| Drug: Penicllin
G (generic,
Pentids, Pfizerpen ®) |
| Drug Class: Antibiotic
(Beta Lactam) |
| Mechanism of Action:
Inhibits bacterial cell wall synthesis by binding and inactivating proteins
(penicillin binding proteins) present in the bacterial cell wall. Penicillins
inhibit the transpeptidation reaction and block cross-linking of the cell
wall. This results in lysis of the cell wall due to high internal osmotic
pressure. Inactivation of the inhibitor of autolysins within the cell also
contributes to cell lysis. |
| Indications:
Penicillin G has the greatest activity against gram-positive organisms,
gram-negative cocci (which lack an outer membrane), and non-beta-lactamase
producing anaerobes. Penicillin G has little activity against gram-negative
rods because it can't penetrate their outer membrane. |
| Contraindications:
hypersensitivity (drug allergy) that can be either IgE-mediated (immediate,
anaphalaxis) or IgG mediated (delayed, rash or urticaria). |
| Side Effects:
neurotoxicity resulting in convulsions can occur with intrathecal injections;
large doses of Na or K salt of penicillin G can produce cation toxicity,
especially in patients with renal failure. |
| Pharmacokinetics:
administered i.v. or i.m. because oral absorption is unreliable (acid labile).
Serum half-life is 35 mins. Rapidly excreted unchanged by tubular secretion
in the renal tubules (probenecid can block this transporter and prolong
Pen G's half life). Partially (60%) bound to plasma proteins. Penetration
into the CNS is poor, but can occur if there is menengial inflammation. |
| Reference:
www.rxlist.com |
| Drug: Isoxazole
penicillins (Oxacillin, Cloxacillin, Dicloxacillin) |
| Drug Class: Semisynthetic
Penicillin |
| Mechanism of Action:
Same as Pen G. Resistant to beta-lactamase. |
| Indications: infections
by gram positive penicillinase producing Staphlococci. |
| Pharmacokinetics: Cloxacillin
or dicloxacillin are prefered for oral administration (they are the most
acid stable). Oxacillin is typically given i.v., and is therefore reserved
for more serious infections. All drugs in this class are eliminated by both
the kidney & biliary excretion and can
therefore be used at full dosage in patients with renal failure.
|
| References: www.rxlist.com -
Oxacillin,
Dicloxacillin ;
healthdigest.org - Cloxacillin |
| Drug: Ampicillin
(generic) |
| Drug Class: Semisynthetic
Penicillin |
| Mechanism of Action:
Same as Pen G, but greater activity against gram negative bacteria due to
enhanced ability to penetrate the gram negative outer membrane. |
| Indications:
infections due to Streptococcus group B & those in the enterococcus
group. Effective against urinary tract infections caused by E. coli
and Proteus mirabilis. Other sensitive gram negative bacilli
include Salmonella & Shigella. Effective in the treatment
of respiratory infections and meningitis cause by susceptible strains of
Hemophilus influenzae. |
| Side Effects:
skin rash, esp. if patient has mononucleosis. Diarrhea & superinfections
are common. |
| Pharmacokinetics:
acid resistant & well absorbed afer oral administration. Can also be
given i.v. or i.m. Significant biliary excretion (hence effective against
Salmonella infections in the biliary tract). Half-life is 1.3 hours. |
| Reference:
www.rxlist.com |
| Drug: Amoxicillin
(generic, Amoxil
®) |
| Drug Class: Semisynthetic
Penicillin |
| Mechanism of Action:
Same as Pen G, but greater activity against gram negative bacteria due to
enhanced ability to penetrate the gram negative outer membrane. |
| Indications:
Antibacterial spectrum similar to ampicillin. Commonly
given to treat urinary tract infections,sinusitis, otitis, and lower respiratory
tract infections. |
| Side Effects:
hypersensitivity (like other penicillins) |
| Pharmacokinetics:
absorbed better than ampicillin upon oral administration. |
| Notes: this
is commonly the active ingredient in the "pink" colored medicine
you typically give to kids |
| References:
www.rxlist.com |
| Drug: Carbenicillin
(Geocillin ®) |
| Drug Class: Semisynthetic
Penicillin |
| Mechanism of Action:
Same as Pen G, but greater activity against gram negative bacteria due to
enhanced ability to penetrate the gram negative outer membrane. |
| Indications: Although
carbenicillin itself is primarily listed as a secondary drug that has to
be given parentally, Indanyl carbenicllin,
an orally effective form is indicated for treatment of urinary tract infections.
Antibacterial activity similar to ampicillin, but has extended activity
against Pseudomonas aeruginosa, Enterobacter & Serratia.
Effective against ampicillin-resistant strains of Proteus &
against Providencia stuartii. |
| Side Effects:
large doses may cause Na overload in renal & cardiac patients, may cause
hypokalemia. |
| Pharmacokinetics:
Acid unstable, give i.v.. Serum half-life of 1 hour. 50% bound to serum
proteins. Indanyl carbenicllin
is an ester derivative that is acid stable & can be given orally in
urinary tract infections. |
| Reference:
Katzung |
| Drug: Ticarcillin
(Ticar, Timentin ®) |
| Drug Class: Semisynthetic
Penicillin |
| Mechanism of Action:
Same as Pen G, but greater activity against gram negative bacteria due to
enhanced ability to penetrate the gram negative outer membrane. Often combined
with clavulanate (Timentin ®)
for inhibition of beta-lactamases. |
| Indications: Same
indications as ampicillin, but also effective against Bacteroides fragilis
(an anaerobe). |
| Side Effects:
less likely to cause hypokalemia & electrolyte abnormalities compared
to carbenicillin. |
| Pharmacokinetics:
parental (i.m. or i.v.) use. Acid unstable. |
| Reference: www.rxlist.com |
| Drug: Piperacillin
(Pipracil, Zosyn ®)
& Mezlocillin (Mezlin
®) |
| Drug Class: Semisynthetic
Penicillins |
| Mechanism of Action:
Same as Pen G, but greater activity against gram negative bacteria due to
enhanced ability to penetrate the gram negative outer membrane. Piperacillin
is combined with tazobactam (Zosyn ®)
to provide protection against beta-lactamase inactivation. |
| Indications: similar
to ticarcillin, but have extended spectrum to include effectiveness against
Pseudomonas, Serratia, Enterobacter, strains
of Klebsiella pneumoniae. More effective agains Bacteroides
fragilis. |
| Pharmacokinetics:
given parentally |
| Reference:
www.rxlist.com |
| Drug:Cephalexin
(generic, Keflex ®) |
| Drug Class: Cephalosporin
1st generation (oral) |
| Mechanism of Action:
Similar to penicillins. Cephalosporins are generally resistant to penicillianase.
|
Indications: Gram
positive cocci except enterococcal group
Gram negative: Includes E. coli, Proteus mirabilis, Klebsiella
Clinical use in upper respiratory infections and urinary tract infections. |
| Side Effects:
hypersensitivity |
| Pharmacokinetics:
orally effective, renal clearance. |
| Reference:
www.rxlist.com |
| Drug: Cefoxitin
(Mefoxin
®) |
| Drug Class: Cephalosporin
2nd generation (parenteral) |
| Mechanism of Action:
Similar to penicillin. Increased activity against Gram negative bacilli
and greater stability against beta-lactamase inactivation. |
| Indications: gonococcus,
Bacteroides fragilis, activity against anerobes-used for abdominal and pelvic
infections, prophylaxis for colorectal surgery and appendectomy. |
| Pharmacokinetics:
parenteral, injection, renal clearance. |
| Reference:
www.rxlist.com |
| Drug: Vancomycin
(generic, Vancocin, Vancoled ®) |
| Drug Class: Inhibitor
of Cell Wall Synthesis / Antibiotic |
| Mechanism of Action:
Inhibits cell wall synthesis by inhibiting peptidoglycan
synthetase. |
| Indications: With
the exception of flavobacterium, it is active only against gram-positive
baceria, esp. staphloccci. Indicated for treatment of methicillin
resistant Staph. aureus, endocorditis due to Strep. viridans or enterococci,
Pseudomenbranous enterocolitis (adminstered orally), Clostridium
difficile (clinically
used in patients allergic to penicillins and cephalosporins). |
| Side Effects:
Phlebosclerotic, nephrotoxicity, ototoxicity, hypersensitivity (maculopapular
skin rash), hypotension if given i.v. in less than 1 hour |
| Pharmacokinetics:
Poor absorption upon oral administration, IV administration (slow), Renal
excretion by glomerular filtration (80-90% in 24 hr) |
| Major drug Interactions:
|
| Notes: www.rxlist.com |
| Drug: Chloramphenicol |
| Drug Class: Antibiotic
(wide spectrum & bacteriostatic) |
| Mechanism of Action:
Binds to 50S ribosomal subunit and inhibits peptidyl transferase and blocks
protein synthesis |
| Indications: Used
outside of the United States. Broad spectrum. Neisseria meningitidis, Clostridium
perfringens, Bacteroides, Hemophilus influenzae (bactericidal effect in
this sensitive organism), Salmonella typhi and Rickettsia. |
| Contraindications:
|
| Side Effects:
Bone marrow suppression and
idiosyncratic aplastic anemia.
Gray baby syndrome. Superinfection. |
| Pharmacokinetics:
Oral absorption, wide distribution in body including CSF, hepatic metabolism
to glucuronide and renal excretion. |
| Major drug Interactions:
|
| Reference:
www.rxlist.com |
| Drug: Ciprofloxacin
(Cipro ®), Levofloxacin
(Levaquin ®) |
| Drug Class: Antibiotic
(DNA Gyrase Inhibitors) |
| Mechanism of Action:
Interference with the activity of DNA gyrase
Bactericidal. Chromosomally mediated acquired resistance. |
| Indications: Methicillin
susceptible and methicillin resistant strains of Staph.
aureaus, Streptococcus. Gram negative bacteria activity comparable to 3rd
generation cephalosporins; Mycoplasma; M. tuberculosis and M.avium. Poor
activity against anerobes [clinically useful in UTI, Prostatitis, STDs (gonorrhea,
chancroid, chlamydial diseases), GI and abdominal infections, bone and joints
(osteomyelitis) and soft tissue infections]. Cipro has weak activity against
anaeorobes, but newer analogues are effective. |
| Contraindications:
|
| Side Effects:
GI (nausea & vomiting), CNS (mainly at high concentrations), skin reactions,
cartilage toxicity and joint
swelling in children, tendonitis (not recommended
in pregnant woman and infants < 8 yr old). |
| Pharmacokinetics:
Orally administered, widely distributed. Anatacids decrease oral bioavailability.
Penetrates in most tissues including prostate, however poor penetration
into the CSF. Metabolism (20%), renal excretion (80%). |
| Reference:
Ciprofloxacin,
Levofloxacin
(www.rxlist.com) |
| Drug: Tetracycline
(generic, Achromycin V ®), Doxycycline
(generic, Vibramycin ®), Minocycline
(Minocin ®) |
| Drug Class: Tetracyclines
(Broad spectrum, bacteriostatic) |
| Mechanism of Action:
Bind to 30S ribosomal subunit and block attachment of aminoacyl t-RNA to
A site: inhibit protein synthesis. Active transport in bacterial cell. Broad
spectrum bacteriostatic. |
| Indications: Broad
spectrum antibiotic & generally 2nd line drugs of choice. Susceptible
bacteria include: Streptococcal pneumoniae, Bacillus anthracis (Anthrax),
Clostridium tetani, Brucella (brucellosis), Helicobacter pylori, Actinomyces,
Rickettsia (Rocky Mountain spotted fever), Chlamydial diseases and Mycoplasma.
|
| Contraindications:
Not recommended for pregnant women, infants
and children 8 years or younger. |
| Side Effects:
Toxicity includes superinfection, GI toxicity, hepatic toxicity (reversible),
staining of teeth, retardation
of bone growth, renal toxicity – elevation of BUN |
| Pharmacokinetics:
Oral administration, antacids and calcium (milk) interfere with absorption,
localization in bone and teeth, cross the placental barrier, poor penetration
into the CSF, renal and hepatic excretion. Doxy and Minocycline are primarily
excreted in feces (and can therefore be used more safely in patients with
renal dysfunction). |
Reference:
Tetracycline,
Doxycycline,
Minocycline
(www.rxlist.com) |
| Drug:Sulfisoxazole;
Sulfamethoxazole with trimethoprim (cotrimoxazole
or Bactrim ®) |
| Drug Class: Antibacterial
|
| Mechanism of Action:
Competitively inhibit incorporation of para-aminobenzoic acid (PABA) into
dihydropteroic acid, a precursor of folic
acid. Bacteriostatic. Resistance can occur due to decreased
drug uptake, altered target enzyme and escape mechanism by alteration in
cell permeability. |
| Indications: Not
commonly used as a single agents. Use of Sulfamethoxazole clinically is
in combination with Trimethoprim in a 5:1 ratio (400 mg+80 mg) known as
Cotrimoxazole (Bacterim ®). Trimethoprim is an inhibitor of dihydrofolate
reductase and provides a sequential blockade of synthesis of tetrahydrofolate.
Cotrimoxazole: Gram+ cocci including MRSA, Gram- cocci, N. meningitidis.
Most Gram- enteric bacilli and Gram- bacilli (Brucella, H. influenzae, Legionella);
Nocardia; Chlamydia; Pneumocystis carinii; Toxoplasma |
| Contraindications:
contraindicated in new borns and during last
two months of pregnancy |
| Side Effects:
Hypersensitivity reactions (rash, photosensitivity and drug fever); erythema
multiforme- Stevens-Johnson Syndrome
(20% fatality), Nephrotoxicity- crystalluria can cause obstruction of the
kidneys. Hematological toxicities: hemolytic
anemia (G-6-P deficiency) ; Hepatitis; Kernicterus
(a toxic encephalopathy) in infants. |
| Pharmacokinetics:
Well absorbed orally. Widely distributed throughout the body fluids and
can cross placental barrier and can enter into the CSF. Metabolism
by hepatic acetylation (fast acetylators may require higher
doses), and renal excretion. |
| Major drug Interactions:
|
| Reference:
Bactrim (www.rxlist.com) |
| Drug: Streptomycin
(generic),
Gentamicin (generic, Garamycin ®),
Tobramycin (generic, Nebcin ®),
Amikacin (generic, Amikin ®)
and Netilmicin (Netromycin
®) |
| Drug Class: Aminoglycosides |
| Mechanism of Action:
Bind to 30S ribosomes, block
protein synthesis at the initiation complex stage, cause mis-coding, and
break up polysomes. Bactericidal.
Oxygen dependent active transport.
Resistance occurs mainly through plasmid mediated phosphorylation, acetylation
and adenylation of aminoglycodsides, and decreased drug uptake. |
Indications: Used
most widely against gram negative enteric bacteria, especially
in bacteremia and sepsis, in combination with vancomycin or a penicillin
for endocarditis, and for treatment of tuberculosis.
Gram
positive cocci: Staph., Strep.
viridans, and enterococcal endocarditis (used in combination with a cell
wall synthesis inhibitor). MRSA.
Not effective against S. pneumoniae. Enterococcus fecalis has become resistant
to aminoglycosides. Not effective against anerobes
Gram negative organisms including Pseudomonas. UTI, pneumonia. infections
of unknown etiology, septicemia, peritonitis. Synergism
with cell wall synthesis inhibitors.
Streptomycin is used for tuberculosis,
brucellosis, plague & tularemia. Neomycin is used only for alteration
in bowel flora & topically with other antibiotics (e.g. Neosporin
®). |
| Contraindications:
other drugs (e.g. anticancer drugs, cisplatin) that are nephrotoxic or cause
auditory toxicity. |
| Side Effects:
Nephrotoxicity (usually reversible),
ototoxicity (vestibular -
reversible, then auditory - irreversible) and neuromuscular
blockade (more commonly seen in patients with Mysthenia
Gravis) |
| Pharmacokinetics:
Minimal oral absorption, minimal metabolism, extracellular distribution
(25% of body weight), and renal excretion (G.F.). Poor penetration into
the CSF. Maintenance doses must be adjusted if creatinine clearance is not
normal. (For example, if serum creatinine increases from 1 to 2, you need
to decrease the maintenance dose by half, or double the dosing interval.
The loading dose is not changed.) |
| Notes: Gentamicin,
tobramycin and amikacin are the most widely used. Neomycin and kanmycin
are limited to topical or oral use. |
| References:
www.rxlist.com: streptomycin,
neomycin , gentamicin,
tobramycin,
amikacin |
| Drug: Erythromycin
(generic, Erythrocin ®, others),
Clarithromycin (Biaxin ®), Azithromycin
(Zithromax ®) |
| Drug Class: Macrolide
antibiotics |
| Mechanism of Action:
Bind to 50S ribosomal subunit and inhibit protein synthesis by preventing
translocation step. Bacteriostatic. |
Indications:
General: Staph., S. pyogenes and S. pneumoniae; Bacillus
anthracis (Anthrax), Legionnaire’s disease (Legionella) and Hemophilus ducreyi (Chancroid disease). Chlamydia, Mycoplasma
(Clinically useful in penicillin hypersensitive patients).
Clarithromycin:
Helicobacter pylori,
Hemophilus influenzae, Mycobacterium avium complex (MAC). (Note:
1st DOC for H. pylori stomach ulcer is amoxicillin + metranidazole
+ bismulth in patients without penicillin allergy).
Azithromycin:
spectrum similar
to erythromycin, MAC
Erythromycin:
a drug of choice for Legionnaire's dx., but is now a 2nd line drug for
other susceptible bacteria.
|
| Contraindications:
|
| Side Effects:
mild GI upset, hypersensitivity, cholestatic jaundice (caused by the estolate
salt of erythromycin). Inhibition of Cytochrome P-450 (drug interactions)
but not with azithromycin. Erythromycin - can cause long QT and cardiac
arrhythmias (mainly associated with i.v. use, or high concentrations). |
| Pharmacokinetics: Orally absorbed as stearate or estolate salt, CSF penetration poor, biliary
and fecal excretion. Erythromycin & Azithromycin need to be given 2
hrs before or after a meal. Absorption of clarithromycin is not as food-sensitive. |
| Major drug Interactions:
Erythromycin metabolites can inhibit cyt P-450 and thus increase the plasma
concentrations of numerous drugs. Use of other drugs that prolong the QT
interval with erythromycin should be done cautiously, since erythromycin
is a known cardiac K channel blocker. |
| Reference:
Erythromycin ,
Clarithromycin,
Azithromycin (www.rxlist.com) |
| Drug: Clindamycin
(generic, Cleocin ®) |
| Drug Class: Antibiotic |
| Mechanism of Action:
Binds to 50S ribosomal subunit and inhibits peptidyl transferase activity
and protein synthesis. Bacteriostatic. |
| Indications: Staphylococcus,
Streptococcus, and anerobes including Bacteroid
fragilis but not Clostridium difficile. Effective against beta-lactamase
producing bacteria & can be used in patients allergic to penecillin
or cephalosporins. Is recommended over erythromycin for prophylaxis of endocarditis
in patients with valvular heart disease who are undergoing dental procedures. |
| Side Effects:
Rash and diarrhea, psuedomembranous enterocolitis (which can be fatal) |
| Pharmacokinetics:
Oral absorption, penetrates in most tissues including bones and joints but
not into the CSF, hepatic metabolism, renal and biliary excretion. Food
does not interfere with it's absorption. |
| Major drug Interactions:
|
| Reference:
www.rxlist.com |
| Drug: Rifampin (generic, Rifadin, Rimactane ®) |
| Drug Class: Antimycobacterial |
| Mechanism of Action: inhibits RNA synthesis by inhibiting DNA-dependent RNA polymerase; bactericidal. |
| Indications: Mycobacterial infections. Gram positive cocci including MRSA. Usually combined with a beta-lactam antibiotic or vancomycin for Rx of serious Staph infections. Gram negative cocci, Gram negative bacilli: legionella, H. influenzae. |
| Side Effects: orange-red color of tears, sweat & urine (harmless - but you need to warn your paitents about it). Occasional rash & GI disturbances. Cholestatic jaundice. |
| Pharmacokinetics: Broad-spectrum induction of P-450 isozymes & P-GP. |
| Drug Interactions: anticoagulants, cardiac glycosides, HIV-protease inhibitors, contraceptives. |
| Reference: www.rxlist.com |
| Drug: Metronidazole
(generic, Flagyl ®) |
| Drug Class: Antiprotozoal
& Antibacterial (against anaerobes) |
| Mechanism of Action:
Penetrates readily into protozoan and bacterial cells but not mammalian
cells. Reduction of nitro function into nitro anion radical and hydroxylamine
which bind with DNA causing single strand breaks. Bactericidal. |
| Indications: Anerobic
organisms: Clostridium perfringens, Clostidium difficile
(useful in pseudomembranous colitis) and Bacteroides fragilis, Helicobacter
pylori, Ambebiasis, giardiasis, Trichomonas vaginalis |
| Contraindications:
Contraindicated in pregnancy due
to mutagenic and carcinogenic potential. |
| Side Effects:
Toxicity: GI (nausesa, vomiting diaarhea), metallic
taste, disulfiram-like reaction,
peripheral neuropathy, |
| Pharmacokinetics:
Absorbed well after oral administration. Serum T1/2 8 hr. Penetrates into
CSF. Metabolism – oxidation and glucuronidation. Renal excretion.
|
| Major drug Interactions:
ethanol |
| Reference:
www.rxlist.com |
| Drug: Mupirocin
(Bactroban ®) |
| Drug Class: Topical
Antibacterial (against gram positive cocci) |
| Mechanism of Action:
Kills staphylococci by inhibiting isoleucyl tRNA synthetase. |
| Indications: Topical
treatment of minor skin infections,
such as impetigo. Also indicated for intranasal
application for elimination
of methicillin-resistant S. aureus carriage by
patients or health care workers. |
| Pharmacokinetics:
rapidly inactivated after absorption, systemic levels are undetectable.
|
| Notes: mupirocin
is pseudomonic acid & is a natural product produced by Pseudomonas
fluorescens. |
| Reference:
Katzung's text |
| Drug: Nitrofurantoin
(generic, Furacin ®) |
| Drug Class: Urinary
Antiseptic |
| Mechanism of Action:
Bacteriostatic and batericidal for many gram-positive and gram-negative
bacteria. P. aeruginosa & many strains of proteus are resistant. |
| Indications: Lower
urinary tract infections. An oral agent that exerts antibacterial
activity in the urine, but has little systemic antibacterial effect. |
| Pharmacokinetics:
Well absorbed after ingestion. It is metabolized & excreted so rapidly
that no systemic antibacterial action is achieved. The drug is excreted
into the urine by both glomerular filtration and tubular secretion. |
| Side Effects:
anorexia, nausea, vomiting. Neuropathies & hemolytic anemia in patients
with G-6-dehydrogenase deficiency. |
| Drug Interactions:
antagonizes the action of nalidixic acid (a synthetic compound used to treat
urinary tract infections). |
| Contraindictions:
In renal failure, high blood levels may cause toxicity. |
| Reference:
Katzung's text |
| Drug: Amphotericin
B (Fungizone ®) |
| Drug Class: Antifungal
agent (broad spectrum) |
| Mechanism of Action:
It is selective
in its fungal effects because the drug acts by binding to ergosterol
in the cell membrane of susceptible fungi with a resultant change in membrane
permeability allowing leakage of intracellular components. (Mammalian cell
membranes contain cholesterol instead of ergosterol. However, some binding
to human membrane sterols does occur, and this may account for it's prominent
toxicity.) Amphotericin B is fungistatic or fungicidal depending on the
concentration obtained in body fluids and the susceptibility of the fungus. |
| Indications: a
drug of choice for nearly all life-threatening mycotic infections due to
its broad spectrum of activity. However it should be not
be used to treat noninvasive forms of fungal disease such as oral thrush,
vaginal candidiasis and esophageal candidiasis in patients with normal neutrophil
counts. |
| Contraindications:
contraindicated in those patients who have shown hypersensitivity to amphotericin
B or any other component in the formulation. |
| Side Effects:
Infusion related toxicity:
fever, chills, muscle spasms, vomiting, headache &hypotension reactions
are nearly universal. Premedication with antipyretics, antihistamines, meperidine,
or corticosteroids can be helpful. Slower
toxicity: some degree of renal damage occurs in most patients
treated with clinically significant doses.There are reversible and irreversible
components (the later usually occurs with prolonged administration of >4
g cumulative dose. Renal toxicity commonly occurs with renal tubular acidosis
& sever K and Mg wasting. Convulsions & other serious CNS sequelae
can occur when amphotericin B is given intrathecally. |
| Pharmacokinetics:
Intravenous form should be administered slowly over a period of approximately
2 to 6 hours. Can be given intrathecally for CNS infections, but is poorly
tolerated, and newer therapies are usually prefered. Liposomal formulations
are also now available for patients patients intollerant to amphotericin
B (more expensive & slightly more efficacious). |
| Reference:
www.rxlist.com,
Katzung's text |
| Drug: Nystatin
(generic, Mycostatin
®) |
| Drug Class: Antifungal
agent (topical) |
| Mechanism of Action:
Nystatin acts by binding to sterols in the cell membrane of susceptible
Candida species with a resultant change in membrane permeability allowing
leakage of intracellular components. Nystatin exhibits no appreciable activity
against bacteria, protozoa, or viruses. |
| Indications:
Nystatin Oral Suspension is indicated for the treatment of candidiasis
in the oral cavity, vaginal candidiasis & intertriginous candidal infections.
Nystatin is both fungistatic and fungicidal in vitro against a wide variety
of yeasts and yeast-like fungi. |
| Pharmacokinetics:
usually given topically. Can be given orally for GI infections, but GI absorption
is insignificant & it has an unpleasant taste. |
| Reference:
www.rxlist.com & Katzung's text |
| Notes: an antimycotic
polyene antibiotic obtained from Streptomyces noursei |
| Drug: Flucytosine
(Ancobon ®) |
| Drug Class: Antifungal
agent |
| Mechanism of Action:
taken up by fungal cells via the enzyme cytosine permease. It gets converted
intracellularly to 5-FU and then to F-dUMP & FUTP, which inhibit DNA
and RNA synthesis, respectively. Human cells are unable to convert the parent
drug to its active metabolites. Narrower spectrum of action compared to
amphotericin B. |
| Indications:
indicated only in the treatment of serious infections caused by susceptible
strains of Candida and/or Cryptococcus. |
| Contraindications:
Use with extreme caution in patients with impaired renal function. Close
monitoring of hematologic, renal and hepatic status of all patients is essential. |
| Side Effects:
related to metabolism (possibly by GI fluora) to fluorouracil, which can
cause reversible bone marrow toxicity (anemia, leukopenia & thrombocytopenia).
Hepatotoxicity can also occur. |
| Pharmacokinetics:
Oral administration only. Flucytosine is rapidly and virtually completely
absorbed following oral administration. Flucytosine is excreted via the
kidneys by means of glomerular filtration without significant tubular reabsorption.
The half-life in normal subjects is between 2-5 hours. The average half-life
in nephrectomized or anuric patients is 85 hours (range: 29.9 to 250 hours).
|
| Reference:
www.rxlist.com
& Katzung's text |
| Drug: Ketoconazole
(generic, Nizoral ®) |
| Drug Class: Antifungal
agent (broad spectrum) |
| Mechanism of Action:
An imidazole that impairs the synthesis of ergosterol, which is a vital
component of fungal cell membranes. It is a broad spectrum antifungal drug. |
| Indications: treatment
of the following systemic fungal infections: candidiasis, chronic mucocutaneous
candidiasis, oral thrush, candiduria, blastomycosis, coccidioidomycosis,
histoplasmosis, chromomycosis, and paracoccidioidomycosis. Ketoconazole
should not be used for fungal meningitis because it penetrates
poorly into the cerebral-spinal fluid. Also indicated for
the treatment of patients with severe recalcitrant cutaneous dermatophyte
infections who have not responded to topical therapy or oral griseofulvin,
or who are unable to take griseofulvin. |
| Contraindications:
Coadministration of terfenadine or astemizole with ketoconazole tablets
is contraindicated. Drug hypersensitivity. |
| Side Effects:
When used orally, ketoconazole has been associated with hepatic toxicity,
including some rare fatalities.
In rare cases anaphylaxis has been reported after the first dose. Antiandrogenic
(lowered testosterone levels) have been reported. |
| Pharmacokinetics:
Oral administration. Plasma elimination is biphasic with half-life of 2
hours during the first 10 hours and 8 hours thereafter. Elimination &
excretion is primarily hepatic/biliary. Antacids and H-2 antihistamines
can interfere with ketoconazole's bioavailability. |
| Major drug Interactions:
Ketaconazole has a greater propensity to inhibit
mammalian cyt P-450 compared to other "azoles".
Coadministration of terfenadine
or astemizole with ketoconazole
tablets is contraindicated. Rare cases of serious cardiovascular adverse
events including death, ventricular tachycardia and torsades
de pointes have been observed. |
| Notes: systemic
ketoconazole is used much less frequently than the other azoles due to it's
effects on P-450 & testosterone levels. It is available in creams and
shampoo for topical use. |
| Reference:
www.rxlist.com
& Katzung's text |
| Drug: Fluconazole
(Diflucan ®) |
| Drug Class: Antifungal
(broad spectrum) |
| Mechanism of Action:
a triazole that is a highly selective inhibitor of fungal cytochrome P-450
sterol C-14 alpha-demethylation. (Note: triazoles have a greater specificity
for fungal P-450 vs. mammalian P-450 compared to the imidazoles, e.g. such
as ketaconazole). The subsequent loss of normal sterols correlates with
the accumulation of 14 alpha-methyl sterols in fungi and may be responsible
for the fungistatic activity of fluconazole. |
| Indications: the
azole of choice in the treatment and secondary
prophylaxis of cryptococcal meningitis. It is also equivalent
to amphotericin B against candidemia in ICU patients with normal white blood
cell counts. It is the agent most commonly used for treating mucocutaneous
candidiasis. Fluconazole displays no activity against aspergillus or other
filamentous fungi. |
| Contraindications:
drug hypersensitivity |
| Side Effects:
minor GI upset |
| Pharmacokinetics:
Very good oral bioavailabitly. An i.v. formulation is also available. Plasma
elimination half-life of approximately 30 hours (range 20-50 hours) after
oral administration. Good penetration into the CSF. Has fewer
hepatic enzyme interactions, and the widest therapeutic
index of the azoles, permitting more aggressive dosing. Renal elimination. |
| Major drug Interactions:
Rifampin enhances the metabolism of concurrently administered fluconazole.
Absorption is not effected by antacids (in contrast to ketoconazole). |
| Reference:
www.rxlist.com
& Katzung's text |
| Drug: Itraconazole
(Sporanox ®)
|
| Drug Class: Antifungal
(broad spectrum) |
| Mechanism of Action:
a triazole that inhibits the cytochrome P-450-dependent synthesis of ergosterol,
which is a vital component of fungal cell membranes. |
Indications:
the treatment of the following fungal infections in immunocompromised
and non- immunocompromised patients: 1) Blastomycosis,
pulmonary and extrapulmonary; 2) Histoplasmosis, including chronic cavitary
pulmonary disease and disseminated, non-meningeal histoplasmosis;3) Aspergillosis,
pulmonary and extrapulmonary, in patients who are intolerant of or who
are refractory to amphotericin B therapy; and 4) Onychomycosis due to
dermatophytes (tinea unguium) of the toenail with or without fingernail
involvement. |
| Contraindications:
Coadministration of terfenadine, astemizole or cisapride with itraconazole
is contraindicated. These combinations can produce long QT intervals, sudden
death, ventricular tachycardia, and torsades de pointes. |
| Side Effects:
minor GI upset |
| Pharmacokinetics:
Oral and IV formulations. Penetrates poorly into the CSF. Absorption is
increased by food and low gastric pH & is reduced after ranitidine (H2
antihistamine) or antacid treatment. Undergoes hepatic metabolism &
biliary excretion. Plasma half-life is ~20 hrs. |
| Major drug Interactions:
Rifampin (P-450 inducer) reduces intraconazole bioavailability, terfenadine,
astemizole or cisapride coadministration can produce QT prolongation &
serious cardiac arrhythmias and/or sudden death. |
| Reference:
www.rxlist.com
& Katzung's text |
