| 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 |
| Drug: Atovaquone (Mepron ®) |
| Drug Class: Antiprotozoal |
| Mechanism of Action: a benzimidazoles
that disrupts mitochondrial electron transport in plasmodia/nematodes |
| Clinical Indications: an alternate
drug (to trimethoprim- sulfamethoxazole) for treatment of
mild to moderate P jiroveci pneumonia. When combined with proguanil
(Malarone ®),
it is highly effective against falciparum malaria. |
| Side Effects: fever, rash, nausea,
vomiting, diarrhea, headache, insomnia |
| Pharmacokinetics: Administering atovaquone
with fatty food enhances its absorption by approximately two- fold. The
half- life of atovaquone is long (2-3 days) due to enterohepatic cycling
and eventual fecal elimination. |
| Major drug Interactions: Rifampin
reduces plasma levels of atovaquone |
| Reference: www.rxlist.com & Katzung's text |
| Drug: Mebendazole (generic, Vermox ®) |
| Drug Class: Antihelminitic |
| Mechanism of Action:a synthetic benzimidazoles
that inhibits microtubule synthesis |
| Clinical Indications: ascariasis,
trichuriasis, hookworm & pinworm infection. It kills
hookworm, ascaris & trichuris eggs. |
| Side Effects: mild nausea, vomiting
(infrequently) |
| Pharmacokinetics: tablets should be
chewed before swallowing. |
| Major drug Interactions: cimetidine
inhibits the metabolism of mebendazole |
| Reference: www.rxlist.com & Katzung's text |
| Drug: Thiabendazole (Mintezol ®) |
| Drug Class: Antihelmintic |
| Mechanism of Action: a benzimidazole
that inhibits microtubule synthesis in nematodes. It is a chelating agent
that forms stable complexes with a number of metals (but not calcium). |
| Clinical Indications: an alternative
drug to ivermectin for treatment of strongyloidiasis (threadworm)
and cutaneous larva migrans (CLM, sandworm disease). |
| Contraindications: pregnancy,
presence of hepatic or renal disease |
| Side Effects: Thiabendazole is much more toxic than other benzimidazoles or ivermectin. Common
side effects include dizziness, anorexia, nausea & vomiting. |
| Pharmacokinetics: rapidly absorbed
after ingestion, plasma half life is 1.2 hrs. Undergoes hepatic metabolism,
with renal clearance of its metabolites. Can be absorbed through the skin. |
| Major drug Interactions: competes
for metabolism with xanthene derivatives (e.g. theophylline) & can result
in toxic levels of these drugs if given cocomitantly without dosage adjustment. |
| Reference: www.rxlist.com & Katzung's text |
| Drug: Albendazole (Albenza, Zentel ®) |
| Drug Class: Antihelmintic (broad spectrum) |
| Mechanism of Action: a benzimidazole
carbamate (prodrug). The active form inhibits microtubule synthesis in nematodes. |
| Clinical Indications: A
drug of choice for ascariasis (roundworm), enterobiasis (pinworm), hookworm,
cutaneous larva migrans, intestinal capillariasis & gnathostomiasis. Also a treatment of choice for surgical removal
or asperation of Hydatid cysts. |
| Contraindications: cirrhosis |
| Side Effects: Relatively free of side
effects. Mild & transient epigastric distress. |
| Pharmacokinetics: Administered on
an empty stomach when used against intraluminal parasites, but with a fatty
meal when used against tissue parasites. Eratic oral absorption (increased
with fatty meal) with first-pass metabolism to produce the active metabolite
albendazole sulfoxide. |
| Reference: www.rxlist.com & Katzung's text |
| Drug: Pyrantel pamoate (Antiminth, Combantrin,
Pin-rid, Pin-X ®) |
| Drug Class: Anthelmintic (broad spectrum) |
| Mechanism of Action: a neuromuscular
blocking agent in mature and immature forms of susceptible helminths within
the GI tract. that causes release of ACh & inhibition of cholinesterase,
resulting in paralysis. This is followed by expulsion of worms. |
| Clinical Indications: highly effective
for treatment of pinworm, ascaris (roundworm)
& Trichostrongylus orientalis infections. Moderately
effective against both species of hookworm.
Not effective against trichuriasis or strongyloidiasis. Effective only within
the GI lumen (it is poorly absorbed) & it is therefore not effective
against migratory stages in tissues or against ova. |
| Contraindications: use with caution
in patients with liver dysfunction (aminotransferase elevations have been
noted in a small number of patients). |
| Side Effects: adverse effects are
infrequent, mild & transient. GI upset, headache. |
| Pharmacokinetics: Poorly absorbed
from the GI tract. Over half of the drug is recovered unchanged in the feces. |
| Reference: www.healthdigest.org/drugs |
| Drug: Ivermectin (Mectizan, Stromectol ®) |
| Drug Class: Antihelmintic |
| Mechanism of Action: paralyzes nematodes
& arthropods by intensifying GABA-mediated signals in peripheral nerves.
In onchocerciasis, ivermectin is microfilaricidal. It does not kill adult
worms, but blocks the release of microfilariae for months after therapy. |
| Clinical Indications: Drug of choice
against strongyloidiasis (a
roundworm) & onchocerciasis (a
worm causing river blindness) |
| Contraindications: Pregnancy. Other
drugs that enhance GABA activity (e.g. barbiturates, benzodiazepines &
valproate). |
| Side Effects:Typically infrequent.
In onchocerciasis, adverse effects can result from the killing of microfilariae
& includes fever, headache, dizziness (the Mazotti reaction). |
| Pharmacokinetics: Plasma half life
is ~16 hrs. |
| Major drug Interactions: Other drugs
that enhance GABA activity (e.g. barbiturates, benzodiazepines & valproate). |
| Reference: www.rxlist.com |
| Drug:Diethylcarbamazine (Hetrazan ®) * |
| Drug Class: Antihelmintic |
| Mechanism of Action: immobilizes microfilariae
& alters their surface structure, displacing them from tissues &
making them more susceptible to destruction by host defense mechanisms.
Mode of action is unknown. |
| Clinical Indications: A drug of choice
against filiariasis, loiasis & tropical
eosinophilia. It is efficacious & lacks serious toxicity.
Microfilariae of all species are rapidly killed; adult parasites are killed
more slowly, often requiring several treatments. |
| Contraindications: use with caution
in patients with hypertension or renal disease. |
| Side Effects: generally mild &
transient |
| Pharmacokinetics: Should be taken
after meals. rapidly absorbed from GI tract; plasma half-life is 2-3 hrs
if urine is acidic, 10 hrs if uring is alkaline. |
| Note: *Available in the USA only from the Parasitic Disease Drug Service, CDC,
Atlanta. |
| Reference: Katzung's text |
| Drug: Nifurtimox * |
| Drug Class: Antihelmintic |
| Mechanism of Action: unclear |
| Clinical Indications:The most commonly
used drug for American trypanosomiasis (Chaga's
disease). Not effective in the treatment
of chronic Chaga's disease. |
| Side Effects: nausea, vomiting, fever,
rash. |
| Pharmacokinetics: Well absorbed orally
with a plasma half life of ~3 hrs. |
| Major drug Interactions: |
| *Available in the USA only from
the Parasitic Disease Drug Service, CDC, Atlanta. |
| Reference: http://www.nlm.nih.gov/medlineplus/druginfo/ & Katzung's text |
| Drug: Suramin * |
| Drug Class: Antihelmintic |
| Mechanism of Action: unknown |
| Clinical Indications: First line therapy
for early hemolymphatic African trypanosomiasis
(African sleeping sickness). |
| Side Effects: Adverse effects are
common & can include fatigue, nausea, vomiting. Later reactions include
proteinuria, hemolytic anemia, agranulocytosis. |
| Pharmacokinetics:Given i.v. &
has complicated pharmacokinetics w/ short initial half-life and a terminal
half-life of ~50 days. It is slowly cleared by renal excretion. It does
not enter the CNS & is therefore ineffective agains advanced disease. |
| *Available in the USA only from
the Parasitic Disease Drug Service, CDC, Atlanta. |
| Reference: http://www.nlm.nih.gov/medlineplus/druginfo/ & Katzung's text |
| Drug: Pentamidine (Pentam 300, Pentacarinat ®) |
| Drug Class: Antiprotozoal |
| Mechanism of Action: |
| Clinical Indications: Alternative
drug for Pneumocystosis caused by P jiroveci. It
has somewhat lower efficacy & greater toxicity than trimethoprim-sulfamethoxazole.
Alternative drug to suramin for African sleeping sickness. |
| Side Effects: significant
toxicity, seen in 50% of patients. The drug should be given
slowly over 2 hours with patient monitoring. (Rapid i.v. administration
can cause severe hypotension, tachycardia, dizziness & dyspnea.) I.m.
use can cause pain at the injection site & sterile abscesses. Pancreatic
toxicity is common. Hypoglycemia due to inappropriate insulin release may
occur 5-7 days after onset of drug therapy. Reversible renal insufficiency
is common. Rash, metalic taste, etc.... |
| Pharmacokinetics: Administered parentally. |
| Reference: www.rxlist.com |
| Drug: Praziquantel (Biltricide ®) |
| Drug Class: Antihelmintic |
| Mechanism of Action: increases the
permeability of trematode & cestode cell membranes to calcium, resulting
in paralysis, dislodgement & death. |
| Clinical Indications: Drug of choice
for treatment of schistosome infections of all species & cestode infections,
including cysticercosis. |
| Pharmacokinetics: tablets are taken
with liquid after a meal, swallowed without chewing (because the bitter
taste can cause retching & vomiting). Most of the drug is metabolized
to inactive forms after a first pass in the liver. Half life is 0.8-1.5
hrs. Excretion is mainly via the kidneys (60-80%) and bile (15-35%). |
| Major drug Interactions: Cimetidine
increases plasma levels of parziquantel. Phenytoin, carbamazepine &
corticosteroids reduce it's bioavailability. |
| Reference: www.rxlist.com |
| Drug: Amantadine (generic, Symmetrel ®) |
| Drug Class: Antiviral,
anti-influenza-A virus |
| Mechanism of Action: Interferes with uncoating of the viral RNA of influenza A within infected
host cells, thus preventing viral replication. |
| Clinical Indications: A Prophylactic DOC for influenza-A virus.
Is not as effective if taken after viral infection. |
| Contraindications: Contraindicated in pregnancy due to teratogenic effects in animals. |
| Side Effects: CNS toxicity, excitability and insomnia, anorexia. |
| Pharmacokinetics: Orally administered, excreted unchanged (90%) in the urine, 12-18 hrs half-life. |
| Major drug Interactions: Anticholinergic drugs, hydrochlorothiazide and triamterene. |
| Notes: Closely
observe patients with history of epilepsy and reduce dosage in patients
with renal function impairment. |
| Reference: www.rxlist.com |
| Drug: Rimantadine (Flumadine ®) |
| Drug Class: Antiviral,
anti-influenza-A virus. |
| Mechanism of Action: Interferes with uncoating of virus |
| Indications: Prophylactic for influenza-A virus. Preferred over amantadine due to lower
CNS toxicity & increased metabolism. |
| Contraindications: Contraindicated in pregnancy due
to teratogenic effects in animals. |
| Side Effects: CNS toxicity is lower than Amantadine, anorexia and GI side effects are
similar to Amantadine. |
| Pharmacokinetics: Orally administered. Extensively metabolized before renal excretion, so
dose reductions are not needed until creatinine clearance falls below 10
ml/min. |
| Major drug Interactions: Anticholinergic drugs, hydrochlorothiazide and triamterene. |
| Notes: Influenza
A viruses cross-resistant to both amantadine and rimantadine can emerge. |
| Reference: www.rxlist.com |
| Drug: Zanamivir (Relenza ®) |
| Drug Class: Antiviral,
anti-influenza virus (A and B) |
| Mechanism of Action: Inhibits influenza neuraminidase which blocks the cellular release of the
virus particle |
| Clinical Indications: Treatment of acute uncomplicated influenza
A and B (oral inhalation). |
| Contraindications: Hypersensitivity. |
| Side Effects: Nasal and throat discomfort. Bronchospasm in patients with reactive airway
disease. |
| Pharmacokinetics: Oral inhalation every 12 hrs. No systemic absorption. |
| Major drug Interactions: not a substrate and does not affect CYP 450 isoenzymes |
| Notes: Drug
resistance can occur. |
| Reference: www.rxlist.com |
| Drug: Oseltamivir (Tamiflu ®) |
| Drug Class: Antiviral,
anti-influenza virus (A and B) |
| Mechanism of Action: Inhibition of influenza neuraminidase to block virus particle release and
aggregation. |
| Indications: Treatment
of acute uncomplicated influenza A and B.
Can decrease the severity and duration of symptoms. |
| Contraindications: Known hypersensitivity. |
| Side Effects: Bronchitis, insomnia, nausea, vertigo and vomiting can occur. |
| Pharmacokinetics: Oral administration of oseltamivir phosphate is readily absorbed from the
gastrointestinal tract. It is extensively converted by hepatic esterases
to oseltamivir carboxylate. At least 75% of an oral dose reaches the systemic
circulation as oseltamivir carboxylate. |
| Major drug Interactions: not a substrate and does not affect CYP 450 isoenzymes. |
| Notes: Drug
resistance can occur. |
| Reference: www.rxlist.com |
| Drug: Idoxuridine (Herplex ®) |
| Drug Class: Anti-viral,
anti-Herpes Simplex Virus (HSV) |
| Mechanism of Action: Iodinated thymidine analog, activated intracellularly to tri-phosphate which
can inhibit DNA polymerases required for incorporation of thymidine into
viral DNA. Idoxuridine, instead of thymidine, is incorporated into viral
DNA, resulting in faulty DNA and the inability of the virus to infect tissue
or reproduce. |
Clinical Indications: Alternate drug for topical use against HSV
keratitis. |
| Contraindications: Hypersensitivity, severe systemic toxicity |
| Side Effects: irritation, pruritis, inflammation |
| Pharmacokinetics: Administered in eye drops, no systemic absorption |
| Major drug Interactions: boric-acid containing solutions |
| Notes: Poorly
selective and can affect host DNA polymerases. The methyl (–CH3) group
of thymine is replaced by iodine (-I). |
| Reference: www.healthdigest.org/drugs |
| Drug: Trifluridine (Viroptic ®) |
| Drug Class: Anti-viral,
anti-Herpes Simplex Virus (HSV-1 and -2) and anti-vaccinia virus. |
| Mechanism of Action: Tri-fluoro thymidine analog, activated intracellularly to tri-phosphates
which then inhibit DNA polymerases. |
| Clinical Indications: A DOC for topical treatment of HSV keratitis. Also effective
in treating cutaneous infections by acyclovir
resistant strains of HSV. |
| Contraindications: Hypersensitivity and chemical intolerance. |
| Side Effects: Severe systemic toxicity. |
| Pharmacokinetics: used topically in eye drops
and ophthalmic preparations. No systemic absorption. |
| Major drug Interactions: None known. |
| Notes: Poorly
selective and can affect host DNA polymerases. The methyl (–CH3) group
of thymine is replaced by a trifluoromethyl (-CF3) moiety. |
| Reference: www.rxlist.com |
| Drug: Vidarabine (Vira-A ®) |
| Drug Class: Antiviral,
anti-herpes simplex virus (HSV types 1 and 2) |
| Mechanism of Action: A purine analog, phosphorylated and activated intracellularly which then
inhibits DNA polymerase activity |
| Clinical Indications: Acute keratoconjunctivitis and recurrent epithelial keratitis due to HSV-1
and HSV-2. Recommended for herpes encephalitis as an alternate drug. |
| Contraindications: Hypersensitivity to vidarabine |
| Side Effects: Causes bone marrow suppression and hepatic toxicity if given systemically. |
| Pharmacokinetics: Ocular (topical) administration with no systemic absorption. Can be given
i.v. (w/ significant side effects). |
| Major drug Interactions: Corticosteroids |
| Notes: Ocular
side effects such as glaucoma or cataract can be seen when coadministered
with corticosteroids |
| Reference: www.rxlist.com |
| Drug: Acyclovir (generic, Zovirax ®) |
| Drug Class: Anti-viral,
anti herpes and varicella zoster virus (HSV and VZV). |
| Mechanism of Action: An acyclic guanosine derivative that causes DNA chain termination. Activated
by viral thymidine kinase (TK) to a monophosphate form. Host enzymes then
convert the monophosphate to di- and then tri-phosphate (active) form which inhibits the viral DNA polymerase by preventing chain elongation due to the lack of a 3' -OH group. |
| Clinical Indications: A DOC for parenteral treatment of herpes zoster (shingles) and oral therapy for recurrent genital
herpes (HSV-2). Also indicated for HSV
encephalitis & Varicella
zoster. |
| Contraindications: Hypersensitivity or chemical intolerance |
| Side Effects: inflammation or phlebitis, malaise, nausea and headache. Encephalopathic
changes and renal function impairment may also occur. |
| Pharmacokinetics: Can be given orally, i.v. or topically. Low bioavailability (15-20%), but
sufficient to achieve therapeutic plasma levels. Renal excretion with half-life
of ~2.5 hrs (15% metabolized, 85% excreted unchanged). Only 50% of plasma
levels penetrate into the CSF, hence dose escalation is required for HSV
encephalitis. |
| Major drug Interactions: Probenecid (inhibits acyclovir elimination) and Zidovudine (minor; drowsiness
& fatigue). |
| Notes: Not
effective against CMV because CMV-TK cannot activate the
drug. Viral resistance can occur dur to mutations in the viral TK enzyme. |
| Reference: www.rxlist.com |
| Drug: Valacyclovir (Valtrex ®) |
| Drug Class: Anti-viral,
anti herpes simplex and varicella zoster virus (HSV and VZV). |
| Mechanism of Action: Valine ester of acyclovir (a prodrug). Stomach acid converts it to acyclovir.
DNA chain termination. Activated by viral thymidine kinase and host enzymes,
inhibits viral DNA polymerase. Produces DNA chain termination. |
| Clinical Indications: A DOC for treatment of herpes zoster (shingles)
and recurrent genital herpes. |
| Contraindications: Hypersensitivity or intolerance to valacyclovir or acyclovir. |
| Side Effects: Thrombotic thrombocytopenic purpura and hemolytic uremic syndrome (TTP/HUS).
Renal function impairment. |
| Pharmacokinetics: Oral administration and conversion to acyclovir, achieving a 3-5 higher
plasma level & thereby requires less frequent dosing. Excretion in urine.
Plasma half-life is 2.5 to 3.3 hrs. |
| Major drug Interactions: Cimetidine/probenecid. |
| Notes: Valine
ester pro-drug of acyclovir and can achieve 3-5 fold higher plasma levels
than acyclovir. |
| Reference: www.rxlist.com |
| Drug: Ganciclovir (Cytovene ®) |
| Drug Class: Anti-viral,
anti herpes simplex (HSV) and cytomegalo virus (CMV). |
| Mechanism of Action: Structure similar to acyclovir but with an additional side group. Activated
by viral thymidine kinase (TK) and host enzymes, which inhibits the viral
DNA polymerase. Produces DNA chain termination. |
| Clinical Indications: A DOC for CMV retinitis in
immunocompromised patients. |
| Contraindications: Hypersensitivity to ganciclovir or acyclovir. |
| Side Effects: Bone marrow toxicity (significant myelosuppression, neutropenia & thrombocytopenia).
Many have CNS toxicity & a possible teratogen. |
| Pharmacokinetics: Recovered unmetabolized in the urine. Half-life is 3.5 hrs following I.V.
and 4.8 hrs following oral use. |
| Major drug Interactions: Imipenem-cilastin, nephrotoxic drugs, probenecid, didanosine, and zidovudine. |
| Notes: May
cause fatal dysfunctions such as pancreatitis, sepsis and multiple organ
failure. |
| Reference: www.rxlist.com |
| Drug: Valganciclovir (Valcyte ®) |
| Drug Class: Anti-viral,
anti herpes simplex (HSV) and cytomegalo virus (CMV). |
| Mechanism of Action: A prodrug of ganciclovir and oral administration results in plasma levels
higher than ganciclovir. Activated by viral thymidine kinase (TK) and host
enzymes, which inhibits the viral DNA polymerase. Produces DNA chain termination. |
| Indications: A
DOC for CMV retinitis in immunocompromised
patients and transplant patients. |
| Contraindications: Hypersensitivity to ganciclovir or acyclovir. |
| Side Effects: Hematologic dysfunctions, renal function impairment. |
| Pharmacokinetics: Administered orally. Recovered unmetabolized in the urine. Half-life is
6-8 hrs following oral use. |
| Major drug Interactions: Imipenem-cilastin, nephrotoxic drugs, probenecid, didanosine, and zidovudine. |
| Notes: May
cause fatal dysfunctions such as pancreatitis, sepsis and multiple organ
failure. |
| Reference: www.rxlist.com |
| Drug: Foscarnet (Foscavir ®) |
| Drug Class: Anti-viral,
anti-cytomegalo virus (CMV) |
| Mechanism of Action: An inorganic pyrophosphate compound that specifically inhibits viral DNA
polymerase, RNA polymerase & HIV reverse transcriptase by competing
for the pyrophosphate binding site. A tri-sodium salt of phosphonoformate. |
| Clinical Indications:A
DOC for acyclovir resistant HSV or VZV infections.
Alternative drug against CMV infections. |
| Contraindications: Hypersensitivity. |
| Side Effects: Cation problems such as hypokalemia & hypomagnesemia. Headache, fever,
nausea, diarrhea, renal function impairment and hematologic dysfunctions. |
| Pharmacokinetics: Poorly absorbed orally, given i.v. Excreted mostly unchanged in urine. Bimodal
timecourse of elimination, with ~80% cleared initially with a half-life
of 4-8 hrs, and ~20 % cleared with a terminal half-life of 3-4 days due
to accumulation in bone with gradual release. |
| Major drug Interactions: Nephrotoxic drugs (e.g. aminoglycoside, amphotericin B, pentamidine). |
| Reference: www.rxlist.com & Katzung's text |
| Drug: Ribavirin (Virazole ®) |
| Drug Class: Antiviral,
anti Respiratory Syncytial Virus (RSV). |
| Mechanism of Action: A triazine riboside analog. Converted intracellularly to a 5'-triphosphate
derivative that inhibits viral RNA polymerase and capping of viral mRNA
at the 5' position. |
| Clinical Indications: Used as an aerosol DOC for treating infections by the respiratory
syncytial virus (RSV) and as a DOC in
combination with Interferon-alpha-2b for hepatitis-C virus infection. |
| Contraindications: Hypersensitivity, Teratogenicity and embryo toxicity. |
| Side Effects: respiratory dysfunctions, hemolytic anemia, cough, pruritus and rash. May
have teratogenic effects. |
| Pharmacokinetics: Administered orally, by inhalation, & i.v. Aerosol is absorbed systemically.
Plasma half-life is 9.5 hrs. Accumulation occurs in RBCs (T1/2= 40 days). |
| Major drug Interactions: None known. |
| Notes: Some
success against influenza A and B as well. |
| Reference: www.rxlist.com |
| Drug: Interferon alpha-2b (Roferon-A ®) |
| Drug Class: Antiviral,
anti-hepatitis virus B and C |
| Mechanism of Action: A recombinant cytokine, with a host of anti-viral properties including inhibition
of viral replication (both RNA and DNA virus) and augmentation of anti-viral
immune responses. Activates ribonucleases that degrade viral mRNA. Blocks
protein synthesis by inhibiting the translation initiation complex. |
| Clinical Indications: Broad spectrum activity against both DNA and RNA viruses. However, primarily
indicated as a DOC against Hepatitis-B and
C infections (it can be combined with other drugs such as
ribavarin) . Also used in combination with ribavirin for RSV. Used to treat
AIDS-related kaposis sarcoma, and malignant melanoma. |
| Contraindications: Hypersensitivity to IFN-alpha-2b or any of the components of the formulation. |
| Side Effects: Cardiovascular abnormalities such as hypotension, arrhythmia, tachycardia,
cardiomyopathy etc. Thyroid dysfunctions, flu
like symptoms and hepato-toxicity. High doses can cause
bone marrow supression. |
| Pharmacokinetics: Administered i.m. or s.c. Kidney may be the main site for IFN catabolism.
Elimination half-life is approximately 2 hours. |
| Major drug Interactions: Aminophylline and Zidovudine. |
| Notes: Standard
hematologic tests should be performed prior to beginning treatment. Photosensitivity
may also occur. |
| Reference: www.rxlist.com |
| Drug:
Zidovudine (azidothymidine; AZT) (Retrovir
®) |
| Drug Class: Antiretroviral,
NRTI |
| Mechanism of Action:
AZT is a deoxythymidine analog (see above) |
| Clinical Indications:
HIV-1 infection (given in combination with other drugs - HAART) |
| Side Effects:
(see above). GI intolerance, headaches, insomnia |
| Pharmacokinetics: well
absorbed from the gut & distributed to most body tissues. Serum half
life is ~1 hr & intracellular half life is ~3.3 hrs. AZT is eliminated
primarily by renal excretion following glucuronidation in the liver. Clearance
is reuced by ~50% in uremic patients & toxicity may increase in patients
with advanced hepatic insufficiency. |
| Drug Interactions: avoid
concurrent myelosuppressive drugs (eg. ganciclovir, ribavirin) |
| Notes: the
first licensed antiretroviral agent. Monotherapy is avoided because of the
need for maximum efficacy & to prevent development of resistance. As
with other NRTIs, resistance may limit clinical efficacy. |
| Reference:
www.rxlist.com
& Katzung's text |
| Drug:
Didanosine (dideoxyinosine, ddI) (Videx
®) |
| Drug Class: Antiretroviral,
NRTI |
| Mechanism of Action:
a synthetic analog of deoxyadenosine (see above). |
| Clinical Indications:
HIV-1 infection (given in combination with other drugs - HAART) |
| Side Effects:
(see above). The major clinical toxicity of ddI is dose-dependent (fatal
& non-fatal) pancreatitis.
Other reported side effects include painful peripheral distal neuropathy,
diarrhea, hyperuricemia, hepatitis, cardiomyopathy. |
| Pharmacokinetics:
Should be taken on an empty stomach. Acid pH will inactivate the compound
by hydrolysis of the glycosidic bond between the sugar & base moieties.
ddIs AUC is reduced by 55% if ingested within 2 hrs after a meal. Elimination
half life is 0.6-1.5 hrs, but the intracellular half life of the activated
compound is 12-24 hrs. The drug is eliminated by glomerular filtration &
tubular secretion. Dosage reduction is required for low creatinine clearance,
after hemodialysis or during ambulatory peritoneal dialysis & for low
body weight. |
| Drug Interactions:ddI
chewable formulation contains antacid (therefore avoid taking fluroquinolones
& tetracycline w/in 2 hrs before or after ddI) avoid alcohol (increased
risk of pancreatitis) & concurrent neuropathic drugs (eg. didanosine,
zalcitabine, isoniazid) |
| Reference:
www.rxlist.com
& Katzung's text |
| Drug:
Lamivudine (3TC) (Epivir ®)
|
| Drug Class: Antiretroviral,
NRTI |
| Mechanism of Action:
a cytosine analog (synergistic with zidovudine & stavudine) effective
against both zidovudine-sensitive and zidovudine-resistant HIV-1 strains |
| Clinical Indications:
HIV-1 infection (given in combination with other drugs - HAART) |
| Side Effects:
(see above). Other: headache, insomnia, fatigue, GI discomfort. |
| Pharmacokinetics: Oral
bioavailability exceeds 80% and is not food dependent. Plasma elimination
half life is 2.5 hrs, intracellular half life of the active 5'-triphosphate
is 11-16 hrs. Majority is eliminated unchaged in the urine. Dose should
be reduced with renal insufficiency or low body weight. |
| Drug Interactions:
Lamivudine's AUC increases then coadministered with trimethoprim - sulfamethoxazole. |
| Reference:
www.rxlist.com
& Katzung's text |
| Drug:
Stavudine (D4T) (Zerit ®)
|
| Drug Class: Antiretroviral,
NRTI |
| Mechanism of Action:a
thymidine analog |
| Clinical Indications:
HIV-1 infection (given in combination with other drugs - HAART) |
| Side Effects:
(see above) The major dose-limiting toxicity isa reversible dose-related
peripheral sensory neuropathy that may be increased when
given with other neuropathy-inducing drugs such as zalcitabine & didanosine.
|
| Pharmacokinetics: High
bioavailability & absorption is not food dependent. Plasma half-life
is ~1 hr; intracellular half-life is 3.5 hrs. Excretion is by active tubular
secretion & glomerular filtration. Dosage should be reduced in patients
with renal insufficiency, those receiving hemodialysis & for low body
weight. |
| Drug Interactions: do
not coadminister with zidovudine since zidovudine may reduce
the phosphorylation of stavudine. |
| Reference:
www.rxlist.com
& Katzung's text |
| Drug:
Abacavir (Ziagen ®)
|
| Drug Class: Antiretroviral,
NRTI |
| Mechanism of Action:
a guanosine analog (in contrast to other NRTIs) |
| Clinical Indications:
HIV-1 infection (given in combination with other drugs - HAART) |
| Side Effects:
severe hypersensitivity reactions,
occasionally fatal in 2-5% of patients. |
| Pharmacokinetics:
well absorbed, unaffected by food, plasma half life is 1.5 hrs. Metabolized
by alcohol dehydrogenase & glucuronosyltranserase to inactive metabolites
that are eliminated in the urine. |
| Reference:
www.rxlist.com
& Katzung's text |
| Drug:
Nevirapine (Viramune ®)
|
| Drug Class:NNRTI |
| Additional Indication:
Also used as a single dose during the onset of labor for the prevention
of HIV transmission from mother to newborn, followed by a single dose to
the newborn after delivery. |
| Side Effects:
(see above). Severe, life-threatening, and in some cases fatal
hepatotoxicity, including fulminant and cholestatic hepatitis,
hepatic necrosis and hepatic failure, has been reported in patients taking
nevirapine. Serial monitoring of liver function tests is recommended. Rash
occurs in ~17% of patients & is dose-limiting in ~7% of patients. Fever,
nausea, headache & somnolence may occur. |
| Pharmacokinetics:
Greater than 90% bioavailability & is not food dependent. Metabolized
by CYP3A to metabolites that are excreted in the urine. |
| Drug Interactions: nevirapine
is both a substrate & moderate inducer
of CYP3A &
will result in a 1.5 - 2 fold increase in oral clearance of itself &
decrease in its half life with repeated dosing. It will decrease the half-life
of indinavir & saquinavir if given concurrently. Do not use ketoconazole
concurrently due to CYP3A interactions. Cimetidine & macrolides (CYP3A
inhibitors) and rifampin (CYP3A inducer) will alter nevirapine plasma levels
& should be used cautiously. |
| Reference:
www.rxlist.com &
Katzung's text |
| Drug:
Delavirdine (Rescriptor ®)
|
| Drug Class: NNRTI |
| Contraindications: Pregnancy |
| Side Effects:
(see above). Skin rashes (18%), severe forms of rash occur rarely. Teratogenic.
Liver function abnormalities. |
| Pharmacokinetics: Oral
bioavailability is reduced by antacids;
little gets into the CSF. Metabolized by CYP3A
& CYP2D6. It also inhibits
CYP3A & thereby increases the plasma levels of many
different drugs. |
| Drug Interactions: Rifampin,
phenytoin, phenobarbital, carbamazepine & rifabutin reduce delavirdine
levels, while & clarithromycin, fluoxetine, dexamethasone and ketoconazole
increase delavirdine levels. |
| Reference:
www.rxlist.com
& Katzung's text |
| Drug:
Efavirenz (Sustiva ®)
|
| Drug Class:NNRTI |
| Clinical Indications:
one of the most commonly used NNTRIs |
| Contradications: pregnancy,
saquinavir |
| Side Effects:
CNS (dizziness, drowsiness, insomnia, headache, nightmares, amnesia, delusions,
euphoria) in up to 50% of patients. These
pyschiatric symptoms may be severe. Mild to moderate skin
rash (up to 28% of patients). Nausea, crystalluria,
increased serum cholesterol, elevated liver enzymes. Teratogenic.
|
| Pharmacokinetics: Bioavailability
is increased from 45 to 65% if taken after a high-fat meal. Can be given
once daily (half life = 40-55 hs). Mainly metabolized by CYP3A4 & CYP2B6
to inactive metabolites & some unchanged drug is excreted in the feces.
Penetrates into the CNS (3x higher levels in CSF compared to unbound drug
in plasma). It is a substrate, inhibitor & moderate inducer of CYP3A4. |
| Drug Interactions: Decreased
plasma concentrations occur in teh presence of drugs that induce CYP3A4
(rifampin, rifabutin, phenobarbital). Do not coadminister with saquinavir
because efavirenz will decrease saquinavir plasma levels |
| Reference:
www.rxlist.com & Katzung's text |
| Mechanism of Action:
Prevent cleavage of precursor molecules associated with structural proteins
of the mature virion core, resulting in the production of immature, noninfectious
viral particles. Resistance is common, thus contraindicating monotherapy. |
| Clinical Indication:
As a component of HAART in the treatment of HIV infection. |
| Common Side Effects:
A syndrome of redistribution and accumulation of body fat, including buffalo
hump, central obesity, peripheral & facial wasting, breast enlargement.
Increased spontaneous bleeding in Hemophelia A & B patients. |
| Common Drug Interactions:
All antiretroviral PIs are
substrates
of CYP3A4.
Some PIs are also inhibitors of CYP3A4 (amprenavir,
indinavir, lopinavir, ritonavir) and can cause decreased clearance of other
drugs. In general, these later drugs should not be given concommitently
with other drugs that are heavily metabolized by CYP3A4. Because even low
(subtherapeutic) doses of ritonavir can cause marked inhibition of CYP3A4,
it is used in combination formulations with other PIs to act as a "PI
booster", increasing efficacy and reducing the number of doses required
per day, with increased compliance (see below). |
| Drug:
Indinavir (Crixivan ®)
|
| Drug Class: Antiretroviral
Protease Inhibitor |
| Side Effects:
Indinavir is not soluble in the urine, and
crystallization of the drug can cause kidney
stones (3-15%) that can result in renal failure & indirect
hyperbilirubinemia. Consumption of a minimum of 48 oz of water daily is
necessary (more in summer). Thrombocytopenia & elevated serum aminotransferases
have been reported. |
| Pharmacokinetics: Must
be consumed on an empty stomach for maximal absorption. Indinavir has the
highest CSF penetration of the PIs (76% of serum levels). Excretion is mainly
fecal. Dose reduction is necessary in hepatic insufficiency. Indinavir is
a substrate & inhibitor of CYP3A4. |
| Drug Interactions: (see
above). Indinavir levels decrease with rifampin, fluconazole, St. John's
wort. Dose reduction of Indinavir is needed when coadministered with delavirdine,
ketoconazole or itraconazole. An increase in dose of Indinavir is needed
when coadministered with efavirenz. |
| Reference:
www.rxlist.com
& Katzung's text |
| Drug:
Lopinavir / Ritonavir (Kaletra ®)
|
| Drug Class: Antiretroviral
Protease Inhibitor Combination |
| Side Effects:
diarrhea, nausea, abdominal pain, asthenia. |
| Pharmacokinetics: Lopinavir
is metabolized by CUP3A. |
| Drug Interactions: (see
above) Inducers of CYP3A (St. John's wort, phenytoin, phenobarbital, rifampin,
dexamethasone, carbamazepine) will reduce levels of lopinavir. |
| Note: A lincensed
combination in which subtherapeutic doses
of ritonavir inhibit the CYP3A-mediated metabolism of lopinavir,
thereby resulting in increased exposure to lopinavir. The combination maintains
a potent viral suppression (plasma trough levels are greater than an HIV-1
50% inhibitory concentration) and helps prevent the emergence of resistance.
The combination also increases patient compliance by reducing the number
of pills taken to twice per day. |
| Reference:
www.rxlist.com
& Katzung's text |
| Drug:
Amprenavir (Agenerase®)
|
| Drug Class: Antiretroviral
Protease Inhibitor |
| Side Effects:
diarrhea, nausea, perioral paresthesias, depression, rash (3% severe enough
to warrant discontinuation). |
| Pharmacokinetics: rapidly
GI absorption, can be taken with or without food, but high fat meals may
decrease absorption & should be avoided. Plasma half life 7-11 hrs.
Metabolized by CYP3A4 - it is both a substrate and inhibitor. |
| Drug Interactions: Because
the oral form contains propylene glycol, it is contraindicated in those
using metronidazole or disulfiram. Interactions occur with other drugs that
induce or are metabolized by CYP3A4. |
| Contraindications:
hepatic insufficiency. Because the oral form contains propylene glycol,
it is contraindicated in young children, pregnancy & those using metronidazole
or disulfiram. |
| Reference:
www.rxlist.com
& Katzung's text |
| Drug:
Enfuvirtide (T-20) (Fuzeon ®)
|
| Drug Class: Antiretroviral
fusion inhibitor |
| Mechanism of Action:
blocks entry of virus into cells by binding to the gp41 subunit of the viral
envelope glycoprotein, preventing the conformational changes required for
fusion of the viral and cellular membranes. |
| Clinical Indications:
treatment-experienced patients with persistent HIV-1 replication despite
ongoing therapy. |
| Side Effects:
local injection site reactions. Hypersensitivity & eosinophilia can
occur. |
| Pharmacokinetics: administered
subcutaneously in combination with other antiretroviral agents.
Metabolism by protein hydrolysis without involvement of cyt P450.
Elimination half life is 4 hrs. |
| Drug Interactions: none |
| Reference:
www.rxlist.com
& Katzung's text |
