updated on September 6, 2007

Drug Profiles Fall Semester

Basic Principles Cancer
Drug Absorption, Distribution, Metabolism    Cancer chemotherapy  
Pharmacokinetics   
Pharmacogenetics   Hematopoetic Pharmacology
PBL- Drug metabolism Antianemia drugs
  Anticoagulants & Thrombolytics
Inflammation Antimalarial drugs
Immunopharmacology  
Eicosanoids Autonomic Pharmacology
Histamine & Antihistamines  ANS (neurotransmitters)
Nonsteroidal analgesics Cholinomimetics
NSAIDs (Rx of gout) Cholinolytics
Antiinflammatory Steroids PBL - Chemical warfare  
Dermatopharmacology  Intro to Sympathetic Pharmacology I & II  
  Sympathomimetics
Antibacterials & Antifungals Sympatholytics
Penicilliins  
Cepalosporins Cardiovascular Pharmacology
Vancomycin Hypolipidemics
Chloramphenicol / Tetracyclines / Quinolones Digoxin
Sulfonamides Antianginal drugs
Metronidazole Vasodilators used to treat heart failure
Aminoglycosides Antiarrhythmics  
Macrolides  
Clindamycin  Pulmonary Pharmacology
Streptogramins Respiratory drugs
Linezolid Antimycobacterials
Daptomycin  
Metronidazole Renal Pharmacology
Rifampin Treatment of BPH & ED
Misc agents Renal Pharm - ACE inhibitors  
Antimicrobial Summary Tables Diuretics
Antifungal Drugs Antihypertensive drugs 
   
Antiparasitics & Antivirals  
Antiparasitics  
Antiviral Drugs   
AIDS Drugs  
Med Pharm Main page

 

Penicillins

The prototype:

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

Repository Penicllins:

Drug: Penicillin G procaine (generic)
Drug Class: Antibiotic (Beta Lactam)
Mechanism of Action: same as penicillin G
Indications: less severe infections due to Group A streptococci, pneumococci, gonococci or Treponema pallidum.
Pharmacokinetics: administered i.m. & maintains adequate serum levels for 12 hours.

Drug: Penicillin G benzathine (Permapen, Bicillin ®)
Drug Class: Antibiotic (Beta Lactam)
Mechanism of Action: Same as penicillin G
Indications: Prophylaxis of rheumatic fever, treatment of Group A Streptococcal pharyngitis & for treatment of syphilis.
Pharmacokinetics: Administered i.m. & maintains adequate serum levels for a month.

First Oral Penicllin:

Drug: Penicillin V or phenoxymethyl penicillin (generic, V-Cillin, others)
Drug Class: Antibiotic (Beta Lactam)
Mechanism of Action: Same as penicillin G. The first synthetic orally effective penicillin.
Indications: Penicillin V potassium is indicated in the treatment of mild to moderately severe infections due to microorganisms whose susceptibility to penicillin G is within the range of serum levels common to this particular dosage form. Therapy should be guided by bacteriologic studies (including susceptibility tests) and by clinical response.Useful in tonsilitis and streptococcal upper respiratory infections.
Reference: www.rxlist.com

Penicillinase Resistant Penicllins:

Drug: Methicillin
Drug Class: Semisynthetic Penicillin
Mechanism of Action: Same as Pen G. Resistant to beta-lactamase.
Indications: Severe infections by gram + penicillinase producing Staphlococci.
Pharmacokinetics: Parenteral administration
Notes: No longer commonly recommended for clinical use because of its nephrotoxicity. Used for determining drug resistance to penicllins (e.g. Methicillin Resistant Staph. Aureus.)

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: Nafcillin (generic, Nafcil®)
Drug Class: Semisynthetic Penicillin
Mechanism of Action: Same as Pen G. Resistant to beta-lactamase.
Indications: Severe infections by gram positive penicillinase producing Staphlococci.
Pharmacokinetics: the most lipid soluble in this subclass. Absorption is eratic when given orally, so it is typically given parentally (i.v.). Primarily excreted in the bile, so it can be used in patients with siginficant renal failure & against Staph infections occuring in the biliary tract.
Reference: www.rxlist.com

Extended or Broad-Spectrum Penicllins:
(inactivated by beta-lactamases, greater activity against gram negative bugs)

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: Clavulanic acid Tazobactam & Sulbactam
Drug Class: inhibtors of beta-lactamase.
Mechanism of Action: inhibtors of "most" beta-lactamases.
Indications: used in combination with amoxicillin or ticarcillin, and ampicillin

Carbapenems:

Drug: Imipenem / cilastatiin (Primaxin ®)
Drug Class: Carbapenem antibiotic
Mechanism of Action: Imipenem is structurally related to beta-lactam antiobiotics
Indications: highly resistant to beta-lactamase. Active against a wide variety of both gram positive & gram negative bacteria, anaerobes.
Pharmacokinetics: Inactivated rapidly in the kidney by dipeptidase. Cilastatin is therefor always given as a drug combination to inhibit this metabolism.
Reference: www.rxlist.com

Monobactams:

Drug: Aztreonam (Azactam ®)
Drug Class: Monobactam
Mechanism of Action: monocyclic beta-lactam ring & relatively resistant to beta-lactamases.
Indications: active against gram negative rods, but have no activity against gram positive bacteria or anaerobes (similar spectrum as aminoglycosides).
Pharmacokinetics: Not absorbed orally. Given i.v. every 8 hours. Half life is prolonged in renal failure.
Reference: www.rxlist.com

Cephalosporins

First Generation:

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: Cefazolin (generic, Kefzol, Ancef ®)
Drug Class: Cephalosporin 1st generation (parenteral)
Indications: used for surgical prophylaxis (same spectrum of activity as cephalexin)
Pharmacokinetics: parenteral administration (injection) only; elimination via the kidney.
Reference: www.rxlist.com

Second Generation:
(more resistant to beta-lactamase & drug-specific extended effects)

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: Cefaclor (generic, Ceclor ®)
Drug Class: Cephalosporin 2nd generation (oral)
Indications: extended effectiveness against against H. influenzae (as well as the organisms affected by 1st generation cephalosporins, gram negative bacilli; it is resistant to beta-lactamase inactivation).
Pharmacokinetics: oral absorption, renal clearance
Reference: www.rxlist.com

Drug: Cefprozil (Cefzil ®)
Drug Class: Cephalosporin 2nd generation (oral)
Indications: active against beta-lactamase producing H. influenzae; lower respiratory infections (as well as the organisms affected by 1st generation cephalosporins, gram negative bacilli; it is resistant to beta-lactamase inactivation).
Pharmacokinetics: oral absorption, renal clearance
Reference: www.rxlist.com

Drug: Cefuroxime axetil (Cefzil ®)
Drug Class: Cephalosporin 2nd generation (oral or parenteral)
Indications: penetrates CSF, useful in meningitis - meningococcus, H. influenzae, Proteus vulgaris. Axetil ester form used for oral administration. (Also affects the organisms sensitive to 1st generation cephalosporins, gram negative bacilli; it is resistant to beta-lactamase inactivation).
Pharmacokinetics: oral or parenteral forms
Notes: www.rxlist.com

Third Generation:
(more active against gram negative bacilli and less active against gram positive cocci;
Ineffective against enterococcal infections)

Drug:Cefotaxime (Claforan ®)
Drug Class: Cephalosporin 3rd generation (parenteral)
Indications: penetrates into CSF, useful in meningitis: meningococcus, H. influenzae. (More active against gram negative bacilli and less active against gram positive cocci Ineffective against enterococcal infections)
Pharmacokinetics: parenteral administration, renal clearance
Reference: www.rxlist.com

Drug:Ceftriaxone (Rocephin ®)
Drug Class: Cephalosporin 3rd generation (parenteral)
Indications: extended effectiveness against gonococcus, meningococcus, H. influenzae. (More active against gram negative bacilli and less active against gram positive cocci Ineffective against enterococcal infections). Drug of choice for treatment of bacterial meningitis.
Pharmacokinetics: Longer half-life (7-8 hr), parenteral administration, excreted via the bile tract, no dosage adjustment required in renal insufficiency.
Notes: www.rxlist.com

Drug:Ceftazidime (generic, Fortaz, Tazdime ®)
Drug Class: Cephalosporin 3rd generation (parenteral)
Indications:extended effectiveness against Pseudomonas aeruginosa. Used clinically for treatment of serious infections in combination with aminoglycosides such as life threatening bacteremia. (More active against gram negative bacilli and less active against gram positive cocci Ineffective against enterococcal infections)
Pharmacokinetics: parenteral administration
Reference: www.rxlist.com

Fourth Generation:
(increased resistance to beta-lactamases vs. 3rd generation & some extended activities)

Drug: Cefepime (Maxipime ®)
Drug Class: Cephalosporin 4th generation (parenteral)
Indications: greater in vitro activity against gram neagaive bacteria (lower mic values), active against Enterobacter, more resistant to beta-lactamases.Not active against methicillin resistant Staph aureus and against enterococcal organisms.
Pharmacokinetics: parenteral administration, renal clearance
Reference: www.rxlist.com

 

Drug: All Cephalosporins
Most Important Side Effects:

Hypersensitivity reactions (Cross-hypersensitivity with penicillins 1-3%)
Superinfections: enterococci, Enterobacter and Candida

 

Vancomycin

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

 

Chloramphenicol

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

Fluoroquinolones

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)

Tetracyclines

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)

Sulfonamides

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)

 

Aminoglycosides

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

Macrolides

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)

Clindamycin

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

Streptogramins

Drug: Synercid ® - combination of dalfospristin (streptogramin A) & quinupristin (streptogramin B)
Drug Class: Antibiotic (cyclic polypeptides)
Mechanism of Action: Similar to macrolides
Indications: Multidrug resistant Gram+ cocci: Staph, Strep and Enterococcus. MRSA and vancomycin resistant strains. Resistance to streptogramin B has been shown to occur due to methylation of the binding site similar to erythromycin
Pharmacokinetics: Administered by intravenous infusion.
Reference: www.rxlist.com

Ozazolidiones

Drug: Linezolid (Zyvox ®)
Drug Class: Synthetic Antibiotic
Mechanism of Action: Binds to 23 S ribosomal RNA of the 50 S subunit during early ribosomal assembly & inhibits protein synthesis. Baceriostatic.
Indications: Multidrug resistant Gram+ cocci: Staph, Strep and Enterococcus. MRSA and vancomycin resistant strains.
Side Effects: Thrombocytopenia (reversible) may occur.
Pharmacokinetics: Administered either orally (100% bioavailability) or by intravenous infusion.
Reference: www.rxlist.com

Daptomycin

Drug: Daptomycin (Zyvox ®)
Drug Class: Antibiotic
Mechanism of Action: Binds to bacterial membrane causing depolarization, K efflux & cell death.
Indications: Multidrug resistant Gram+ cocci: Staph, Strep and Enterococcus. MRSA and vancomycin resistant strains. Indicated for complicated skin & soft tissue infections & right sided infective endocarditis.
Side Effects: myopathy (monitor phosphokinase).
Pharmacokinetics: Administered by intravenous infusion, renal excretion (dose adjustments necessary w/ renal impairment.
Reference: www.rxlist.com

Rifamycins

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

Metronidazole

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

Miscellaneous Agents

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


Summary Tables on Antimicrobials (by Elizabeth Jensen)

Drugs contraindicated in children & pregnancy
  • Tetracycline (retardation of bone growth; stains teeth)
  • Fluoroquinolones (cartilage toxicity)
  • Thalidomide (severe birth defects)
  • Metronidazole (mutagenic and carcinogenic potential)
  • Chloramphenicol is contraindicated in infants (Gray baby syndrome because infants don’t produce enough glucoronyl transferase)

 

Alternative drugs in patients with a history of severe (anaphylactic) penicillin allergy
  • Aztreonam (a monobactam; primarily indicated for Gram - organisms and is not a drug of first choice)
  • Macrolides
  • Vancomycin
  • Clindamycin

 

Synergistic drug combinations (& their mechanisms)
  • Cell Wall Synthesis Inhibitor + Aminoglycoside (CWSI increases permeability of organism to aminoglycosides)
  • Trimethoprim + Sulfa drug (blocks two steps in the synthesis of folic acid, which bacterial cells need to survive)

 

Mechanisms for drug resistance
  • Intrinsic resistance (gram- bacteria have outer membrane impermeable to penicillin)
  • Escape from antibiotic effect (cell membranes become permeable to folic acid to escape the effect of sulfonamides and trimethoprim)
  • Penicillinase production (previously penicillinase- can become penicillinase+ and be resistant to some penicillins and cephalosporins)
  • Methylase gene (50S subunit receptor gets methylated so macrolides and strepogramins no longer work)
  • Plasmid mediated phosphorylation, acetylation, and adenylation (affects aminoglycosides—at the amine group on the drug, or methylation of the S12 protein to which they bind; remember, amikacin is the least likely aminoglycoside to which bacteria become resistant, so it may keep on truckin’ while streptomycin has fallen by the wayside)
  • Decreased drug uptake (tetracyclines & aminoglycosides)

 

Drugs with unusual types of toxicity
  • Aminoglycosides have vestibular & auditory toxicity, nephrotoxicity & NMJ blockade
  • Vancomycin -if not administered slowly enough by IV, hypotension and the “Red Man Syndrome” may result
  • Sulfonamides can cause Stevens-Johnson (erythema multiforme)
  • Metronidazole causes metallic taste and disulfiram-like reaction (antabuse)
  • Fluoroquinolones causes cartilage toxicity
  • Erythromycin & Clarithromycin - IV erythromycin or high concentrations of these two macrolides, and/or concomitant administration with other drugs that prolong the QT interval (e.g. pimozide, astemizole, terfenadine) can result in potentially fatal arrhythmias
  • Chloramphenicol causes majorly fatal aplastic anemia (rare but fatal)
  • Tetracyclines cause yellowing of the teeth and can inhibit bone growth
  • Rifampin and Clofazimine can cause reddened urine
  • Ethambutol can cause red-green colorblindness
  • Drugs which can cause Hemolytic Anemia (particularly in G-6-P Dehydrogenase deficient individuals) and incidentally are also metabolized by acetylation (so their dosing needs to be adjusted in fast acetylators):
    • Isoniazid (INH)
    • Dapsone
    • Sulfonamides

 

Drug Interactions
  • Erythromycin, clarithromycin & ketoconazole - inhibit P-450 enzymes
  • Rifampin - induces P-450 enzymes

 

Drugs cleared by the kidney (drugs potentially useful for kidney tract infections if the bacteria are also sensitive; drugs requiring dosage adjustment with renal dysfunction)
  • Penicillins and Cephalosporins (with a few exceptions shown in the next table)
  • Aminoglycosides *** Must figure out Creatinine clearance before maintenance dosing ***
  • Tetracyclines (except doxy & mino)
  • Chloramphenicol
  • Fluroquinolones (80% excreted through kidney)
  • Sulfonamides & Trimethoprim
  • Pyrazinamide
  • Clindamycin (is excreted by both kidney and via bile tract)
  • Nitrofurantoin

Cleared by the kidney, but not used for UTI:

  • Isoniazid (INH) & Pyrzinamide (primarily used for M. tuberculosis)
  • Vancomycin
  • Metronidazole

 

Let’s say I have complete renal failure. Now what can I take for my infection? (drugs typically not requiring dosage adjustments with renal dysfunction)

Primarily biliary excretion:

  • Nafcillin
  • Ceftriaxone

Both biliary & renal clearance:

  • Oxacillin, Coxacillin & Dicloxacillin
  • Ampicillin (however, dosage adjustment required in renal failure)

 

Okay, I have complete renal failure and I’m allergic to penicillin. Now what can I take for my infection?
  • Macrolides
  • Rifampin (antimycobacterial)
  • Clofazimine (for Mycobacterium species)

 

Which drugs work on anaerobes?*
  • Clindamycin (drug of choice against B. fragilis)
  • Metronidazole (drug of choice against B. fragilis & Clostridium species)
  • Penicillin G (Clostridium perfringens)
  • Ticarcillin (somewhat effective against Bacteroides fragilis)
  • Piperacillin & Mezlocillin (more effective against B. fragilis)
  • Imipenem (effective against anaerobes)
  • Cefoxitin (also some other cephalosporins)
  • Chloramphenicol

*Note: Bacteroides is the most frequent anaerobic pathogen in man (80% of anaerobic infections). Bacteroides species are common in the terminal ileum & colon and are a major component of fecal matter.

Antifungal Drugs

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

Antiparasitic Drugs

Benzimidazoles

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

Helminth neuromuscular blocking agent

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

other agents

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

Antiviral Drugs

Inhibitors of viral uncoating

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

Inhibitors of viral packaging & release

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

Thymidine analogs (end w/ 'dine)

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

Purine analog

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

Guanosine analogs

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

pyrophosphate analog

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

riboside analog

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

recombinant cytokine

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

 

AIDS Drugs

HAART
Highly Active Antiretroviral Therapy. A cocktail of 3 or 4 drugs used to produce a more effective reduction in plasma HIV as well as an increase in CD4 cell counts. Typical drug combinations include 2 "acceptable" NRTI's plus either an NNRTI or a PI.
Note: Not all NRTI's can be combined to produce adequate antiviral efficacy, e.g. don't combine stavudine with zidovudine (see below).
References: http://www.fda.gov & http://www.aegis.com & Katzung's text

Nucleoside Reverse Transcriptase Inhibitors (NRTIs)

NRTI Mechanism of Action: competitively inhibit HIV-1 reverse transcriptase & can be incorporated into the growing viral DNA chain to cause DNA chain termination. Each requires intracytoplasmic activation as a result of phosphorylation by cellular enzymes to the triphosphate form.

Common Clinical Indication: HIV-1 infection (given in combination with other drugs - as a component of HAART)
Common Side Effects of NRTIs: myelosuppression, including neutropenia & severe anemia, especially in patients with advanced HIV disease; symptomatic myopathy; lactic acidosis & severe hepatomegaly with steatosis, including fatal cases have been reported with the use of nucleoside analogs. NRTI treatment should be suspended in the setting of rapidly rising aminotransferase levels, progressive hepatomegaly, or metabolic or lactic acidosis of unknown cause.

 

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

Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)

Common Mechanism of Action: The NNRTIs bind directly to a site on the HIV-1 RT, resulting in blockade of RNA- and DNA-dependent DNA polymerase activities. The binding site is near to, but distinct from that of the NRTIs. Unlike the NRTIs, the NNRTIs do not compete with nucleoside triphosphates or require intracellular phosphorylation to be active. Resistance to NNRTI is generally rapid if given as a monotherapy. There is no cross-resistance between the NNRTIs, NRIs and protease inhibitors.
Common Clinical Indications: as components of a combination antiretroviral regimen.
Common Side Effects: A syndrome of drug hypersensitivity can occur in patients receiving NNRTIs, as well as in those receiving amprenavir (a protease inhibitor). Serious possibly life-threatening skin rashes, including Stevens-Johnson syndrome have occured.

 

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

Protease Inhibitors

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: Nelfinavir (Viracept ®)
Drug Class: Antiretroviral Protease Inhibitor
Side Effects: diarrhea & flatulence
Pharmacokinetics: absorption is increased 2-3 fold if taken with food. Metabolized by CYP3A with half life of 4-5 hrs. Also inhibits CYP3A
Drug Interactions: (see above)
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

Fusion Inhibitors

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

Immune Modulators

Drug: Interlukin-2
Clinical Indications & Mechanism: A cytokine secreted by Th1 CD4 cells to stimulate CD8 cytotoxic T lymphocytes. IL-2 also increases the proliferation and maturation of the CD4 cells themselves. During HIV infection, IL-2 production gradually declines. Commercially, IL-2 is produced by recombinant DNA technology and is approved by the FDA for the treatment of metastatic renal (i.e., kidney) cell cancer. Although not yet FDA approved for treatment of HIV, recent data indicate that therapy with subcutaneous IL-2, in combination with antiretroviral drugs, has the potential to halt the usual progression of HIV disease by maintaining an individual's CD4+ T cell count in the normal range for prolonged periods of time.
Reference: www.health-dictionary, http://www.aids.org/factSheets/472-Interleukin-2.html