Beta-Lactam Antibiotics: Antibiotics Affecting the Bacterial Cell Wall
- penetrate the cell wall and bind to targets on the cytoplasmic membrane
- disrupts the synthesis and maintenance of the cell wall, killing the bacterium through an increase in osmotic pressure
Drug
Penicillins
Beta-Lactamases
(Penicillinases)
Beta-Lactamase
Inhibitors
Cephalosporins
Carbapenems
Mechanism of
Action
- affects the
bacterial cell
wall=>cell is
crushed
Uses
Target Populations Routes
Side Effects
Drug Interactions
Other
Examples
- therapeutic: kill
g+ and a few g(ngonorea and
syphilis)
-prophylactic:
prevent bacteremia
in pts at risk for
endocarditis
- gram-positive
- may or may not
bacteria, such as
be orally active
Staph and Strep
- depot forms
- some, but not all,
will cover
anaerobes, such as
Enterobacter,
Pseudomonas, and
Klebsiella
- GI symptoms
- suprainfections due
to loss of normal
flora
- overdose --neurologic problems
(seizures)
- synergistic with
aminoglycosides, but
not in the same IV
line
- most have a short halflife
- excrete in the kidneys
- do not cross the BBB
well
- Depot forms/deep IM:
benzathine penicillin G procaine penicillin G
- cut the betalactam ring,
inactivating beta
lactam
antibiotics
- bind to the
active site of
beta-lactamases,
preventing them
from cutting the
beta-lactam rings
Similar to
penucillins,
weaken the
bacterial cell
wall
- broad spectrum
-Skin test is a BAD
IDEA (can cause
anaphlax)
- can be administered
along with betalactams
- gram positive
cocci
- gram negative
cocci and bacilli
- anaerobes
- IV only
- suprainfection
- increased bleeding
with warfarin
(cefmetazole,
cefoperazone,
cefotetan)
- disulfiram-like
reaction when taken
with alcohol (vomit)
- cross allergy with
penicillin
- widely distributed to
body fluids and bone
- 1st and 2nd generations
do not cross the BBB,
3rd and 4th do Cross
- eliminated by the
kidneys
- used to treat gram - Clostridium
- ototoxicity
- synergism with
- cephalothin
- cefamandole
- cefotaxime
- cefepime
- cefeperazon
- cefemetazole
- cefetetan
- imipenem
- meropenem
- ertapenem
Non-Beta Lactam Antibiotics: Antibiotic Affecting the Bacterial Cell Wall
- not a beta-
Lots of orals: ie amoxicillin
- augmentin
- unasyn
- timentin
- zosyn
Azetronam
Vancomycin
IV/Inject
potassium penicillin G
- poor penetration into
lactam
- interferes with
cell wall
synthesis
positive infections difficile
in penicillinallergic patients
- used for serious
infections
- nephrotoxicity
aminoglycosides
- multiple drug
interactions
- rapid infusion leads
to flushing,
tachycardia, and
hypotension
- irritating to the skin
the CSF
Bacteriostatic Inhibitors of Protein Synthesis
Drug
Tetracyclines
Macrolides
Clindamycin
Mechanism of
Action
- bind to the 30S
ribosomal
subunit and
prevent the
elongation of the
peptide chain
Uses
- braod spectrum
- Chlamydia
- rickettsial
diseases (rocky
mountain spotted
fever)
- acne
- periodontal
disease
- inhibit protein - Chlamydia
synthesis by
- Legionella
inhibiting the
(Legeneir’s
50S ribosomal disease)
subunit
- alternative to
penicillin in
allergic patients
- inhibits the 50S - reserved for
ribosomal
serious infections
subunit
Target Populations Routes
- mainly oral
- rarely Iv
- gram positive
bacteria
- gram negative
bacteria
- gram positive
aerobes
- anaerobes
Side Effects
Drug Interactions
- discolor developing
teeth
- suprainfection with
bowedl organisms or
Candida
- form insoluble
- porr CSF penetration
compounds with
calcium, iron,
magnesium,
aluminum, and zinc
(no laxatives,
antacids, dairy, or
iron)
- corrosive to the GI - erythromycin and
tract
clarithromycin are
- IV erythromycin is strong inhibitors of
corrosive to the veins cytochrome P450
- hepatotoxicity
Other
- poor CSF penetration
Examples
- tetracycline
- doxycycline
- minocycline
- erythromycin
- clarithromycin
- azithromycin
- IV infusion must - suprainfection with - should not be given - poor penetration of the
be slow
C. diff
with a macrolide
brain
because they work by
the same MOA
Chloramphenicol
Bacteriocidal Inhibitors of Protein Synthesis
Drug
Aminoglycosides
Mechanism of Uses
Action
- bind to the 30S
ribosomal
subunit
- promote the
formation of
abnormal
proteins whose
Target Populations Routes
- gram-negative
bacteria, such as
Pseudomonas,
Klebsiella, and
Serratia
- do not work
against anaerobes
Side Effects
- IV
- otoxicity
- topic to sterilize - nephrotoxicity
the gut, skin, or
eye
- is not absorbed
Drug Interactions
Other
Examples
- tobromycin
- gentamycin
- amakacin
abnormal
functioning kills
the cell
Antibiotics Affecting DNA
Drug
Sulfamethoxazoletrimethropim
(Bactrim)
Fluoroquinones
Metronidazole
(Flagyl)
Mechanism of Uses
Target Populations Routes
Action
- blocks bacterial - broad spectrum - gram negative
enzymes
- UTI
- gram positive
important in the - Pneumocystis
synthesis of
carinii pneumonia
DNA, RNA, and of AIDS
proteins
- inhibit DNA
gyrase important
in bacterial DNA
replication
- aerobic organisms
- most gram
negative
- some gram
negative
- C. difficile
- Bacteriodes
- Entameba
histolytica
- anaerobic
organisms
- parasites
- bacteria
Side Effects
- hypersensitivity
reactions
- Stevens Johnson
- blood dyscrasias
(abnormal amounts
of the components of
blood)
- crystalluria
- CNS effects –
headaches, sudden
psychosis
- irreversible joint
disease in children
under 18
- tendon rupture
- photosensitivity
- Candida
suprainfections,
especially of the
oropharynx
- infrequent but
serious CNS effects
- darkening of the
urine
CNS effects
- avoid during
pregnancy
Drug Interactions
Other
Examples
- combination of a sulfa
drug
(sulfamethoxazole)and an
inhibitor of a bacterial
enzymes called
dihydrofolate reductase
(trimethroprim)
- the two drugs combine
to form bactrim and block
different steps in the
pathway (synergistic)
- should not be taken
with aluminum, iron,
calcium, or zinc
supplements
- can increase plasma
levels of theophylline
and warfarin
- ciprofloxacin
- levoflaxacin
- oxofloxacin
- cytochrome p450
interactions
- prodrug that is activated
only in anaerobic cells
Side Effects
Drug Interactions
Other
- infusion reactions –
phlebitis, fever,
chills, rigors, nausea,
headache
- nephrotoxic
- use with caution
- binds to the cholesterol
with aminoglycosides in cell membranes so it is
because they are also toxic to mammalian cells
nephrotoxic
- drug reduction
when used with
flucytosine
Antifungals
Drug
Amphotericin B
Mechanism of Uses
Action
- binds to sterols - systemic fungal
in the fungal
infections
membrane and
increases
permeability
- the fungal cell
swells and bursts
Target Populations Routes
Examples
Ketaconazole
- inhibits the
- oral alternative to
synthesis of a
amphotericin B
sterol component - systemic fungal
of the fungal cell infections
membrane
- oral
- hepatic necrosis
(synergistic)
- strong inhibitor of
cytochorme p450
enzymes
Antivirals
Drug
Acyclovir
Ganciclovir
Mechanism of
Action
- suppresses the
synthesis of viral
DNA
Uses
- herpes viruses –
herpes simplex,
herpes zoster,
CMV
- herpes viruses –
herpes simples,
herpes zoster,
CMV
Target Populations Routes
- topical
- oral
- IV
Side Effects
- nephrotoxic
- granulocytopenia
- thrombocytopenia
- terotogenic
- embyrotoxic
Drugs for Influenza
Amantidine
Rimantadine
Neurominidase
Inhibitors
Drug Interactions
- prophylaxis
during epidemics
- treatment
- only effective
against influenza A
- prophylaxis
during epidemics
- treatment
- only effective
against influenza A
- must be taken - tamiflu – oral
soon after
drug used as
symptoms appear prophylaxis or to
to be effective shorten duration of
the flu
- relenza is inhaled
but is NOT
approved for
prophylaxis
HIV Drugs
Other
Examples
- resistance is common - valacyclovir (Valtrex) is a
due to thymidine kinase prodrug that is more
deficiency
bioavailable
- poor
bioavailability is
slightly increased
by food
Drug
Nucleoside Reverse
Transcriptase
Inhibitors (NRTIs)
Mechanism of Uses
Action
- inhibit the viral
enzyme, reverse
transcriptase, that
converts viral
RNA into DNA
- inhibit human
DNA polymerase
so that the drugs
are toxic to
dividing cells
Non-nucleoside
- bind to the
Reverse Transcriptase active site of the
Inhibitors (NNRTIs) reverse
transcriptase
enzyme
- more specific
for the viral
reverse
transcriptase
- do not affect
human DNA
polymerase the
way that NRTIs
do
Protease Inhibitors
- inhibit viral
(PIs)
protease, which
is responsible in
the final step in
maturation of the
infective virus
- cannot cut the
long viral
proteins into
functional units
so the virus
remains
immature and
non-infective
Entry Inhibitors
- inhibits entry of
HIV into CD4
positive cells
Target Populations Routes
Side Effects
Drug Interactions
Other
Examples
- mitochondrial
toxicity in the liver
- hepatomegaly
- failing liver
- lactic acidosis
- bone marrow
depression
- anemia
- neutropenia
- GI toxicity
- peripheral
lipoatrophy (d4t)
- peripheral
neuropathy
- Stevens Johnson
- cytochrome p450
syndrome
interactions
- severe hepatotoxicity - delavirdine and
efavirenz are
inhibitors
- nevirapine is an
inducer
- avoid St. John’s
wort
- AZT
- ddi
- ddc
- 3tc
- d4t
- central obesity
- metabolized by
- hyperglycemia/
cytochrome p450
diabetes
enzymes
- hyperlipidemia
- avoid St. John’s
- increased bleeding in wort
patients with
- avoid garlic
hemophilia
preparations
- reduced bone mineral
density
- elevation of serum
transaminases (liver
enzymes)
- ECG changes with
atazanavir (prolonged
QT)
- GI effects
- idinavir
- ritonavir
- saquinavir
- nelfinavir
- amprenavir
- fosamprenavir
- atazanavir
- tirpranavir
- lopinavir
- nevirapine
- delaviridine
- efavirenz
- includes fusion
inhibitors and
attachments
inhibitors
Fusion Inhibitors
- binds to gp41, a - for patients who
viral envelope
have failed more
protein
standard HAART
with RT inhibitors
and protease
inhibitors
Attachment Inhibitors - blocks the
CCR5 receptor
so that HIV does
not attach to the
CD4 cell
Integrase Inhibitors
- blocks
integrase, which
integrates HIV
viral genetic
information into
the host cell
DNA, turning the
host cell into a
viral factory
- must be given
subcutaneously
twice a day
- given twice per
day
- injection site
reactions
- increased risk of
bacterial pneumonia
- extremely expensive
- hard to manufacture
- limited supply
- pregnancy category - dosage depends on
B
whether or not it is
- cough
given with a
- fever
cytochrome p450
- rash
inducer or inhibitor
- muscle and joint pain
- stomach pain
- dizziness
- liver toxicity
- diarrhea
- plasma
- there is only one
- nausea
concentrations may opportunity for this to be
- headache
be reduced by
effective because after
- pregnancy category enzyme inducers, the first time the virus is
C
particularly
already incorporated into
rifampin
the host cell
- the only fusion inhibitor on
the market is enfuvirtide
- the only CCR5 antagonist is
Maraviroc (Selenztry)
- raltegravir is the only
approved drug
Tuberculosis Drugs
Drug
Isoniazid
Rifampin
Mechanism of
Action
- inhibits the
formation of the
mycobacterial
cell wall
Uses
- used to treat
latent TB
- used along with
at least one other
drug for active TB
- used with at least
one other drug for
active TB
Target Populations Routes
Side Effects
Drug Interactions
Other
- hepatotoxic
- increases the level - distributed to all body
of phenytoin
tissues and fluids
- crosses the BBB to
achieve therapeutic levels
- hepatotoxic
- turns the body
fluids red
- increases the
- distributed to the CSF
hepatotoxicity of
isoniazif and
pyrazinamide
- decreases the levels
of birth control pills,
Examples
seizure meds, and
others
Pyrazinamide
- often combined
with isoniazid,
rifampin, and
ethambutol
- hepatotoxic
Ethambutol
- optic neuritis
- allergic reactions
- NOT
HEPATOTOXC!!
- distributed widely but
does not penetrate the
brain
Diuretics
Drug
Thiazide
Mechanism of Uses
Action
edema
PREVENT
Reabsorb NA and
Cl in early distal
tubule
High Ceiling/loop
(Lasix)
K sparing
Osmotic
Inhibit RAAS
Target Populations Routes
Side Effects
Too little K, too little
NA, too little Cl,
dehydration
Drug Interactions
Other
Examples
ALL DIURETICS are BAD
for Lithium.
All K losing are bad for
Digoxin.
ALL Avoid in Preg, If
possible.
Same
OTOTOXIC
Can Cause Too much
K/Hyperkalemia
Endocrine effects
Prevent reabsorb
NA (no kick out
of K) in collecting
duct
Osmosis
Too much fluid in
Brain, Eye
Watch with
ACE/ARB
Can cause
paradoxical edema
Can cause too much
K/ Hyperkalemia
Angioedema
Preg cat D
Spironolactone prolongs life
in CHF pts
Not metabolized- inert.
All RAAS, Preg Cat D
Ace Inhibitors “–opril” Dry
Cough Prevent renal failure,
Death from MI or CHF.
ARBs “-sartan”– prevent
nephropathy