyclovir
13.
14. (D) Uses of antibiotics
Antibacterial
A. Gram positive bacteria Penicillin, Erythromycin
B. Gram negative bacteria Streptomycin, Gentamicin
C. Broad spectrum Chloramphenicol, Tetracycline,fluroquinalones
D. Antitubercular Streptomycin, rifampicin
kanamycin capriomycin
(Riviere 2009)
15. Prophylactic – prior to surgical procedure best time half an hr prior to
surgery e.g. Penicillin
Use a growth promoter – use in adult ruminants
monencin & salinomycin
Antifungal -systemic antifungal agent amphotericin-B
-topical antifungal agent Griseofulvin,
(Riviere
2009)
16. Antiviral antibiotics- inhibit viral mRNA
polymerase and interfere viral protein and
maturation e.g. Rifampin
interfere viral protein synthesis e.g. Mytomycin,
Puromycin
Antineoplastic – prevent RNA transcription and
protein synthesis e.g. actinomycin-D
inhibition of RNA & DNA synthesis e.g.
Doxorubincin, Daunorubicin
( Riviere 2009)
17. Uses of antibiotics (contd.)
• Potentiation of inhibitory neurotransmitters in
nematodes and ectoparasite e.g. Ivermectin,doramectin
Milbemycin-D & Milbemycin oxime active against HWP
in dog
Moxidectin active against nematodes and ectoparasite in
cattle
( Riviere 2009)
18. Uses
Anticoccidial
inhibit coccidial protein synthesis
e.g. Oxytetracycline (curative) and chlortetracycline
(prophylactic)
Use as preventive e.g. Monencin
Antianaplasmic
Tetracycline
Antitheilerial
Oxytetracycline & rolitetracycline
( Riviere 2009)
19. Advantages
Easily available, cheap and least toxic
Easily distributed in body tissues and fluids
least untoward reaction
If used properly drugs resistant does not developed
Antibiotics have saved countless lives
Broad-spectrum antibiotics which work equally well on
bacteria and fungus
Each antibiotic is effective only for some types of
disease
Right antibiotic cures the disease in the shortest span of
time
20. Disadvantages
Toxicity
Pain, abscess formation on I/M injection
Thrombophlebitis on I/V injection
Tetracycline, erythromycin &
chloramphenicol
Ototoxic & nephrotoxic
Aminoglycoside
Hepatotoxic & nephrotoxic
Tetracycline
Bone marrow depression and aplastic anemia
Chloramphenicol
(Adams 2001)
21. Disadvantages
Allergic reaction -hypersensitivity reaction
Penicillins, aminoglycosides & cephalosporin
Superinfection - Tetracycline,
Chloramphenicol
Microbial resistance-
Staphylococcus to penicillin
Enterococci to streptomycin
Vitamin deficiencies- vitamin-B & vitamin-K
Production of residues in animal products
( Adams 2001)
22. Disadvantages of combination
Increase chance of toxicity
Increase intensity of toxicity of a drug by another drug
Increase in nephrotoxicity (gentamycin + cephaloridine)
Chance of Superinfection increase
Increase cost of therapy
( Adams 2001)
23. Do’s and don’t antibiotics
Newborn can not metabolized and excreted because
lack of metabolizing enzyme e.g. Chloramphenicol &
tetracycline
Young animal accumulate in developing teeth and bone
e.g. tetracycline
Old animal poor renal function slow excretion
e.g. aminoglycoside
24. Pregnancy penicillin and erythromycin can safely
given
avoid all antibiotic in first trimester period of
organogenesis
× tetracycline, aminoglycoside
Milking animal
Iprinomectin nil milk withholding period
(radostits 2000)
× Chloramphenicol & ivermectin
25. Renal dysfunction
× tetracycline, aminoglycoside, amphotericin-B
Hepatic dysfunction
Don’t- erythromycin, chloramphenicol, & rifampin
Drug allergy
Erythromycin is alternative to penicillin allergy
× Penicillin, aminoglycoside, erythromycin & trimethoprim
26. Presence of blood, pus, CSF
penicillin
× aminoglycoside
Food animal
follow withdrawal time
× chloramphenicol
28. Toxicity
prefer penicillin, cephalosporin's & erythromycin
× Aminoglycoside, tetracycline chloramphenicol,
vancomycin
Follow directions
Dos- full course of antibiotics
× Don’t - stop antibiotics too early
Spectrum
narrow spectrum drugs
× Broad spectrum drugs
Combination
bacteriostatics + bacteriostatics or bactericidal +
bactericidal
× bacteriostatics + bactericidal
29. Mechanism by which small doses of an antimicrobial can lead toMechanism by which small doses of an antimicrobial can lead to
propagation/selection of resistant strains of bacteriapropagation/selection of resistant strains of bacteria
47. REQUISITES FOR RATIONAL ANTIBACTERIAL THERAPY
1) Lesion management and supportive care (Davis,1985)
2) Following the “five rights” of drug administration:
a) Right drug
b) Right dose
c) Right patient
d) Right route
e) Right time (Galbraith, 1999)
3) Monitoring of patient
4) Client education
5) Monitoring response to therapy (Rock, 2007)
48. a. RIGHT DRUG
• Necessary conditions:
In vitro susceptibility: by CST/AST (Rock, 2007)
In vivo susceptibility
Host tolerance (Bill, 2006)
• Other considerations:
Cost, client compliance, ease of administration & convenient dosage interval
(Bill, 2006)
Risks/ interactions: avoid compounding (never mix cationic & anionic drugs)
(Papich, 2007; Mir, 1998)
Impact of the disease process on drug pharmacokinetics (e.g.,
aminoglycosides) and pharmacodynamics (e.g., sulfonamides)
(Novotny 1993; Wilcke 1986)
• Check name (Rock, 2007)
49. b. RIGHT DOSE
• Optimum concentrations at site of infection (Bill, 2006)
• Formula:
• Under doing (larger dogs) → more serious
• Over dosing (cats) (Barragry, 1994)
No diuretics (Mir, 1998)
Check strength (Rock, 2007)
52. d. RIGHT ROUTE
• PO:
Giving a drink of water before administration
Enteric-coated formulations/capsules : do not break
(Rock, 2007)
Empty stomach (Scherer, 1992)
Vomiting
Suspensions : SC or IM
• Severe dehydration: ↓ SC absorption (Novotny, 2001)
53. e. RIGHT TIME
• Frequency: t1/2= 2-3 h: time & concentration dependent (Bill, 2004)
• Time dependent drugs: 100% contact time → compromised IS; ≥ 50%
contact time → working IS (Aucoin, 2002)
• Duration (Novotny, 2001)