ANTIBIOTICS Flashcards
vancomycin mechanism of action
prevents cell wall synthesis and promotes cell lysis
vancomycin spectrum of activity
ONLY gram positive organisms
includes MRSA
pharmacokinetics of vancomycin
- VERY poor oral absorption
- ONLY give PO when treating C. diff
adverse effect of vancomycin
- nephrotoxicity
- red man syndrome
- Characterized by flushing, rash, pruritus, urticaria, tachycardia and possibly hypotension
- Treat symptomatically with anti-histamines
- SLOW the infusion rate
1 gram of vancomycin should be given over a minimum of 60 minutes
if a person is allergic to pencillin you give them?
cephalosporins
therapeutic index of vancomycin
Vancomycin has a narrow therapeutic index
vancomycin monitoring
- Vancomycin levels must be monitored once drug is at steady state
- Trough levels are preferred
mechanism of action of fosomycin
Prevents cell wall synthesis
administration of fosfomycin
- Medication is a powder in a packet
- Educate patient to dissolve powder in water and drink the entire dose
drugs of tetracylines
tetracyline
doxycycline
minocycline
doxy and amino are long lasting
tetracylines mechanism of action
Inhibits growth of the peptide chain and production of vital proteins
what are the beta-lactam antibiotics (bacteriocidal)
penicillins
cephalosporins
carbapenems
monobactams
mechanisms of resistance of tetracycline
Increased drug inactivation
Decreased access to the ribosome
↓ accumulation of drug intracellularly
contraindications of tetractclines
Pregnancy category D
Do NOT use in children < 8 years old
monitoring/counseling points for taking tetracycline, doxycycline, minocycline
- Do NOT take tetracyclines with diary products, calcium, magnesium or aluminum containing products
- administer tetracycline 1 hour before or 2 hours after
adverse effects of tetracycline, doxycycline, minocycline
- Discoloration of teeth if taken during pregnancy or childhood
- Superinfection
- Photosensitivity
what drugs are macrolides
- Azithromycin
- Clarithromycin
- Erythromycin
Mechanism of resistance:
of macrolides (Azithromycin
Clarithromycin
Erythromycin)
↓ intracellular concentrations of the drug – efflux pumps
Decrease access to the ribosome
Monitoring/ Counseling Points for macrolide( azithromycin, clarithromycin, erythromycin)
- Avoid combining these agents with other QTc prolonging drugs
- Take with food to decrease GI upset
- Ensure erythromycin formulation can be taken with food
Mechanism of action:
clindamycin
Inhibits growth of the peptide chain and production of vital proteins
Mechanisms of resistance:
clindamycin
↓ intracellular concentrations of the drug – efflux pumps
Decrease access to the ribosome
adverse effect of clindamycin
Clostridium difficile
- Clostridium difficile-associated diarrhea (CDAD)
- Leads to superinfection of the bowel
- Characterized by:
Profuse, watery diarrhea
10 to 20 stools per day
Abdominal pain
Fever - Can start as soon as 1 week after antibiotics treatment
- Educate patients on signs and symptoms of CDAD
mechanism of action linezoid
- Inhibits growth of the peptide chain and production of vital proteins
Spectrum of activity linezoid
- Gram positive organisms only
MRSA
Vancomycin-resistant enterococcus (VRE)
adverse effect of linezolid
Thrombocytopenia – typically occurs about 2 weeks after therapy
mechanism of action of tigecycline
- Bind to 30s ribosomal subunit
- Inhibit binding of transfer RNA to the messenger RNA
- Inhibits growth of the peptide chain and production of vital proteins
adverse effects of tigecycline
Nausea/vomiting
Photosensitivity
Black box warning for increased risk of mortality
Mupirocin
Topical antibiotic active against gram positive bacteria
INDICATION OF MUPIROCIN
elimination of MRSA
drugs for herpes simplex virus and varicella zoster virus
Acyclovir
Valacyclovir
Famciclovir
Famciclovir mechanism of action
- inhibits viral DNA polymerase and prevents replication of viral DNA
- Blocks further DNA strand growth after being incorporated into viral DNA
whats meant by valacyclovir being a prodrug?
it is converted to acyclovir after absorption from the GI tract
adverse effect of acyclovir
- IV therapy
– phlebitis, nephrotoxicity
Monitoring/ Counseling Points
for acyclovir
- Oral administration requires three to five doses daily
- Prevent nephrotoxicity:
Hydrate patient
Decrease other nephrotoxic medications
topical drugs for herpes labialis (cold sores)
- penciclovir cream
- docosanol cream
drugs for cytomegalovirus
Ganciclovir
Valganciclovir
Cidofovir
Foscarnet
mehcanisms of actions for Ganciclovir and Valganciclovir
- Inhibits viral DNA polymerase
- Blocks further DNA strand growth after being incorporated into viral DNA
what does it mean for Valganciclovir to be a prodrug?
After absorption from the GI tract it is converted to ganciclovir
adverse effects of ganciclovir
- Agranulocytosis
- Thrombocytopenia
- Reproductive toxicity
- Nausea
- Liver dysfunction
monitoring/ counseling points for ganciclovir
Monitor white blood cell count, platelets, liver function tests, serum creatinine (Scr)
Avoid use in pregnancy
Avoid pregnancy for 90-days following therapy
Handle with caution. Should be treated as a cytotoxic drug
mechanism of action of cidofovir
- inhibits viral DNA polymerase
- Inhibits viral DNA strand growth after being incorporated
adverse effect of cidofovir
nephrotoxicity
monitoring/ counseling points of cidofovir
- Prevention of nephrotoxicity:
Hydrate patient with IL NS prior to dose
Avoid other nephrotoxic medications
foscarnet mechanism of action
- Inhibits viral DNA polymerase and reverse transcriptase
- Inhibits synthesis of viral nucleic acids
foscarnet adverse effects
nephrotoxicity
prevention of nephrotoxicty
Hydrate patient with IL NS prior to dose
Avoid other nephrotoxic medications
mechanism of action of interferon-alfa
- Interferon alfa binds to the host cell membranes
- Binding to the host cell membrane inhibits viral entry into the cell
- Interferon alfa stimulates cell to turn on genes for antiviral proteins
- Antiviral proteins block viral reproduction
clinical effects of interferon-alfa
- 30 to 40% response rate with sustained virologic response (SVR)
- Up to 50% of patients with - - SVR will relapse
- SVR is maintained only in 5-15% of patients
- Best effects when combined with another agent
mechanism of actions: nucleoside analogs
- Inhibits viral DNA strand growth after being incorporated
mechanism of actions of ribavirin
Interferes with RNA metabolism needed for viral replication
ribavirin is used in combination with inteferon BUT NEVER used as……
monotherapy for HCV
adverse effects for ribavarin
- Hemolytic anemia (10%)
( Develops in 1 to 2 weeks of therapy ) - Fetal injury
( Contraindicated during pregnancy ) - Pancreatitis
prevention with vaccination is…..
key
types of influenza vaccines
- Inactivated influenza vaccine
- Live-attenuated vaccine
vaccine contraindications of everyone 6 months and older
- Prior history of anaphylactic reaction to influenza vaccine
Patients at high risk for influenza complications:
Children < 5 years
Pregnant women
Adults > 65
People living in long-term care facilities
American Indians or Alaskan Natives
Confirmed history of Guillain-Barre syndrome occurred within 6 weeks following previous vaccination and LOW risk for influenza complication
neuraminidase inhibitors drugs
Oseltamivir
Zanamivir
Peramivir
mechanisms of actions of neuraminidase ( Oseltamivir, Zanamivir. Peramivir ) inhibitors
Inhibit neuraminidase
adverse effects of Oseltamivir
- Nausea
- Delirium or abnormal behavior in children
monitoring/ counseling point of oseltamivir
take with food to decrease nausea
respiratory syncytial virus (RSV)
- Ribavirin (inhaled)
- Palivizumab
indications of respiratory syncytial virus (RSV)
Prevention of RSV in premature infants or children with chronic lung disease
AIDS is defined by:
- CD4 counts below a certain level
- Contracting an AIDS defining illness
without CD4 helper T cells, the immune system experiences .
progressive decline
CD4 helper T cells are required for
production of antibodies by B lymphocytes, and activation of cytotoxic T cells.
HIV replication cycle
Co-receptors CCR5
HIV lipid bilayer fuses with the host cell membrane. Viral RNA is released into the cell.
Reverse transcriptase converts
single-strand DNA to double-strand
HIV DNA is integrated into host cell DNA by what enzyme
integrase
HIV RNA is transcribed into DNA by
reverse transcriptase
Protease cleaves large?
viral polyproteins.
Mutations may lead to
drug resistance
Higher viral loads increase the chance of
developing resistance
To combat resistance:
- Treat HIV infection with multiple agents
- Ensure compliance with HAART therapy
what are the 5 classes of antiretroviral drugs
- Reverse transcriptase inhibitors
- Nucleoside/nucleotide reverse transcriptase inhibitors
- Non-nucleoside reverse transcriptase inhibitors
2. Integrase strand transfer inhibitors
3. Protease inhibitors
4. Fusion inhibitors
5. Chemokine receptor 5 (CCR5) antagonists
ALL clinicians should check drug-drug interactions before ?
administering HAART therapy
Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTI)
DO NOT USE AS MONOTHERAPY
mechanism of action of Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTI)
Incorporated into the DNA strand and cause strand termination
adverse effects of abacavir
Associated with mitochondrial toxicity:
- Lactic acidosis
- Hepatic steatosis
- Pancreatitis
- Myopathies
- GI upset
Monitoring/ Counseling for NRTI
MUST check if patient has genetic variation *HLA-B5701
Non-nucleoside Reverse Transcriptase Inhibitors (NNRTI)
Used in combination with NRTIs
mechanisms of actions of Non-nucleoside Reverse Transcriptase Inhibitors (NNRTI)
Terminates DNA strand formation
adverse effects of Non-nucleoside Reverse Transcriptase Inhibitors (NNRTI)
- Rash
can be life-threatening, counsel patient to seek medical advice immediately if rash occurs - CNS symptoms
- Hepatotoxicity
Protease Inhibitors (PI)
MUST be used in combination with other antiviral medications
Mechanism of action: protease inhibitors (PI)
- Inhibits the HIV protease enzyme
- Prevents maturation of the HIV virus
- Immature HIV virus is non-infectious
drug-drug interactions of protease inhibitors (PI)
- all protease inhibitors inhibit certain CYP enzymes
- Some protease inhibitors (PI) can therefore increase serum concentrations of other protease inhibitors
Ritonavir
often combined with other drugs for this purpose – RITONAVIR BOOSTING
adverse effects of protease inhibitors (PI)
- Hyperglycemia/ diabetes
- Lipodystrophy
- Hyperlipidemia
↑ LFTs (Liver Function Test)
↑ risk of bleeding in patients with hemophilia
Integrase Strand Transfer Inhibitors
Used in combination with other antiviral drugs
Mechanism of action: Integrase Strand Transfer Inhibitors
Inhibits the enzyme integrase
Prevents HIV from inserting its viral DNA into the host cell DNA
adverse effects for dolutegravir (integrease stand transfer inhibitor)
↑ LFTs
- Insomnia
- Headache
- Diarrhea/nausea
monitoring/counseling for dolutegravir (integrease stand transfer inhibitor)
DDI interaction with drugs containing calcium, iron or magnesium
– give dolutegravir 2 hours before these agents
what is dolutegravir
an Intergrease Stand Transfer Inhibitor (INSTI)
HIV Fusion Inhibitors
Enfuvirtide
usage of Enfuvirtide
treatment-resistant HIV-1
mechanism of action of enfuvirtide
Blocks entry of HIV into CD4 cells
adverse effects of enfuvirtide
- Injection site reactions (98%), especially in first week of treatment
- Pneumonia
- Hypersensitivity reactions
( If this develops, discontinue therapy and never use again)
what is maraviroc (CCR5 ANTAGONIST) used for?
treatment-resistant HIV-1 in patients ≥ 16 years old
Pathophysiology of maraviroc
Some HIV strains require CCR5 binding to access the host cell = CCR5 tropic
mechanism of action of maraviroc
Prevents HIV from binding to the host cell
maraviroc requires genetic testing to identify if…
patient’s strain of HIV is CCR5 tropic
adverse effects of maraviroc
Upper respiratory tract infections
↑ LFTs
intial therapy for HIV
always a multi-drug regimen
INSTI + 2 NRTI
Laboratory Tests and Resistance for HIV
- CD4 T cell count - how much immunocompetency is left
- Viral Load - magnitude of viral replication
pre-exposure prohylaxis (PrEP) for hiv is rommended for
patients at high-risk of HIV transmission:
Post-exposure Prophylaxis
- Goal to start therapy AS SOON AS POSSIBLE (1 to 2 hours)
- Therapy can be started up to 72 hours after exposure
Non-occupational exposure
of post- exposure prophylaxis
- Unprotected intercourse, sharing needles, sexual assault
- 28-day HAART regimen
occupational exposure
of post- exposure prophylaxis
- Accidental needle stick, blood or body fluid splashes
- 28-day HAART regimen
what is selective toxicity
ability of a drug to injure a target organism without injuring other cells or organisms inclose contact with the target
( Kill bacteria, don’t kill host )
Narrow spectrum of antimicrobial drugs
active against a few different microbial species
Broad spectrum of antimicrobial drugs
= active against wide range of different microbial species
Bactericidal effects of antimicrobial drugs
kill bacteria
Bacteriostatic effects of antimicrobial drugs
slow bacterial growth
How do bacteria develop resistance to antibiotics?
Bacteria may become resistant to antimicrobials over time and with repeat exposure
( Acquired resistance )
Resistance to one drug or class may confer
resistance to other drug classes as well
Spontaneous mutation method of bacterial resistance to antimicrobial drugs
- random changes in bacterias DNA
- Spontaneous mutations confer resistance to one drug
spontaneous mutations confer
confer resistance to one drug
Conjugation method of bacterial resistance to antimicrobial drugs
- Extrachromosomal DNA is transferred from one bacteria to another
- Primarily occurs in gram negative organisms
- Confers resistance to multiple drugs
Reduction of Drug Concentration at its Active Site
mechanisms of bacteria resistance
- Decrease active uptake of the drug
- Increase active export of the drug
Alteration of Drug Target Molecules
mechanisms of bacteria resistance
If a drug binds to a certain site on the ribosome, the bacteria will change the shape of the ribosome
Antagonist Production
mechanisms of bacteria resistance
-bacteria produce a compound that antagoizes the drugs action
Drug Inactivation
mechanisms of bacteria resistance
Produce enzymes that breakdown the drug
The more antimicrobials are used more often,
the faster resistant organisms will emerge. Need to be judicious with use.
Broad-spectrum are less likely to cause resistance than narrow spectrum
false. Broad-spectrum are more likely to cause resistance than narrow spectrum since they affect more bacteria
Resistant organisms are especially common in
hospitals.
Hospital Acquired Infections (HAI)
Very difficult to treat due to limited antimicrobial options
does antimicrobial directly cause changes to bacterial DNA?
Antimicrobials do not directly cause changes to bacterial DNA that make them resistant. They promote resistance via “survival of the fittest”
If some bacteria are resistant
antimicrobials create a more favorable environment for them to grow
what is a superinfection
New infection that appears during a course of antibiotic treatment for a different infection.
Superinfections are more common with what spectrum antimicrobials
broad- spectrum
Goal of antimicrobial therapy =
produce maximal antibiotic effects while minimizing harm to the patients
Three key principles of selecting antimicrobials
- Identification of the infecting organism
- Organism susceptibility to the drug
- Host factors – site of infection, immunocompetence, etc.
what is empiric therapy of antimicrobial
starting the antimicrobial treatment before the infecting organism can be identified =
Empiric therapy may use what spectrum antibitics
broad-spectrum antibiotics.
After the organism is identified the therapy can be de-escalated
Most infections will have a ‘first-choice’ drug to treat it; however, a patient may not be able to take the ‘first-choice’ drug from a number of reasons such as
allergies or inability for drug to penetrate the site of infection
abcess and antibiotics
Abscesses _ must be drained first, antibiotics will not penetrate them
= Foreign bodies _ very difficult to treat
Dose of antibiotic must be optimized to:
- Achieve maximum concentrations of antibiotic at site of infection
- Maintain concentrations for longest possible duration
- Goal is typically 4 to 8 times the MIC of the organism
Duration of antibiotic therapy depends on the type of infection
- Patients MUST take the full course of antibiotics
- Patients must be educated not to stop antibiotic early since this leads to increased risk of resistance
Why would multiple antibiotics be used at once?
- Empiric therapy for a severe infection
- Mixed infections
- Preventing resistance
- Decreased toxicity
- Enhanced antibacterial action
When should antimicrobial prophylaxis be used?
- Surgery
- Bacterial endocarditis
- Neutropenia
- Recurrent urinary tract infections
What are ways in which antibiotics are misused
- Treatment of a VIRAL infection
- Treatment of fever with unknown origin
- Improper dosage
- Lack of source control (eg. undrained abscess or no removal of necrotic tissue)
What antibiotics are included in the beta-lactam class?
- Penicillins
- Cephalosporins
- Carbapenems
- Monobactams
are beta-lactam antibiotics bacteriostatic or bacteriocidal?
bactericidal,
Penicillin Mechanism of Action
Inhibits actions of transpeptidases
Increases actions of autolysins
Weakens the structure of the cell wall → cell lysis
penicillin weakens what?
the structure of the cell wall = cell lysis
what does penicillin bind to
Penicillins bind to penicillin-binding proteins (PBPs) on the cell membrane
penicillin does not penetrate what system?
DOES NOT PENETRATE CNS. eyes or joints well. unless inflammation is present
since 90% of penicillin is excreted by kidneys, doses must be…..
doses MUST be reduced in patients with renal impairment
common adverse effects of penicillin
- Allergic reaction
- Rash
- Neurotoxicity
List the narrow spectrum penicillins and their route of administration.
pencillin G
Sodium IV
Potassium IV
Procaine IM
Benzathine IM
Penicillinase-Resistant Penicillins
- Nafcillin
- Oxacillin
- Dicloxacillin
(not effective agaisnt methicillin-resistant MRSA)
NARROW SPECTRUM
How does broad spectrum penicillin differ from penicillin G?
increased coverage of gram negative bacteria
Are broad spectrum penicillin affected by beta-lactamases?
inactivated by beta-lactamase enzymes
what are the broad spectrum penicillins
- Ampicillin IV/PO
- Amoxicillin PO
what are the extended spectrum penicillins
Piperacillin
extended spectrum penicillin are…
Highly susceptible to beta-lactamases
what bacterias do extended spectrum penicillin cover
- Gram positive organisms
- Gram negative organisms
- PSEUDOMONAS aeruginosa - Anaerobic organisms
WHAT ARE Beta-lactamase inhibitor
drug that inhibits beta-lactamase enzymes.
tazobactam
sulbactam
clavulanate
Piperacillin combined with
tazobactam
Ampicillin combined with
Sulbactam
Amoxicillin combined with
Clavulanate
what is anaphylaxis?
an immediate allergic reaction mediated by IgE.
treatment = epinephrine
- often associated with airway swelling, hypotension and cardiovascular collapse
If a patient is allergic to penicillin, they are considered allergic to…
ALL penicillins
Most patients will be able to take cephalosporins since there is only a ~1% risk of cross-reactivity BUT
- If reaction is mild = give cephalosporins
- If reaction is severe (anaphylaxis) = do NOT give cephalosporins, select alternative agent
are cephalosporins bactericidal or bacteriostatic
bactiricidal
cephalosporins are more resistance to
beta-lactamase enzymes
How are cephalosporin antibiotics categorized?
Note that not all cephalosporins are equally susceptible to beta-lactamase enzymes.
- 1st generation tend to be the most susceptible to beta-lactamase enzymes
- the fifth generation are the most resistant.
Beta-lactam antibiotics;
- chemical structure composed of a beta-lactam ring with varying side chains
what generation of cephalosporins are more resistant
5th generation are more resistant.
1st generations are most susceptible
Which generations of cephalosporins can be used to treat CNS infections?
3-5
Which generations have the most gram negative coverage?
2-5
Which generations have the leastgram negative coverage?
1
Describe the pharmacokinetics of cephalosporins?
Poor oral absorption; most agents are given IV
What is the drug-drug interaction between ceftriaxone and calcium?
- Precipitates can form
- Do NOT reconstitute or mix ceftriaxone with calcium-containing solutions
- Do NOT administer through the same line at the same time
List the carbapenem antibiotics.
- Imipenem/ cilastin
- Meropenem
- Doripenem
- Ertapenem
What bacteria do carbapenem antibiotics cover?
Broad-spectrum of antimicrobial activity
- gram positive (no MRSA)
- Gram negative
Anaerobes
carbapenem MRSA or no MSRA
no MSRA
carbapenems relation with beta-lactase enzymes
Very resistant to beta-lactamase enzymes
What serious adverse effect is associated with meropenem and Imipenem/cilastin?
seizure
What are monitoring/counseling points for beta-lactam antibiotics?
Monitor for
- Clinical signs of improvement
- Allergic reactions
- Signs of worsening or new infections
- Adverse effects including seizure
- Ensure patient completes and appropriate course of therapy
Dose adjustments for renal impairment
Imipenem has DDI with…………. and can……… of valproic acid
valproic acid, decrease levels
What type of antibiotic is aztreonam?
Unique type of beta-lactam called a monobactam
When is aztreonam the drug of choice?
Drug of choice for gram negative coverage in a patient with a penicillin allergy
What types of bacteria does aztreonam cover?
ONLY gram negative organisms, including Pseudomonas
mechanism of actions of macrolides
inhibits growth of the peptide chain and production of vital proteins
