antibiotics
a class of drugs that inhibit the growth of bacteria without harming the human host
selective toxicity
important feature of antibiotics that enable them to target and kill bacteria without harming the infected host
Alexander Fleming
1929 discovered PCN
Gram-positive bacteria
those bacteria that create a positive result in the Gram stain test for bacteria
Gram-negative bacteria
bacteria that give a negative result on the Gram stain for bacteria
Bactericidal
- cidal = “to kill or have killing power”
- bactericidal antibiotics typically kill the bacteria it targets
Bacteriostatic
- static = stopping or controlling
- bacteriostatic antibiotics stop bacteria growth and replication. The host’s immune system must complete the task of clearing the body of the invading bacterial species
Antibiotic Mechanisms of Action
- inhibit cell wall synthesis
- inhibit protein synthesis
- interfere with essential bacterial enzymes
Antibiotic Classes
- ß-lactam
- Other cell-wall synthesis inhibitors (cell wall inhibitors that lack the beta-lactam ring)
- Protein-synthesis inhibitors
- Quinolone
ß-lactam
works by inhibiting bacterial cell-wall synthesis by use of the beta-lactam ring molecular structure that interferes with the bacteria enzymes used to build its cell walls; ultimately killing the bacteria.
This class of antibiotics includes:
- PCN
- cephalosporins
- carbapenems
- monobactams
ß-lactamase
enzymes bacteria have developed to become resistant to beta-lactam antibiotics. the lactamase reacts with the beta-lactam ring in the antibiotic, deactivating it = deactivating the antibitoic.
Penicillinase
the specific beta-lactamase that dectivates PCN
ß-lactamase inhibitor
one way around the inactivation of antibiotics is to give a beta-lactamase inhibitor such as:
- clavulanic acid
- sulbactam
which increase the effectiveness of the antibiotic
Penicillins
- group of antibiotics derived from Penicillium fungi
- bactericidal
- natural PCN’s are made from the fungi or mold
- chemically modified PCN’s developed to improve resistance to beta-lactamases
- -cillin
paresthesia
numbness and tingling
unicaria
hives
PCN Allergic Reactions
- itching
- paresthesia
- wheezing
- choking
- fever
- swelling
- generalized uticaria
cephalosporins
- beta-lactams derived from cephalosporium fungi
- ceph- or cef-
- classified by their generation (1st, 2nd, 3rd, etc.)
carbapenems
- -enem
- broad spectrum beta-lactam
- highly resistant to most beta-lactamases
- not very soluble an have poor oral bioavailability
- delivered via IV in hospital setting
- used for serious infections as an antibiotic of last resort
Poor Oral Bioavailability
given in oral dosage, the medication is difficult to absorb into the body and become effective
monobactams
- aztreonam is the only currently available drug in this class
- works against gram-negative bacteria
- highly resistant to beta-lactamases
Other Antibiotic Cell-Wall Synthesis Inhibitors
(those lacking the ß-lactam ring)
- vancymycin
- bacitracin
- fosfomycin
- daptomycin
these medications work similar to the beta-lactam antibiotics, however these medications lack the ß-lactam ring.
additionaly, eacy one of these drugs is different in structure and mechanism of action against the bacterial cell wall
protein-synthesis inhibitors
works by preventing protein synthesis in bacteria with selective toxicity
- three main categories
- aminoglycosides
- tetracyclines
- macrolides
aminoglycosides
- -mycin
- broad-spectrum antibiotics
- poorly absorbed from GI tract
- administered by IV or other parenteral means
- Important to note:
- ototoxic
- nephrotoxic
- neuromuscular toxic
- small safety margin between toxic concentration and therapeutic effect
tetracyclines
- -cycline
- broad-spectrum antibiotics used for both gram-positive and gram-negative bacteria
- can be given orally – without food – food impares absorption (exceptions are doxycycline and minocycline)
- major side effects:
- insoluble chelates - kind of calcium bond that discolors the teeth and inhibits bone growth
- should not be used with children or pregnant women
macrolides
- some end with -mycin
- most end with -thromycin
- can be given orally with relatively few side effects
- useful in treating:
- mycoplasma infections
- pneumonia
- Legionnaires disease
- diptheria
- pertussis
quinolones
- relatively new class of antibiotics
- work by inhibiting DNA synthesis
- -oxacin
- primarily used to treat UTIs
- broad spectrum
- used orally
antifungals
used to treat fungal infetions; either superficial infections that effect the outer layers of skin, nails and hair -or- systemic fungal infections
- fungal infections replicate more slowly making treatment problematic
- these drugs are poorly soluble - making distribution to the site of infection problematic
- as a result, antifungals typically work to assist the host’s immune system in fighting against the infection
- must have selective toxicity to be effective
Antifungal Classes
- polyene antifungals
- azole antifungals
- echinocandins
polyene antifungals
- polyene refers to the chemical structure that maks up this class
- most popular is
- amphotericin B
- works by binding to sterols in the fungal cell membrane which disrupts membrane function causing leakage of electrolytes from the cell leading to cell death for the fungus
- nephrotoxic
- must be given by IV or topically
azole antifungals
- azole = chemical structure of the class
- work by inhibiting an enzyme fungi use to make sterol, leading to cell death
- ergosterol
echinocandins
- used to treat candida and aspergillus
- inhibits fungi cell-wall production by targeting glucan
- given by injection
terbinafine
- an antifungal given for superficial infections
- targets poorly vascularized tissues such as hair, skin and nails
- administered topically
Antivirals
- treat viral infections through the selective targeting of the viral-development cycle
- vaccination is traditional method
- a preventative strategy
- selective toxicity
antiviral chemotherapeutics
- developed as an additional fight against viral infections
- successful in treating HIV, herpes, hepatitis B & C, and influenza A & B
Anti-HIV
- drugs in this category work by a variety of mechanisms
- multiple drugs, targeting different mechanisms, are given as a “cocktail”
- targets an enzyme called reverse transcriptase
- “cocktail” drugs are called RTIs - reverse transcriptase inhibitors
- anti-HIV cocktails usually include one NNRTI and 2 NRTIs used in combinations
- -ine
RTI
- reverse transcriptase inhibitors
- further divided into:
- NRTIs - nucleotide reverse transcriptase inhibitors
- NNRTIs - non-nucleotide reverse transcriptase inhibitors
- -ine
PI
- protease inhibitors
- also anti-HIV
- work by interfering with the processing of viral proteins, preventing the formation of new viral particles
- -vir
- used in combination:
- 2 PIs + 2 NRTIs
Influenza Drugs
- vaccination is standard approach
- some antivirals have been developed that work as an alternative to vaccination
- work by targeting the development cycle of of the flu virus and stopping its replication
- oseltamivir (Tamiflu)
- used for influenza A, administered within 48 hours of infection, shortens the duration of symptoms by 1/2
- oseltamivir (Tamiflu)