ANTI - INFECTIVE AGENTS

Anti-bacterial Agents
Prepared by: Laica Lao Amizol, RN, MANc
Definitions
• Also known as antibacterials, are
medications that destroy or slow down the
growth of bacteria.
• Powerful medicines that fight certain
infections and can save lives when used
properly.
What is Bacteria?

• are everywhere: ​
• soil, water, air, and the bodies of every person and animal.​
• Bacteria do not have a membrane enclosing their nucleus
(part containing DNA)​
• Virus invade plant or animal cell​
• Bacteria reproduce on their own (Some need to live in
another cell like viruses)​
Spread of diseases​

• Ways: contaminated water​

• food​
• sexual contact​
• Air​
• when infected people sneeze or cough​
• animal contact or contact with infected people. ​
ANTIBIOTIC THERAPY​

• Goal: to decrease bacteria so the human immune system

can effectively deal with the invader (bacteria).​
• Determine the effective antibiotic :culture, sensitivity​
• AVOID: OVERUSE OF ANTIBIOTICS ​
Gram Stain
• Used to detect the presence of bacteria and sometimes fungi in a sample
taken from the site of a suspected infection
• Gram Positive
• are those whose cell wall retains a stain known as Gram’s stain or
resists decolorization with alcohol during culture and sensitivity testing
• Commonly associated with infections of the respiratory tract and soft
tissues​
• Examples: streptococcus pneumoniae – common cause of pneumonia​
• Gram Negative
• are those whose cell walls lose a stain or are decolorized by alcohol
• frequently associated with infections of the genitourinary tract or GI tract​
• Examples: E. coli- common cause of cystitis​
BACTERIA AND OXYGEN​

• AEROBIC BACTERIA​
– Depend on oxygen to survive​

• ANAEROBIC BACTERIA ​
– (eg. Bacteria assoc. with gangrene)​
– Do not need oxygen
AMINOGLYCOSIDES

• are a group of powerful antibiotics used to treat

serious infections caused by gram-negative aerobic
bacilli
• Prevents the bacteria from synthesizing protein
• They inhibit protein synthesis in susceptible strains of
gram-negative bacteria.
– Pseudomonas aeruginosa, E. coli, Proteus species, the
Klebsiella–Enterobacter–Serratia group, Citrobacter species,
and Staphylococcusspecies such as Staphylococcus aureus.
AMINOGLYCOSIDES

Pharmacokinetic:
• Poorly absorbed from the GI tract but rapidly
absorbed after intramuscular (IM) injection, reaching
peak levels within 1 hour
• These drugs have an average half-life of 2 to 3 hours
• They are widely distributed throughout the body, cross the
placenta and enter breast milk, and are excreted
unchanged in the urine
AMINOGLYCOSIDES

• Pharmacokinetic:
§ Amikacin is available for short-term IM or intravenous (IV) use.
§ Gentamicin is available in many forms: ophthalmic, topical, IV,
intrathecal, impregnated beads on surgical wire, and liposomal
injection.
§ Kanamycin is available in parenteral forms.
§ Neomycin is available in topical and oral forms.
§ Streptomycin is only available for IM use.
§ Tobramycin is used for short-term IM or IV treatment and is
also available in an ophthalmic form and as a nebulizer solution.
AMINOGLYCOSIDES

• Contraindications and Cautions

üKnown allergy to any of the aminoglycosides

üRenal or hepatic disease
üPre-existing hearing loss
ümyasthenia gravis or parkinsonism
ülactation
üduring pregnancy
AMINOGLYCOSIDES

Adverse effect
• Neurotoxicity
• Ototoxicity
• Nephrotoxicity
• GI effects
• Cardiac effects - palpitations, hypotension, and hypertension.
• Hypersensitivity reactions - purpura, rash, urticaria, and exfoliative dermatitis.
Note: Avoid combining aminoglycosides with potent diuretics; this increases
the incidence of ototoxicity, nephrotoxicity, and neurotoxicity
 Carbapenems
• The carbapenems are a relatively new class of broad-
spectrum antibiotics effective against gram-positive and gram-
negative bacteria.
• The carbapenems are bactericidal. They inhibit cell membrane
synthesis in susceptible bacteria, leading to cell death
• These drugs are used to treat serious infections caused by
susceptible strains of :
– S. pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, S. aureus,
Streptococcus pyogenes, E. coli, Peptostreptococcus, Klebsiella
pneumoniae, Clostridium clostridiiforme, Eubacterium lentum, Bacteroides
fragilis, Bacteroides dis-tasonis, Bacteroides ovatus, Bacteroides thetaiotamicron,
Bacteroides uniformis, Proteus mirabilis, P. aeruginosa, Acinetobacter
baumannii, Streptococcus agalactiae, Porphyromonas asaccharolytica,
Prevotella bivia,
Carbapenems
Pharmacokinetics

• Rapidly absorbed if given IM

• Reach peak levels at the end of the infusion if given IV

• Carbapenems are excreted unchanged in the urine

and have an average half-life of 1 to 4 hours.
Carbapenems
Pharmacokinetics
• Doripenem is one of the newer drugs of the class. It is given IV every
8 hours by a 1-hour IV infusion for 5 to 14 days.
• Ertapenem can be given IV or IM. It is given once a day for 5 to 14 days,
depending on the infection.
• Imipenem–cilastatin is a combination of imipenem, which interferes
with cell wall synthesis and causes bacterial cell death, and cilastatin,
which inactivates the imipenem and leads to increased urinary excretion of
the drug and decreased renal toxicity. It can be given IM or IV and is
approved for use in children.
• Meropenem is the first drug of this class, has limited use because of
the severe risk for potentially fatal GI toxicities. It is given IV over 1 hour,
every 8 hours for 5 to 14 days.
Carbapenems
Contraindications and Cautions
üknown allergy to any of the carbanems or beta-lactams
üseizure disorders
ümeningitis
ülactation
üUse caution during pregnancy because carbapenems are
used to treat only severe infections, and the benefi ts of
the drug must be carefully weighed against potential
adverse effects on the fetus
Carbapenems
Adverse Effects
ü Pseudomembranous colitis - swelling or irritation of large intestine
ü Clostridium difficile - diarrhea
ü Nausea and vomiting - lead to serious dehydration and electrolyte imbalance
ü Superinfections
ü Headache
ü Dizziness
ü Altered mental state
ü Seizures have been reported when carbapenems are
combined with other drugs
CEPHALOSPORINS
• The cephalosporins are both bactericidal and
bacteriostatic, depending on the dose used and the
specific drug involved
• These agents basically interfere with the cell
wall–building ability of bacteria when they divide
CEPHALOSPORINS

Pharmacokinetics
• The following cephalosporins are well absorbed from
the GI tract:
§ the first-generation drugs cefadroxil and cephalexin;
§ the second-generation drugs cefaclor, cefprozil, and
cefuroxime;
§ the third-generation drugs cefdinir, cefpodoxime, and
ceftibuten;
§ fourth-generation drugs cefditoren and cefepime
• Some can also absorbed well after IM injection and IV
administration
CEPHALOSPORINS
CEPHALOSPORINS
CEPHALOSPORINS
CEPHALOSPORINS
CEPHALOSPORINS
CEPHALOSPORINS

Contraindications and Cautions

• With known allergies to cephalosporins or penicillins

• Use with caution in patients with hepatic or renal
impairment
• Use with caution in pregnant or lactating patients
CEPHALOSPORINS

Adverse Effects Adverse Effects

• GI tract • CNS symptoms
– nausea
– vomiting – headache
– diarrhea – dizziness
– anorexia
– abdominal pain
– lethargy
– flatulence – paresthesias
– Pseudomembranous colitis
– bloody diarrhea
• Nephrotoxicity
– abdominal pain
FLUOROQUINOLONES
• The fluoroquinolones are a relatively new synthetic class of antibiotics
with a broad spectrum of activity
• It enter the bacterial cell by passive diffusion through channels in the cell
membrane. Once inside, they interfere with the action of DNA enzymes
necessary for the growth and reproduction of the bacteria
• The fluoroquinolones are indicated for treating infections caused by
susceptible strains of gram-negative bacteria, including:
– E. coli, P. mirabilis, K. pneumoniae, Enterobacter cloacae, Proteus vulgaris, Proteus
rettgeri, Morganella morganii, M. catarrhalis, H. infl uenzae, H. parainfl uenzae, P.
aeruginosa, Citrobacter freundii, S. aureus, Staphylococcus epidermidis, some
Neisseria gonorrhoeae, and group D streptococci.
• These infections frequently include urinary tract, respiratory tract, and
skin infections
FLUOROQUINOLONES
Pharmacokinetics
• The fluoroquinolones are absorbed from the GI tract, metabolized in
the liver, and excreted in the urine and feces. These drugs are widely
distributed in the body and cross the placenta and enter breast milk
• Ciprofloxacin is available in injectable, oral, and topical forms.
• Gemifloxacin, lomefloxacin, and moxifloxacin are oral agents
• Levofloxacin is available in oral and IV forms
• Norfloxacin is only available in an oral form.
• Ofloxacin can be given IV or orally and is also available as an
ophthalmic agent for the treatment of ocular infections caused by
susceptible bacteria.
FLUOROQUINOLONES
FLUOROQUINOLONES
Contraindications and caution
• known allergy to any fluoroquinolones
• pregnant or lactating patients
• Use with caution in the presence of renal dysfunction
• seizures
• These drugs have been associated with lesions in
developing cartilage and therefore are not recom-
mended for use in children younger than 18 years of age.
FLUOROQUINOLONES

Adverse Effects
§ headache, dizziness, insomnia, and depression
related to possible effects on the CNS membranes.
§ nausea, vomiting, diarrhea, and dry mouth, related to
direct drug effect on the GI tract
§ risk of tendinitis and tendon rupture
§ Immunological effects include bone marrow depression
§ Other adverse effects include fever, rash, and
photosensitivity
PENICILLINS AND PENICILLINASE-RESISTANT ANTIBIOTICS

• The penicillins are indicated for the treatment of

streptococcal infections, including pharyngitis, tonsillitis,
scarlet fever, and endocarditis; pneumococcal infections;
staphylococcal infections; fusospirochetal infections; rat-
bite fever; diphtheria; anthrax; syphilis; and uncompli-
cated gonococcal infections.
• At high doses, these drugs are also used to treat
meningococcal meningitis
PENICILLINS AND PENICILLINASE-RESISTANT ANTIBIOTICS

• With the prolonged use of penicillin, more and more bacterial

species have synthesized the enzyme penicillinase to
counteract the effects of penicillin.

• Researchers have developed a group of drugs with a

resistance to penicillinase, which allows them to remain
effective against bacteria that are now resistant to the penicillins.
PENICILLINS AND PENICILLINASE-RESISTANT ANTIBIOTICS

Pharmacokinetics
• Most of the penicillins are rapidly absorbed from the GI
tract, reaching peak levels in 1 hour.
• Penicillins are excreted unchanged in the urine, making
renal function an important factor in safe use of the drug.
• Penicillins enter breast milk and can cause adverse
reactions
PENICILLINS AND PENICILLINASE-RESISTANT ANTIBIOTICS

Contraindications and Cautions

• These drugs are contraindicated in patients with allergies
to penicillin or cephalosporins or other allergens
• Use with caution in patients with renal disease
• use in patients who are pregnant and in lactating patients
should be limited to situations in which the mother clearly
would benefit from the drug
PENICILLINS AND PENICILLINASE-RESISTANT ANTIBIOTICS

Adverse Effects
• Common adverse effects include nausea, vomiting,
diarrhea, abdominal pain, glossitis, stomatitis, gastritis,
sore mouth, and furry tongue
• Pain and inflammation at the injection site can occur with
injectable forms of the drugs
• Hypersensitivity reactions may include rash, fever,
wheezing, and, with repeated exposure, anaphylaxis that
can progress to anaphylactic shock and death.
SULFONAMIDES

• The sulfonamides, or sulfa drugs, are drugs that inhibit

folic acid synthesis
• The sulfonamides competitively block paraaminobenzoic
acid to prevent the synthesis of folic acid in susceptible
bacteria that synthesize their own folates for the
production of RNA and DNA
• This includes gram-negative and gram-positive bacteria
such as Chlamydia trachomatis and Nocardia and some
strains of H. influenzae, E. coli, and P. mirabilis.
SULFONAMIDES

Pharmacokinetics
• The sulfonamides are teratogenic; they are distributed into breast milk
• These drugs, given orally, are absorbed from the GI tract, metabolized in the
liver, and excreted in the urine. The time to peak level and the half-life of the
individual drug vary
– Sulfadiazine is an oral agent slowly absorbed from the GI tract, reaching peak levels
in 3 to 6 hours.
– Sulfasalazine is rapidly absorbed from the GI tract, reaching peak levels in 2 to 6
hours. After being metabolized in the liver, it is excreted in the urine with a half-life of
5 to 10 hours
– Cotrimoxazole is rapidly absorbed from the GI tract, reaching peak levels in 2
hours. After being metabolized in the liver, it is excreted in the urine with a half-life of
7 to 12 hours.
SULFONAMIDES

Contraindications and Cautions

• any known allergy to any sulfonamide, to sulfonylureas, or
to thiazide diuretics
• during pregnancy
• during lactation
• used with caution in patients with renal disease or a
history of kidney stones
SULFONAMIDES

• Adverse Effects
§ includes GI effects such as nausea, vomiting, diarrhea,
abdominal pain, anorexia, stomatitis, and hepatic injury
§ Renal effects include crystalluria, hematuria, and proteinuria,
which can progress to a nephrotic syndrome and possible toxic
nephrosis
§ CNS effects include headache, dizziness, vertigo, ataxia,
convulsions, and depression
§ Dermatological effects include photosensitivity and rash related
to direct effects on the dermal cells
TETRACYCLINES

• As semisynthetic antibiotics based on the structure of a

common soil mold.
• The tetracyclines work by inhibiting protein synthesis in a
wide range of bacteria, leading to the inability of the
bacteria to multiply
Tetracyclines are indicated for treatment of infections
caused by Rickettsiae, Mycoplasma pneumoniae,
Borrelia recurrentis, H. infl uenzae, Haemophilus ducreyi,
Pasteurella pestis, Pasteurella tularensis, Bartonella
bacilliformis, Bacteroides species, Vibrio comma, Vibrio
fetus, Brucella species, E. coli, E. aerogenes, Shigella
species, Acinetobacter calcoaceticus, Klebsiella species,
Diplococcus pneumoniae, and S. aureus; against agents
that cause psittacosis, ornithosis, lymphogranuloma
venereum, and granuloma inguinale
TETRACYCLINES

Pharmacokinetics
»Tetracyclines are absorbed adequately, but not
completely, from the GI tract
»Their absorption is affected by food, iron, calcium, and
other drugs in the stomach.Tetracyclines are
concentrated in the liver and excreted unchanged in
the urine, with half-lives ranging from 12 to 25 hours.
»Tetracycline, Doxycycline, minocyclines,
Tigecyclines
TETRACYCLINES

Contraindications and Cautions

Tetracyclines are contraindicated in patients with known
allergy to tetracyclines or to tartrazine (e.g., in specifi c
oral preparations that contain tartrazine) and during
pregnancy and lactation because of effects on developing
bones and teeth.
TETRACYCLINES

Adverse Effects
• GI tract and include nausea, vomiting, diarrhea,
abdominal pain, glossitis, and dysphagia
• Dermatological effects include photosensitivity and rash
• Superinfections, including yeast infections, occur when
bacteria of the normal flora are destroyed
• Hematological effects are less frequent, such as
hemolytic anemia and bone marrow depression
secondary to the effects on bone marrow cells that turn
over rapidly
ANTIMYCOBACTERIALS

The group of bacteria that contain the

pathogens that cause tuberculosis and leprosy—are classifi
ed on the basis of their ability to hold a stain even in
the presence of a “destaining” agent such as acid. Because
of this property, they are called “acid-fast” bacteria.
ANTIMYCOBACTERIALS

Mycobacterium leprae
Causes leprosy, also known
as Hansen’s disease, which is
characterized by disfiguring skin
lesions and destructive effects on the
respiratory tract. Leprosy is also a
worldwide health problem; it is
infectious when the mycobacteria
invade the skin or respiratory tract of
susceptible individuals
ANTIMYCOBACTERIAS

• ANTITUBERCULOSIS DRUGS
– Tuberculosis can lead to serious damage in the lungs,the GU
tract, bones, and the meninges. Because M. tuberculosis is so
slowly growing, the treatment must be continued for 6 months
to 2 years.

– The first-line drugs for treating tuberculosis are isoniazid

(Nydrazid), rifampin (Rifadin), pyrazinamide (generic),
ethambutol (Myambutol), streptomycin (generic), and
rifapentine (Priftin).
ANTIMYCOBACTERIALS

• LEPROSTATIC DRUGS
– The antibiotic used to treat leprosy is dapsone (generic), which
has been the mainstay of leprosy treatment for many years,
although resistant strains are emerging.

– Most of the antimycobacterial agents act on the DNA and/or

RNA of the bacteria, leading to a lack of growth and eventually
to bacterial death.
LEPROSTATIC DRUGS

• Pharmakonetics
– These drugs, given orally, are metabolized in the liver and
excreted in the urine; they cross the placenta and enter breast
milk, placing the fetus or child at risk for adverse reactions (see
contraindications and cautions).
Leprostatic Drug

• Contraindications and Cautions

– Antimycobacterials are contraindicated for patients
with any known allergy to these agents; in those with
severe renal or hepatic failure, which could interfere
with the metabolism or excretion of the drug; in those
with severe CNS dysfunction, which could be
exacerbated by the actions of the drug; and in
pregnancy because of possible adverse effects on the
fetus.
LEPROSTATIC DRUGS

• Adverse Effects
– CNS effects, such as neuritis, dizziness, headache,
malaise, drowsiness, and hallucinations, are often
reported and are related to direct effects of the drugs
on neurons.
– These drugs also are irritating to the GI tract,
causing nausea, vomiting, anorexia, stomach upset,
and abdominal pain. Rifampin, rifabutin, and
rifapentine cause discoloration of body fluids from
urine to sweat and tears.
OTHER ANTIBIOTICS

• Ketolides

• Lincosamides

• Lipoglycopeptides

• Macrolides

• Monobactams
OTHER ANTIBIOTICS

• KETOLIDES
– The ketolides block protein synthesis within
susceptible bacteria, leading to cell death, which
makes them structurally related to the macrolide
antibiotics .
KETOLIDES

– Telithromycin is effective against S.

pneumoniae, including certain multidrug-
resistant strains, H. influenzae, M. catarrhalis,
Chlamydophila pneumoniae, and M.
pneumoniae. It is only approved for use in
treating mild to moderate community-acquired
pneumonia
KETOLIDES

• PHARMACOKINETICS
– It is rapidly absorbed through the GI tract, reaching peak levels
in 1 hour.
KETOLIDES

• ADVERSE EFFECTS
–The adverse effects associated with
telithromycin are largely secondary to
toxic effects on the GI tract: nausea,
vomiting, taste alterations, and the
potential for pseudomembranous colitis.
OTHER ANTIBIOTICS

• LINCOSAMIDES
– These drugs include clindamycin (Cleocin) and
lincomycin (Lincocin).

– These drugs are used in the treatment of severe

infections when a less-toxic antibiotic cannot be used.
LINCOSAMIDES

• PHARMACOKINETICS
– The lincosamides are rapidly absorbed from the GI tract or from
IM injections and are metabolized in the liver and excreted in
the urine and feces.

– Clindamycin has a half-life of 2 to 3 hours. It is available in

parenteral and oral forms, as well as in topical and vaginal
forms for the treatment of local infections.

– Lincomycin has a half-life of 5 hours. It can be given orally, IM,

or IV.
LINCOSAMDIES

• ADVERSE EFFECTS
–Lincosamide may be the drug of choice.
Some other toxic effects that limit
usefulness are pain, skin infections, and
bone marrow depression.
OTHER ANTIBIOTICS

• LIPOGLYCOPEPTIDES
– They inhibit bacterial cell wall
– synthesis by interfering with the polymerization and
– cross-linking of peptidoglycans
LIPOGLYCOPEPTIDES

• Membrane barrier function causing bacterial cell

death. Televancin is effective against susceptible
strains of the gram-positive organisms:
– S. aureus (including methicillin-susceptible and
methicillin-resistant isolates), S. pyogenes, S.
agalactiae, Streptococcus anginosus, Enterococcus
faecalis (vancomycin-susceptible isolates only)
LIPOGLYCOPEPTIDES

• PHARMACOKINETICS
– Its site of metabolism is not known; it has a half-life of 8 to
9 hours.

– Televancin is contraindicated with known allergy to any

component of the drug to avoid hypersensitivity reactions;
with pregnant and lactating patients because of the
potential for toxic effects on the fetus or infant. Televancin
has a Black Box Warning regarding serious fetal risk.
LIPOGLYCOPEPTIDES

• ADVERSE EFFECT
–A transfusion reaction called red man
syndrome with flushing, sweating, and
hypotension can occur with rapid
infusion. Infusion site reactions with pain
and redness have also been reported.
OTHER ANTIBIOTICS
• MACROLIDES
– Include erythromycin (Ery-
Tab, Eryc, and others),
– azithromycin (Zithromax),
clarithromycin (Biaxin), and
– Dirithromycin (Dynabac).
The macrolides, which may be
bactericidal or bacteriostatic,
exert their effect by binding to
the bacterial cell membrane
and changing protein function
MACROLIDES

• PHARMACOKINETICS
– Erythromycin is metabolized in the liver, with excretion
mainly in the bile to feces. The half-life of erythromycin is
1.6 hours.
– The half-life of azithromycin is 68 hours, making it useful for
patients who have trouble remembering take pills because
it can be given once a day.
– The half-life of clarithromycin is 3 to 7 hours.
– Most of the drug is excreted through the feces. It has a half-
life of 2 to 36 hours
MACROLIDES

• ADVERSE EFFECTS
These include ;
– abdominal cramping, anorexia, diarrhea, vomiting, and
– pseudomembranous colitis. Other effects include
neurological symptoms such as confusion, abnormal
thinking, and uncontrollable emotions, which could be
related todrug effects on the CNS membranes;
hypersensitivity reactions ranging from rash to anaphylaxis;
and superinfections related to the loss of normal flora.
OTHER ANTIBIOTICS

• MONOBACTAM ANTIBIOTIC
–The drug is indicated for the treatment of
urinary tract, skin, intra-abdominal, and
gynecological infections, as well as
septicemia caused by susceptible bacteria,
including E. coli, Enterobacter, Serratia,
Proteus, Salmonella, Providencia,
Pseudomonas, Citrobacter, Haemophilus,
Neisseria, and Klebsiella.
MONOBACTAM ANTIBIOTIC

• PHARMACOKINETICS
– Aztreonam is available for IV and IM use only and reaches peak
effect levels in 1 to 1.5 hours. Its half-life is 1.5 to 2 hours.

– because of the possibility of cross-reactivity, in those with renal or

hepatic dysfunction that could interfere with the clearance and
excretion of the drug, and in pregnant and lactating women
because of potential adverse effects on the fetus or neonate
MONOBACTAM ANTIBIOTIC

• ADVERSE EFFECT
– Hepatic enzyme elevations related to direct drug
effects on the liver may also occur.

– Other effects include inflammation, phlebitis, and

discomfort at injection sites, as well as the potential
for allergic response, including anaphylaxis
NEW ANTIBIOTICS AND ADJUNCTS

• Daptomycin was introduced in the fall of 2003

as a cyclic lipopeptide antibiotic
• Fidaxomicin was approved in 2011 as an orphan
drug to treat C. difficile infections
• Linezolid (Zyvox) was introduced in 2000. This
drug is indicated specifically for treatment of
infections caused by vancomycin-resistant and
methicillinresistant strains of bacteria
 NEW ANTIBIOTICS AND ADJUNCTS

• Tigecycline, approved by the Food and Drug Administration in

2005, was the first drug of a new class of antibiotics called
glycylcyclines.
• Streptogramins became available in 1999 and include
quinupristin and dalfopristin, which are available only in a
combination form called Synercid
• Rifaximin (Xifaxan) was approved in 2004 for the treatment of
traveler’s diarrhea
Antiviral Agents
Definition
• Antiviral drugs are a class of medication used for treating viral infections. Most
antivirals target specific viruses, while a broad-spectrum antiviral is effective
against a wide range of viruses.
• antiviral drugs concluded that they can increase the cell's resistance to a virus
(interferons)
AGENTS FOR INFLUENZA A AND RESPIRATORY VIRUSES

• The exact mechanism of action of

drugs that combat Influenza A and
respiratory viruses is not known.
• The belief is that these agents
prevent shedding of the viral protein
coat and entry of the virus into the
cell
• This action prevents viral replication,
causing viral death.
AGENTS FOR INFLUENZA A AND RESPIRATORY VIRUSES
Pharmacokinetics
• Amantadine is slowly absorbed from the
gastrointestinal (GI) tract, reaching peak
levels in 4 hours. Excretion occurs
unchanged through the urine, with a half-
life of 15 hours.
• Ribavirin, an inhaled drug, is slowly
absorbed through the respiratory tract. It is
metabolized at the cellular level and is
excreted in the feces and urine with a half-
life of 9.5 hours. It is teratogenic and is
rated pregnancy category X.
Pharmacokinetics
• Rimantadine is absorbed from the GI tract
with peak levels achieved in 6 hours. This
drug is extensively metabolized in the liver
and excreted in the urine
• Zanamivir must be delivered by a
Diskhaler device, which comes with every
prescription of zanamivir. It is absorbed
through the respiratory tract and excreted
unchanged in the urine with a half-life of
2.5 to5.1 hours.
• Oseltamivir is readily absorbed from the
GI tract, extensively metabolized in the
urine, and excreted in the urine with a half-
life of 6 to 10 hours.
AGENTS FOR INFLUENZA A AND RESPIRATORY VIRUSES
Contraindications and Cautions
• Amantadine must be used at reduced
doses and with caution in patients who
have any renal impairment to avoid altered
metabolism and excretion of the drug.
Amantadine should be used during
pregnancy and lactation only if the benefits
clearly outweigh the risks to the fetus or
neonate
• Patients with renal dysfunction who are
taking oseltamivir require reduced doses
and close monitoring to avoid altered
metabolism and excretion of the drug. It
should be used during pregnancy and
lactation only if the benefits clearly
outweigh the risks to the fetus or neonate
• Contraindications and Cautions
• Women of childbearing age should be
advised to use barrier contraceptives if
they are taking ribavirin. The drug has
been associated with serious fetal effects.
• Rimantadine is embryotoxic in animals
and should be used during pregnancy only
if the benefits clearly outweigh the risks,
Use in children should be limited to
prevention of influenza A infections.
• Zanamivir must be used cautiously in
patients with any renal impairment. It
should be used during pregnancy and
lactation only if the benefits clearly
outweigh the risks to the fetus or neonate.
AGENTS FOR INFLUENZA A AND RESPIRATORY VIRUSES

Adverse Effects
• These adverse effects
include :
• light-headedness
• dizziness
• insomnia
• nausea
• orthostatic hypotension
• urinary retention
AGENTS FOR HERPES AND CYTOMEGALOVIRUS
• Herpes viruses account for a
broad range of conditions,
including cold sores,
encephalitis, shingles, and
genital infections.
• Cytomegalovirus (CMV),
although slightly different from
the herpes virus, can affect the
eye, respiratory tract, and liver
and reacts to many of the
same drugs.
• Drugs that combat herpes and
CMV inhibit viral DNA
replication by competing with
viral substrates to form shorter,
noneffective DNA chains.
• These antiviral agents are
indicated for treatment of the
DNA viruses herpes simplex,
herpes zoster, and CMV
 AGENTS FOR HERPES AND CYTOMEGALOVIRUS
Pharmacokinetics
• Most of the agents for herpes and CMV are readily
absorbed and excreted through the kidney
• Cidofovir has been proven to be embryotoxic in
animals, no adequate studies have been completed
for the other agents, Cidofovir, which is given by
intravenous (IV) infusion, reaches peak levels at the
end of the infusion and in studies was cleared from
the system within 15 minutes after the infusion. It is
excreted unchanged in the urine and must be given
with probenecid to increase renal clearance of the
drug.
• Acyclovir, which can be given orally and parenterally
or applied topically, reaches peak levels within 1 hour
and has a half-life of 2.5 to 5 hours. It is excreted
unchanged in the urine. It crosses into breast milk,
which exposes the neonate to high levels of the drug.
Pharmacokinetics
• Famciclovir, an oral drug, is well absorbed from the
GI tract, reaching peak levels in 2 to 3 hours.
Famciclovir is metabolized in the liver and excreted
in the urine and feces. It has a half-life of 2 hours and
is known to cross the placenta.
• Foscarnet is available in IV form only. It reaches
peak levels at the end of the infusion and has a half-
life of 4 hours. About 90% of foscarnet is excreted
unchanged in the urine, making it highly toxic to the
kidneys. Use caution and at reduced dose in patients
with renal impairment
• Ganciclovir is available in IV and oral forms. It has a
slow onset and reaches peak levels at 1 hour if given
IV and 2 to 4 hours if given orally. This drug is
primarily excreted unchanged in the feces with some
urinary excretion, with a half-life of 2 to 4 hours.
AGENTS FOR HERPES AND CYTOMEGALOVIRUS

Pharmacokinetics
• Valacyclovir is an oral agent and is rapidly absorbed
from the GI tract and metabolized in the liver to acyclovir.
Excretion occurs through the urine, so caution should be
used in patients with renal impairment.
• Valganciclovir is the oral prodrug, that is, it is
immediately converted to ganciclovir once it is in the
body. It is rapidly absorbed and reaches peak levels in 3
hours. It is primarily excreted unchanged in the feces
with some urinary excretion, with a half-life of 2.5 to 3
hours.
AGENTS FOR HERPES AND CYTOMEGALOVIRUS

• Contraindications and Cautions • Contraindications and Cautions

• Should not be used during pregnancy or • Use cidofovir with caution in children with
lactation, use only if the benefits clearly AIDS because of the potential carcinogenic
outweigh the potential risks to the fetus or effects and effects on fertility. If no other
infant. treatment option is available, monitor the
• Avoid use in patients with known allergies child very closely.
to antiviral agents • For famciclovir, safety of use in children
• In patients with renal disease younger than 18 years of age has not been
• In patients with severe CNS disorders: established.
– headache, • Foscarnet has been shown to affect bone
development and growth. Foscarnet, as
– neuropathy,
well as ganciclovir and valganciclovir,
– paresthesias, should not be used in children unless the
– confusion, benefit clearly outweighs the risk and the
– hallucinations child is monitored very closely.
AGENTS FOR HERPES AND CYTOMEGALOVIRUS
Adverse Effects
• nausea
• vomiting
• headache,
• depression
• paresthesias
• neuropathy
• hair loss
• Rash
• inflammation
• burning often occur at sites of IV injection and
topical application.
• Renal dysfunction and renal failure
AGENTS FOR HIV AND AIDS
• The human immunodeficiency
virus (HIV) attacks the helper T
cells (CD4 cells) within the immune
system.
• This virus (an RNA strand) enters
the helper T cell, where it uses
reverse transcriptase to copy the
RNA and produce a double-
stranded viral DNA
• The DNA enters the host cell
nucleus and slides into the
chromosomal DNA to change the
cell’s processes to ones that
produce new viruses.
• Loss of helper T cell function
causes acquired immune
deficiency syndrome (AIDS) and
AIDS-related complex (ARC),
diseases that are characterized by
the emergence of a variety of
opportunistic infections and cancers
that occur when the immune
system is depressed and unable to
function properly
NONNUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS

• Have direct effects on the HIV virus activities within

the cell.
• Bind directly to HIV reverse transcriptase, blocking
both RNA- and DNA-dependent DNA polymerase
activities.
• They prevent the transfer of information that would
allow the virus to carry on the formation of viral DNA
• As a result, the virus is unable to take over the cell
and reproduce
NONNUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS
Pharmacokinetics
• Delavirdine is rapidly absorbed from the GI tract, with peak levels occurring within 1 hour.
Delavirdine is extensively metabolized by the cytochrome P450 system in the liver and is
excreted through the urine.
• Efavirenz is absorbed rapidly from the GI tract, reaching peak levels in 3 to 5 hours.
Efavirenz is metabolized in the liver by the cytochrome P450 system and is excreted in the
urine and feces with a half-life of 52 to 76 hours.
• Etravirine is rapidly absorbed from the GI tract, reaching peak levels in 2.5 to 4 hours.
Etravirine is metabolized in the liver by the cytochrome P450 system and is excreted in feces
and urine with a half-life of 21 to 61 hours.
• Nevirapine is recommended for use in adults and children older than 2 months. After rapid
GI absorption with a peak effect occurring at 4 hours, nevirapine is metabolized by the
cytochrome P450 system in the liver. Excretion is through the urine with a half-life of 45
hours
• Rilpivirine (Edurant) is the newest drug in this class. It is rapidly absorbed from the GI tract,
reaching peak levels in 4 to 5 hours. It is metabolized in the liver and excreted in feces and
urine with a half-life of 50 hours.
NONNUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS

Contraindications and Cautions

• There are no adequate studies of nonnucleoside reverse
transcriptase inhibitors in pregnancy, so use should be limited to
situations in which the benefits clearly outweigh any risks.
• It is suggested that women not breastfeed if they are infected with
HIV.
• Safety for the use of delavirdine in children has not been
established.
NONNUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS

Adverse Effects
• GI related—dry mouth, constipation or diarrhea, nausea,
abdominal pain, and dyspepsia
• Dizziness, blurred vision, and headache have also been
reported
• A flu-like syndrome of fever, muscle aches and pains,
fatigue, and loss of appetite often occurs with the anti-
HIV drugs, but these signs and symptoms may also be
related to the underlying disease.
NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS

• The nucleoside reverse transcriptase inhibitors were

the first class of drugs developed to treat HIV infections
• These are drugs that compete with the naturally
occurring nucleosides within a human cell that the virus
would need to develop
• These nucleosides, however, lack a substance needed
to extend the DNA chain.
• As a result, the DNA chain cannot lengthen and cannot
insert itself into the host DNA
NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS

Pharmacokinetics
• Abacavir is an oral drug that is rapidly absorbed from the GI tract. It is metabolized in the liver
and excreted in feces and urine with a half-life of 1 to 2 hours.
• Didanosine is rapidly destroyed in an acid environment and therefore must be taken in a
buffered form. It reaches peak levels in 15 to 75 minutes. Didanosine undergoes intracellular
metabolism with a half-life of 8 to 24 hours. It is excreted in the urine
• Emtricitabine has the advantage of being a onecapsule-a-day therapy. Emtricitabine has a
rapid onset and peaks in 1 to 2 hours. It has a half-life of 10 hours, and after being metabolized
in the liver is excreted in the urine and feces
• Lamivudine is rapidly absorbed from the GI tract and is excreted primarily unchanged in the
urine. It peaks within 4 hours and has a half-life of 5 to 7 hours. Because excretion depends on
renal function, dose reduction is recommended in the presence of renal impairment
• Stavudine is rapidly absorbed from the GI tract, reaching peak levels in 1 hour. Most of the
drug is excreted unchanged in the urine, making it important to reduce dose and monitor
patients carefully in the presence of renal dysfunction
NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS

Pharmacokinetics
• Tenofovir is a newer drug that affects the virus at a slightly different
point in replication—a nucleotide that becomes a nucleoside. It is
used only in combination with other antiretroviral agents. It is rapidly
absorbed from the GI tract, reaching peak levels in 45 to 75 minutes.
Its metabolism is not known, but it is excreted in the urine.
• Zidovudine was one of the first drugs found to be effective in the
treatment of AIDS. It is rapidly absorbed from the GI tract, with peak
levels occurring within 30 to 75 minutes. Zidovudine is metabolized
in the liver and excreted in the urine, with a half-life of 1 hour.
NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS

Contraindications and Cautions

• Of the nucleosides, zidovudine is the only agent that has
been proven to be safe when used during pregnancy.
• Women infected with HIV are urged not to breast-feed.
• Tenofovir, zidovudine, and emtricitabine should be
used with caution in the presence of hepatic dysfunction or
severe renal impairment
• Zidovudine should also be used with caution with any
bone marrow suppression because it could aggrevate the
suppression.
NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS

Adverse Effects
• Serious-to-fatal hypersensitivity reactions have occurred with abacavir, and it
must be stopped immediately at any sign of a hypersensitivity reaction (fever,
chills, rash, fatigue, GI upset, flu-like symptoms)
• Serious pancreatitis, hepatomegaly, and neurological problems have been
reported with didanosine
• Emtricitabine has been associated with severe and even fatal hepatomegaly
with steatosis
• Severe hepatomegaly with steatosis has been reported with tenofovir
• Patients also need to be alerted that the drug may cause changes in body fat
distribution, with loss of fat from arms, legs, and face and deposition of fat on
the trunk, neck, and breasts.
PROTEASE INHIBITORS

• The protease inhibitors block protease activity within

the HIV virus
• Protease is essential for the maturation of an infectious
virus; without it, an HIV particle is immature and
noninfective, unable to fuse with and inject itself into a
cell
PROTEASE INHIBITORS

Pharmacokinetics
• All are taken thru PO
§ Atazanavir
§ Darunavir
§ Fosamprenavir
§ Indinavir
§ Lopinavir
§ Tipranavir
§ Nelfinavir
§ Ritonavir
§ Saquinavir
PROTEASE INHIBITORS

Adverse Effects
• As with the other antivirals, patients
taking these drugs often experience GI
effects, including nausea, vomiting,
diarrhea, anorexia, and changes in liver
function.
• Elevated cholesterol and triglyceride
levels may occur
• Rashes, pruritus, and the potentially
fatal Steven–Johnson syndrome have
also occurred.
FUSION INHIBITOR

• This agent acts at a different site than do other HIV

antivirals. The fusion inhibitor prevents the fusion of the
virus with the human cellular membrane, which
prevents the HIV-1 virus from entering the cell
• Enfuvirtide (Fuzeon) is used in combination with other
antiretroviral agents to treat adults and children older
than 6 years who have evidence of HIV-1 replication
despite ongoing antiretroviral therapy
FUSION INHIBITOR

Pharmacokinetics Contraindication and Caution

• Enfuvirtide is contraindicated with
• Enfuvirtide is given by hypersensitivity to any component
subcutaneous injection of the drug
and peaks in effect in 4 to • It should be used with caution in
8 hours. After metabolism the presence of lung disease or
in the liver, it is recycled in pregnancy
the tissues and not Adverse Effect
excreted. The half-life of • The drug has been associated with
enfuvirtide is 3.2 to 4.4 insomnia, depression, peripheral
neuropathy, nausea, diarrhea, pneumonia,
hours and injection-site reactions
CCR5 CORECEPTOR ANTAGONIST

• Maraviroc (Selzentry) is a CCR5 coreceptor

antagonist. It blocks the receptor site on the cell
membrane to which the HIV virus needs to interact to
enter the cell
• It is indicated for the treatment of HIV in adults as
part of combination therapy with other antivirals
CCR5 CORECEPTOR ANTAGONIST
Pharmakonetics
• Maraviroc is rapidly absorbed from
the GI tract, metabolized in the liver,
and excreted primarily through the
feces. It has a half-life of 14 to 18
hours.
Adverse Effect
• Severe hepatotoxicity has been
reported with thisdrug, often
preceded by a systemic allergic
reaction with eosinophilia and rash
Contraindications
• Maraviroc should not be used with
known hypersensitivity to any
component of the drug . The safety
and efficacy of maraviroc in children
has not been established.
• Caution should be used in the
presence of liver disease or
coinfection with hepatitis B,
because of the risk of serious
hepatic toxicity.
INTEGRASE INHIBITOR

• The drug raltegravir (Isentress) belongs to this class.

• Raltegravir inhibits the activity of the virus-specific enzyme
integrase, an encoded enzyme needed for viral replication.
Blocking this enzyme prevents the formation of the HIV-1
provirus and leads to a decrease in viral load and increase in
active CD4 cells
• It is reserved for use in patients who have been treated with
other antivirals and have evidence of a return to viral
replication
INTEGRASE INHIBITOR

Pharmacokinetics Contraindications and Caution

• Raltegravir is contraindicated with known
• Raltegravir is rapidly absorbed hypersensitivity to any component of the
from the GI tract and drug, as initial treatment in adults, for use
metabolized in the liver. It has in children
• Caution should be used if the patient is at
a half-life of 3 hours and is risk for rhabdomyolysis or myopathy and
excreted primarily in the feces during pregnancy.
• Patients taking this drug must be very
Adverse Effect careful to continue the drug regimen to
• Headache, dizziness, and an help decrease the development of resistant
strains of the virus.
increased risk for the
development of
rhabdomyolysis and myopathy
ANTI–HEPATITIS B AGENTS
• Hepatitis B is a serious-to-potentially fatal
viral infection of the liver.
• The hepatitis B virus can be spread by
blood or blood products, sexual contact, or
contaminated needles or instruments.
• Health care workers are at especially high
risk for contracting hepatitis B due to
needle sticks.
• Hepatitis B has a higher mortality than
other types of hepatitis. Individuals infected
may also develop a chronic condition or
become a carrier
ANTI–HEPATITIS B AGENTS
• These antiviral drugs are indicated • Adefovir (Hepsera) and
for the treatment of adults with entecavir (Baraclude) were
chronic hepatitis B who have
approved specifically for
evidence of active viral replication
and either evidence of persistent treating chronic hepatitis B.
elevations in serum • In 2006, another NRTI,
aminotransferases or histologically Telbivudine (Tyzeka) was
active disease found to be very effective in
• The drugs inhibit reverse preventing viral replication in
transcriptase in the hepatitis B virus
active hepatitis B patients
and cause DNA chain termination,
leading to blocked viral replication
and decreased viral load
ANTI–HEPATITIS B AGENTS
Pharmacokinetics
• These drugs are rapidly absorbed from the
GI tract, with peak effects occurring in 0.5
to 1.5 hours (entecavir), 0.5 to 4 hours
(adefovir), and 1 to 4 hours (telbivudine).
Adverse Effect
• Headache, dizziness, nausea, diarrhea,
and elevated liver enzymes.
• Severe hepatomegaly with steatosis,
sometimes fatal, has been reported with
adefovir and telbivudine use
• Lactic acidosis and renal impairment have
been reported with entecavir and adefovir
• A potential risk for hepatitis B exacerbation
could occur when the drugs are stopped
Contraindications and
Cautions
• These drugs are contraindicated
with any known allergy
• with lactation
• Use caution when administering
these drugs to patients with renal
impairment and severe liver
disease
• those who are pregnant because
the effects on the fetus are not
known.
ANTI–HEPATITIS C AGENTS
• In 2011, two new drugs were
approved for the treatment of
hepatitis C, boceprevie (Victrelis)
and telaprevir (Incivek)
• People can get HCV in a number of
ways, including:
ü exposure to blood that is infected with the
virus,
ü being born to a mother with HCV,
ü sharing a needle,
ü having sex with an infected person,
ü sharing personal items such as a razor or
toothbrush with someone who is infected
with the virus
ü from unsterilized tattoo or piercing tools
LOCALLY ACTIVE ANTIVIRAL AGENTS
• Some antiviral agents are
given locally to treat local
viral infections.
These agents include:
– docosanol (Abreva),
– ganciclovir (Vitrasert),
– imiquimod (Aldara),
– penciclovir(Denavir),
– trifluridine (Viroptic).
• These antiviral agents act
on viruses by interfering
with normal viral
replication and metabolic
processes.
• They are for specific, local
viral infections
LOCALLY ACTIVE ANTIVIRAL AGENTS

Contraindications and Adverse Effect

Cautions • Because these drugs are not
• Locally active antiviral absorbed systemically, the
adverse effects most
drugs are not absorbed
commonly reported are local
systemically, but caution burning, stinging, and
must be used in patients discomfort.
with known allergic • These effects usually occur at
reactions to any topical the time of administration and
drugs. pass with time.
ANTIFUNGAL AGENTS
What is Fungal Infection?

• Fungal infections in humans range from conditions such

as the annoying “athlete’s foot” to potentially fatal
systemic infections
• An infection caused by a fungus is called a mycosis.
• Fungi differ from bacteria in that the fungus has a rigid
cell wall that is made up of chitin and various
polysaccharides and a cell membrane that contains
ergosterol
• The composition of the protective layers of the fungal cell
makes the organism resistant to antibiotics
What are the Anti fungal Agents
SYSTEMIC ANTIFUNGALS
• The drugs used to treat systemic
fungal infections can be toxic to the
host and are not to be used
indiscriminately.
• It is important to get a culture of the
fungus causing the infection to
ensure that the right drug is being
used so that the patient is not put at
additional risk from the toxic
adverse effects associated with
these drugs
TOPICAL ANTIFUNGALS
• Some antifungal drugs are
available only in topical forms for
treating a variety of mycoses of the
skin and mucousmembranes
• Fungi that cause these mycoses
are called dermatophytes. These
diseases include a variety of tinea
infections, which are often referred
to as ringworm, although the causal
organism is a fungus, not a worm
SYSTEMIC ANTIFUNGALS
AZOLE ANTIFUNGALS List of Azole
• The azoles are a large group of antifungals
used to treat systemic and topical fungal • Fluconazole (Diflucan)
infections
• These drugs bind to sterols and can cause • Itraconazole (Sporanox)
cell death (a fungicidal effect) or interfere
with cell replication (a fungistatic effect), • Ketoconazole (Nizoral)
depending on the type of fungus being
affected and the concentration of the drug
• Posaconazole (Noxafil)
• Although azoles are considered less toxic • Terbinafine (Lamisil)
than some other
• Antifungals,they may also be less effective • Voriconazole (Vfend)
in very severe and progressive infections.
SYSTEMIC ANTIFUNGALS - AZOLE

Pharmacokinetic
• Fluconazole and voriconazole are available in oral and
intravenous (IV) preparations, making it possible to start the drug
intravenously for a serious infection and then switch to an oral
form when the patient’s condition improves and he or she is able
to take oral medications.
• Ketoconazole, itraconazole, posaconazole, and terbinafine
are administered orally.
• Ketoconazole is also available as a shampoo and a cream
• Terbinafine is also available in a sprinkle formulation for children
SYSTEMIC ANTIFUNGALS - AZOLE
Contraindications and Cautions
• Ketoconazole has been associated with severe hepatic toxicity and should be avoided in
patients with hepatic dysfunction to prevent serious hepatic toxicity. In addition, ketoconazole is
not the drug of choice for patients with endocrine or fertility problems because of its effects on
these processes.
• fluconazole should be used with caution in the presence of liver or renal impairment, because it
could cause liver or renal toxicity
• itraconazole has been associated with hepatic failure, should not be used in patients with
hepatic failure,
• It is not known whether posaconazole crosses the placenta or enters breast milk, so it should
not be used during pregnancy or lactation unless the benefits clearly outweigh the potential risk
• Terbinafine has been associated with severe liver toxicity and is contraindicated with liver
failure. It may cross the placenta and may enter breast milk, and so it should not be used in
pregnant
SYSTEMIC ANTIFUNGALS - AZOLE

Adverse Effects
• Many of the azoles are associated with liver
toxicity and can cause severe effects on a fetus
or a nursing baby.
SYSTEMIC ANTIFUNGALS - Echinocandin Antifungals

Echinocandin Antifungals • The echinocandins work by

• The echinocandin antifungals inhibiting glucan synthesis.
are another group of antifungals. • Glucan is an enzyme that is
Drugs in this class include: present in the fungal cell wall
but not in human cell walls.
–Anidulafungin
• If this enzyme is inhibited, the
–Caspofungin fungal cell wall cannot form,
leading to death of the cell
–Micafungin. wall.
SYSTEMIC ANTIFUNGALS - Echinocandin Antifungals

Pharmacokinetics
• Anidulafungin is given as a daily IV infusion for at least 14 days. It has a
rapid onset of action, is metabolized by degradation, and has half-life of
40 to 50 hours. This drug is excreted in the feces.
• Caspofungin is available for IV use. This drug is slowly metabolized in
the liver, with half-lives of 9 to 11 hours, then 6 to 48 hours, and then 40 to
50 hours. It is bound to protein and widely distributed throughout the body.
It is excreted through the urine
• Micafungin is an IV drug. It has a rapid onset, a halflife of 14 to 17 hours,
and is excreted in the urine.
SYSTEMIC ANTIFUNGALS - Echinocandin Antifungals
Contraindications and Cautions Adverse Effect
• Anidulafungin may cross the placenta and enter
breast milk and should not be used by pregnant • Anidulafungin and caspofungin are
or lactating women. Caution must be used in associated with hepatic toxicity, and
the presence of hepatic impairment because it
liver function should be monitored
can be toxic to the liver
• Caspofungin can be toxic to the liver; therefore,
closely when using these drugs.
reduced doses must be used if a patient has • Potentially serious hypersensitivity
known hepatic impairment. Caspofungin is
embryotoxic in animal studies and is known to
reactions have occurred with
enter breast milk; therefore, it should be used micafungin. In addition, bone
with great caution during pregnancy and marrow suppression can occur;
lactation.
monitor patients closely.
• micafungin should be used during pregnancy
and lactation only if the benefi ts clearly
outweigh the risks
SYSTEMIC ANTIFUNGALS - Other Antifungal

OTHER ANTIFUNGAL AGENTS • Other antifungal agents work to

• Other antifungal drugs that are
available do not fit into either of
• The drug binds to the sterols in the
these classes.
• These include:
– Amphotericin B (Abelcet,
AmBisome, Amphotec)
– Flucytosine (Ancobon)
– Griseofulvin (generic)
– Nystatin (Mycostatin, Nilstat)
cause fungal cell death or to
prevent fungal cell reproduction
fungus cell wall, changing cell wall
permeability.
• This change can lead to cell death
(fungicidal effect) or prevent the
fungal cells from reproducing
(fungistatic effect)
SYSTEMIC ANTIFUNGALS - Other Antifungal
Pharmacokinetics Adverse Effects
• Amphotericin B and flucytosine are available in
IV form. They are excreted in the urine, with an • Toxic effects on the liver and
initial half-life of 24 hours and then a 15-day kidneys
half-life. Their metabolism is not fully
understood • Bone marrow suppression
• Flucytosine is well absorbed from the GI tract, • Rash and dermatological changes
with peak levels occurring in 2 hours. Most of
the drug is excreted unchanged in the urine and • GI irritation with nausea, vomiting,
a small amount in the feces, with a half-life of and potentially severe diarrhea,
2.4 to 4.8 hours. anorexia and weight loss
• Griseofulvin is administered orally and reaches
peak levels in around 4 hours. It is metabolized
in the liver and excreted in the urine with a half-
life of 24 hours.
• Nystatin is not absorbed from the GI tract and
passes unchanged in the stool.
TOPICAL ANTIFUNGALS
Topical antifungals include the
• azole-type antifungals:
• The topical antifungal – butoconazole (Gynazole)
– clotrimazole (Lotrimin, Mycelex)
drugs work to alter the cell – econazole(Spectazole)
– ketoconazole (Extina, Nizoral, Xolegel),
permeability of the fungus, – miconazole (Fungoid, Lotrimin AF, Monistat)

causing prevention of
– oxiconazole (Oxistat)
– sertaconazole nitrate (Ertaczo)

replication and fungal –

–
sulconazole (Exelderm)
terbinafine (Lamisil)

death –
–
terconazole (Terazol),
tioconazole (Vagistat-1, Monistat-1)
• Other antifungals:
• They are indicated only for – butenafine (Mentax)

local treatment of mycoses, –

–
ciclopirox (Loprox, Penlac Nail Lacquer)
gentian violet (generic)

including tinea infections –

–
naftifine (Naftin),
tolnaftate (Aftate, Tinactin)
– undecylenic acid (Cruex,Desenex, Pedi-Dri, Fungoid
AF)
TOPICAL ANTIFUNGALS

Pharmacokinetics Adverse Effects

• When these drugs are applied locally as a
• These drugs are not cream, lotion,or spray, local effects include
absorbed systemically and irritation, burning, rash, and swelling
• When they are taken as a suppository or
do not undergo troche, adverse effects include nausea,
metabolism or excretion in vomiting, and hepatic dysfunction (related
to absorption of some of the drug by the GI
the body tract) or urinary frequency, burning, and
change in sexual activity (related to local
absorption in the vagina).
TOPICAL ANTIFUNGALS

Contraindications and Cautions

• Because these drugs are not absorbed systemically, contraindications are limited to a known
allergy to any of these drugs and open lesions
• Econazole can cause intense, local burning and irritation and should be discontinued if these
conditions become severe
• Gentian violet stains skin and clothing bright purple; in addition, it is very toxic when absorbed, so
it cannot be used near active lesions
• Naftifine, oxiconazole, and sertaconazole nitrate should not be used for longer than 4 weeks due
to the risk of adverse effects and possible emergence of resistant strains of fungi
• Sulconazole should not be used for longer than 6 weeks due to the risk of adverse effects and
possible emergence of resistant strains of fungi
• Terbinafine should not be used for longer than 4 weeks. This drug should be stopped when the
fungal condition appears to be improved or if local irritation and pain become too great to avoid
toxic effects.
ANTIPROTOZOAL AGENTS
Protozoal Infection
• Infections caused by
protozoa—single-celled
organisms that pass through
several stages in their life
cycles, including at least one
phase as a human parasite
• Protozoa thrive in tropical
climates, but they may also
survive and reproduce in any
area where people live in very
crowded and unsanitary
conditions
• protozoal infections that
are caused by insect bites
(malaria, trypanosomiasis,
and leishmaniasis)
• and those that result from
ingestion or contact with
the causal organism
(amebiasis, giardiasis, and
trichomoniasis)
ANTIMALARIALS
• Antimalarial drugs (Table 12.1) are
usually given in combination form to
attack the Plasmodium at various
stages of its life cycle.
• This drug enters human red blood
cells and changes the metabolic
pathways necessary for the
reproduction of the Plasmodium
• this agent is directly toxic to
parasites that absorb it; it is acidic,
and it decreases the ability of the
parasite to synthesize DNA, leading
to a blockage of reproduction
These drugs can be
• Schizonticidal (acting against the red-
blood-cell phase of the life cycle)
• Gametocytocidal (acting against the
gametocytes)
• Sporontocidal (acting against the
parasites that are developing in the
mosquito)
• Quinine (Qualaquin) was the first drug
found to be effective in the treatment of
malaria
• Chloroquine (Aralen Phosphate)
• Mefloquine (Lariam)
• Primaquine (generic)
• Pyrimethamine (Daraprim
ANTIMALARIALS

Pharmacokinetics • Pyrimethamine is readily absorbed from

• Chloroquine is readily absorbed from the the GI tract, with peak levels occurring
gastrointestinal (GI) tract, with peak serum within 2 to 6 hours. It is metabolized in the
levels occurring in 1 to 6 hours. It is liver and has a half-life of 4 days. It usually
concentrated in the liver, spleen, kidney, maintains suppressive concentrations in
and brain and is excreted very slowly in the the body for about 2 weeks
urine, primarily as unchanged drug
• Mefloquine is a mixture of molecules that
• Quinine is rapidly absorbed from the GI
are absorbed, metabolized, and excreted
tract, with peak serum levels occurring in 1
at different rates. The terminal half-life is
to 3 hours. It is metabolized in the liver with
13 to 24 days. Metabolism occurs in the
a half-life of 4 to 6 hours and is excreted in
liver.
the urine.
• Primaquine is readily absorbed and
metabolized in the liver. Excretion occurs
primarily in the urine. Safety for use during
pregnancy has not been established.
ANTIMALARIALS
Contraindications and
Cautions
• presence of known patient
allergy to any of these
drugs
• liver disease or alcoholism
• lactation because the
drugs can enter breast
milk and could be toxic to
the infant
• avoided during pregnancy
• Use caution in patients
with retinal disease or
damage because many of
these drugs can affect
vision and the retina
• with psoriasis or porphyria
because of skin damage
ANTIMALARIALS
Adverse Effects
• Central nervous system (CNS) effects
include headache and dizziness
• Immune reaction effects related to the
release of merozoites include fever,
shaking, chills, and malaise.
• GI effects like Nausea, vomiting,
dyspepsia, and anorexia
• CNS control of vomiting caused by the
products of cell death and protein changes.
• Hepatic dysfunction is associated with
the toxic effects of the drug on the liver and
the effects of the disease on the liver.
• Dermatological effects include
rash, pruritus, and loss of hair
associated with changes in protein
synthesis of the hair follicles.
• Visual changes, including possible
blindness related to retinal damage
from the drug
• ototoxicity related to other nerve
damage may occur
• Cinchonism (nausea, vomiting,
tinnitus, and vertigo) may occur
with high levels of quinine or
primaquine.
OTHER PROTOZOAL INFECTIONS
• Other protozoal infections that are
encountered in clinical practice
include:
§ Amebiasis
§ Leishmaniasis
§ Trypanosomiasis
§ Trichomoniasis
§ Giardiasis
§ These infections, which are caused by
single-celled protozoa, are usually
associated with unsanitary, crowded
conditions, and use of poor hygienic
practices
OTHER PROTOZOAL AGENTS
• These antiprotozoal agents
act to inhibit DNA synthesis in
susceptible protozoa,
interfering with the cell’s ability
to reproduce, subsequently
leading to cell death
• These drugs are indicated for
the treatment of infections
caused by susceptible
protozoa
• Other antiprotozoals include:
§ Atovaquone (Mepron)
§ Metronidazole (Flagyl, MetroGel,
Noritate)
§ Nitazoxanide (Alinia)
§ Pentamidine (Pentam 300,
NebuPent)
§ Tinidazole (Tindamax)
OTHER PROTOZOAL AGENTS
Pharmacokinetics
• Atovaquone is slowly absorbed
and is highly protein bound in
circulation. It is excreted slowly
through the feces, with a half-life of
67 to 76 hours.
• Metronidazole is well absorbed
orally, reaching peak levels in 1 to 2
hours. It is metabolized in the liver
with a half-life of 8 to 15 hours.
Excretion occurs primarily through
the urine
• Nitazoxanide is rapidly absorbed after oral
administration, reaching peak levels in 1 to
4 hours. Nitazoxanide is metabolized in the
liver and excreted in the urine and feces; it
has a half-life of 8 to 12 hours.
• Pentamidine is readily absorbed through
the lungs. Excretion occurs in the urine,
with traces found in the urine for up to 6
weeks.
• Tinidazole is rapidly absorbed after oral
administration, reaching peak levels within
60 to 90 minutes. It is excreted in the urine
with a half-life of 12 to 14 hours.
OTHER PROTOZOAL AGENTS
Contraindications and Cautions
• presence of any known allergy or
hypersensitivity to any of these drugs
• pregnancy because drug effects on
developing fetal DNA and proteins
can cause fetal abnormalities and
even death
• Use caution when administering these
drugs to patients with CNS disease
because of possible disease
exacerbation due to drug effects on
the CNS
• hepatic disease
• candidiasis because of the risk of
superinfections
• women who are lactating
• The safety and effi cacy of
pentamidine in children have not
been established
• Tinidazole should never be
combined with alcohol
• should be used with caution in
patients with renal dysfunction
OTHER PROTOZOAL AGENTS

Adverse Effects
• CNS effects such as headache, dizziness, ataxia, loss
of coordination, and peripheral neuropathy related to
drug effects on the neurons
• GI effects include nausea, vomiting, diarrhea,
unpleasant taste, cramps,
• changes in liver function
• Superinfections also can occur when the normal fl ora
are disrupted.
ANTIHELMINTIC AGENTS
Helminthic infections

• Are infections in the gastrointestinal (GI) tract or other

tissues due to worm infestation
• The helminths that most commonly infect humans are of
two types: the nematodes (or roundworms) and the
platyhelminths (or flatworms) that cause intestine-
invading worm infections and tissue-invading worms
Helminthic infections
 Helminthic infections
Tissue-Invading Worm Infections
• Trichinosis - is the disease caused by ingestion of the encysted larvae of the roundworm,
Trichinella spiralis, in undercooked pork. They can penetrate skeletal muscle and can cause
an inflammatory reaction in cardiac muscle and in the brain. Fatal pneumonia, heart failure,
and encephalitis may occur.
• Filariasis - refers to infection of the blood and tissues of healthy individuals by worm
embryos, which enter the body via insect bites.These thread-like embryos, or filariae, can
overwhelm the lymphatic system and cause massive inflammatory reactions. This may lead
to severe swelling of the hands, feet, legs, arms, scrotum, or breast—a condition called
elephantiasis
• Schistosomiasis - is a platyhelminthic infection by a fluke that is carried by a snail. Eggs
that are excreted in the urine and feces of infected individuals hatch in fresh water into a
form that infects a certain snail. About 1 or 2 months later, affected individuals may
experience several weeks of fever, chills, headache, and other symptoms. Chronic or severe
infestation may lead to abdominal pain and diarrhea, as well as blockage of blood fl ow to
areas of the liver, lungs, and CNS.
Anthelmintics
• The anthelmintic drugs act on
metabolic pathways that are
present in the invading worm
but are absent or significantly
different in the human host
• Anthelmintics interfere with
metabolic processes in
particular worms
• Anthelmintic drugs include:
– Albendazole (Albenza)
– Ivermectin (Stromectol)
– Mebendazole (Vermox)
– Praziquantel (Biltricide)
– Pyrantel (Antiminth, Pin-Rid,
Pin-X, Reese’s Pinworm)
Anthelmintics
Pharmacokinetics
• Mebendazole is available in the form of a
chewable tablet, and a typical 3-day
course can be repeated in 3 weeks if
needed Very little of the mebendazole is
absorbed systemically, so adverse effects
are few. The drug is not metabolized in the
body, and most of it is excreted unchanged
in the feces. A small amount may be
excreted in the urine
• Albendazole is poorly absorbed from the
GI tract, reaching peak plasma levels in
about 5 hours. It is metabolized in the liver
and primarily excreted in urine.
• Ivermectin is readily absorbed from the GI
tract and reaches peak plasma levels in 4
hours. It is completely metabolized in the
liver with a half-life of 16 hours; excretion is
through the feces.
• Praziquantel is taken in a series of three
oral doses at 4- to 6-hour intervals. It is
rapidly absorbed from the GI tract and
reaches peak plasma levels within 1 to 3
hours. It is metabolized in the liver with a
half-life of 0.8 to 1.5 hours. Excretion of
praziquantel occurs primarily through the
urine.
• Pyrantel is poorly absorbed, and most of
the drug is excreted unchanged in the
feces, although a small amount may be
found in the urine.
Anthelmintics
Contraindications and Cautions
• Overall contraindications to the use of
anthelmintic drugs include:
§ the presence of known allergy to any of
these drugs
§ lactation, because the drugs can enter breast
milk and could be toxic to the infant
§ pregnancy (in most cases), because of
reported associated fetal abnormalities or
death
§ Women of childbearing age should be
advised to use barrier contraceptives while
taking these drugs
• Pyrantel has not been established as safe
for use in children younger than 2 years.
• Albendazole should be used only after the
causative worm has been identified
• Use caution in the presence of renal or
hepatic disease
• In cases of severe diarrhea and
malnourishment, which could alter the
effects of the drug on the intestine and any
preexisting helminths.
Anthelmintics

Adverse Effects
• Mebendazole and pyrantel, which
are not absorbed systemically, may
cause abdominal discomfort, • Renal failure and severe bone
diarrhea, or pain but have very few marrow depression are associated
other effects and are well tolerated. with albendazole, which is toxic to
• Anthelmintics that are absorbed some human tissues.
systemically may cause the • Patients taking this drug require
following effects: headache and careful monitoring
dizziness; fever, shaking, chills, and
malaise associated with an immune
reaction to the death of the worms;
rash; pruritus; and loss of hair
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