D.

Drugs Treating Urinary Tract Infections

1

1. Sulphamethoxazole-Trimethoprim
(SMZ-TMP)
2. Nitrofurantoin
 Information: Sulphamethoxazole-
Trimethoprim (SMZ-TMP) 2

• Class:
Sulfonamides
Prototype: SMZ-
TMP
SMZ-TMP
Pharmacotherapeutics 3

• Broad range of therapeutic uses

• Used for UTI, prophylaxis and treatment of
Pneumocystis jiroveci pneumonia
• Infection by Legionella, Shigella, or Salmonella
species; Haemophilus influenzae; or Streptococcus
pneumoniae
SMZ-TMP
Pharmacokinetics 4

• Completely absorbed following oral administration

• Metabolized in the liver to inactive
• Excreted primarily in the urine
• Peak: 4 hr (blood plasma); 1 hr (IV) – age
dependent!
• SMZ-TMP is well distributed throughout the body
• Crosses the blood–brain barrier and the placenta
• Excreted in breast milk
SMZ-TMP
Pharmacodynamics 5

• Interfering with the synthesis of tetrahydrofolic

acid (THF)
• THF inhibits thymidine synthesis and
subsequently DNA synthesis
• TMP and SMX are weak bactericidal agents
when given alone
• Combination is highly bactericidal
SMZ-TMP
Contraindications/ Precautions 6

• Hypersensitivity to agent and thiazide diuretics or

sulfonylureas (cross- sensitivity)
• Deficiencies in G6PD or other folates, porphyria,
• Urinary obstruction,
• Term pregnancy just ready to deliver,
• Age less than 2 months old
SMZ-TMP
Adverse Effects 7
Most Serious adverse effects:
 Three classic potential adverse reactions:
 Hematologic effects (such as anemia), allergic
reactions, and crystalluria
1. Hematologic due to direct action on bone marrow
2. More severe reaction is Stevens-Johnson syndrome
and exfoliative dermatitis
3. Crystalluria: If the urine volume and pH value drop,
these drugs may crystallize in the renal tubules
Most common adverse effects:
 nausea, vomiting, diarrhea
Other adverse effects p. 834
SMZ-TMP: Stevens-Johnson syndrome 8
 Nursing Role 9

• Discuss your role as a nurse before

administering SMZ-TMP considering:
1. Core Patient variables
2. Core drug knowledge

• Refer to Page 884-885

SMZ-TMP 10
Maximizing therapeutic effects:
1. Administer SMZ-TMP 1 hour before or 2 hours after a meal
with a full glass of water
2. Patients who experience adverse GI effects may take the
drug with food
Minimizing adverse effects, how:
1. 60-90 minutes slow IV infusion
2. 1.5 L fluid/ day
3. Sun exposure precaution
Patient and Family Health Education:
1. Teach the patient strategies to avoid disulfiram-like
reactions, photosensitivity, and crystalluria
Nitrofurantoin 11

• Class: Urinary Tract Antiseptics

• Prototype: Nitrofurantoin
Nitrofurantoin 12

• Broad spectrum of activity

• Highly effective against gram-negative and gram-
positive organisms in the urinary system
• Rapidly excreted by the kidneys
• macrocrystalline nitrofurantoin is absorbed more
slowly and induces less GI distress
• It works by interfering with several bacterial enzyme
systems - lack of bacterial resistance to it!
Nitrofurantoin 13

• Contraindicated in patients with renal impairment, in

infants younger than 1 month and in pregnant women
at term
• Caution: elderly, G6PD deficiency, anemia, vitamin
B deficiency, diabetes mellitus, or electrolyte
abnormalities
• Pregnancy category B drug
Pregnancy Category (MUST KNOW!) 14
Nitrofurantoin 15

Most serious adverse reactions:

 Peripheral neuropathy especially with diabetes
mellitus, anemia, and vitamin B deficiency
 acute and chronic pulmonary reactions
Most common adverse reactions:
 Anorexia, nausea, and vomiting
Nitrofurantoin may induce an asthma attack
Nitrofurantoin may cause hematopoietic effects e.g. folate
anemia
E. Drugs treating Mycobacterial
Infections 16

• Isoniazid, Ethambutol/Pyrazinamide
• Rifampicin
Isoniazid, Ethambutol/Pyrazinamide
17
Pharmacotherapeutics
Isoniazide:
Antibacterial drug used to treat or prevent TB and other
susceptible mycobacterial infections
M. avium, M. bovis, M. intracellulare, M. kansasii, M. szulgai, and
M. xenopi
Ethambutol & Pyrazinamide: more effective and less toxic than
other antitubercular drugs
Ethambutol is effective against INH and rifampin-resistant bacilli
Pyrazinamide is indicated only for use in treating M. tuberculosis &
most effective in the induction phase of treatment
Rifampin is the drug of choice for managing leprosy
Isoniazid, Ethambutol/Pyrazinamide
18
Pharmacokinetics
IM and oral
Absorbed rapidly from the GI tract – PEAK 12 hrs
Crosses the blood–brain barrier, placenta and is distributed into
breast milk
Metabolized in the liver to inactive metabolites
Excreted in the urine (75%)
The rest is excreted in the feces, saliva, and sputum
Ethambutol:
19
Pharmacokinetics
Oral
Partially metabolized in the liver, and excreted primarily in
urine
A widely distributed drug – high concentration in kidneys,
lungs and saliva
Penetrates inflamed meninges
Crosses the placenta and is distributed into breast milk – no
adverse effects on fetus and baby!
Pyrazinamide
20
Pharmacokinetics
Oral
Metabolized into active metabolites
Excreted in the urine by glomerular filtration
A widely distributed drug & penetrates inflamed meninges
Whether PZA crosses the placenta is unknown
Enter breast milk
Pharmacodynamics 21

INH: bactericidal or bacteriostatic

It works by disrupting the synthesis of the bacterial cell
wall
Ethambutol:Inhibit the synthesis of certain metabolites,
with subsequent impairment of cell metabolism leading to
cell death
Pyrazinamide: The exact mechanism of action is not known
– bacterialcidal!
Contraindications/ Precautions 22

Contraindications:
Acute hepatic disease
History of INH-induced hepatic disease
Cautions:
Chronic hepatic disease, alcoholism, or severe renal
impairment
Diabetes mellitus, malnutrition, or alcoholism
Pregnancy category C
Contraindications/ Precautions 23

Contraindications:
Ethambutol: children <13 years & children whose visual
acuity cannot be adequately assessed

Cautions:
Ethambutol: patients with a history of gout
Pyrazinamide: pregnant and those with alcoholism, gout, or
hepatic disease
Adverse Effects 24
Most Serious adverse effects:
 Hepatotoxicity (BLACK BOX!): Elevated hepatic enzyme levels (aspartate
transaminase, alanine transaminase), bilirubinemia and jaundice
 Peripheral neuropathy: paresthesias in the hands and feet
 Ethambutol: optic neuritis, hepatotoxicity, peripheral neuropathy and
blood dyscrasias
 Hyperuricemia (other adverse effects)
 Pyrazinamide: hepatotoxicity
 Other common adverse effects: arthralgias, GI disturbances, and
photosensitivity. Non-gouty arthritis
 Other adverse effects p. 894 & 897
 Nursing Role 25

• Discuss your role as a nurse before

administering INH considering:
1. Core Patient variables
2. Core drug knowledge

• Refer to Page 894-896

Planning & Intervention 26
Minimizing adverse effects:
1. Advise patients to report any of the prodromal symptoms of
hepatitis, including anorexia, malaise, fatigue, jaundice, or nausea
2. Advise patients to report burning or pain in the extremities,
numbness or tingling, or symptoms of anemia
3. Discontinue the drug if LFT three to five times higher than the
upper limit of normal values
4. Ethambutol: Baseline ophthalmic examination
5. Pyrazinamide: CBC, liver and renal function tests, and uric acid
level
Planning & Intervention 27
Maximizing therapeutic effects:
1. Administer INH 1 hour before or 2 hours after a meal
2. Patients who experience adverse GI effects may take the drug with
food
3. Do not administer antacids less than 1 hour before or 2 hours after
administering INH.
Patient & Family Health Education:
1. Teach patients about the role of adherence in avoiding drug
resistance & strict follow up (eye exam & labs!)
2. S&S of hepatotoxicity and neurotoxicity
3. Avoid alcohol
F. Drugs Treating Fungal Infections 28

1. Amphotericin B
2. Fluconazole
3. Griseofulvin
Amphotericin B
29
Pharmacotherapeutics
• Treat progressive and potentially fatal
systemic fungal or protozoal infections
• Aspergillus, Blastomyces, Candida,
Coccidioides, Cryptococcus and
Histoplasma
Amphotericin B
30
Pharmacokinetics
• Available as IV form (limited)
• It crosses the placenta and may pass into breast milk
• Amphotericin B must be given intrathecally to achieve
fungistatic concentrations within the CSF
• The metabolism of amphotericin B is unknown
• Amphotericin B can be detected for up to 4 weeks in
blood and 4 to 8 weeks in urine!
• Initial half life: 12 hrs vs. second as 15 days!
Amphotericin B
31
Pharmacodynamics
• Works by binding to sterols in fungal cell membranes
• Forming pores or channels and results in increased cell
permeability, cell leakage and death
• Fungistatic & fungicidal activity
Amphotericin B
32
Contraindication/Caution
Contraindications: Hypersensitivity

Cautions:
• Anemia, hypokalemia and hypomagnesemia
• pre-existing renal impairment
• Pregnancy and lactation
• Pregnancy category B
Amphotericin B
33
Adverse Effects
Most Serious adverse effects:
 Nephrotoxicity: renal insufficiency, azotemia, hyposthenuria,
renal tubular acidosis and frank renal failure
 Infusion- related reactions: headache, chills, fever, rigors,
hypotension, bronchospasm, and nausea and vomiting
 Electrolyte abnormalities, including hypokalemia, hypo-
magnesemia, hypochloremia, and hypocalcemia
 A normocytic & normochromic anemia
 Leukopenia and thrombocytopenia
 Other adverse effects p. 910
 Nursing Role 34

• Discuss your role as a nurse before

administering Amphotericin B considering:
1. Core Patient variables
2. Core drug knowledge

• Refer to Page 910-911

Amphotericin B 35

• Minimizing adverse effects:

1. Do not administer with other nephrotoxic drugs to minimize the
potential for nephrotoxicity
2. Administer test dose as ordered by provider (reaction occur 15
minutes – 3 hrs! after initiating infusion)
3. Administer preordered drugs (diphenhydramine and acetaminophen)
4. Dantrolene or meperidine if rigors occur

• Maximizing therapeutic effects:

• Prepare the patient for the possibility of an infusion reaction so that
the patient does not cease therapy
Amphotericin B 36

• Patient & Family Health Education:

1. Discuss the potential for an infusion reaction
2. Need to monitor the hematopoietic and renal systems closely
Fluconazole
37
Pharmacotherapeutics
• A wide spectrum of activity
• Esophageal or oropharyngeal candidiasis,
candida vaginitis, candiduria, disseminated
candidiasis, and cryptococcal meningitis
• Prophylactically against fungal infections
Fluconazole
38
Pharmacokinetics
• Oral and IV form
• GI absorption is rapid and almost complete
• Peak 1-2 hrs (oral)
• Fluconazole is distributed widely into body tissues and fluids.
Saliva, sputum, nail, blister, and vaginal secretion
• Fluconazole distributes well into the CSF
• Fluconazole crosses the placenta and enters breast milk
• Elimination is mainly renal (unchanged)
Fluconazole
39
Pharmacodynamics
• Alter the fungal cell membrane
• Inhibits synthesis of ergosterol
• Increased cellular permeability, causing leakage of
cellular contents
Fluconazole
40
Contraindications/ Precautions
Contraindications:
• NONE!
Cautions:
• Pregnancy
• Patients with pre-existing hepatic and renal dysfunction
Fluconazole
41
Adverse Effects
Most Common adverse effects:
 nausea, abdominal pain, vomiting and diarrhea
 Mild elevations in levels of alanine transaminase,
aspartate transaminase, alkaline phosphatase and
bilirubin, so which system is being affected?
 HIV & malignancy: alopecia and exfoliative skin
disorders such as Stevens-Johnson syndrome
 Other adverse effects p. 914
Fluconazole in HIV & malignancy: Stevens- 42
Johnson syndrome
 Nursing Role 43

• Discuss your role as a nurse before

administering Fluconazole considering:
1. Core Patient variables
2. Core drug knowledge

• Refer to Page 918-919

Fluconazole 44
Planning & Intervention
• Minimizing adverse effects:
1. Do not give with any drugs that increase the potential
for adverse effects
2. Administer adjunct medications for nausea and diarrhea
• Maximizing therapeutic effects:
• Administer adjunct medications for nausea and diarrhea
• Administer fluconazole in evenly divided intervals
throughout the day
Fluconazole 45
Planning & Intervention
• Patient & Family Health Education:
1. Advise patients to avoid Fluconazole if they have
reaction to any medication end with “azole”
2. Watch for signs and symptoms of adverse effects
3. Assure that alopecia is temporary
Griseofulvin 46

• Class: Antifungal agents

• Prototype: Griseofulvin
Griseofulvin 47

• Indication:
• Treat superficial dermatophytic infections,
such as ringworm and tinea
• Mechanism of action:
• Disrupt the mitotic spindle structure of the
fungal cell, stopping cell division
• May cause defective DNA that is unable to
replicate
Griseofulvin 48

• The therapy may take 6 to 12 months in treating tinea

• Contraindication: pregnancy and breast-feeding
• Caution: hepatic dysfunction, porphyria, or systemic lupus
erythematosus
• Common adverse effect:
 GI: nausea, vomiting, flatulence and epigastri distress
 CNS: Headache, fatigue, dizziness, insomnia, confusion, psychotic
symptoms and paresthesias of the hands and feet
 Integumentary: maculopapular rash, urticaria and photosensitivity
 High/ long course: hepatitis, elevated hepatic enzymes,
granulocytopenia and leukopenia
Griseofulvin 49

• It interacts with oral contraceptives and warfarin

• Barbiturates can decrease the antifungal activity of
griseofulvin
• Griseofulvin may increase the adverse effects of alcohol
G. Drugs Treating Viral Infections 50

1. Acyclovir
2. Oseltamivir
Acyclovir
51
Pharmacotherapeutics
• Management of herpes simplex virus, herpes
zoster virus, Epstein-Barr virus, and
cytomegalovirus
• Treat herpes genitalis, recurrent herpes
labialis and varicella
52
Acyclovir
53
Pharmacokinetics
• Oral, parenteral, and topical antiviral agent
• Acyclovir distributes extensively, with the highest
concentrations in the kidneys, liver and intestines
• Acyclovir crosses the placenta and enters breast milk
• Acyclovir is metabolized minimally
• Eliminated by the kidneys unchanged
• Half-life in patients with normal renal function is about 2.5
hours
• Renal failure – half life 20 hrs!
Acyclovir
54
Pharmacodynamics
• Acyclovir must undergo phosphorylation, a process by
which a phosphate combines with an organic compound
• Competes for a position in the DNA chain
• Terminates DNA synthesis
Acyclovir 55
Contraindications/ Precautions
Contraindications:
• None
Cautions:
• Caution in patients with ganciclovir or valganciclovir
hypersensitivity
• Pregnant or breast-feeding
• Renal disease and pre-existing neurologic disorders
Acyclovir 56
Adverse Effects
More serious adverse effects:
 Confusion, tremors, hallucinations, seizures or coma
 Nephrotoxic (crystalization)

Most Common adverse effects:

 light-headedness, anorexia, nausea, vomiting,
abdominal pain, and headache
Acyclovir 57
Planning & Intervention
• Minimizing adverse effects:
1. GI upset: administer the drug with food
2. Advise the patient to drink at least eight 8-oz glasses of water a day
3. Monitor the patient’s urine output for 2 hours after the infusion –
notify if urine output less than 500 ml/g of administered acyclovir
• Maximizing therapeutic effects:
• Administer acyclovir tablets or capsules with a full glass of water,
with or without food.
• Administering the drug at regular intervals is important.
Acyclovir 58
Planning & Intervention
• Patient & Family Health Education:
1. Advise patients to avoid Acyclovir if they have reaction to
any medication end with “vir”
2. Emphasize that acyclovir does not prevent the transmission
of infection to another person and does not cure the
infection
3. Instruct patients to complete the full course of drug therapy

Other teaching points p. 931-932

Oseltamivir
59
Pharmacotherapeutics
• Neuraminidase inhibitor used to
manage infection with influenza A or
B virus
• H5N1 (Bird virus)
• H1N1 (swine)
Oseltamivir 60
Pharmacokinetics/ Pharmacodynamics
Pharmacokinetics
• Oral capsule or as powder

Pharmacodynamics
• Inhibit the release of viruses from infected cells,
• Reducing spread to adjacent cells and limiting tissue damage
and the duration of symptoms
• The earlier the treatment the better efficacy!
Oseltamivir 61
Contraindications/ Precautions
Contraindications:
• Hypersensitivity
Cautions:
• Pregnancy, breastfeeding, asthma and patients
with renal insufficiency
Oseltamivir 62
Adverse Effects
More Common adverse effects:
 Nausea and vomiting, bronchitis, insomnia and vertigo
 In children: neurologic and behavioral symptoms such
as hallucinations, delirium, and abnormal behavior
Oseltamivir 63
Planning & Intervention
• Minimizing adverse effects:
• Nausea and vomiting can be reduced by administration with milk, a
snack, or a meal
• Maximizing therapeutic effects:
• Question the patient regarding the duration of symptoms
• Administer the solution directly in the mouth–do not mix with any
liquid
• To prepare the solution, add 23 mL of water to the bottle
containing the powder and shake well for 15 seconds
• Store the unused solution in the refrigerator.
• Shake the solution prior to each dose.
• Store the oseltamivir capsules at room temperature
Oseltamivir 64
Planning & Intervention
• Patient & Family Health Education:
1. Instruct the patient on the correct way to prepare,
administer, and store the solution
2. Encourage the patient to take the medication for the full
course of therapy as prescribed (5 days for acute illness;
10 days for prophylaxis)
3. Instruct families to monitor children closely throughout
therapy
4. Teach the patient oseltamivir is not a substitute for yearly
influenza vaccine
Read other teaching points p. 936