ANTIMICROBIAL DRUGS Flashcards
Chemicals used to treat microbial infections
ANTIMICROBIAL DRUGS
resistance that develops through mutation or acquisition of new genes
acquired resistance
an antimicrobial drug used to treat a disease caused by bacteria
antibacterial drug
a compound naturally produced by certain molds and bacteria that inhibits the growth or kills other microorganism
antibiotic
a chemical that inhibits the growth of or kills microorganisms. This terms encompasses antibiotics and chemically synthesized drugs
antimicrobial drug (or antimicrobial)
a drug that interferes with the replication of viruses. all antiviral drugs are chemically synthesized; none are antibiotics
antiviral drug
an antimicrobial drug that kills bacteria
bactericidal drug
an antimicrobial drug that inhibits the growth of the bacteria
bacteriostatic drug
an antimicrobial that is effective against a wide range of microorganisms often including both Gram-positive and gram-negative bacteria
Broad-spectrum antimicrobial
a chemical used to treat a disease
chemotherapeutic agent
resistance due to an inherent characteristics of the microorganism
intrinsic resistance
an antimicrobial that is effective against a limited range of microorganism
Narrow-spectrum antimicrobial
A plasmid that encodes resistance to one or more antimicrobial drugs
R plasmid
a measure expressing the relative toxicity of a chemotherapeutic drug. It is the lowest dose toxic to the patient divided by the dose used for therapy
Therapeutic index
Cause greater harm to microorganisms than to host
Selective Toxicity
inhibit growth of microorganisms
Bacteriostatic
Kill microorganisms
Bactericidal
Antimicrobial Action
Bacteriostatic; Bactericidal
kill only limited range
Narrow-spectrum antimicrobial
kill wide range of microorganisms
Broad-spectrum antimicrobial
action of one drug enhances the activity of another or vice versa
Synergistic
activity of one drug interferes with the action of another
Antagonistic
some people develop hypersensitivities to antimicrobials
Allergic Reactions
some antimicrobials toxic at high concentrations or cause adverse effects
Toxic Effects
b-lactam drugs include
penicillins and cephalosporins
very active against non-β-lactamase producing gram+ bacteria.
AMPICILLIN AND AMOXICILLIN
- Used for treatment of meningitis, pneumonia, and septicemia.
- Same mech and p’col as that of penicillins.
CEPHALOSPORINS
(for UTI) in case of antibacterial resistance
Cefadroxil
Resistant to inactivation by β-lactamases and used in severe infections (others ineffective)
Cefuroxime
wide range of activity against gram- including Pseudomonas aeruginosa), but is less active than cefurozime against gram+ bact (S aureus).
Ceftazidime
• Not well absorbed orally.
• Inhibits peptidoglycan formation.
• Active against most gram+ organisms.
• I.V. treatment for septicemia or endocarditis caused by MRSA.
• Used for pseudomembranous colitis (superinfection of the bowel by Clostridium
difficile – produces a toxin that damages the colon mucosa)
VANCOMYCIN
bind to 30S subunit causing it to distort and malfunction; blocks initiation of translation
Aminoglycosides
bind to 30S subunit blocking attachment of tRNA
Tetracyclines
bind 50S subunit and prevents protein synthesis from continuing
Macrolides
used for acute, life-threatening gram- infections. Has synergism
with pen and van and combo
Gentamicin
used for bacteria that are gent-resistant
Amikacin
less toxic than gentamicin.
Netilmicin
too toxic for parenteral use. Used for topically for skin infections
and orally for sterilizing bowel before surgery.
Neomycin
active against Mycobacterium tuberculosis. But because of its ototoxicity, rifampicin replaces
Streptomycin
resistance develops quickly alone; so, with TB, combine with
isoniazid, ethambutol, and pyrazinamide for the 1st 2 mos of treatment, followed
by another 4 mos with rifampicin and isoniazid
Rifampicin
- Very safe drugs.
* Usually given orally.
MACROLIDES
macrolides example drugs
Erythromycin and clarithromycin
in high doses, may cause nausea and vomiting
Erythromycin
very long t1/2 (~40-60 hr) and a single dose is as effective in
treating chlamydial non-specific urethritis as tretracycline admin over 7 days,
Azithromycin
• Broad-spectrum.
• Penetrate microorganisms well.
• Sensitive organisms accumulate it through partly passive diffusion and partly
through active transport.
• Resistant organisms develop an efflux pump and do not accumulate the drug.
• Genes for tet-resistance transmitted by plasmids.
• Closely assoc with those for other drugs to which the organisms will also be
resistant (e.g., sulphonamides, aminoglycosides, chloramphenicol).
• Tets bind to Ca in growing bones and teeth → can discolor teeth. So, should be
avoided in children < 8 yrs old
TETRACYCLINES
• Broad-spectrum.
• Serious side-effects: bone marrow aplasia, suppression of RBCs, WBCs,
encephalopathy, optic neuritis.
• So, periodic blood counts required, especially in high doses.
• Large Vd, including CNS.
• Inhibits the actions of other drugs and may increase the actions of phenytoin,
sulphonylureas, and warfarin.
• Neonates cannot met the drug rapidly → accumulation →‘grey baby’ syndrome
(pallor, abdominal distension, vomiting, and collapse
CHLORAMPHENICOL
inhibit enzymes that maintain the supercoiling of closed
circular DNA
Fluoroquinolones
block prokaryotic DNA-dependent RNA polymerase from initiating
transcription
Rifamycins
well-absorbed orally. Used to treat UTIs.
Sulfadiazine
SULPHONAMIDES- Adverse effects
allergic rxns, skin rashes, fever
used for UTIs and Resp TIs
Trimethoprin
used mostly for pneumonia,
neocarditis, and toxoplasmosis
Co-trimoxazole (trimethoprin + sulfamethoxazole)
• Inhibit DNA gyrase.
• Nalidixic acid – used only for UTIs.
• Ciprofloxin (6-fluoro substituent) that greatly enhances its effectiveness against
both gram- and gram+ bacteria.
• Well-absorbed both orally and I.V.
• Eliminated largely unchanged by the kidneys.
• Side-effects (headache, vomiting, nausea) are rare; but convulsions may occur
QUINOLONES (GABA ANTAGONISTS)
against anaerobic bacteria and protozoan infections
Metronidazole
longer duration of action
Tinidazole
Diffuses into the organism where the nitro group is reduced → chemically reactive
intermediates are formed that inhibit DNA synthesis and/or damage DNA
5-NITROIMIDAZOLES
binds to membrane of G- bacteria and alters permeability
• This leads to leakage of cellular contents and cell death
• These drugs also bind to eukaryotic cells to some extent, which limits their use to
topical applications
Polymyxin B
nterferes with replication of influenza A by inhibiting the
transmembrane M2 protein that is essential for uncoating the virus
Has a narrow spectrum; so, flu vaccine is usually preferable
Amantadine
– inhibits both influenza A and B neuraminadase. Decr duration of
symptoms if given within 48 hr of the onset of symptoms. Prophylactic in healthy
adults.
Zanamivir
Human Ig contains specific Abs against superficial Ags of
viruses → can interfere with their entry into host cells. Protection against hepA,
measles, and rubellla (German measles)
Immunoglobulins
used to treat genital herpes
Acyclovir
used for treatment of cytomegaloviral infections of the eye
Cidofovir
used to treat Hepatitis B
Lamivudine
• HSV and VZV contain a thymidine kinase (TK) that → acyclovir to a monophosphate
—→ phosphorylated by host cell enzymes to acycloguanosine triphosphate, which
inhibits viral DNA pol and viral DNA synthesis.
• Selectively toxic (TK of uninfected host cells activates only a little of the drug).
• Viral enzymes have a much higher affinity than the host enzymes for the drug.
• Effective against HSV, but does not eradicate them.
• Need high doses to treat shingles.
ACYCLOVIR
• Quite toxic (neutropenia) –so, given only for severe CMV infections in
immunosuppressed patients.
• CMV is resistant to acyclovir because it does not code for TK
GANCICLOVIR
Currently implies a drug used to treat HIV
ANTIRETROVIRALS
nucleotide reverse transcriptase inhibitor
Tenofovir
- nucleoside analog – inhibits RT of HIV and is only used orally for AIDS
Zidovudine
- inhibitors of the
enzyme neuominidase
Used to treat influenza
Zanamivir (Relenza) and Oseltamivir phosphate (Tamiflu)
protease inhibitors. Inhibit the synthesis of essential viral proteins (e.g.,
RT) by viral-specific proteases.
Indinavir
• Cells infected by a virus often produce interferon, which inhibits further spread of
the infection
Interferons
drug for treatment of viral hepatitis infections
Alpha-interferon
