I.

Terms and Concepts

Several terms are used to describe these drugs

Chemotherapeutic agents

Antimicrobial agents

Antibiotics

2
 II. Selective toxicity

What is selective toxicity?

The ability of a drug to injure a target cell or target organism
without injuring other cells or organisms that are in intimate
contact with the target

How is selective toxicity achieved?

Examples
Disruption of the bacterial cell wall
Inhibition of an enzyme unique to bacteria
Disruption of Bacterial Protein Synthesis

3
III. Classification of antimicrobial drugs

Various schemes are employed to classify antimicrobial drugs

Classification by susceptible organism

Classification by mechanism of action

4
Classification of antimicrobial drugs

A. Classification by susceptible organism

Antibiotics differ widely in their antimicrobial activity

Narrow-spectrum antibiotics: active against only a few
species of microorganisms

Broad-spectrum antibiotics: active against a wide variety

of microbes

NB: narrow-spectrum drugs are generally preferred

to broad-spectrum drugs
5
 Classification of antimicrobial drugs

B. Classification by mechanism of action

The antimicrobial drugs fall into five major groups based on

mechanism of action

1) Drugs that inhibit bacterial cell wall synthesis or

activate enzymes that disrupt the cell wall

These drugs (eg, penicillins, cephalosporins) weaken

the cell wall and thereby promote bacterial lysis &
death 6
Classification of antimicrobial drugs

2) Drugs that increase cell membrane permeability

Drugs in this group (eg, amphotericin B) increase the

permeability of cell membranes, causing leakage of
intracellular material

3) Inhibition of bacterial protein synthesis

Drugs that cause lethal inhibition of bacterial

protein synthesis
The aminoglycosides (eg, gentamicin)
7
 Classification of antimicrobial drugs

Drugs that cause nonlethal inhibition of protein

synthesis

These drugs (eg, tetracyclines) inhibit bacterial protein

synthesis.

However, in contrast to the aminoglycosides, these

agents only slow microbial growth

They do not kill bacteria at clinically achievable

concentrations
8
 Classification of antimicrobial drugs

4) Drugs that inhibit bacterial synthesis of DNA & RNA or

disrupt DNA function

These drugs inhibit synthesis of DNA or RNA by binding

directly to nucleic acids or by interacting with enzymes
required for nucleic acid synthesis

They may also bind with DNA & disrupt its function

Members of this group include rifampin, metronidazole,

& the fluoroquinolones (eg, ciprofloxacin)
9
 Classification of antimicrobial drugs

5) Antimetabolites
These drugs disrupt specific biochemical reactions

The result is either a decrease in the synthesis of

essential cell constituents or synthesis of nonfunctional
analogs of normal metabolites

Examples of antimetabolites include trimethoprim and

the sulfonamides

10
 Classification of antimicrobial drugs

When considering the antibacterial drugs, it is useful to

distinguish b/n agents that are bactericidal & agents that
are bacteriostatic
Bactericidal drugs are directly lethal to bacteria at
clinically achievable concentration
Bacteriostatic drugs can slow bacterial growth but do not
cause cell death
When a bacteriostatic drug is used, elimination of
bacteria must ultimately be accomplished by host
defenses (ie, the immune system working in concert 11
with phagocytic cells)
 IV. Resistance to antimicrobial drugs

Microbes have several mechanisms for resisting drugs

They can:

the conc of a drug at its site of action/ increase in

efflux

Enzymatic inactivation of a drug

Alter the structure of drug target molecules

Produce a drug antagonist

12
V. Rational use of antimicrobial drugs

Inappropriate use of antibiotics:

Increases:
ADRs, infections with drug resistant MOs, & health
care costs

Decreases:
The number of effective drugs for serious or
antibiotic-resistant infections
13
 Rational use of antimicrobial drugs

Guidelines to promote more appropriate use of the drugs

include:
Avoid the use of broad-spectrum antibacterial drugs to treat
trivial or viral infections
Use narrow-spectrum agents when likely to be effective

Give antibacterial drugs only when a significant bacterial

infection is diagnosed or strongly suspected or when there is an
established indication for prophylaxis
These drugs are ineffective & should not be used to treat viral 14

infections
 Rational use of antimicrobial drugs
Minimize antimicrobial drug therapy for fever unless other
clinical manifestations or lab data indicate infection

Use the drugs along with other interventions to microbial

proliferation, such as:
Universal precautions, medical isolation techniques, frequent &
thorough hand washing, & preoperative skin & bowel cleansing

Follow recommendations of the STG

Consult physicians, senior nurses, & pharmacists about local

patterns of drug-resistant organisms & Tx of complicated
15

infections
 VI. Selection of antibiotics

When treating infection, the therapeutic objective is to

produce maximal antimicrobial effects while causing
minimal harm to the host

To achieve this goal, we must select the most appropriate

antibiotic for the individual pt

When choosing an antibiotic, 3 principal factors must be

considered:
the identity of the infecting organism
drug sensitivity of the infecting organism
host factors, such as the site of infection & the status of host
16
defenses
Selection of antibiotics

For most infections, there is usually one drug that is

superior to the alternatives

The drug of first choice may be preferred for several

reasons, such as greater efficacy, lower toxicity, or more
narrow spectrum

Whenever possible, the drug of first choice should be

employed

17
 Selection of antibiotics

Alternative agents should be used only when the first-choice

drug is inappropriate

Conditions that might rule out a first-choice agent include:

allergy to the drug of choice

inability of the drug of choice to penetrate to the site of

infection

unusual susceptibility of the pt to toxicity of the first-

choice drug
18
 Selection of antibiotics

A. Empiric therapy prior to completion of lab tests

Optimal antimicrobial therapy requires identification of

the infecting organism and determination of its drug
sensitivity

However, when the pt has a severe infection, we may

have to initiate treatment before test results are
available

19
Selection of antibiotics

Under these conditions, drug selection must be based on:

Clinical evaluation &

knowledge of which microbes are most likely to cause

infection at a particular site

If necessary, a broad-spectrum agent can be used for initial

treatment

Once the identity & drug sensitivity of the infecting

organism have been determined, we can switch to a more
selective antibiotic 20
 Selection of antibiotics
B. Identifying the infecting organism

The first rule of antimicrobial therapy is to match the drug

Whenever possible the infecting organism should be identified
prior to initiation of therapy

If treatment is begun in the absence of a definitive dx, positive

identification should be established as soon as possible

Therefore, lab finding permit adjustment of the regimen to

better conform with the drug sensitivity of the infecting
organism
21
 Selection of antibiotics

C. Determining drug susceptibility

Because of the emergence of drug-resistant organisms,

testing for drug sensitivity is common

However, sensitivity testing is not always needed

Rather, testing is indicated only when the infecting

organism is one in which resistance is likely

22
Selection of antibiotics

D. Host factors

May modify drug choice, route of administration, or

dosage

Two host factors w/c are host defenses & the site of
infectionare unique to the selection of antibiotics

Other host factors, such as age, pregnancy, & previous

drug reactions, are the same factors that must be
considered when choosing any other drug
23
 Selection of antibiotics

E. Dosage size and duration of treatment

Dosages should be adjusted to produce drug concentrations

that are equal to or greater than the MIC for the infection
being treated

Duration of therapy depends on a number of variables,

including the status of host defenses, the site of the infection,
and the identity of the infecting organism

24
 Selection of antibiotics

F. Therapy with antibiotic combinations

Antimicrobial drugs are often used in combination
Indications for combination therapy may include:
Infections caused by multiple Microorganims
Nosocomial infections
Serious infections in which a combination is synergistic
Likely emergence of drug-resistant organisms if a single
drug is used
Fever or other signs of infection in immunocompromised
clients

25
Selection of antibiotics

G. Prophylactic use of antimicrobial drugs

Antimicrobial agents are given to prevent infection
rather than to treat an established infection
Whenever prophylaxis is attempted, the benefits must
be weighed against the risks of toxicity, allergic
reactions, suprainfection, and selection of drug-
resistant organisms
Surgical & non-surgical prophylaxis

26
 Selection of antibiotics

Surgical prophylaxis
Prophylactic use of antibiotics can decrease the
incidence of infection in certain kinds of surgery
When antibiotics are given for prophylaxis, they should
be administered before the surgery
If the procedure is unusually long, re-administration during
surgery may be indicated
As a rule, postoperative antibiotics are unnecessary
For most operations, a first-generation cephalosporin
(eg, cefazolin) will suffice

27
VII. Misuses of antimicrobial drugs

Misuses of antimicrobial drugs

Attempted treatment of untreatable infection
Treatment of fever of unknown origin
Improper dosage
Treatment in the absence of adequate bacteriologic
information
Omission of surgical drainage

28
VIII. Monitoring antimicrobial therapy

Antimicrobial therapy is assessed by monitoring clinical

responses and laboratory results

The frequency of monitoring is directly proportional to

the severity of infection

Important clinical indicators of success are reduction

of fever and resolution of signs & symptoms related
to the affected organ system

Various laboratory tests are used to monitor

treatment 29
IX. Antimicrobial Drugs & Nursing considerations

a) Administer accurately
Schedule at evenly spaced intervals around the clock

Give most oral antimicrobials on an empty stomach,

approx 1 h before or 2 h after meals

For oral & parenteral solutions from powder forms,

follow label instructions for mixing & storing

Check expiration dates

30
Antimicrobial drugs & Nursing considerations:
Administration

Give parenteral antimicrobial solutions alone; do not

mix with any other drug in a syringe or IV solution
Give IM antimicrobials deeply into large muscle
masses, & rotate injection sites
For IV administration, use dilute solutions, give direct
injections slowly & intermittent infusions over 30 - 60
min
After infusions, flush the IV tubing with at least 10 mL
of IV solution
For children, check references about individual drugs
to avoid excessive concentrations & excessive fluids
31
Antimicrobial drugs & Nursing
considerations: Administration
b) Observe for therapeutic effects
With local infections, observe for ed redness, edema,
heat, & pain
With systemic infections, observe for ed fever & WBC
count, ed appetite, & reports of feeling better
With wound infections, observe for ed signs of local
inflammation & ed drainage
With RTIs, observe for ed dyspnea, coughing, &
secretions
With UTIs, observe for sed urgency, frequency, &
dysuria
Absence of signs &symptoms of infection when given
prophylactically
32
 Antimicrobial drugs & Nursing considerations:
Administration

c) Observe for adverse effects

i. Hypersensitivity
Anaphylaxishypotension, respiratory distress, urticaria,
angioedema, vomiting, diarrhea
Serum sicknesschills, fever, vasculitis, generalized
lymphadenopathy, joint edema and inflammation,
bronchospasm, urticaria
Acute interstitial nephritis (AIN), hematuria, oliguria,
proteinuria, pyuria

33
 Antimicrobial Drugs & Nursing considerations:
Administration

ii. Superinfection
Recurrence of systemic signs and symptoms (eg, fever,
malaise)
New localized signs and symptomsredness, heat,
edema, pain, drainage, cough
Stomatitis or thrushsore mouth; white patches on
oral mucosa; black, furry tongue
Pseudomembranous colitissevere diarrhea
characterized by blood, pus, and mucus in stools
Monilial vaginitis rash in perineal area, itching, vaginal
discharge
34
Antimicrobial Drugs & Nursing considerations:
Administration

iii. Phlebitis at IV sites; pain at IM sites

iv. Nausea & vomiting
v. Diarrhea
vi. Nephrotoxicity
vii. Neurotoxicityconfusion, hallucinations, NM
irritability, convulsive seizures
viii.Bleedinghypoprothrombinemia, platelet
dysfunction
d) Observe for drug interactions

35
X. Pt Information for Antimicrobial Medication

The patient must be told:

To take all the medication even after the symptoms
subside
Not to take medication left over from a previous illness
Not to share drinks, food, & utensils until the
healthcare provider determines that the pt is no longer
infected

36
Pt Information for Antimicrobial Medication

How to recognize the therapeutic effects, SEs, &

ADRs that might occur as a result of taking the
medication

To call the healthcare provider if the pt experience

SEs or ADRs to the medication

To wear a med-alert bracelet if the pt has allergies to

medication

37
Antibacterial Drugs
 Cell-wall synthesis inhibitors are bactericidal
agents
Includes:
Beta-lactam antibiotics:
Penicillins, cephalosporins, carbapenems, &
monobactams
Vancomycin, etc

39
A. Penicillins
MOA
Bacterial cell wall is cross-linked polymer of
polysaccharides & pentapeptides

Penicillins interact with cytoplasmic Membrane

binding proteins (PBP) to inhibit transpeptidation rxns
involved in cross-linking the final step in cell wall
synthesis.

40
Penicillins: MOA & Mechanism(MZM) of resistance

MZM of resistance
Penicillinases (-lactamases): break lactam ring
structure eg. Staphylococci

Structural change in PBPs : Eg . MRSA

Change in porin structure: Eg. Pseudomonas

41
Penicillins: Subgroups & activity

There are 4 types of penicillin:

Basic or natural (Narrow spectrum)

Penicillinase-resistant (Very narrow spectrum)

Aminopenicillins (broad-spectrum)

Extended-spectrum (antipseudomonal)

42
 Penicillins: Subgroups & activity

Spectra at a Glance
G-(+): very good, esp. for the narrow-spectrum pen.

G- (-): good for amino & antipseudomonal penicillins

Anaerobes: very good but only with antipseudomonal penicillins

Resistant organisms:

Methicillin-resistant Staph aureus (MRSA): resistant

Vancomycin-resistant Enterococcus (VRE): resistant

Pseudomonas: good, but only with antipseudomonal penicillins

Special sensitivities:

Neisseria meningitidis (G- (-) coccus): susceptible to IV penicillin 43

G
Penicillins: Subgroups & activity

a) Narrow spectrum, - lactamase sensitive

Penicillin G & Penicillin V
Spectrum: streptococci, Pneumococci, Meningococci,
Treponema pallidum
b) Very narrow spectrum, - lactamase resistant
Naficillin, Cloxacillin, Methicillin, Oxacillin
Spectrum: known or suspected staphylococci (not
MRSA)

44
 Penicillins: Subgroups & activity
c) Broad spectrum, aminopenicillins, - lactamase sensitive
Ampicillin & Amoxacillin
Spectrum: G- (+) cocci (not Staph), E.coli, H. influenzae, L.
monocytogens (ampicillin), Borrelia bugdorferi (amoxicillin), H.
pylori (amoxicillin)
d) Extended spectrum, antipseudomonal, -lactamase
sensitive
Ticarcillin, Piperacillin, Azlocillin
Spectrum: ed activity against G-(-) rods, including pseudomonas
aeruginosa

45
 Penicillins: General considerations & SEs

General considerations
Activity enhanced if used in combination with - lactamase
inhibitors (Clavulanic acid, Sulbactam)

Synergy with aminoglycosides against pseudomonal &

enterococcal spp

Side effects
Hypersensitivity: most commonly only a rash, but can
include anaphylaxis
Nausea, Vomiting, Diarrhea if given orally
Stinging in the vein if given IV 46
 Penicillins: Contraindications

Hypersensitivity (allergy)

Incidence is as high as 10%.

Signs and symptoms are as follows:

Maculopapular rash (mostly flat & confluent, not itchy)
Urticarial rash (hives)
Anaphylaxis
Cross-reactivity b/n penicillin allergy & other -lactam
antibiotics (cephalosporins & carbapenems)

47
Penicillins: Nursing implication

Any patient taking a penicillin should be carefully

monitored for an allergic reaction for at least 30 minutes
after its administration

The effectiveness of oral penicillin is decreased when

taken with caffeine, citrus fruit, cola beverages, fruit
juices, or tomato juice

48
49
 B. Cephalosporins
MOA & resistance: Identical to penicillins
Prototypes & common drugs:
1st -generation agent: cephalexin

Others: cefazolin, cefadroxil, cephalothin, cephapirin, cephradine

2nd -generation agents: cefaclor & cefuroxime

Others: cefoxitin, cefamandole, cefmetazole, cefonicid, cefotetan,

cefprozil, loracarbef

3rd -generation agent: ceftazidime

Others: ceftriaxone, cefixime, cefdinir, cefditoren, cefoperazone,

cefotaxime, cefpodoxime, ceftibuten, ceftizoxime
50
4th -generation agent: cefepime
 Cephalosporins: Generations & activity
Spectra at a Glance
G-(+): v. good, esp. the 1st -generation agents

G-(-): 3rd -generation agents v. good, 2nd -generation agents good

Anaerobes: resistant against 1st -generation agents, good with 2nd

- & 3rd -generation agents

Resistant organisms:

MRSA & VRE : resistant

Pseudomonas: v. good with ceftazidime & - Cefepime only

Special sensitivities:

N. meningitidis (G- (-) coccus: susceptible to IV 3rd -generation

51
agents
 Cephalosporins: Generations & activity

a) 1st generations: Cephalexin

G-(+) cocci (not MRSA), E.coli, Klebsiella pneumoniae, &

some proteus spp

Common use in surgical prophylaxis

PK: not enter CNS

b) 2nd generation: Cefuroxime

Spectrum: G (-) coverage, including some anaerobes

PK: no drugs enter the CNS, except Cefuroxime 52

 Cephalosporins: Generations & activity

c) 3rd generations: Ceftriaxone (IM) & Cefotaxime

(parentral), cefditoren & Cefixime (oral)

Spectrum: G (+) & G (-) cocci, plus many G-(-)rods

PK: most enter CNS (not cefoperazone); important in

empiric management of meningitis

d) 4th generation: Cefepime (IV)

Even wider spectrum
Resistance to most beta-lactamases
Enter CNS
53
 Cephalosporins: Side effects

Hypersensetivity: incidence: 2%

Wide range, but rashes & drug fever most common

Assume complete-allerginicity b/n individual cephalosporins

& partial cross allergenicity with penicillins (<10%)

54
Cephalosporins: Nursing implication

Orally administered forms should be given with food to

decrease GI upset, even though this will delay absorption

Some of these agents may cause a disulfiram (Antabuse)-

like reaction when taken with alcohol

55
C. Vancomycin
MOA:

Cell wall synthesis inhibition but does not interfere

with PBP

Spectrum : MRSA, Enterococci, C.difficile (back up

drug)

Resistance:
Vancomycin-resistance staphylococcal (VRSA),
enterococcal (VRE) strains
Enterococcal resistance involves change in the
muramyl pentapeptide target, such that the 56
terminal D-ala is replaced by D-lactate
Vancomycin: Spectra at a Glance

Gram-positive: very good

Gram-negative: resistant
Anaerobes: resistant
Resistant organisms:
MRSA: very good
VRE: resistant
Pseudomonas: resistant
Special:
C. difficile
Enterococcus (excluding VRE)
57
Vancomycin: Side effects

Red man syndrome (histamine release)

Ototoxicity (usually permanent, additive with other drugs)

Nephrotoxicity (mild, but additive with other drugs)

58
 Vancomycin: Nursing implication

Should be infused over 60 minutes

Monitor IV site closely

Redmans syndrome may occur

Decreased BP, flushing of neck and face

Antihistamine may be ordered to reduce these effects

Ensure adequate hydration (2 L fluids/24 hr) if not

contraindicated to prevent nephrotoxicity

59
B. Inhibitors of Bacterial Protein Synthesis

60
Fig. Inhibition of protein synthesis
61
A. Aminoglycosides (AGs)
Activity & clinical use
Bactericidal, accumulated intracellularly in M.O
Via O2dependent uptake anaerobes are innately
resistant
Useful spectrum includes G-(-) rods
Gentamicin, tobramycin, & amikacin often used in
combinations
Synergistic actions occur for infections caused by
Enterococci ( with penicillin G or ampicillin)
P.aeruginosa (with an extended spectrum penicillin
or 3rd generation cephalosporin)

62
Aminoglycosides: Spectra at a Glance

G-(+): poor, unless in combination with other antibiotic active

against G-(+) organisms
G-(-): very good
Anaerobes: resistant
Resistant organisms:
MRSA & VRE : resistant
Pseudomonas: good
Special sensitivities:
MDR organisms: amikacin
Intestinal parasites (Entamoeba, Cryptosporidium): paromomycin
TB: streptomycin

63
 Ags

Streptomycin used in TB
Neomycin used topically

Side effects
Nephrotoxicity (6-7% incidence)
Ototoxicity (2 % incidence)
Neuromuscular blockade

64
Aminoglycosides: Nursing Implications

Monitor peak and trough blood levels of these agents to

prevent nephrotoxicity and ototoxicity

Symptoms of ototoxicity include dizziness, tinnitus, and

hearing loss

Symptoms of nephrotoxicity include urinary casts,

proteinuria, and increased BUN and serum creatinine
levels

65
66
B. Tetracyclines (TTCs)

Activity & clinical uses

Bacteriostatic drugs, actively taken up by susceptible
bacteria

Broad spectrum antibiotics, with good activity versus

chlamydial & mycoplasmal spp, H.pylori, Rickettsia,
Borrelia bugdorferi, Brucella, Vibria, & Treponema
(backup drug)

67
Tetracyclines: Spectra at a Glance

Gram-positive: good
Gram-negative: good
Anaerobes: poor to good
Resistant organisms:
MRSA & VRE : resistant
Pseudomonas: resistant
Special sensitivities:
Intracellular organisms: Chlamydia, Mycoplasma, &
Rickettsia
Spirochetes (syphilis and borreliosis)
Plasmodium spp.
Stenotrophomonas (minocycline only)
68
Tetracyclines

Specific drugs:
Doxycycline: more activity overall than TTC & has particular
usefulness in prostatitis b/c it reaches high level in prostatic fluid

Minocycline: in saliva & tears at high conc. & used in

meningococcal carrier state

Tigecycline: used in complicated skin, soft tissue, & intestinal

infections due to resistant G (+) (MRSA, Vancomycin susceptible
Enterococcus Faecalis), G (ve), & anaerobes

69
Clinical uses
TTC is drug of choice in infections with:
Mycoplasma pneumoniae; chlamydiae, some
spirochetes

They are used in combination regimens to treat gastric and

duodenal ulcer disease caused by H. pylori

They may be employed in various G+ and G- bacterial

infections, including Vibrio infections

70
 Rickettsial Infections
Tetracyclines are effective and may be life saving in
rickettsial infections, including :
Rocky mountain spotted fever
Recrudescent epidemic typhus (brill's disease)
Murine typhus
Scrub typhus
Rickettsial pox, and Q fever
Doxycycline is the drug of choice for treatment of
suspected or proven Rocky Mountain spotted fever in
adults and in children, including those <9 years of age,
in whom the risk of staining of permanent teeth is
outweighed by the seriousness of this potentially fatal
71
infection
 TTCs are sometimes employed in the treatment of E. histolytica or
P. falciparum
Non pregnant penicillin-allergic patients who have primary,
secondary, or latent syphilis can be treated with a tetracycline
regimen such as doxycycline, 100 mg orally twice daily for 2
weeks
Anthrax
Doxycycline, 100 mg every 12 hours (2.2 mg/kg every 12 hours for
children weighing <45 kg), is indicated for prevention or treatment
of anthrax
The recommended duration of therapy is 60 days for exposures
occurring as an act of bioterrorism
Local Application
Except for local use in the eye, topical use of the tetracyclines is not
recommended
Minocycline sustained-release microspheres for subgingival
administration are used in dentistry

72
Tetracyclines

Side effects

Tooth enamel dysplasia

possible bone growth in children (avoid)

Phototoxicity ( demeclocycline, Doxycycline)

GI distress (NVD), superinfections leading to

candidiasis or colitis

73
Tetracyclines

Restrictions for using tetracyclines are:

Not for pts who are pregnant or breastfeeding

Not for children under 8 yrs of age

Not for pts who have renal problems except for

doxycycline & minocycline

74
 TTCs : Nursing implications

Milk products, iron preparations, antacids, and

other dairy products should be avoided because of
the chelation and drug-binding that occurs
All medications should be taken with 6 to 8 ounces
of fluid, preferably water
Due to photosensitivity, avoid sunlight and tanning
beds

75
 C. Chloramphenicol (CAF)

Activity & clinical uses

Bacteriostatic with a wide spectrum of activity
Currently a backup drug for infection due to Salmonella
typhi, B. fragilis, Rickettisia, & possibly in bacterial
meningitis
Side effects
NVD
Dose dependent bone marrow suppression
Irreversible bone marrow toxicity, Aplastic anemia
Gray baby syndrome in neonates

76
Chloramphenicol

Restrictions for using CAF are:

Not for use in pts who are pregnant or are
breastfeeding
Neonates may develop gray syndrome (blue-
gray skin, hypothermia, irregular breathing,
coma, & CV collapse)
Not for use in pts who are undergoing radiation
therapy or who have bone marrow depression
Not for use in pts who have bone marrow
depression

77
Chloramphenicol & Pt Education

The pt must be instructed to monitor for:

Rash, Fever, Dyspnea
Blurred vision, loss of vision, eye pain
(neuritis)
Tingling, numbness, & burning pain of the
hands & feet (neuritis)
Confusion, delirium (neurotoxic reaction)
Hypoglycemia if taking diabetic medication

78
 D. Macrolides

Drugs: erythromycin, Azithromycin, Clarithromycin

Activity & clinical use
Gram-postive cocci (not MRSA)
Atypical organisims Chlamydia, Mycoplasm &
Ureaplasm spp
Legionella pneumonphia
Campylobacter jejuni
Mycobacterium avium-intracellulare (MAC)
H.pylori

79
 Macrolides: Spectra at a Glance

Gram-positive: very good (but resistance to

erythromycin has developed)
Gram-negative: very good
Anaerobes: resistant
Resistant organisms:
MRSA & VRE : resistant
Pseudomonas: resistant
Special sensitivities:
Atypical bacteria (many of w/c are IC organisms):
Mycoplasma, Rickettsia, Chlamydia, Legionella

80
Macrolides

Side effects
Macrolides stimulate motilin receptors & cause GI
distress (erythromycin, Azithromycin > clarithromycin)
Macrolides cause reversible deafness at high dose

Telithromycin
A ketolide active against macrolide-resistant
S.pneumonia

81
Macrolides : Nursing implications

These agents are highly protein-bound and will cause

severe interactions with other protein-bound drugs

The absorption of oral erythromycin is enhanced

when taken on an empty stomach, but because of
the high incidence of GI upset, many agents are
taken after a meal or snack

82
83
 E. Lincosamides (Clindamycin)

Not a macrolide, but has the same MOA & resistance

It is usually bacteriostatic
It does not cross BBB
It is active against most anaerobic bacteria (G+ and G-)
and most G+ aerobes
G- aerobes are generally resistant

84
 Susceptible anaerobes include bacteroides
fragilis,fusobacterium, C. perfringens and anaerobic
streptococci

It is drug of choice for severe group A streptococcal

infection and for gas gangrene (caused by Cl. Perfringens)

PK: Concentration in bone has clinical value in

osteomyelitis due to G (+) cocci

85
Clindamycin: Spectra at a Glance

Resistant organisms:
MRSA: poor to good
VRE: resistant
Pseudomonas: resistant

Common side effects: Abdominal cramps, Diarrhea,

Weight loss & Weakness
pseudomembranous colitis (more likely cause)
This lead to discontinuation of clindamycin
Oral vancomycin or metronidazole is used

86
Clindamycin : Nursing implications

Before administering Clindamycin to the pt:

Assess the pt for the same conditions as for other
antibiotics
Determine if the pt has a Hx of GI, kidney, or liver
disease
Those pts should not take Clindamycin

After administering Clindamycin to the pt:

Request a WBC count to determine if the
Clindamycin is effective

87
88

It is a new class of antibiotic, oxazolidinones
It is bacteriostatic
MOA
It binds to the 23S portion of the 50S ribosomal subunit
Thereby, blocks formation of the initiation complex
Cross-resistance with other antibiotics is unlikely b/c of this unique
MOAs
It has activity against
multi-drug resistant gram-positive pathogens, including VRE,MRSA
Staphylococcus epidermidis(including MR strain)
Streptococcus Pneumonia (penicillin sensitive and resistant strain)
89
 Adverse effects
Diarrhea
Nausea
b/c of the presence of phenylalanine in oral
suspension it is not used in pts with phenylketonuria
It causes mylosuppression
CBC should be done weekly
Drug interaction
Linozolid is weak inhibitor of MAO
With MAOI, it causes hypertensive crisis
90
C. Nucleic acid synthesis inhibitors
 1. Quinolones

Includes: Ciprofloxacin, Norfloxacin, levofloxacin, moxifloxacin

MOA:
Inhibit bacterial DNA gyrase (important for coiling DNA) and
topoisomerase (required to segregate DNA to daughter cells)

Rapidly cidal, with concentration-dependent killing

92
 Fluoroquinolones

Usage
Upper & lower respiratory tract infections
UTIs
Intra-abdominal infections
Skin & soft tissue infections
Osteomyelitis
Infectious diarrhea
Gonorrhea
Anthrax

93
Fluoroquinolones

ADR for the drug class: Most common

Headache, dizziness, confusion,
photosensitivity, N, D

ADR for the drug class: Rare/severe/important

QT prolongation, hypotension, tremor, seizures,
skin reactions, hepatitis, acute interstitial
nephritis, arthropathy, tendon rupture (Achilles
tendon), hypoglycemia, pseudomembranous
colitis

94
Fluoroquinolones

Major drug interactions

Drugs affecting fluoroquinolones
Di- & trivalent cations: Greatly
fluoroquinolone absorption

Fluoroquinolone effects on other drugs

QT-prolonging drugs:
Potentiated QT prolongation, possibly leading to
polymorphic ventricular tachycardia

95
Fluoroquinolones

Key points for the drug class

The safety & efficacy of fluoroquinolones in children
<18 years of age (except for the use of ciprofloxacin
in inhalational anthrax for postexposure & children
with cystic fibrosis), pregnant women, & lactating
women has not been established
They are generally avoided in these populations for
that reason

96
Fluoroquinolones: Nursing Implications

Should be taken with at least 3 L of fluid per day,

unless otherwise specified

Intake of alkaline foods and drugs, such as

antacids, dairy products, peanuts, and sodium
bicarbonate should be limited

Wear sunglasses & avoid bright lights, sunlight, &

sunlamps

97
98
D. Sulfonamides & pyrimidines
1. Sulfonamides

Pharmacodynamics:

They are structural analogs of para-amino-

Benzenesulfonic acid amide, or sulfanilamide

They inhibit the formation of dihydrofolate

Bacteriostatic

The effect can be overcome by high levels of PABA

substrate

100
101
Sulfonamides

Indications:
Generally indicated for Tx of uncomplicated UTI's
Sulfasalazine: Used for the Tx of IBD
The drug is cleaved by bacteria in the colon, into
sulfonamide & amino-salicylate
Amino-salicylate then has local anti-inflammatory
effects in the colon
Drug interactions:
Procaine interferes with the therapeutic of the
sulfonamides, by competitive inhibition

102
Sulfonamides

Adverse effects:
Hypersensitivity: Common
Rashes in 5% of pts
SJS: Severe hypersensitivity.
Fever, malaise, erythema multiforme, ulcers of
skin & mucous Mns, including mouth & genitalia
Liver: Kernicterus, hepatitis
Hemolytic anemia in pts with G6PD Deficiency
Crystalluria: Sulfonamides can precipitate in the urinary
tract at acidic PH
Maintain adequate hydration to prevent this

103
Sulfonamides : Nursing Implications

Should be taken with at least 2000 mL of fluid per

day, unless contraindicated
Due to photosensitivity, avoid sunlight and
tanning beds
These agents reduce the effectiveness of oral
contraceptives
Oral forms should be taken with food or milk to
reduce GI upset

104
2. Pyrimidines: Trimethoprim

Pharmacodynamics:

Competitively inhibits dihydrofolate reductase,

preventing the formation of THF ---> block
synthesis of purines

Indications: Co-trimoxazole: Very common usage

Synergistic effects (they are both

bacteriostatic)

105
D. Antimycobacterial agents
General considerations

TB is caused by Mycobacterium tuberculosis

Complicating factors
Slow growing, dormant killed very slowly
Mycolic acid, waxy impermeable to drugs
Intracellular organisms
inaccessible for most drugs
Increased risk of resistance
Combination therapy with 2 or more drugs

107
General considerations

The objective of therapy:

To eliminate sxs & prevent relapse
To accomplish this goal must kill actively dividing &
resting
Since the response of mycobacterial infection to
chemotherapy is slow, Tx is prolonged
Prevent the emergence of resistance
Combination of drugs are required
To limit drug adverse effects

108
Antitubercular Agents

First-Line Agents Second-Line Agents

Isoniazid capreomycin
Ethambutol Cycloserine
pyrazinamide (PZA) Ethionamide
Rifampin Kanamycin
streptomycin para-aminosalicyclic
acid (PAS)
Levofloxacin
RESPI - as in TB is
most commonly a
RESPIratory infection
109
a) Isoniazid (INH)

Antimicrobial activity and therapeutic use

It blocks the synthesis of mycolic acids in the
mycobacterial cell wall
Bactericidal, but only in proliferating cells
It is indicated for:
Tx of TB: used in combination with other drugs
Chemoprophylaxis of TB: used alone for 6
months to a yr after exposure
Pharmacokinetics
It is inactivated in the liver, primarily by acetylation

110
Isoniazid (INH)

Major adverse effects

Peripheral Neuropathy

Hepatotoxicity

Other ADRs includes:

CNS effects: seizures, dizziness
GI distress
Allergy to isoniazid can produce fever, rashes, &
a syndrome resembling lupus erythematosus

111
b) Ethambutol

Antimicrobial activity and therapeutic use

The drug is bacteriostatic, not bactericidal
It is employed for initial treatment of TB & for
treating pts who have received therapy
previously
Like other drugs for TB, ethambutol is always
employed as part of a multidrug regimen
Pharmacokinetics
Ethambutol undergoes little hepatic
metabolism & is excreted primarily in the urine

112
Ethambutol

Adverse effects

Ethambutol is generally well tolerated

The only significant adverse effect is optic

neuritis

Other Adverse Effects

Allergic reactions (dermatitis, pruritus), GI
upset, and confusion
Asymptomatic hyperuricemia

113
c) Rifampin

Antimicrobial activity and therapeutic use

It inhibits RNA synthesis by binding to the beta-
subunit of bacterial RNA-Polymerase
It is a bactericidal drug
Useful against G-(+) & G-(-) cocci, & chlamydia, as
well as mycobacteria
Other common uses:
In combination with dapsone, for Leprosy
For prophylaxis in kids exposed to H. Influenzae
type b
To treat chronic Meningococcal carriers

114
Rifampin

Pharmacokinetics
It is well absorbed if taken on an empty
stomach
It is eliminated primarily by hepatic metabolism
It induces hepatic drug-metabolizing enzymes

115
Rifampin

Adverse effects & Interactions

Major adverse effects
Hepatotoxicity
Discoloration of Body Fluids
Other Adverse Effects
GI disturbances (anorexia, nausea, abdominal
discomfort)
Cutaneous reactions (flushing, itching, rash)
Drug Interactions
Accelerate the Metabolism of Other Drugs

116
d) Pyrazinamide

Antimicrobial activity and therapeutic use

Pyrazinamide is bactericidal to M. tuberculosis
Pharmacokinetics
Metabolism is in the liver & excretion is renal,
primarily as inactive metabolites
Adverse effects
Major Adverse effects:
Hepatotoxicity in 5% of pts
Other Adverse Effects
Hyperuricemia (gout arthritis)
GI disturbances (NVD), rashes, & photosensitivity
117
e) Streptomycin

Used only in severe TB infections, due to its high

incidence of adverse effects

It is still considered a first-line drug

Acts mainly on extracellular tubercle bacilli

IM injection

118
Second-line antituberculosis drugs

In general, these drugs are less effective, more toxic, and

more expensive than the first-line drugs
As a result, their principal indication is TB caused by
organisms that have proved resistant to first-line
agents
In addition, second-line drugs are used to treat severe
pulmonary TB as well as disseminated
(extrapulmonary) infection
The second-line drugs are always employed in
conjunction with a major anti-TB drug

119
Antitubercular Agents: Nursing Implications

Obtain a thorough medical history and assessment

Perform liver function studies in patients who are to

receive isoniazid or rifampin (especially in elderly patients
or those who use alcohol daily)

Assess for contraindications to the various agents,

conditions for cautious use, and potential drug interactions

120
 Nursing Implications

Patient education is critical

Therapy may last for up to 24 months
Take medications exactly as ordered, at the same time
every day
Emphasize the importance of strict compliance to regimen
for improvement of condition or cure
Remind patients that they are contagious during the initial
period of their illness instruct in proper hygiene and
prevention of the spread of infected droplets
Emphasize to patients to take care of themselves, including
adequate nutrition and rest

121
 Nursing Implications

Patients should not consume alcohol while on these

medications or take other medications, including OTC,
unless they check with their physician
Diabetic patients taking INH should monitor blood glucose
levels because hyperglycemia may occur
INH and rifampin cause oral contraceptives to become
ineffective; another form of birth control will be needed

122
Nursing Implications

Patients who are taking rifampin should be told that

their urine, stool, saliva, sputum, sweat, or tears may
become reddish orange; even contact lenses may be
stained
Pyridoxine may be needed to combat neurologic side
effects associated with INH therapy
Oral preparations may be given with meals to reduce
GI upset, even though recommendations are to take
them 1 hour before or 2 hours after meals

123
Nursing Implications

Monitor for side effects

Instruct patients on the side effects that should be reported to the
physician immediately
These include fatigue, nausea, vomiting, numbness and tingling
of the extremities, fever, loss of appetite, depression, jaundice
Monitor for therapeutic effects
Decrease in symptoms of TB, such as cough and fever
Lab studies (culture and sensitivity tests) and CXR should
confirm clinical findings
Watch for lack of clinical response to therapy, indicating possible
drug resistance

124
Antibacterial Drugs

E.Miscellaneous agents
a) Metronidazole

Produces short-lived, highly cytotoxic free radicals that

damage DNA
Indicated for Tx of anaerobic or mixed intra-abdominal
infections, vaginitis (trichomonas infection, bacterial
vaginosis), C difficile colitis, & brain abscess
Side effects
Metallic taste , GI disterbance
Disulfiram like effects
A structurally similar agent: Tinidazole
once-daily drug approved for Tx of trichomonas
infection, giardiasis, & amebiasis
126
 b) Nitrofurantoin

Reduction inside the bacterial cell by nitrofuran reductase to multiple

reactive intermediates
Attack ribosomal proteins, DNA, respiration, pyruvate metabolism &
other macromolecules within the cell
Effect is bactericidal for many G- (+) & G- (-) bacteria
Used to treat lower UTIs (including E. coli)
Oral agent that exerts antibacterial activity in the urine, but has little
systemic antibacterial effect
Excreted into the urine
SEs: anorexia, N, V, Neuropathies & hemolytic anemia in pts with G-6-
dehydrogenase deficiency

127
c) Mupirocin

Kills staphylococci by inhibiting isoleucyl tRNA synthetase

Topical Tx of minor skin infections, such as impetigo
Intranasal application for elimination of MRSA carriage by pts or
health care workers
Rapidly inactivated after absorption
systemic levels are undetectable
Mupirocin effectively eliminates S aureus nasal carriage by
pts or health care workers,
But results are mixed with respect to its ability to prevent
subsequent staphylococcal infection

128
d) Fusidic acid

Fusidic acid binds to elongation factor G (EF-G) on the ribosome

Inhibits release of EF-GDP, blocking further elongation
Bacteriostatic
Topical use against staph. infections
Systemic use
Tx of skin & soft tissue infections or osteomyelitis caused by
staph. aureus
Tx of pneumonia, septicemia, endocarditis
Ophthalmic: Tx of superficial infection of the eye & conjunctivitis

129
e) Polymyxins

Includes: polymyxin B & polymixin E (colistin)

Active against G- (-)

There use largely restricted to topical use

Mostly for skin & eye infections

Neurotoxic & nephrotoxic

Colistin (parentral)

A last resort antibiotic for multidrug resistant Pseudomonas

aeruginosa (e.g. Cystic fibrosis pts) & Acinetobacter
130
3. Antifungal Drugs
Antifungal Agents

Antifungal Agents
Systemic
Example: Amphotericin B, fluconazole,
ketoconazole, itraconazole

Topical
Examples: clotrimazole, miconazole,
nystatin

132
133
A. Polyenes: Amphotericin-B

Bind to sterols in cell membrane lining

Result: fungal cell death

Do not bind to human cell membranes or kill human

cells

Agent of choice for the treatment of many severe

systemic fungal infections

Given by PO for fungal overgrowth superinfections

Intrathecal administration is required for Tx of fungal

134
meningitis
Amphotericin-B

Adverse reactions: Most Common

Nephrotoxicity, electrolyte wasting (primarily K+ &

Mg2+ , infusion reactions (fever, chills, N, flushing,
tachycardia, hypotension)

Adverse reactions: Rare/Severe/Important

Bronchospasm, hypoxia, arrhythmias, anemia,

hypersensitivity

135
Polyenes Nystatin

Only used topically

B/c the adverse effects are too severe
Oral administration for the topical Tx of fungal GI
infections
Adverse reactions: Most common
Mild nausea, vomiting (tablet)

Counseling Point
Do not apply in large quantity to open wound
Cover medicated area with a gauze/bandage

136
B. Azole antifungals

Includes: ketoconazole, miconazole, clotrimazole,

fluconazole, itraconazole

Inhibit an enzyme, resulting in cell membrane

leaking

Lead to altered cell membrane

Result: fungal cell death

137
Azole antifungals

Adverse reactions for the drug class:

Most common
V, abdominal pain, N, D, rash
Rare/Severe/Important
Elevated liver function tests (rare severe
hepatic toxicity), hypersensitivity

Major drug interactions for the drug class

Azoles inhibit the CYP450 system & conc of
drugs metabolized via this pathway

138
C. Other antifungal drugs

Flucytosine
Also known as 5-fluorocytosine (antimetabolite)
Taken up by fungal cells & interferes with DNA synthesis
Result: fungal cell death
Side effects: N, V, anorexia, headache, dizziness, others

Griseofulvin
Disrupts cell division
Result: inhibited fungal mitosis (reproduction)
Side effects: rash, urticaria, headache, nausea, vomiting,
anorexia, others

139
Antifungal Agents: Nursing Implications

Before beginning therapy, assess for hypersensitivity,

possible C/Is, & conditions that require cautious use
Obtain baseline VS, CBC, liver function studies, and
ECG
Assess for other medications used (prescribed & OTC)
in order to avoid drug interactions
Follow manufacturers directions carefully for
reconstitution & administration
Monitor VS of pts receiving IV infusions every 15 to 30
min
During IV infusions, monitor I&O & urinalysis findings to
identify adverse renal effects
140
Nursing Implications

Amphotericin B
To reduce the severity of the infusion-related
reactions, pretreatment with an antipyretic
(acetaminophen), antihistamines, & antiemetics
may be given
A test dose of 1 mg per 20 mL DW infused over
30 min should be given
Use IV infusion pumps & the most distal veins
possible

141
Nursing Implications

Tissue extravasation of fluconazole at the IV site

may lead to tissue necrosis monitor IV site
carefully
Oral forms of griseofulvin should be given with
meals to decrease GI upset
Monitor carefully for side/adverse effects
Monitor for therapeutic effects
Easing of the Sxs of infection How can you avoid this medication error?

Amphotericin B is ordered for Mr. Epherem, who

has aspergillosis. You collect the following
information before administering the medication:
BP110/68, pulse 92, respiratory rate 18,

Improved energy levels

temperature 37.8C. Laboratory test results
include K+ 3.2 mEq/L, Na+ 140 mEq/L,
hemoglobin 14 g/dL, hematocrit 43%, BUN 48
mg/dL, and creatinine 3.5 mg/dL.
1

Normal vital signs, including temperature

142
4. Antiviral Drugs
Introduction: Characteristics of Viruses

Use host cell to replicate host targets cause toxicity

Intracellular pathogens drug must enter infected
cells
Few unique viral functions few selective viral
targets
Establish latency difficult to eliminate if not
replicating
Differ in their coded functions difficult to make
selective wide spectrum agents
Higher mutation rate resistance emergence
Limited coded targets cross resistance
144
Steps of Viral replication

Attachment of the virus to receptors on the host cell surface

Entry of the virus through the host cell membrane
Uncoating of viral nucleic acid
Synthesis of early regulatory proteins, eg. NA-polymerases
Synthesis of new viral RNA or DNA
Synthesis of late, structural proteins
Assembly (maturation) of viral particles
Release from the cell
Antiviral agents can potentially target any of these steps

145
A. Antiviral drugs other than ARV drugs
 Antiviral drugs other than ARV drugs

a) Amantadine
Indications: Influenza A, Rubella
Used prophylactically for Influenza-A infection
Adverse effects:
CNS effects, including insomnia, restlessness,
nervousness, depression
b) Rimantadine
Alternative to Amantadine
Adverse effects:
May have lower adverse CNS effects than Amantadine

147
 Antiviral drugs other than ARV drugs

c) Acyclovir: Acycloguanosine
Safest & most widely used agent to combat Herpes
viruses
Adverse effects: May involve kidney, skin, soft tissues,
CNS
d) Others: Ganciclovir, RIBAVIRIN, VIdarabine

148
B. ANTIRETROVIRAL DRUGS
Antiretroviral drugs

Classification of ARV drugs

Agents w/c inhibit enzymes required for HIV
replication

Reverse transcriptase inhibitors (NRTIs &

NNRTIs), Integrase inhibitors, protease
inhibitors (PIs)

Agents w/c block viral entry into cells

Fusion inhibitors & CCR5 antagonists

150
 Classes of ARV drugs
I. NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS
(NRTIs)
CLASS EFFECTS:
MOA: require intracellular phosphorylation to the
5-triphosphate moiety to be active
The 5-triphosphate competes with endogenous
deoxynucleotides for reverse transcriptase (RT)
enzyme & prematurely terminates DNA elongation
due to the modified 3-hydroxyl group

151
 Classes of ARV drugs: NRTIs

Specific for HIV RT, but ADRs may in part be owing to

some inhibition of human DNA polymerases,
particularly mitocondrial DNA polymerase

Lactic acidosis, Pancreatitis,

lipodystrophy/lipoatrophy
(ddC>d4T>ddI>AZT>ABC=3TC=FTC=TDF)

All drugs are renally eliminated

152
 Drug Adverse effects Other comments

Zidovudine Bone marrow suppression Do not use w/d4T

(AZT, ZDV) GI
Headache
Myopathies Used in pregnancy
Metabolic abnormalities
(lipoatrophy, lipids, insulin
resistance)
Mitochondrial toxicity
Lamivudine Has activity against
(3TC) Has minimal side effects Hepatitis B

Emtricitabine Very well tolerated; however Similar to 3TC (do

(FTC) there have been reports of skin not use in
hyperpigmentation combination)
Has activity against
Hepatitis B
153
 Drug Adverse effects Other comments

Stavudine - Pancreatitis Do not use

(d4T) - peripheral neuropathy w/AZT (both are
- N/V/D thymidine
- Metabolic abnormalities analogues)
(lipoatrophy, lipids, insulin
resistance)
- Mitochondrial toxicity
- Myopathies
Didanosine - Pancreatitis - Do not use w/d4T
(ddI) - Peripheral neuropathy (similar toxicity)
- N/V/D
- Metabolic abnormalities
(lipoatrophy, lipids, insulin
resistance)
- Mitochondrial toxicity

154
 Drug Adverse effects Other comments

Abacavir HLA*B5701 test: should be

(ABC) Hypersensitivity performed prior to starting ABC
reaction (2-9%) Never use the drug if HLA is
positive
No renal adjustment b/c it is
metabolized to inactive
metabolites. (this is the only one)

Tenofovir N/V/D Nucleotide analogue

(TDF) Rare reports of (monophosphorylated)
renal dysfxn Has activity against Hepatitis B
Generally very
well tolerated

155
 Classes of ARV drugs: NNRTIs

II. NON NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS (NNRTIS)

CLASS EFFECTS:
MOA: bind noncompetitively to RT & cause a conformational
change; do not require IC phosphorylation & do not compete
w/endogenous deoxynucleotides

All are metabolized by CYP-450 multiple drug interactions!!

Very long half-lives

Rash & LFT are associated with all the agents

They are all metabolized in the liver, no renal adjustment needed

156
 Drug Adverse effects Other Comments

Efavirenz CNS effects: drowsiness,

(EFV) dizziness, vivid/strange dreams;
RASH (up to 10% of people)
Teratogenic in monkeys
(Pregnancy category D)
Nevirapine Rash (up to 25%)
(NVP) SJS has been reported
Drug induced hepatitis; LFTs
Black box warning: DON NOT
in women with >250 CD4s or men
with > 400 CD4s due to
hepatotoxicity
Etravirine Rash, including SJS
(ETV) Nausea
P-450 substrate & inducer
ATRIPLA = EFV+FTC+TDF
P-450 autoinducer & inducer of
other drugs
Multiple drug interactions
Substrate for P-450 3A4, 2C9,
2C19
Inducer of 3A4
Inhibitor of 2C9 and 2C19
Currently approved for ARV Ds
experienced Pts only

157
 Classes of ARV drugs: Protease Inhibitors

III. PROTEASE INHIBITORS (PIS)

CLASS EFFECTS:
MOA: block the maturation process, thereby resulting
in the production of immature, noninfectious virions
All are metabolized by CYP-450 multiple drug
interactions!!
GI side effects, lipodystrophy, hyperlipidemia,
hyperglycemia, pancreatitis, LFT are common

158
 Generic Adverse Effects Other Comments

Most potent CYP-450

Ritonavir (RTV) GI inhibitor; now only used for
boosting
No documented lipid
Atazanavir (ATV) GI abnormalities when used
Hyperbilirubinemia unboosted; a.k.a the lipid
Nephrolithiasis friendly protease inhibitor

Acid-dependent absorption
C/I with high dose PPIs
Darunavir (DNV) GI
Sulfa moiety (rash)

Lopinavir/ritonavir GI Mainly used in pregnancy

(LPV/r)

159
 Generic Adverse Effects Other Comments

Fosamprenavir GI
(FPV) Sulfa moiety

Indinavir (IDV) -
GI, dry skin, Rarely used in clinical practice
alopecia, ingrown toe - Do NOT use w/ atv due to
nails, nephrolithiasis hyperbilirubinemia

Nelfinavir (NFV) Diarrhea Rarely used in clinical practice

Saquinavir (SQV) GI Rarely used in clinical practice

Tipranavir (TPV) GI, LFTs, sulfa Only approved for ARVDs

moiety experienced pts

Dorsocervical Fat Pad

Source: Dominic C. Chow, MD, University of Hawaii; Larry J. Day, MD, 1

1 University of Michigan; Cecilia M. Shikuma, MD, University of Hawaii

160
 Classes of ARV drugs: Entry Inhibitors

MOA: inhibits the fusion of HIV with the CD4 cells

MZM Drug Adverse Effects Other Comments

Fusion Enfurvitide Injection site BID SQ injection; no known

inhibition (T-20) reactions drug-drug interactions
ARVDs experienced pts
only
CCR5 Maraviroc Hepatotoxicity Only approved for
receptor +/- systemic ARVDs experienced pts
antagonist allergic reaction Pts who have CCR5 tropic
(pruritic rash, virus
eosinophilia or P-450 3A4 substrate
elevated IgE) Dose depends on
coadministered agents

161
Classes of ARV drugs: INTEGRASE INHIBITORS

V. INTEGRASE INHIBITORS
MOA: Prevent covalent bonds from forming b/n integrase & host
DNA HIV integrase unable to incorporate the viral DNA into
the CD4 cell chromosome prevention of strand transfer & viral
replication

Drug Adverse Effects Other Comments

Raltegravir No significant side effects in No P-450 metabolism;

clinical trials It is glucuronidated by
UGT 1A1

162
 Antiretroviral Drugs

General Use
The goal of antiretroviral therapy in the management of
HIV infection:
To improve CD4 cell counts & viral load
If accomplished, this generally results in slowed
progression of the disease, improved quality of life,
& ed opportunistic infections
PMTCT
Post-exposure prophylaxis (PEP)

163
ART or HAART

Combination of at least 3 drugs, usually:

2 NRTIs
&
1 NNRTI or 1-2 PIs
Rarely Triple NRTIs

Therapy with only one or 2 agents allows HIV to

overcome therapy through resistance mutations

164
ARV Drugs: pt/family teaching

Instruct pt to take medication exactly as directed,

around the clock, even if sleep is interrupted

Instruct pt that ARVs should not be shared with

others

Inform pt that ARV therapy does not cure HIV &

does not reduce the risk of transmission of HIV
to others through sexual contact or blood
contamination
165
ARV Drugs: pt/family teaching

Advise pt to avoid taking any Rx, OTC, or herbal

products without consulting health care
professional

Emphasize the importance of regular follow-up

exams & blood counts to determine progress & to
monitor for SEs
Case study

Elsa, a 40 year-old woman, presents to the ART

clinic for her 2 wk follow-up after starting ART
(efavirenz, lamivudine & zidovudine)

She appears tired and feels fatigue. When you ask

her how she is doing on her medication, she replies
that she does not understand why she is feeling
worse after starting ART. She occasionally feels N.
Also, she has trouble falling asleep, & during the
night she is awoken with nightmares

166
5. Antiprotozoals Drugs

1) Antimalarial Drugs
Antimalarial drugs

Malaria
Caused by Plasmodium protozoa (4 types)
Cause: the bite of an infected adult female anopheline
mosquito
Can also be transmitted by infected individuals via
blood
Diagnosis must be confirmed with lab testing
Susceptibility of infecting parasites are determined by
geographic location

168
Antimalarial drugs

Malarial Parasite (Plasmodium): 2 interdependent

life cycles
Sexual cycle: occurs in the mosquito
Asexual cycle: occurs in the human
(exoerythrocytic & erythrocytic stages)
Knowledge of the life cycles is essential in
understanding antimalarial drug treatment
Drugs are effective only during the asexual
cycle

169
Malaria Life
Cycle Oocyst

Sporozoites

Mosquito Salivary
Zygote Gland

Exo-
erythrocytic Hypnozoites
(hepatic) cycle
Gametocytes

Erythrocytic
Cycle

170
Antimalarial Drugs

Drug classification:
Tissue schizonticides: drugs that eliminate
developing or dormant liver forms
Blood schizonticides: drugs that act on erythrocytic
parasites
Gametocides: drug that kill sexual stages &
prevent transmission to mosquitoes

Radical Cure: Elimination of both hepatic & erythrocytic stages

NOTE: No one available agent can reliably affect a radical cure

171
Antimalarials: Mechanism of Action

Chloroquine, quinine & Mefloquine

Bind to parasite nucleoproteins & interfere with
protein synthesis; also alter pH within the
parasite
Interfere with parasites ability to metabolize &
use erythrocyte hemoglobin
Effective only during the erythrocytic phase
Primaquine
Only exoerythrocytic drug (works in both phases)
Binds & alters parasitic DNA

172
Antimalarials: Mechanism of Action

Artemisinin derivatives
Involves the production of free radicals within
the plasmodium food vacuole, following
cleavage of the drug's endoperoxide bridge by
heme iron in parasitized erythrocytes
It is also believed to covalently bind to and
damage specific malarial proteins

173
Adverse effects of Antimalarial drugs

Artemether/lumefantrine (Coartem)
Headache, dizziness, anorexia, fever, arthralgia, myalgia, N
Hypersensitivity,QT prolongation
Atovaquone & proguanil (Malarone)
NVD, abdominal pain,, headache,myalgia
Neutropenia, hypotension
Chloroquine
NVD; visual changes, including blurred vision,
photophobia & difficulty focusing
Hemolytic anemia in pts with G6PD deficiency;
irreversible retinal damage

174
Adverse effects of Antimalarial drugs

Mefloquine
NVD, myalgia, dizziness, anorexia, abdominal pain
AV block, bradycardia, tachycardia, psychosis
Primaquine
NVD, myalgia, headache, anorexia, abdominal pain
Hemolytic anemia in pts with G6PD deficiency
Quinine
NVD, Cinchonism (tinnitus, ototoxicity, vertigo, fever,
visual impairment),hypothermia, coma, CV collapse,
agranulocytosis

175
Antimalarial drugs: Nursing Implications

Chloroquine
Perform baseline and periodic ophthalmic
examinations
Report blurred vision, increased sensitivity to light, &
muscle weakness to the physician
Consult the physician about altering therapy if muscle
weakness occurs
Suggest an audiometric examination before, during,
and after therapy
Caution the pt to avoid excessive exposure to the sun
to prevent exacerbating drug-induced dermatoses

176
Antimalarial drugs: Nursing Implications

Primaquine
Give drug with meals or antacids
Discontinue administration if you observe a
sudden fall in hemoglobin concentration or in
RBC or WBC count or a marked darkening of
urine, suggesting an impending hemolytic
reaction

177
Antimalarial drugs: Nursing Implications

Quinine
Use with caution in the pt with a CV condition
Discontinue administration if you see any signs of
idiosyncrasy or toxicity headache, epigastric distress,
diarrhea , rash, or pruritus in a mild reaction or delirium,
seizures, blindness, CV collapse, asthma, hemolytic
anemia , or granulocytosis in a severe reaction
Frequently monitor BP while administering quinine
I.V Rapid administration causes marked hypotension

178
Antiprotozoals Drugs

2) Other Antiprotozoals
a) Metronidazole

Pharmacodynamics:
A nitro-imidazole, that is activated similar to
Nitrofurantoin
Nitro group of the drug is reduced in the
Amoeba, forming oxidative intermediates that
do oxidative damage to the bugs
Tissue amebicide

180
Metronidazole

Indications:
Wide variety of intestinal & tissue parasitic
infections
Trichomoniasis, Giardiasis, Intestinal Amebiasis
Adverse effects: Common
N, headache, dry mouth
Disulfiram-like effect: do not use with alcohol
This can affect pt-compliance
Metallic taste in mouth
Dark urine

181
b) Pentamidine

Pharmacodynamics: Unknown
May involve inhibition of synthesis of proteins,
nucleic acids, or phospholipids
Indications:
First-line therapy for PCP (aerosol
administration) in AIDS pts
Second-line therapy for many other parasitic
infections, due to its bad SEs

182
c) Diloxanide furoate

Pharmacodynamics:
Given orally, Diloxanide is the active drug,
released by gut bacteria
Indications:
Mild drug used to combat intestinal amebiasis
Adverse effects: Well-tolerated

183