Anti-infective Agents - Module 3 Flashcards
common infectious diseases
Aid chiken Pox Cholera Leprosy Mad Cow disease Measles Polio Pneumonia
uncommon infectious diseases
Anthrax Lockjaw Rabies Runny nose SARS Stomach Ulcers Diarrhea Ebola
3 Anti-infective Agents
- Antibacterials (Antibiotics - treat bacterial infections
- Antivirals - use in viral infections
- Antifungal agent - use for fungi
Antibiosis meaning
against life
drug that kill or inhibit the growth of bacteria
All organisms are split into 5 kg
- Animal kingdom - organisms that usually move around and find their own food
- Plant kingdom - organisms that make their own food and do not actively move around
- Fungi kingdom - organisms that absorb food from living and non-living things
- Protist Kingdom - organisms that have single, complex cells
- Moneran kingdom - organisms that have single, simple cell
Salvarsan
Ehrlich - from Germany
- the organic arsenic compound. first modern antibacterial drug - 1910
- drug for treating syphilis until penicillin became available in the 1940.
Sulfanilamide(Prontosil)
Gerhard Domagk - from Germany
Sulfa antibiotics
the sulfa drugs that have anitbacterial properties work by interfering with “folic acid synthesis” - thereby inhibiting the growth of some bacteria.
Penicillin
The antibacterial properties of the common bread mold
- discovered in 1928 by Alexander Flemming - USA and Scottish biologist.
- used for the allies in WWII 1942
Penicillins are
“bactericidal” meaning they kill bacteria by interfering with cell wall synthesis
- they all share a common ring structure (the beta lactam ring)
- work best on “gram-positive” bacteria
Gram-Positive
- Thick cell wall more peptidoglycan
- Teichoic acid
- bluish purple color of crystal violet
- Penicillins work well with gram-positive
Gram-negative
- Thinner layer of peptidoglycan cell wall
- High lipoprotein - lipopolysaccharides LPS
- gram-negative cells are resistant to penicillin attack.
Gram-positive and Gram-negative
both have a cell wall made up of a sugar called peptidoglycan and a fat-based phospholipid membrance bilayer with membrane-spanning proteins to hold it all together.
Mechanism of Action (MOA) for penicillin type drugs
is to inhibit cell wall synthesis
Beta-lactam antibacterials inhibit the synthesis of components of the cell wall
Antimicrobial Activity
- the drug must reach the site of infection
- must be able to penetrate the cell
- Reach the target and kill the organism…and not kill the host
Sulfonamide antibacterials
work by inhibiting Folic Acid (FA) synthesis. Bacteria need to make their own FA, humans ingest it
***inhibiting the growth of some bacteria
Sulfonamide Antibioltics
the first named sulfa drug, Prontosil, is a prodrug: it is converted in the body to sulfanilamide
Modern examples of sulfa antibiotiecs
- Sulfadiazine is one of the ingredients in silver sulfadiazine cream, which is extensively used tor burns
- Sulfamethoxazole is one of two ingredients in the combination antibacterial drug Septra
Sulfa allergies
are common, cause hypersensitivity reations
Sulfates and Sulfites
are chemically unrelated to the sulfonamide group, and do not cause the same hypersensitivity reactions seen in the sulfonamides.
Antibiotic (ABX) Resistance
Over use of Abx and indiscriminate use in animals has led to a serious problem world wide.
ABX resistant infections cause illnesses and deaths in the USA more than drug overdoses, car accidents, or fire arm assaults
Mechanisms of Resistance - 4 main types
- Decreased Permeability - ex. Pseudomonas
- antibiotic Efflux Pump - ex. S. pneumoniae vs quinolones, macrolides
- Drug Inactivation - ex. Beta-lactamase from H. influenzae, Staph, E. Coli, Klebsiella
- Altered Target Site
ex. S. pneumoniae (altered PBPS), S. pneumonia vs macrolides (ribosomal methylase), S. pneumoniae vs quinolones (GyrA, Topo $)
Penicillin Rash
Occasionally penicillin type drugs can case a rash but not the allergic dangerous rash. RED WELT that looks like hives
Penicillin Allergy
Confirm by doing skin testing
The raised RED rash of hives - penicillin that produces these types of reactions should be taken seriously.
The Penicillins
are “bactericidal”, meaning they kill bacteria by interfering with cell wall synthesis.
* they all share a common righ structure (the beta-lactam ring)
Beta-lactam antibacterials
inhibit the synthesis of components of the cell wall - inhibiting folate synthesis
Traditional antibiotic function by
inhibiting DNA or RNA synthesis
Fluoroquinolones
are “broad spectrum” drugs that interfere with the synthesis of bacteria DNA
aminoglycoside antibacterilas work
MOA
by inhibiting bacterial protein systhesis
sulfa drugs or depolarizing membrane
potential (daptomycin)
Methicillin resistant Staphylococcus aureus (MRSA)
is a major problem around the world, causing hospital-acquired infections and more recently, infections in the coomunity
The glycopeptides, particularly vancomycin
have been the mainstays of therapy for MRSA
Penicillin V
was developed that was stable in acid and could be taken orally.
**first broad spectrum penicillins
Ampicillin and Amoxicillin
later became available for the broad spectrum penicillins
Broad spectrum penicillins
including those of the 3rd and 4th generation are call broad spectrum.
Pnicillin V, Ampicillin, Amoxicillin, and Ticarcillin
Penicillin G (Bicillin)
I.M, I.V
Penicillin V or “pen-vee”
oral
Ticarcillin
is one of the newer 3rd - 4th generation drugs
Aminoglycosides
were discovered next (1943) from studying species of soil bacteria that secrete chemicals that kill other bacteria
Aminoglycosides administered
most of them have to be administered parenterally (or topically) - usually in the hospital with monitoring of blood levels (due to kidney and hearing toxicities)
Streptomycin or gentamicin
the first drug discovered in this class of Aminoglycosides
Aminoglycoside mechanism of action
work by inhibiting bacterial protein synthesis
Beta- lactam (penicillin-like)
Cephalosporins - drug developed later on in 1949.
- secretion from a mold that inhibited nearby bacteria
- have a beta-lactam ring like penicillins that interferes with bacterial cell wall synthesis
the fungus Cephalosporium
was first discovered in a sewer outlet in Sardinia (off the coast of Italy - this is were the first generation cephalosprorins came from
Sulfonamide group
- Antidiabetec properties ( Chlorpropamide, Diabinese and glipizide
- Diuretics - thiazide and loop diuretics
Tetracyclines MOA
ANTIBACTERIALS INHIBIT BACTERIAL PROTEIN sysnthesis.
**used to be used to treat the STI gonorrhea and syphilis.
Generic Tetracyclines cause
has a strong affinity of Ca++ and it can cause staining of the teeth in young children.
Fluoroquinolones MOA
Inhibit DNA/RNA synthesis directly
Fluoroquinolones - black fox warning by FDA
pt on fluoroquinolone antibiotics are at risk of tendinitis and tendon rupture.
Fluoroquinolones Adverse Effects
Tendon rupture
Children
Macrolides
are the erythromycin-like” drugs. broad spectrum ABX that interfere with bacterial protein systhesis
- can be used in people who are allergic to penicillins
Macrolides and Ketolide MOA
antibacterials work by inhibiting bacterial protein sysnthesis
Narrow-spectrum
- it only owrked against either gram + or gram - organisms.
Ex. Penicillin first came out like the sulfonamides.
Aminoglycosides like streptomycin,
Glycopeptides like vancomycin
Broad Spectrum
worked equally well against a variety of gram + and gram-
Ex. Tetracycline, Cephalosporins, Fluroquinolones, carbapenems and Monobactams
