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NU 322 Pharmacology

Study Guide: Anti-infective and Antiinflammatory Drugs

Anti-infective Drugs
Antibiotics
REF: Chapter Basic Principles of Antimicrobial Therapy

Mechanism of Action:

What is Selective Toxicity?


-selective toxicity of antibiotics means that they must be highly against the microbe but
have minimal or no toxicity to humans.

How do antibiotics work?


-antibiotics are drugs that either destroy bacteria or prevent their reproduction.
-antibiotics that kill bacteria = bactericidal
-the ones that stop the growth of bacteria = bacteriostatic

Classification of antimicrobial drugs:

Differentiate between broad spectrum and narrow spectrum antibiotics. State


when one or the other would be preferred as a therapeutic approach and why.
BROAD- effective a variety of gram negative and gram positive bacteria
NARROW- effective ONLY against gram negative OR gram positive

How does it work?


Cell wall synthesis, cell membrane synthesis, bacterial protein synthesis, nucleic acid
synthesis, other metabolic processes

Antibiotic Therapy

Empiric therapy: treatment of an infection before specific culture information has been reported or
obtained

Broad spectrum antibiotics

Definitive therapy: antibiotic therapy tailored to treat organism identified with cultures

Prophylactic therapy: treatment with antibiotics to prevent an infection, as in surgery or after trauma

Define bactericidal and bacteriostatic.


Which antibiotic drug classes are bactericidal ?
Bactericidal- drug kills bacteria, usually antibiotic of choice for infections in sites where
host defenses are ineffective (endocardium or the meninges)
Fluroquinolones
Penicillins
Aminoglycosides
Cephalosporins
Macrolides-at high concentrations (erythromycin is the prototype)
Vancomycin (MRSA infection)
Others:
Metronidazole
Nitrofurantoin
Isoniazid (specific for tuberculosis)

Which antibiotic drug classes are bacteriostatic?


Bacteriostatic-inhibit multiplication and growth of microorganism, therefore, bodys
defense system destroys the disease (phagocytosis by WBCs, antibodies from B-cells)
*Macrolides-at low concentrations
*tetracyclines
*sulfonamides-(family) sulfanilamide
Other:
Chloramphenicol (first synthetic antibiotic), Clindamycin, Trimethoprim

Drug resistance:

Which antibiotic class promotes the emergence of resistance? (see text)


Tetracyclines
Alteration in intestinal flora may result in: superinfection (overgrowth of nonsuceptible
organism such as Candida)
DIARRHEA
What is a superinfection?
Superinfection is a special example of the emergence of drug resistance. A superinfection
is defined as a new infection that appears during the course of treatment for a primary
infection. New infections develop when antibiotics eliminate the inhibitory influence of
normal flora, thereby allowing a second infectious agent to flourish. Because broad-
spectrum antibiotics kill off more normal flora than do narrow-spectrum drugs,
superinfections are more likely in patients receiving broad-spectrum agents. Because
superinfections are caused by drug-resistant microbes, these infections are often difficult
to treat.

Selection of antibiotics:

What is the goal of antibiotic therapy? (see text)

Page 947
The goal of drug therapy is 1 to alleviate symptoms, 2 promote healing, 3 prevent
complications (hemorrhage, perforation, obstruction,), and 4 prevent recurrences. Create
conditions conducive to healing.

What role do cultures play in treating infections? When should you obtain a
culture? What should the nurse know about timing of blood cultures when an
antibiotic is ordered?
-Ideally , before beginning antibiotic therapy, the suspected areas of infection should be
cultured to identify the causative organism and potential antibiotic susceptibilities.

Differentiate between empiric therapy, definitive therapy and prophylactic


therapy.
*Empiric therapy: treatment of an infection before specific culture information
has been reported or obtained;broad spectrum antibiotics
*Definitive therapy: antibiotic therapy tailored to treat organism identified with
cultures
*Prophylactic therapy: treatment with antibiotics to prevent an infection, as in
surgery or after trauma

Differentiate between minimum inhibitory concentration (MIC) and minimum


bactericidal concentration (MBC). (see text)

The minimum inhibitory concentration of an antibiotic is defined as the lowest


concentration needed to completely suppress bacterial growth.

The minimum bactericidal concentration is defined as the concentration that decreases


the number of bacterial colonies by 99.9%

What is the concern when a bacteriostatic agent is combined with a bactericidal


drug? (see text)
In certain cases, a combination of two antibiotics may be less effective than one of the
agents by itself, indicting antagonism between the drugs. Antagonism is most likely when
a bacteriostatic agent (eg, tetracycline) is combined with a bactericidal drug (eg,
penicillin). Antagonism occurs because bactericidal drugs are usually effective only
against organisms that are actively growing. Hence, when bacterial growth has been
suppressed by a bacteriostatic drug, the effects of a bactericidal agent can be reduced.
If host defenses are intact, antagonism between two antibiotics may have little
significance. However, if host defenses are compromised, the consequences can be dire.

Use of multiple antibiotics has several drawbacks, including (1) increased risk of toxic
and allergic reactions, (2) possible antagonism of antimicrobial effects, (3) increased risk
of superinfection, (4) selection of drug-resistant bacteria, and (5) increased cost.
Accordingly, antimicrobial combinations should be employed only when clearly
indicated.
Side effects-Risks of antibiotic therapy:

Which class of antibiotics are most frequently associated with anaphylactic


reactions?
Penicillin

Antibiotic use is strongly associated with the potential for the development of
diarrhea, why?

How do antibiotics affect the action of oral contraceptives?

Bactericidal antibiotic drugs:

"Van's going to CAP you, MF" - Vancomycin , Cephalosporins, Aminoglycosides,


Penicillins, Macrolides, Fluoroquinolones

"Very Finely Proficient at Cell Murder" - Vancomycin, Fluoroquinolones, Penicillins,


Aminoglycosides, Cephalosporins, Macrolides
Others: metronidazole, nitrofurantoin, isoniazid (specific for tuberculosis)

Penicillins

Penicillins are usually prescribed to treat what class of bacteria?


They are active against a variety of bacteria
Because they have a beta-lactam ring in their structure, the penicillins are known as beta-
lactam antibiotics including ( cephalosporins, carbapenems, and aztreonam)
Same mechanism of action: disruption of the bacterial cell wall
Patients who are allergic to penicillin may also be hypersensitive to which class of
antibiotics?
Any member of the penicillin family. Use of cephalosporins depends on the intensity of
allergic response.

Primary adverse reactions?


Allergic reactions are the principal adverse effects

Drug interactions: Red flags.

Sodium penicillin G should be used with caution in patients on sodium-restricted diets.


*Aminoglycosides
Should never be mixed in the same IV solution. Rather administered separately.
*Probenecid
Probenecid can delay renal excretion of penicillin, thereby prolonging antibacterial
effects.
*Bacteriostatic Antibiotics
Since penicillins are most effective against actively growing bacteria, concurrent use of a
bacteriostatic antibiotic (tetracycline) could reduce the bactericidal effects of the
penicillin

Review Key Points in text\

Penicillin undergoes minimal metabolism, and is eliminated by the kidneys, primarily as


the unchanged drug.

Cephalosporins

How are cephalosporins similar to penicillins? Inhibit bacterial cell wall synthesis

Like penicillins, cephalosporins and vancomycin weaken the bacterial cell wall, and can
act in concert with aminoglycosides to enhance bacterial kill
Primary adverse reactions? Think ABC
Allergy, Anemia, Alcohol
Bleeding
Clostridium dif.

Cephalexin (Keflex)
Vancomycin

Effective against what bacterial class? Primary indications? MRSA

Inhibits cell wall synthesis and promotes bacterial lysis and death. ONLY AGAINST
GRAM-POSITIVE BACTERIA. Especially active against Staph. Aureus and
Staphlyococcus epidermidis, including strains of both species that are methicillin
resistant.

Major toxicity?
What is Red Man Syndrome? How can it be prevented?
Rapid infusion can cause red man syndrome, characterized by flushing, rash, pruritus,
urticaria, tachycardia, and hypotension. To minimize risk, infuse vancomycin slowly,
over 60 minutes or longer.

Review Key Points in text

Aminoglycosides - the "cins"

Effective against what bacterial class? Primary indications?


Inhibit protein synthesis in many gram negavitve and some gram positive organisms
Aerobic gram-negative bacilli. Sensitive organisms include E. coli, Klebsiella
pneumoniae, Serratia marcescens, Proteus mirabilis, and Pseudomonas aeruginosa.
Aminoglycosides are INACTIVE against most gram-positive bacteria.
Aminoglycosides cannot kill anaerobes. To produce antibacterial effects,
aminoglycosides must be transported across the bacterial cell membrane, a process that is
oxygen dependent. Since, by definition, anaerobic organisms live in the absence of
oxygen, these microbes cannot take up aminoglycosides, and hence are resistant. For the
same reason, aminoglycosides are inactive against facultative bacteria when these
organisms are living under anaerobic conditions
The principal use for parenteral aminoglycosides is treatment of serious infections due to
aerobic gram-negative bacilli. Primary target organisms are P. aeruginosa and the
Enterobacteriaceae (eg, E. coli, Klebsiella, Serratia, P. mirabilis).

One aminoglycosidegentamicinis now commonly used in combination with either


vancomycin or a beta-lactam antibiotic to treat serious infections with certain gram-
positive cocci, specifically Enterococcus species, some streptococci, and Staphylococcus
aureus.

Major toxicity? Which toxic effect is irreversible?


OTOTOXICITY

The aminoglycosides can produce serious toxicity, especially to the inner ears and
kidneys. The inner ears and kidneys are vulnerable because aminoglycosides become
concentrated within cells of these structures

All aminoglycosides can accumulate within the inner ears, causing cellular injury that can
impair both hearing and balance. Hearing impairment is caused by damage to sensory
hair cells in the cochlea. Disruption of balance is caused by damage to sensory hair cells
of the vestibular apparatus

Nephrotoxicity correlates with (1) the total cumulative dose of aminoglycosides and (2)
high trough levels.

Why is it critical to measure drug trough levels (lowest) when administering


aminoglycosides? (see text)
The aminoglycosides are bactericidal. Cell kill is concentration
dependent. Hence, the higher the concentration, the more
rapidly the infection will clear. Of note, bactericidal activity
persists for several hours after serum levels have dropped below
the minimal bactericidal concentration, a phenomenon known as
the postantibiotic effect.

What types of infection/ organisms are commonly treated with aminoglycosides? Why
are they contraindicated in pregnancy?
Narrow-spectrum antibiotics used primarily against aerobic gram-negative bacilli. These
drugs disrupt protein synthesis, resulting in rapid bacterial death. They cause serious
injury to the inner ears and kidneys. Because of these toxicities, indications for these
drugs are limited.
There is evidence that use of aminoglycosides in pregnancy can harm the fetus.
Pregnancy risk category D.

Key Points
Aminoglycosides are narrow-spectrum antibiotics, used primarily against aerobic gram-
negative bacilli.

Aminoglycosides disrupt protein synthesis and cause rapid bacterial death.

Aminoglycosides are highly polar polycations. As a result, they are not absorbed from
the GI tract, do not cross the blood-brain barrier, and are excreted rapidly by the kidneys.

Aminoglycosides can cause irreversible injury to sensory cells of the inner ears,
resulting in hearing loss and disturbed balance.

The risk of ototoxicity is related primarily to persistently elevated trough drug levels,
rather than to excessive peak levels.

Aminoglycosides are nephrotoxic, but renal injury is usually reversible.

The risk of nephrotoxicity is related to the total cumulative dose and elevated trough
levels.

Because the same aminoglycoside dose can produce very different plasma levels in
different patients, monitoring serum levels is common. Peak levels must be high enough
to cause bacterial kill; trough levels must be low enough to minimize toxicity to the inner
ears and kidneys.

Fluoroquinolones

Indications? Preferred dug for what disease?


ANTHRAX, UTI, STD, bone infections, URI, skin infections

Are generally avoided in children under 18 years old. Why?

Bacteriostatic antibiotic drugs:

Go to the MaTS
(Macrolides,Tetracyclines & Sulfonamides)
Macrolides

Bacteriostatic or bacterocidal? (slides)


The macrolides are bacteriostatic, (at low doses), binding with bacterial ribosomes to
inhibit protein synthesis
BacterioCIDAL (at high doses)

Why is it important to assess GIT function in patients treated with clindamycin? )

Tetracyclines

Broad spectrum or narrow spectrum?


Wide spectrum; gram- and gram+ organisms, protozoa, mycoplasma, rickettsia,
chlamydia, syphilis, lyme disease, acne, others

Adverse Effects:
Why are the tetracyclines contraindicated in children and pregnant women?
Can damage developing teeth, PHOTOSYNSITIVITY
Red Flag!!! Tetracycline antibiotics should not be used in children under the age of 8, and
specifically during periods of tooth development. Tetracyclines are classed as pregnancy
category D. Use during pregnancy may cause alterations in bone development.

What food groups must be avoided with this class?


*dairy products, antacids, and iron salts reduce oral absorption of tetracyclines

The tetracyclines have an increased risk of superinfection, why?


Drugs in the tetracycline class become toxic over time. Expired drugs can cause a
dangerous syndrome resulting in damage to the kidneys

Sulfonamides - the first drugs available for systemic treatment of bacterial


infections

Primary indication?

UTI, meningococcal starins, and as a prophylactic for rheumatic fever.


Anticoagulants, urinary acidifiers, PABA preparations

Other bactericidal antibiotic drugs:

Metronidazole is a drug of choice for what anaerobic bacteria?


Is used for protozoal infections and infections caused by OBLIGATE (poisoned by
oxygen) ANAEROBIC BACTERIA. Metronidazole is active against obligate
anaerobes only. Sensitive bacterial pathogens include Bacteroides fragilis (and other
Bacteroides species), C. difficile (and other Clostridium species), Fusobacterium species,
Gardnerella vaginalis, Peptococcus species, and Peptostreptococcus species.
For initial treatment of serious bacterial infections, metronidazole is administered by
IV infusion. Under appropriate conditions, the patient may switch to oral therapy.

Metronidazole [Flagyl, Flagyl ER] is supplied in capsules (375mg), immediate-


release tablets (250 and 500mg), and extended-release tablets (750mg). The adult dosage
for anaerobic infections is 7.5mg/kg every 6 hours. For bacterial vaginosis in adults, a
dosage of 750mg (extended-release formulation) once daily for 7 days is effective. The
dosage for CDI is 500mg 3 times a day for 10 to 14 days.

Metronidazole can cause hypersensitivity reactions, including


potentially fatal Stevens-Johnson syndrome. There is cross-reactivity
with tinidazole, another member of the nitroimidazole family.

What foods must be avoided with metronidazole (Flagyl)?


Avoid alcohol

Antitubercular Drugs:

The nurse is counseling a woman who has been diagnosed with TB who will be starting
isoniazide and rifampin. What patient teaching needs to be included?

Antifungal agents: Systemic

Amphotericin B. (Think-ampho-terrible)

Indications?

How is it administered?

What are common side effects or adverse effects that the nurse must be aware of
during administration?

What nursing interventions may lessen side effects?

Antifungal agents: Topicals

Azoles

Indications?

How administered?

Bottomline:
Review the classes of antibiotics and antifungals. How do they work? What are the major
precautions? Again, keep it simple!
Know the side effects to watch for/ pt teaching for the drug class prototypes

Penicillins are usually prescribed to treat what class of bacteria?

Why are the tetracyclines contraindicated in children and pregnant women? What food
groups must be avoided with this class?

Why is it critical to measure peak (highest) drug levels and trough (lowest) when
administering aminoglycosides? What are the signs of aminoglycocide toxicity?
What types of infection/ organisms are commonly treated with aminoglycosides? Why
are they contraindicated in pregnancy?

Fluoroquinolones have a "black box warning"---why?

Which antibiotic drug class is used to treat anthrax exposure?

Why is it important to assess GIT function in patients treated with clindamycin?

What foods must be avoided with metronidazole (Flagyl)? Alcohol

What is the current antibiotic of choice for the treatment of MRSA infection?
What is Red Man Syndrome?

Bottomline:
Review the classes of antibiotics. How do they work? What are the major precautions?
Again, keep it simple!
Know the side effects to watch for/ pt teaching for the:
Sulfonamides
Penicillins
Macrolides
Tetracyclines
Aminoglycosides
Fluoroquinalones
Misc - clindamycin, metronidazole (Flagyl), vancomycin

Key Points
In antimicrobial therapy, the term selective toxicity refers to the ability of a drug to
injure invading microbes without injuring cells of the host.
Narrow-spectrum antibiotics are active against only a few microorganisms, whereas
broad-spectrum antibiotics are active against a wide array of microbes.
Bactericidal drugs kill bacteria, whereas bacteriostatic drugs only suppress growth.
Emergence of resistance to antibiotics is a major concern in antimicrobial therapy.
Mechanisms of resistance include increased drug efflux, altered drug targets, and
enzymatic inactivation of drugs.
Bacteria with the NDM-1 gene are resistant to nearly all available antibiotics.
An important method by which bacteria acquire resistance is conjugation, a process in
which DNA coding for drug resistance is transferred from one bacterium to another.
Antibiotics do not cause the genetic changes that underlie resistance. Rather, antibiotics
promote emergence of drug-resistant organisms by creating selection pressures that favor
them.
Broad-spectrum antibiotics promote the emergence of resistance more than do narrow-
spectrum antibiotics.
In the hospital, we can delay the emergence of antibiotic resistance in four basic ways:
(1) preventing infection, (2) diagnosing and treating infection effectively, (3) using
antimicrobial drugs wisely, and (4) preventing patient-to-patient transmission.
1014
Use of antibiotics to promote growth in livestock is a major force for promoting
emergence of resistance.
Effective antimicrobial therapy requires that we determine both the identity and drug
sensitivity of the infecting organism.
The minimum inhibitory concentration (MIC) of an antibiotic is defined as the lowest
concentration needed to completely suppress bacterial growth.
The minimum bactericidal concentration (MBC) is defined as the concentration that
decreases the number of bacterial colonies by 99.9%.
Host defensesthe immune system and phagocytic cellsare essential to the success
of antimicrobial therapy.
Patients should complete the prescribed course of antibiotic treatment, even though
symptoms may abate before the full course is over.
Although combinations of antibiotics should generally be avoided, they are appropriate
in some situations, including (1) initial treatment of severe infections, (2) infection with
more than one organism, (3) treatment of tuberculosis, and (4) treatment of an infection
in which combination therapy can greatly enhance antibacterial effects.
Appropriate indications for prophylactic antimicrobial treatment include (1) certain
surgeries, (2) neutropenia, (3) recurrent urinary tract infections, and (4) patients at risk of
bacterial endocarditis (eg, those with prosthetic heart valves or congenital heart disease).
Important misuses of antibiotics include (1) treatment of viral infections (eg, the
common cold and most other acute infections of the upper respiratory tract), (2) treatment
of fever of unknown origin (except in the immunocompromised host), (3) treatment in the
absence of adequate bacteriologic information, and (4) treatment in the absence of
appropriate surgical drainage.
Antivirals
REF: Chapter 93 Antiviral Agents I

Know the patient teaching expectations, routes, side effects, and adverse effects of
acyclovir. Acyclovir is indicated in what type of viruses?

What is Tamiflu? When is Tamiflu indicated? How long should a person take Tamiflu?

What is the goal of HIV antiviral therapy? (Cure, decrease symptoms, decrease
opportunistic diseases?) What is an undetectable viral load?

Antitubercular Drugs
REF: Chapter 90 Antimycobacterial Agents

The nurse is counseling a woman who has been diagnosed with TB who will be starting
isoniazide and rifampin. What patient teaching needs to be included?

Antifungals
REF: Chapter 92 Antifungal Agents

Drug focus- amphotericin B. How is it administered, what are common side effects or
adverse effects that the nurse must be aware of during administration? What nursing
interventions may lessen side effects?

GOOD LUCK!

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