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ahmad badawy

on 30 December 2012

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Transcript of Antibiotics

/Antibiotics ANTI- HELMINTHIC ANTIBIOTICS ANTI- FUNGAL ANTIBIOTICS ANTI- VIRAL ANTIBIOTICS ANTI-PROTOZOAL ANTIBIOTICS they are compounds that have a natural or semi-synthetic or synthetic origin that kills or inhibits the growth of a microorganism hence the name ANTI-MICROBIAL chemotherapy Anti : Against Biotic : Life What is an antibiotic?
a. Is it a toxin used by bacteria to kill molds.
b. Is it a drug that can kill infectious bacteria.
c. Is it a chemical produced by the body to defend itself
against viruses.
d. Is it an area with conditions that don’t support life. Anti - Microbial chemotherapy
are further classified into : A- Anti bacterial chemotherapy
B- Anti Fungal chemotherapy
C- Anti viral chemotherapy
D- Anti protozoal chemotherapy
E- Anti helminthic chemotherapy ANTI -BACTERIAL ANTIBIOTICS : A step by step Over-view : * Source
*spectrum of activity
*Adverse effects SOURCE : *Natural
*synthetic Pharmacokinetics: *Absorption:
- Poorly absorbed chemotherapeutic should be given parenterally to treat systemic infections while given orally for local GIT infections .
-Plasma protein binding: antibiotics that are highly bounded to plasma proteins like sulphonamides can displace other drugs and substances with weak binding ability like warfarin and bilirubin leading to hyperbilirubinemia .
-Some antibiotics can pass blood brain barrier and are used in ttt of meningitis while others cannot penetrate normal meninges but inflamed meninges like penicillin .
- Some antibiotics may be teratogenic like teracyclines and quinolones while others are safely used in pregnancy like penicillin .
-Some antibiotics are metabolized in the liver and so they are safe in patients with renal impairment but are avoided in patient with hepatic insufficiency .
-Others are excreted in urine unchanged and are accordingly useful in ttt of UTIs and better avoided in patient with renal impairment
-Few antibiotics are excreted in bile and are very effective in ttt of GIT infections as typhoid and in billiary tract infections they undergo “entero- hepatic circulation and so have long duration of action . pharmacodynamics : 1-ACTION :
* Antibiotics may be either :
-Bactericidal : kill active and multiplying bacteria
ex; B-lactam ,vancimycin ,quinolons
-Bacteristatic : stop growth and multiplication of bacteria
ex; sulphonamides , tetracyclins
-Few may be both according to their concentration
ex; Erythromycin can be bactericidal in high
concentration and bacteriostatic in low concentration 2-Mechanism of action : *Bacteria have their own enzymes for
-Cell wall formation
-Protein synthesis
-DNA replication
-RNA synthesis
-Synthesis of essential metabolites
*Viruses use host enzymes inside host cells
*Fungi and protozoa have own eukaryotic enzymes Cell Wall Synthesis Inhibitors Beta Lactams
Penicillins (PCN)
Polymyxin spectrum of activety: *Antibiotics are classified according to spectrum into :
-Narrow spectrum ( aminoglycosides - macrolides )
-Broad spectrum ( chloramphenicole - tetracyclines ) Beta Lactams : B-Lactam Characteristics MOA: Inhibit cell wall synthesis through inhibiting transpeptidase
Bactericidal (except against Enterococcus sp.)
Short elimination half-life
Primarily renally eliminated (except nafcillin, oxacillin, ceftriaxone, cefoperazone)
Cross-allergenicity - except aztreonam B-lactams Pharmacology Absorption: Variable depending on product
Widely distributed into tissues and fluids
Pencillins only get into CSF in the presence of inflamed meninges; parenteral 3rd and 4th generation cephs, meropenem, and aztreonam penetrate the CSF
most eliminated primarily by the kidney, dosage adj required in the presence of renal insufficiency
Nafcillin, oxacillin, ceftriaxone-eliminated by the liver
ALL -lactams have short elimination half-lives except for a few cephalosporins (ceftriaxone) PENICILLINS : B-Lactams Adverse Effects : *Hypersensitivity – 3 to 10 %
Higher incidence with parenteral administration or procaine formulation
Mild to severe allergic reactions – rash to anaphylaxis and death
Antibodies produced against metabolic by-products or penicillin itself
Cross-reactivity exists among all penicillins and even other -lactams
Desensitization is possible

especially with penicillins and carbapenems (imipenem and meropenem)
Especially in patients receiving high doses in the presence of renal insufficiency
Irritability, confusion, seizures Gastrointestinal
Increased LFTs, nausea, vomiting, diarrhea, pseudomembranous colitis (C. difficile diarrhea)

Interstitial Nephritis
Cellular infiltration in renal tubules (Type IV hypersensitivity reaction – characterized by abrupt increase in serum creatinine; can lead to renal failure
Especially with methicillin or nafcillin Source :
The discovery of penicillin is attributed to Scottish scientist and Nobel laureate Alexander Fleming in 1928
It is Derived from Penicillium chrysogenum fungi.
PCN G and PCN V are unaltered products of Penicillium fermentation.
Semi-synthetic penicillins are formed by addition of R groups to the main 6-aminopenicillanic acid ring Hematologic
Leukopenia, neutropenia, thrombocytopenia – prolonged therapy (> 2 weeks 1- Natural penicillin (short acting)
2- Long acting penicillins
3- Penicillinase-Resistant Penicillins
4- Aminopenicillins ( broad spectrum)
5- Anti-pseudomonal Penicillins
(extended spectrum) Natural penicillins : PCN G (IV/IM)
PCN V (Oral)
Active against :
Gram-positive Gram-negative
pen-susc S. pneumoniae Neisseria sp.
Group A/B/C/G strep Anaerobes
viridans streptococci Above the diaphragm
Enterococcus Clostridium sp.
Treponema pallidum (syphilis) Penicillinase-Resistant Penicillins: long acting penicillins : Prepared as suspension and sould not be given IV
-Procaine penicillin
-Fortified procaine penicillin : compination of penicillin G
and procaine penicillin with longer duration of action .
-Benzathine penicillin : used only for prophylaxis against rheumatic fever and not for ttt of infections
Dis-advantages :
B-lactamase sensitive
Narrow spectrum Methicillin, Nafcillin,
Oxacillin, Cloxacillin and dicloxacillin.
-Developed to overcome the penicillinase enzyme of S. aureus
which inactivated natural penicillins
-Useful for treating S. aureus senstive to methicillin - not effective against MRSA
-No added benefit in treating Strep. species.
-Methicillin is rarely used due to nephro-toxicity.
-Dicloxacillin - highest serum levels orally.
-Nafcillin- preferred parenteral drug . Aminopenicillins
(Broad spectrum) : Developed to increase activity against gram-negative aerobes
-Ampicillin (IV).
Ampicillin/sulbactam (Unasyn; IV)
-Amoxicillin (Oral).
Amoxicillin/clavulanate (Augmentin)
Sulbactam and clavulanic acid increase activity against B-lactamase producing organisms.
-Extended antimicrobial spectrum.
Gram negatives: E. coli, Proteus, Salmonella, Haemophilus, M. catarrhalis, Klebsiella, Neisseria, Enterobacter, Bactoroides.
Used as first line therapy for acute otitis media and sinusitis. Antipseudomonal Penicillins:
(Extended spectrum) Ureidopenicillins
(piperacillin, azlocillin) Carboxypenicillins
(carbenicillin, ticarcillin) Developed to further increase activity
against resistant gram-negative aerobes
Gram-positive Gram-negative
marginal Proteus mirabilis
Salmonella, Shigella
some E. coli
L- H. influenzae
Enterobacter sp.
Pseudomonas aeruginosa Developed to further increase activity
against resistant gram-negative aerobes Gram-positive Gram-negative
viridans strep Proteus mirabilis
Group strep Salmonella, Shigella
some Enterococcus E. coli
 L- H. influenzae
Anaerobes Enterobacter sp.
Fairly good activity Pseudomonas aeruginosa
Serratia marcescens
some Klebsiella sp. Indications : - Chemo-prophylaxis
- Curative Prophylaxis curative Rheumatic fever Endocarditis Gonorrheal ophthalmia Benzathine penicillin
1,200,000 IU IM for 5 years
life long therapy Procain penicillin 300,00 - 600,000 IU IM in patients with valve disease or prothetic valve before operations causing bacteremia as tonsillectomy and dental procedure Bezyle penicillin
eye drops to neonates Respiratory
tract infections UTIs GIT infections H Pylori inpeptic ulcer Meningitis Pyigenic infections Endocarditis Syphilis cephalosporins: source: Semisynthetic B-lactams derived from chemical side chains added to 7-aminocephalosporanic acid.
Generally more resistant to B-lactamases
-5-10% cross-sensitivity with pcn allergic pts.
1-2% hypersensitivity reactions in non-pcn allergic pts.
Broader spectrum leads to opportunistic infections
(candidiasis, C. difficile colitis).
-Superinfection with orall administration
- Pain and diarrhea Adverse reactions. Classification and Spectrum of Activity of Cephalosporins : Classification and Spectrum of Activity of penicillins : -Divided into 4 major groups called “Generations” based on :
-antimicrobial activity
-resistance to beta-lactamase -First G - Second G
-Third G - Fourth G First Generation Best activity against gram-positive aerobes, with limited activity
against a few gram-negative aerobes Gram-positive Gram-negative
meth-susc S. aureus E. coli
pen-susc S. pneumoniae K. pneumoniae
Group A/B/C/G streptococci P.mirabilis
viridans streptococci

Cefazolin (Ancef; IV), Cephalexin (Keflex; Oral) Use: S. aureus infection, surgical prophylaxis Second Generation: Gram-positive Gram-negative
meth-susc S. aureus E. coli
pen-susc S. pneumoniae K. pneumoniae
Group A/B/C/G strep P. mirabilis
viridans streptococci H. influenzae
M. catarrhalis
Neisseria sp.
Cefuroxime (Ceftin; IV; Oral)

The cephamycins (cefoxitin and cefotetan) are the only 2nd generation cephalosporins that have activity against anaerobes
Bacteroides fragilis
Bacteroides fragilis group Third Generation: - gram negative > gram positive.
- Gram-negative aerobes
E. coli, K. pneumoniae, P. mirabilis
H. influenzae, M. catarrhalis, N. gonorrhoeae (including beta-lactamase producing); N. meningitidis
Citrobacter sp., Enterobacter sp., Acinetobacter sp.
Morganella morganii, Serratia marcescens, Providencia - Ceftriaxone (Rocephin; IM/IV), Cefotaxime .
Useful for meningitis.
- Ceftriaxone used for highly resistant and multi drug resistant -strep pneumo along with vancomycin.
- Ceftazidime active against pseudomonas. Fourth Generation: 4th generation cephalosporins for 2 reasons
-Extended spectrum of activity
gram-positives: similar to ceftriaxone
gram-negatives: similar to ceftazidime, including Pseudomonas aeruginosa; also covers beta-lactamase producing Enterobacter sp.
-Stability against -lactamases; poor inducer of extended-spectrum- lactamases
-Only cefepime (IV) is currently available INDICATIONS: Respiratory
tract infections
and UTIs Meningitis Tuberculosis
viomycin Septicemia Wound and burn
infections Gentanycin GIT infections Carbapenems:
Most broad spectrum of activity of all antimicrobials
Have activity against gram-positive and gram-negative aerobes and anaerobes
Bacteria not covered by carbapenems include MRSA, VRE, coagulase-negative staph, C. difficile, Nocardia
Additional ertapenem exceptions:
Pseudomonas and Enterococcus
Imipenem-Cilastin ( Primaxin ).
Cilastin - dehydropeptidase inhibitor that inhibits degradation into a nephrotoxic metabolite.
Meropenem and Ertapenem
PCN allergy cross reactivity.
Seizures noted in Imipenem studies. Monobactams -Aztreonam (Azactam IM/IV)
B-lactamase resistant.
Narrow antibacterial spectrum.
Aerobic gram negative rods (H. flu, N. gonorrhea (penicillinase producers), E. coli, Klebsiella, Proteus, Pseudomonas).
Ineffective against gram positive and anaerobic organisms.
Antipseudomonal activity is greater than Timentin and Zosyn but less than the carbapenems.
adverse reaction:
Very little cross-allergenicity due to its low immunogenic potential. May be a safe alternative for pcn allergic patients.
Gram positive superinfection (20-30%) VANCOMYCIN Pharmacology: Absorption
absorption from GI tract is negligible after oral administration except in patients with intense colitis
Use IV therapy for treatment of systemic infection
widely distributed into body tissues and fluids, including adipose tissue; use TBW for dosing
inconsistent penetration into CSF, even with inflamed meninges
primarily eliminated unchanged by the kidney via glomerular filtration
elimination half-life depends on renal function Mechanism of Action -Inhibits bacterial cell wall synthesis at a site different than beta-lactams
-Inhibits synthesis and assembly of the second stage of peptidoglycan polymers
-Binds firmly to D-alanyl-D-alanine portion of cell wall precursors
-Bactericidal (except for Enterococcus) Spectrum of Activity -Gram-positive bacteria
Methicillin-Susceptible AND Methicillin-Resistant S. aureus and coagulase- negative staphylococci
-Streptococcus pneumoniae (including PRSP), viridans streptococcus, Group A/B/C/G streptococcus
-Enterococcus sp.
-Corynebacterium, Bacillus. Listeria, Actinomyces
-Clostridium sp. (including C. difficile), Peptococcus, Peptostreptococcus
-No activity against gram-negative aerobes or anaerobes Adverse Effects -Red-Man Syndrome
flushing, pruritus, erythematous rash on face and upper torso
related to RATE of intravenous infusion; should be infused over at least 60 minutes
resolves spontaneously after discontinuation
may lengthen infusion (over 2 to 3 hours) or pretreat with antihistamines in some cases
Nephrotoxicity and Ototoxicity
rare with monotherapy, more common when administered with other nephro- or ototoxins
risk factors include renal impairment, prolonged therapy, high doses, ? high serum concentrations, other toxic meds
Dermatologic - rash
Hematologic - neutropenia and thrombocytopenia with prolonged therapy
Thrombophlebitis INDICATIONS Infections due to methicillin-resistant staph including bacteremia, empyema, endocarditis, peritonitis, pneumonia, skin and soft tissue infections, osteomyelitis
Serious gram-positive infections in -lactam allergic patients
Infections caused by multidrug resistant bacteria
Endocarditis or surgical prophylaxis in select cases
Oral vancomycin for refractory C. difficile colitis Bacitracin -Polypeptide antibiotic produced by Bacillus subtillis. ( ineffective orally)
-MOA: Inhibits regeneration of phospholipids receptors involved in peptidoglycan synthesis.
-spectrum : gram +ve bacteria especially staph.aureus
-Indications : topically only in ttt of skin and wound infections
never used systemically as it is extremely nephrotoxic
Adverse effects.
Contact dermatitis – top 10 allergen.
Reports of anaphylaxis
Neosporin – neomycin, polymyxin B, bacitracin
Polysporin – polymyxin B, bacitracin Polymyxin -Bacillus polymyxa
-Decapeptide that disrupts the phospholipid layer in cell membranes.
-Limited spectrum.
-Decreased gram positive coverage.
-Active against Pseudomonas, Proteus, Serratia, E. coli, Klebsiella and Enterobacter.
-Cross reaction with bacitracin Protein synthesis inhibitors Amino glycosides
Lincocamines Nucleic acid synthesis
Inhibitors -Quinolones
-Sulphonamides Aminoglycosides Pharmacology Absorption - poorly absorbed from GIT tract
primarily in extracellular fluid volume; are widely distributed into body fluids but NOT the CSF
distribute poorly into adipose tissue, use LBW for dosing
eliminated unchanged by the kidney via glomerular filtration; 85-95% of dose
elimination half-life dependent on renal fxn
normal renal function - 2.5 to 4 hours
impaired renal function - prolonged Mechanism of Action -Multifactorial, but ultimately involves inhibition of protein synthesis
-Irreversibly bind to 30S ribosomes
-must bind to and diffuse through outer membrane and cytoplasmic membrane and bind to the ribosome
-disrupt the initiation of protein synthesis, decreases overall protein synthesis, and produces misreading of mRNA
-Are bactericidal Spectrum of Activity Gram-Positive Aerobes
most S. aureus and coagulase-negative staph (but not DOC)
viridans streptococci (in combination with a cell-wall agent)
Enterococcus sp. (only in combination with a cell-wall agent)
Gram-Negative Aerobes (not streptomycin)
E. coli, K. pneumoniae, Proteus sp.
Acinetobacter, Citrobacter, Enterobacter sp.
Morganella, Providencia, Serratia, Salmonella, Shigella
Pseudomonas aeruginosa (amik>tobra>gent)
tuberculosis - streptomycin
atypical - streptomycin or amikacin Adverse Effects Nephrotoxicity
nonoliguric azotemia due to proximal tubule damage; increase in BUN and serum Cr; reversible if caught early
risk factors: prolonged high troughs, long duration of therapy (> 2 weeks), underlying renal dysfunction, elderly, other nephrotoxins
8th cranial nerve damage - vestibular and auditory toxicity; irreversible and saturable
vestibular: dizziness, vertigo, ataxia
auditory: tinnitus, decreased hearing
risk factors: same as for nephrotoxicity Source: Most of them are natural Endocarditis Ammonia neomycin
encephalopathy group MACROLIDES Examples: Strptomycin : Endocarditis , Plague
Gentamycin : Endocarditis , septic wounds , MRSA infection but with limited use due to high toxicity
Tobramycin : as Genta mycin but inactive against pseudomonas
Amikamycin : Broad spectrum - less bacterial resistance
Neomycin : Extremly toxic -never used systemically INDICATIONS Respiratory
tract infections UTIs Meningitis Gonorrhea Typhoid fever Alternative
to penicillin Anaerobic
infections Serious infections Ceftriaxone is drug of choice Cefoperazone 3rd and 4th except cefoperazone Cefotixin Pharmacology Absorption
Erythromycin – variable absorption (15-45%); food may decrease the absorption
Base: destroyed by gastric acid; enteric coated
Esters and ester salts: more acid stable
Clarithromycin – acid stable and well-absorbed, 55% bioavailable regardless of presence of food
Azithromycin –acid stable; 38% bioavailable; food decreases absorption of capsules
Extensive tissue and cellular distribution – clarithromycin and azithromycin with extensive penetration
Minimal CSF penetration
Clarithromycin is the only macrolide partially eliminated by the kidney (18% of parent and all metabolites); requires dose adjustment when CrCl < 30 ml/min
Hepatically eliminated: ALL
NONE of the macrolides are removed during hemodialysis!
Variable elimination half-lives (1.4 hours for erythro; 3 to 7 hours for clarithro; 68 hours for azithro Mechanism of Action Inhibits protein synthesis by reversibly binding to the 50S ribosomal subunit
Suppression of RNA-dependent protein synthesis
Macrolides typically display bacteriostatic activity, but may be bactericidal when present at high concentrations against very susceptible organisms
Time-dependent activity Spectrum of Activity Gram-Negative Aerobes – newer macrolides with enhanced activity (Azithro>Clarithro>Erythro)

H. influenzae (not erythro), M. catarrhalis, Neisseria sp., Campylobacter jejuni, Bordetella pertussis
Do NOT have activity against any Enterobacteriaceae or Pseudomonas

Anaerobes –
activity against upper airway anaerobes
Atypical Bacteria –
all macrolides have excellent activity against atypical bacteria including:
Legionella pneumophila - DOC
Chlamydia sp.
Mycoplasma sp.
Ureaplasma urealyticum
Other Bacteria – Mycobacterium avium complex (MAC – only A and C), Treponema pallidum, Campylobacter, Borrelia, Bordetella, Brucella. Pasteurella Gram-Positive Aerobes – erythromycin and clarithromycin display the best activity
Methicillin-susceptible Staphylococcus aureus
Streptococcus pneumoniae (only PSSP) – resistance is developing
Group A/B/C/G and viridans streptococci
Bacillus sp., Corynebacterium sp. Adverse Effects Gastrointestinal – up to 33 %
Nausea, vomiting, diarrhea, dyspepsia
Most common with erythro; less with new agents
Cholestatic hepatitis - rare
> 1 to 2 weeks of erythromycin estolate
Thrombophlebitis – IV Erythro and Azithro
Dilution of dose; slow administration
Other: ototoxicity (high dose erythro in patients with RI); QTc prolongation; allergy Examples: Erythromycin:
-Drug of choice in ttt of respiratory tract infections
-Alternative to tetracyclins in ttt of chlamydia
-Alternative to penicillins in pencillin allergic patients
-Prokinetic in cases of diabetic gastroparesis
-Ototoxic with Azithromycin
-Avoided in liver diseases
more active against chlamydia
effective against H.influenza
used in peptic ulcer to eradicate H.pylori
as clarithromycin with longer duration Lincocamines
Clyndamycin Pharmacology Absorption – available IV and PO
Rapidly and completely absorbed (90%); food with minimal effect on absorption
Good serum concentrations with PO or IV
Good tissue penetration including bone; minimal CSF penetration
Clindamycin primarily metabolized by the liver; half-life is 2.5 to 3 hours
Clindamycin is NOT removed during hemodialysis Mechanism of Action Inhibits protein synthesis by binding exclusively to the 50S ribosomal subunit
Binds in close proximity to macrolides – competitive inhibition
Clindamycin typically displays bacteriostatic activity,
but may be bactericidal when present at high concentrations against very susceptible organisms Spectrum of Activity Gram-Positive Aerobes
Methicillin-susceptible Staphylococcus aureus (MSSA)
Methicillin-resistant Staphylococcus aureus (MRSA) – some isolates
Streptococcus pneumoniae (only PSSP) – resistance is developing
Group and viridans streptococci
Anaerobes –
activity against Above the Diaphragm Anaerobes (ADA)
Peptostreptococcussome Bacteroides sp
Actinomyces Prevotella sp.
Propionibacterium Fusobacterium
Clostridium sp. (not C. difficile)
Other Bacteria – Toxoplasmosis gondii, Malaria Adverse Effects Gastrointestinal – 3 to 4 %
Nausea, vomiting, diarrhea, dyspepsia
C. difficile colitis – one of worst offenders
Mild to severe diarrhea
Requires treatment with metronidazole
Hepatotoxicity - rare
Elevated transaminases
Allergy - rare INDICATIONS Used for deep neck space infections,
chronic tonsillo-pharyngitis,
odontogenic abscesses, and surgical prophylaxis
in contaminated wounds.
Concomitant use of macrolides or
Chloramphenicol adds no benefit.
Resistance: MLSB – ribosomal alteration. QUINOLONES SOURCE Gram negative Escherichia coli Mechanism of action Mechanism of action : Quinolones inhibit the action of bacterial DNA gyrase enzyme. This enzyme is responsible to supercoil and compact bacterial DNA molecules into the bacterial cell during replication Adverse effects -Photosensitivity reactions -
-Convulsions particularly concurrent administration of NSAID -Arthralgia and
-Joint swelling - in children Classifications 1st generation: Cinoxacin, flumequine, nalidixic acid, oxolinic acid, piromidic acid, pipemidic acid.
2nd generation: Ciprofloxacin, enoxacin, lomefloxacin, nadifloxacin, norfloxacin, ofloxacin, pefloxacin, rufloxacin.
3rd generation: Balofloxacin, grepafloxacin, levofloxacin, pazufloxacin, sparfloxacin, temafloxacin, tosufloxacin. Classification 4th generation: Clinafloxacin, gemifloxacin, moxifloxacin, gatifloxacin, sitafloxacin, trovafloxacin. In development: Ecinofloxacin, prulifloxacin. INDICATIONS Fluoroquinolones are used to treat:
-upper and lower respiratory infections
- bacterial gastroenteritis,
-skin and soft tissue infections,
-urinary tract infections,
-bone and joint infections,
-against tuberculosis. Sulphonamides : synthetic antimicrobial agents from Prontosil which breaks down to form sulfanilamide .Sulfonamides are synthetic derivatives of
sulfanilamide. Spectrum of activity -broad-spectrum
-G+ bacteria: group A Streptococcus
pyogenes and Streptococcus pneumoniae.
-G- bacteria: meningococcus, gonococcus
Escherichia coli, shigella, etc.
-Others: bacillus anthracis, Nocardia
actinomyces, Chlamydia trachomatis, and
some protozoa. Mechanisms of action -Sulfonamides could compete for dihydrofolic
acid synthetase with PABA (para aminobenzoic acid)
and affect the synthesis of dihydrofolic acid.
②Susceptible bacteria need PABA because
they are incapable of using folic acid directly.
③Human cells use exogenous folic acid
exclusively and thus a lack of PABA does not
affect them.
④-bacteriostatic drugs pharmacokinetics ① -Most sulfonamides are well absorbed orally
and they are widely distributed including to the
② -The concentrations in the kidney are the
highest. So they are suitable for treating
urinary tract infections.
③ -lower solubility in the urine, most sulfonamides
and their metabolites easily cause crystalluria,
bloody urine, and kidney damage. Adverse Reactions ① -Urinary Tract Disturbances
1- Sulfonamides may precipitate in urine producing
crystalluria, hematuria or even obstruction.
2- Crystalluria is treated by administration of sodium
bicarbonate to alkalinize the urine.
② Hematological Disturbances
3- Sulfonamides can cause hemolytic or aplastic anemia.
4- On the other hand, Sulfonamides may provoke
hemolytic reactions in patients whose red cells are
deficient in glucose-6-phosphate dehydrogenase
hypersensitivity reactions. When used in large doses, they may cause a strong allergic reaction. Two of the most serious are Stevens–Johnson syndrome and toxic epidermal necrolysis (also known as Lyell syndrome).[2] SOURCE Examples: *Antibacterial Drugs
Sulfisomidine (also known as sulfaisodimidine)
Mafenide INDICATIONS -general infections (UTIs , RTIs meningitis)
by sulfisoxazole,sulfamethoxazole and sulfadoxine;
-inflammatory bowel disease.
-intestinal tract infections by sulfasalazine
-thiazide diuretics hydrochlorothiazide, metolazone, and indapamide
- loop diuretics (including furosemide, bumetanide, and torsemide),
-topical cream for burn unfections
-topical eye drops for eye infections Highly protein binding
Accumulates in skin , nails, fat.
Severely hepatotoxic, liver failure even death.
Accumulate in breast milk , should not be given to nursing mother.
GIT upset (diarrhea, dyspepsia, nausea )
Taste & visual disturbance. Fungicidal ,its activity is limited to candida albicans & dermatophytes.
Effective for treatment of onychomycoses
6 weeks for finger nail infection & 12 weeks for toe nail infections .
Well absorbed orally , bioavailability decreases due to first pass metabolism in liver. Absorption is less than 0.5% from intact skin, 3-10% from vagina (its activity remains for 3 days ).
Used in dermatophytes , cutaneous candidiasis & vulvovaginal candidiasis.
Causes : Erythema, edema, , urticaria & mild vaginal burning sensation. CLOTRIMAZOLE In the form of vaginal creams, suppositories, tablets for vaginal candidiasis given once daily . Azoles for topical use Used in superficial fungal infections , such as :
Dermatophytosis ( ring worm), candidiasis, fungal keratitis.
They are not effective in mycoses of the nails & hair or subcutaneous mycoses.
The preferred formulation for cutaneous application is cream or solution. Topical Antifungal Agents Nausea, vomiting, headache, skin rash , diarrhea, abdominal pain , reversible alopecia.
Hepatic failure may lead to death
Highly teratogenic ( as other azoles)
Inhibit P450 cytochrome
No endocrine side effects Side effects Candidiasis
( is effective in all forms of mucocutaneous candidiasis)
Cryptococcus meningitis
Histoplasmosis, blastomycosis, , ring worm.
Not effective in aspergillosis Clinical uses Drug interactions are less common
Penetrates well BBB so, it is the drug of choice of cryptococcal meningitis
Safely given in patients receiving bone marrow transplants (reducing fungal infections)
Excreted mainly through kidney
Half-life 25-30 hours
Resistance is not a problem Fluconazole (cont.) Water soluble
Completely absorbed from GIT
Excellent bioavailability after oral administration
Bioavailability is not affected by food or gastric PH
Conc. in plasma is same by oral or IV route
Has the least effect on hepatic microsomal enzymes Fluconazole Contraindicated in :
Prgnancy, lactation ,hepatic dysfunction
Interact with enzyme inhibitors , enzyme inducers.
H2 blockers & antacids decrease its absorption Contraindications & Drug interactions Nausea, vomiting ,anorexia
Inhibits human P 450 enzymes
Inhibits adrenal & gonadal steroids leading to :
Menstrual irregularities
Loss of libido
Gynaecomastia in males Adverse Effects Used topically or systematic (oral route only ) to treat :
1- Oral & vaginal candidiasis.
2- Dermatophytosis.
3- Systemic mycoses & mucocutaneous candidiasis. Clinical uses Inactivated in liver & excreted in bile (feces ) & urine.
Does not cross BBB. Ketoconazole (cont.) Well absorbed orally .
Bioavailability is decreased with antacids, H2 blockers , proton pump inhibitors & food .
Cola drinks improve absorption in patients with achlorhydria.
Half-life increases with the dose , it is (7-8 hrs). Ketoconazole Ketoconazole
They lack selectivity ,they inhibit human gonadal and steroid synthesis leading to decrease testosterone & cortisol production.
Also, inhibit human P-450 hepatic enzyme. Imidazoles They are antibacterial , antiprotozoal, anthelminthic & antifungal.
They are fungistatic agents.
They are classified into :
Imidazole group
Triazole group Azoles 1-Inhibit the fungal cytochrome P450 enzyme, (α-demethylase) which is responsible for converting lanosterol to ergosterol ( the main sterol in fungal cell membrane ).
2- Inhibition of mitochondrial cytochrome oxidase leading to accumulation of peroxides that cause autodigestion of the fungus.
3- Imidazoles may alter RNA& DNA metabolism. Mechanism of Action A group of synthetic fungistatic agents with a broad spectrum of activity .
They have antibacterial , antiprotozoal anthelminthic & antifungal activity . Azoles Prevent or treat superficial candidiasis of mouth, esophagus, intestinal tract.
Vaginal candidiasis
Can be used in combination with antibacterial agents & corticosteroids. Clinical uses It is a polyene macrolide ,similar in structure & mechanism to amphotericin B.
Too toxic for systemic use.
Used only topically.
It is available as creams, ointment , suppositories & other preparations.
Not significantly absorbed from skin, mucous membrane, GIT . Nystatin 1- Slow I.V.I. For systemic fungal disease.
2- Intrathecal for fungal C.N.S. infections.
Topical drops & direct subconjunctival injection for Mycotic corneal ulcers & keratitis.
3- Local injection into the joint in fungal arthritis.
4- Bladder irrigation in Candiduria. Routes of Administration Has a broad spectrum of activity & fungicidal action.
The drug of choice for life-threatening mycotic infections.
For induction regimen for serious fungal infection.
Also, for chronic therapy & preventive therapy of relapse.
In cancer patients with neutropenia who remain febrile on broad –spectrum antibiotics. Clinical uses Most serious is renal toxicity (nearly in all patients ).
Impaired liver functions
Anemia 2- Slower toxicity 1- Immediate reactions ( Infusion –related toxicity ).
Fever, muscle spasm, vomiting ,headache, hypotension.
Can be avoided by :
A. Slowing the infusion
B. Decreasing the daily dose
C. Premedication with antipyretics, antihistamincs or corticosteroids.
D. A test dose. Adverse Effects It is a selective fungicidal drug.
Disrupt fungal cell membrane by binding to ergosterol , so alters the permeability of the cell membrane leading to leakage of intracellular ions & macromolecules ( cell death ). Mechanism of action Poorly absorbed orally , is effective for fungal infection of gastrointestinal tract.
For systemic infections given as slow I.V.I.
Highly bound to plasma protein .
Poorly crossing BBB.
Metabolized in liver
Excreted slowly in urine over a period of several days.
Half-life 15 days. Pharmacokinetics Amphotericin A & B are antifungal antibiotics.
Amphotericin A is not used clinically.
It is a natural polyene macrolide
(polyene = many double bonds )
(macrolide = containing a large lactone ring ) Amphotericin B Squalene epoxidase inhibitors : Terbinafine &
White field ointment : 12% Benzoic acid & 6% Salicylic acid .
Castellani paint. In Dermatophytes : Systemic :
Griseofulvin , Amphotericin- B , Ketoconazole , Fluconazole , Terbinafine.
In candidiasis :
Imidazoles : Ketoconazole , Miconazole.
Triazoles : Terconazole.
Polyene macrolides : Nystatin , Amphotericin-B
Gentian violet : Has antifungal & antibacterial. Classification According to Route of Administration Flucytosine
Squalene epoxidase inhibitors : e.g.
Terbinafine & Naftifine. Synthetic Antifungal ( contin…) 1- Antifungal Antibiotics :
Polyene macrolide : Amphotericin- B & Nystatin
2- Synthetic :
Azoles :
A) Imidazoles : Ketoconazole , Miconazole
B) Triazoles : Fluconazole , Itraconazole Classification of Antifungal Drugs Synthetic nucleoside analog

Given orally, or oral or nasal inhalation

Inhalation form (Virazole) used for hospitalized infants with RSV (respiratory syncytialvirus) infections Antivirals Drugs-Nonretroviral
Ribavirin oseltamivir (Tamiflu) and zanamivir (Relenza)
Active against influenza types A & B

Use: Reduce duration of illness

oseltamivir: causes nausea & vomiting

zanamivir: causes diarrhea, nausea, sinusitis

Treatment should begin within 2 days of influenza symptom onset Antivirals Drugs-Nonretroviral
Neuraminidase Inhibitors ganciclovir and zidovudine
Bone marrow toxicity

foscarnet and cidofovir
Renal toxicity Antivirals Drugs-Nonretroviral
Dose-Limiting Toxicities Synthetic nucleoside analog

Used to treat infection with cytomegalovirus (CMV)

Oral, parenteral forms

CMV retinitis
Ophthalmic form surgically implanted
Ocular injection (fomivirsen) Antivirals Drugs-Nonretroviral
Ganciclovir (Cytovene) Same spectrum of activity, mechanism of action, and indications as amantadine

Fewer CNS adverse effects

Causes GI upset Antivirals Drugs-Nonretroviral
Rimantadine (Flumadine)
Narrow antiviral spectrumactive only against influenza A

Used prophylactically when vaccine is not available or cannot be given

Therapeutic use can reduce recovery time

CNS effects: insomnia, nervousness, lightheadedness

GI effects: anorexia, nausea, others Antivirals Drugs-Nonretroviral
Amantadine (Symmetrel) Mechanism of action
Inhibit viral replication
Used to treat non-HIV viral infections
Influenza viruses
HSV (herpes simplex virus), VZV (vericella zoster virus)
CMV (cytomegalovirus)
Hepatitis A, B, C (HAV, HBV, NCV)
Adverse Effects
Vary with each drug
Healthy cells are often killed also, resulting in serious toxicities Antiviral Drugs: Nonretroviral Antiviral drugs
Used to treat infections caused by viruses other than HIV
Antiretroviral drugs
Used to treat infections caused by HIV, the virus that causes AIDS
Herpes-Simplex Viruses
HSV-1 (oral herpes)
HSV-2 (genital herpes)
Varicella Zoster Virus
Shingles Antiviral Medications Key characteristics of antiviral drugs

Able to enter the cells infected with virus

Interfere with viral nucleic acid synthesis and/or regulation

Some drugs interfere with ability of virus to bind to cells

Some drugs stimulate the body’s immune system

Best responses to antiviral drugs are in patients with competent immune systems

A healthy immune system works synergistically with the drug to eliminate or suppress viral activity Antivirals Synthetic nucleoside analog

Used to suppress replication of:
HSV-1(oral herpes), HSV-2(genital herpes),
VZV (Varicella – chickenpox or shingles)

Drug of choice for treatment of initial and recurrent episodes of these infections

Oral, topical, parenteral forms Antivirals Drugs-Nonretroviral
Acyclovir (Zovirax) Effects will vary with each drug
Common adverse effects:
Nausea, vomiting, diarrhea, dizziness, headache
May cause myelosuppression
Adverse Effects
mebendazole (Vermox)
Inhibits uptake of glucose and other nutrients, leading to autolysis and death of the parasitic worm
Used to treat cestodes and nematodes (hookworm, pinworm, roundworm, whipworm, tapeworm)

oxamniquine (Vansil) and praziquantel (Biltricide)
Paralyze worms’ musculature and immobilize their suckers
Cause worms to dislodge from mesenteric veins to the liver, then killed by host tissue reactions
Used to treat trematodes; praziquantel is used to treat cestodes also
Mechanism of Action and Indications diethylcarbamazine (Hetrazan)
Inhibits rate of embryogenesis of nematodes
thiabendazole (Mintezol)
Inhibits the helminth-specific enzyme, fumarate reductase
Both used for nematodes
(tissue and some roundworms)
pyrantel (Antiminth)
Blocks acetylcholine at the neuromuscular junction, resulting in paralysis of the worms, which are then expelled through the GI tract
roundworm infections, ascariasis, enterobiasis, nematodes (giant worm and pinworm), other helminthic infections
Mechanism of Action and Indications albendazole (Albenza)
diethylcarbamazine (Hetrazan)
ivermectin (Stromectol)
mebendazole (Vermox)
praziquantel (Biltricide)
pyrantel (Antiminth)
thiabendazole (Mintezol)

It is VERY IMPORTANT to identify the causative worm
Done by finding the parasite ova or larvae in feces, urine, blood, sputum, or tissue

Cestodes (tapeworms)
Nematodes (roundworms)
Trematodes (flukes)
Platyhelminthes (flatworm) Anthelmintics Drugs used to treat parasitic worm infections: helminthic infections

Unlike protozoa, helminths are large and have complex cellular structures

Drug treatment is very specific to the organism Anti-helminthics paromomycin (Humatin)
Kills by inhibiting protein synthesis
Used to treat amebiasis and intestinal protozoal infections, and also adjunct therapy in management of hepatic coma

Adverse Effects: paromomycin (Humatin)
Nausea, vomiting, diarrhea, stomach cramps, hearing loss, dizziness, tinnitus Antiprotozoals:
Mechanism of Action and Indications iodoquinol (Yodoxin)
Acts primarily in the intestinal lumen of the infected host
Directly kills the protozoa
Used to treat intestinal amebiasis

Adverse Effects: iodoquinol (Yodoxin)
Nausea, vomiting, diarrhea, anorexia, agranulocytosis, many others Antiprotozoals
Mechanism of Action and Indications Pentamidine
Inhibits DNA and RNA
Binds to and aggregates ribosomes
Directly lethal to Pneumocystis jiroveci
Mainly used to prevent & treat P. jiroveci pneumonia
Used for other protozoal infections

Adverse Effects: pentamidine
Bronchospasms, leukopenia, thrombocytopenia, acute pancreatitis, acute renal failure, increased liver function studies, hypotension, many others Antiprotozoals
Mechanism of Action and Indications Metronidazole (Flagyl)
Disruption of DNA synthesis as well as nucleic acid synthesis
Bactericidal, amebicidal, trichomonacidal
Used for treatment of trichomoniasis, amebiasis, giardiasis,and antibiotic-associated pseudomembranous colitis
Also has anthelmintic activity

Adverse Effects: Metronidazole (Flagyl
Metallic taste, nausea, vomiting, diarrhea, abdominal cramps, many others Antiprotozoals
Mechanism of Action and Indications atovaquone (Mepron)
Protozoal energy comes from the mitochondria
atovaquone: selective inhibition of mitochondrial electron transport
Result: no energy, leading to cellular death
Used to treat mild to moderate Pneumocystis jiroveci

Adverse Effects: atovaquone (Mepron)
Nausea, vomiting, diarrhea, anorexia, altered liver function, many others Antiprotozoals:
Mechanism of Action and Indications atovaquone (Mepron)- Pneumocystis jirovecii pneumonia

metronidazole (Flagyl) – anti-bacterial / anaerobes

pentamidine (Pentam-300) – P. jiroveci pneumonia

iodoquinol (Yodoxin)- intestinal amebiasis; Giardia; Trichomonas vaginalis

paromomycin (Humatin) – acute hepatic coma Antiprotozoals Amebiasis

Person to person
Ingestion of contaminated water or food
Direct contact with the parasite
Insect bite (mosquito) Protozoal Infections Patients with compromised immune systems are at risk for acquiring these infections
Taking immunosuppressive drugs after a transplant

Protozoal infections are often fatal in these cases Protozoal Infections Many adverse effects for the various drugs

Primarily gastrointestinal: nausea, vomiting, diarrhea, anorexia, and abdominal pain Antimalarials
Adverse Effects Kill parasitic organisms
Chloroquine and hydroxychloroquine also have antiinflammatory effects

Kills Plasmodium organisms, the parasites that cause malaria
The drugs have varying effectiveness on the different malaria organisms
Some drugs are used for prophylaxis against malaria
2 weeks prior and 8 weeks after return
Chloroquine is also used for rheumatoid arthritis and systemic lupus erythematosus Antimalarials
Drug Effects Primaquine
Only exoerythrocytic drug (works in both phases)
Binds and alters parasitic DNA

Sulfonamides, tetracyclines, clindamycin

Used in combination with antimalarials to increase protozoacidal effects Antimalarials:
Mechanism of Action Diaminopyrimidines (pyrimethamine (Daraprim) & trimethoprim)

Inhibit protein synthesis essential for growth and survival

Only effective during the erythrocytic phase

These drugs may be used with sulfadoxine or dapsone or synergistic effects Antimalarials:
Mechanism of Action 4-Aminoquinoline derivatives: quinine and
Mefloquine (Lariam)
Alter pH within the parasite

Interfere with parasite’s ability to metabolize and use erythrocyte hemoglobin

Effective only during the erythrocytic phase Antimalarials:
Mechanism of Action
4-Aminoquinoline derivatives: chloroquine and hydroxychloroquine

Bind to parasite nucleoproteins and interfere with protein synthesis; also alter pH within the parasite

Interfere with parasite’s ability to metabolize and use erythrocyte hemoglobin

Effective only during the erythrocytic phase Antimalarials:
Mechanism of Action
Attack the parasite during the asexual phase, when it is vulnerable

Erythrocytic phase drugs: chloroquine, hydroxychloroquine, quinine, mefloquine
Primaquine: kills parasite in both phases

May be used together for synergistic or additive killing power Antimalarial Drugs
Parasitic protozoa: live in or on humans
Trichomoniasis Protozoal Infections REFERENCES : Boyce, John M. Epidemiology; prevention; and control of methicillin-resistant Staphlyococcus aureus in adults. Up To Date (12.3). 2004.
Lowy, Franklin D. Treatment of Methicillin-Resistant Staphlyococcus aureus Infection in Adults. Up To Date (12.3). 2004.
Lowy, Franklin D. Mechanisms of Antibiotic Resistance in Staphylococcus aureus. Up To Date (12.3). 2004.
Richard, Grady. Safety profile of quinolone antibiotics in the pediatric population. The Pediatric Infectious Disease Journal. 22(12): p1128-1132: 2003.
Fiebelkorn, K. R., Crawford, S.A., McElmeel, M.L., and Jorgensen J.H. Practical Disk Diffusion Method for Detection of Inducible Clindamycin Resistance in Staphlyococcus aureus and Coaulase-Negative Staphylococci. Journal of Clinical Microbiology. 41(10): p4740-4744: 2003.
Kiri, N. Archer, G. and Climo, M. W. Combinations of Lysostaphin with Beta-Lactams are Synergistic against Oxacillin-Resistant Staphylococcus epidermidis. Antimicrobial Agents and Chemotherapy. 46(6): p2017-2020: 2002.
Patron, R.L., Climo, M. W., Goldstein, B. P., and Archer, G. L. Lysostaphin Treatment of Experimental Aortic Valve Endocarditis Caused by a Staphylococcal aureus Isolate with Reduced Susceptibility to Vancomycin. Antimicrobial Agents and Chemotherapy. 43(7): p1754-1755: 1999.
Spann, C. T., Tutrone, W. D., Weinberg, J. M., Scheinfeld, N., and Ross, B. Topical Antibacterial Agents for Wound Care: A Primer. Dermatologic Surgery. 29(6): p620-626: 2003.
Jacob, S. E., and James, W. D. From Road Rash to Top Allergen in a Flash: Bacitracin. Dermatologic Surgery. 30(4): p521-524: 2004.
Eliopoulos, G. M. Current and New Antimicrobial Agents. American Heart Journal. 147(4): p587-592: 2004.
Patron, R.L., Climo, M. W., Goldstein, B. P., and Archer, G. L. Lysostaphin Treatment of Experimental Aortic Valve Endocarditis Caused by a Staphylococcal aureus Isolate with Reduced Susceptibility to Vancomycin. Antimicrobial Agents and Chemotherapy. 43(7): p1754-1755: 1999.
Spann, C. T., Tutrone, W. D., Weinberg, J. M., Scheinfeld, N., and Ross, B.
Topical Antibacterial Agents for Wound Care: A Primer. Dermatologic Surgery. 29(6): p620-626: 2003.
Jacob, S. E., and James, W. D. From Road Rash to Top Allergen in a Flash: Bacitracin. Dermatologic Surgery. 30(4): p521-524: 2004.
Eliopoulos, G. M. Current and New Antimicrobial Agents. American Heart Journal. 147(4): p587-592: 2004. SPECIAL THANKS TO Prof.DR.
MERVAT MATAR BY : Ahmed Mohamed Badawy 71
Ahmed Mohamed Faramawy 72
Ahmed Mohamed Hassan 73
Ahmed Mohamed Rashwan 74
Ahmed Mohamed salah 76
Ahmed Mohamed Abd-El-Aal 78
Ahmed Mohamed Abd-El-Moteleb 79
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