Antimicrobial Drugs

antimicrobial agents

agents that kill microorganisms or inhibit their growth

antibacterials

inhibit cell wall synthesis, alter membrane permeability, inhibit protein synthesis, inhibit nucleic acid synthesis, and/or interferes with cellular metabolism.

types of antimicrobial drugs

antibacterial, antifungal, antiprotozoan, antihelminthic

acquired resistance

When bacteria become resistant to a drug that they were once susceptible to; develops through mutation or acquiring of new genes

antibacterial drug

an antimicrobial drug used to treat a disease caused by bacteria

antibiotic

a compound naturally produced by certain molds and bacteria that inhibits the growth of microorganisms

antimicrobial

a chemical that inhibits the growth of or kills microorganisms; this includes antibiotics and chemically synthesized drugs

antiviral drug

a drug that interferes with the replication of viruses; all antiviral drugs are chemical synthesized

bactericidal drug

an antimicrobial agent that kills bacteria; inhibit cell wall biosynthesis

bacteriostatic drug

an antimicrobial drug that inhibits the growth of bacteria

broad-spectrum antimicrobial

an antimicrobial that is effective against a wide range of microorganisms, often including both gram-positive and gram-negative bacteria

chemotherapeutic agent

a chemical used to treat a disease

intrinsic resistance

resistance due to an inherent characteristic of the microorganism

narrow-spectrum antimicrobial

an antimicrobial that is effective against a limited range of microorganisms

R plasmid

a plasmid that encodes resistance to one or more antimicrobial drugs

therapeutic index

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

selective toxicity

this is what distinguishes antibiotics from disinfectants; cause greater harm to microorganisms than to host

features of antimicrobial drugs

selectively toxic for bacteria; bacteriostatic and/or bactericidal; minimize harm to patient; damage structures present in bacteria NOT present in host

antibiotics work together with the _______________________

immune system

minimal inhibitory concentration (MIC)

lowest concentration of an antibiotic that stops visible growth

Kirby Bauer

tests the effectiveness of antibiotics against pathogens; check for MIC

Dilution Technique

dilutes bacteria into broth tubes to check for MIC

synergistic

drugs that work together so the total effect is greater than if given separately

antagonistic

activity of one drug interferes with the action of another

Adverse Effects of Antimicrobial Drugs

Allergic Reactions; Toxic Effects; Suppression of normal flora

Development of resistance to antimicrobials

occurs through spontaneous mutations or acquisition of new genes (conjugative transfer of R plasmid)

Characteristics of an ideal antibiotic

selectively toxic to microbe but nontoxic to host; soluble in body; remains in body long enough to be effective; long shelf life; does not lead to resistance; not cost-prohibitive; hypoallergenic; microbiocidal rather than microbiostatic; does not suppress normal flora

mechanisms of action of antibacterial drugs

inhibit synthesis of protein nucleic acid, or essential metabolites; injure plasma membrane

antibiotics which inhibit cell wall synthesis

beta-lactam drugs such as-penicillin, ampilillin, amoxicillin, cephalosporins; also, drugs such as cycloserine, bacitracin, vancomycin

mechanism of antibiotics which inhibit cell wall synthesis

The peptidoglycan chains (mureins) are cross-linked by transpeptidases, located in the cytoplasmic membrane, closely associated with penicillin-binding proteins (PBPs). Beta-lactam antibiotics bind to PBPs and inhibit transpeptidation, the final step in cell wall synthesis.

beta lactam ring

common in all antibiotics that are cell wall synthesis inhibitors.

beta lactam drugs

Penicillin G.
Amoxicillin.
Cephalosporin C.
Cefoxitin.
Thienamycin.
Aztreonam.
Clavulanic Acid.

Penicillins

generally effective against gram-positive bacteria; broad-spectrum penicillins such as amoxicillin and ampicillin are more hydrophilic and can be effective against gram-negatives

Cephalosporins

used for treatment of meningitis, pneumonia, and septicemia

Cycloserine

used in treatment of tuberculosis

Bacitracin

generally effective against gram-positive bacteria; used for topical treatment of a variety of localized skin and eye infections, as well as for the prevention of wound infections.

Vancomycin

generally effective against most gram-positive organisms; used as IV treatment for septicemia or endocarditis caused by MRSA, as well as pseudomembranous colitis

Antibiotics that inhibit protein synthesis

aminoglycosides; tetracyclines; macrolides

mechanism of antibiotics which inhibit protein synthesis

target either 30s or 50s subunit of ribosome

Aminoglycosides

effective against many gram-negative and some gram-positive organisms

Types of aminoglycosides

gentamycin, amikacin, netilmicin, neomycin, streptomycin, rifampicin, tobramycin, kanamycin

Macrolides

effective against gram-negative bacteria; can be used as alternative to penicillin-sensitive patients for gram-positives, such as streptococci, staphylococci, and pneumococci; very safe drugs; usually given orally

Types of macrolides

erythromycin, clarithomycin, azithromycin

Tetracycline

broad-spectrum antibiotic; used to treat many different bacterial infections of the skin, intestines, respiratory tract, urinary tract, genitals, lymph nodes, and other body systems. It is often used in treating severe acne, or sexually transmitted diseases such as syphilis, gonorrhea, or chlamydia.

Chloramphenicol

broad-spectrum antibiotic; known to have serious side-effects; used as an eye ointment to treat conjunctivitis, and to treat meningitis, plague, cholera, and typhoid fever.

Antibiotics that inhibit nucleic acid synthesis

quinolones (fluoroquinolones) and rifamycins

mechanism of antibiotics that inhibit nucleic acid synthesis

inhibit topoisomeraes (wind/unwind DNA, such as DNA gyrase) or inhibiting RNA polymerase

Quinolones

Fluoroquinolones are broad-spectrum antibiotics (effective for both gram-negative and gram-positive bacteria) that play an important role in treatment of serious bacterial infections, especially hospital-acquired infections and others in which resistance to older antibacterial classes is suspected.

Rifamycins

particularly effective against mycobacteria, and are therefore used to treat tuberculosis, leprosy, and mycobacterium avium complex (MAC) infections.

Antibiotics that injure plasma membranes

Polymyxin B

mechanism of antibiotics that injure plasma membranes

binds membrane of grm-negative bacteria and alters permeability; specifically binds to LIPID A (also binds to phospholipids). Therefore, can be quite toxic because host membranes are composed of phospholipids.
Disrupts outer membranes (has to be a GN). This leads to leakage of cellular contents and cell death.
Not typically a first-line drug.

Antibiotics that inhibit synthesis of essential metabolites

Sulfonamides

mechanism of antibiotics that inhibit synthesis of essential metabolites

impair the function of folic acid, mimic the structure of metabolic pyrimidines, or mimic the structure of metabolic purines.

Sulfonamides

Sulfa drugs were the first chemical substances systematically used to treat and prevent bacterial infections in humans;They may be prescribed to treat urinary tract infections (UTIs), bronchitis, eye infections, bacterial meningitis, pneumonia, ear infections, severe burns, traveler's diarrhea, and other conditions

Anaerobic & Parasitic Drugs

5-Nitroimidazoles; wide-spectrum; Metronidazole - against anaerobic bacteria and protozoan infections; Tinidazole - against amoebic/parasitic infection; longer duration of action.

Diffuses into the organism where the nitro group is reduced chemically reactive intermediates are formed that inhibit DNA synthesis and/or damage DNA.

Antiviral Drugs

Designing safe and effective antiviral drugs is difficult, because viruses use the host's cells to replicate. It must attach to and enter a host cell. This makes it difficult to find targets for the drug that would interfere with the virus without also harming the host organism's cells.

mechanism of antiviral drugs

targets are various points of viral reproduction

Types of antiviral drugs

(wide-spectrum); metronidazole; tinidazole, amantadine, zanamivir, immunoglobulins, acyclovir, cidofovir, lamivudine, alpha-interferon, ganciclovir, famciclovir, fosarnet

Anti-tuberculosis drugs

blocks mycelia acid synthesis

isoniazid, ethionamide, ethambutol, cycloserine