ANTI-INFECTIVES

Outline:  off the market due to the high

incidence of INTERSTITIAL
1. Antibacterials
NEPHRITIS
2. Antifungals
ISOXAZOLYL PENICILLINS
3. Anti-tubercular Agents
 Oxacillin, Cloxacillin, Dicloxacillin,
4. Scabicides and Anti-Pedicular Agents
Flucloxacillin
5. Antimalarials
Nafcillin
6. Anti-helminthics
 relatively small amounts are
1. ANTIBACTERIALS excreted through kidneys, with the
Antibiotics—substance produced by major portion excreted in the bile
microorganisms which has the capacity to  can be given to patients with renal
inhibit the growth and to cause the destruction problems
of other microorganisms
C. Aminopenicillins
1.1. Cell Wall Synthesis Inhibitors  have an antibacterial spectrum
1.1.1. Penicillin similar to that of pen G but are
MOA: more effective against gram-
 interfere with the last step of bacterial NEGATIVE bacilli
cell wall synthesis Ampicillin
 transpeptidation or cross-linking of  poor GI absorption
peptidoglycan chains  more frequently administered
 beta lactam attached to thiazolidine parenterally
ring
 nucleus: 6-aminopenicillanic acid Amoxicillin
 better GI absorption than ampicillin
A. Natural Penicillins
Hetacillin, bacampicillin, cyclacillin
Penicillin G (benzyl penicillin)
 prodrugs of ampicillin
 poorly absorbed from the intestinal
tract, oral doses must be very large D. Antipseudomonal penicillins
 Not effective orally Carboxypenicillins (Carbenicillin,
 its rapid elimination from the Ticarcillin)
bloodstream led to the  Pseudomonas
development of repository forms  Enterobacter
 REPOSITORY FORMS (IM):  Proteus
o PENICILLIN G PROCAINE  Bacteroides
o PENICILLIN G BENZATHINE Ticarcillin
 + clavulanic acid
Penicillin V (phenoxymethylpenicillin)
 2-4x as active as carbenicillin
 acid stable against Pseudomonas aeruginosa
B. Anti-staphylococcal/Penicillase resistant
penicillins Ureidopenicillins (Piperacillin – most
 narrow spectrum potent, Azlocillin, Mezlocillin)
+ Klebsiella
Methicillin (2,6-dimethoxyphenylpenicillin)
Piperacillin
 prototype drug

Suzette B. Sagun, RPh, MD 1

 ANTI-INFECTIVES
 + tazobactam  There are no adequate and well-
 10x as active as carbenicillin controlled studies in humans, but
against Pseudomonas potential benefits may warrant use of
the drug in pregnant women despite
Pens are relatively safe.
potential risks.
Adverse effects:
Category D
 Hypersensitivity rxns (mild
 There is positive evidence of human
rash→anaphylaxis)
fetal risk based on adverse reaction
 Seizure particularly in patients with data from investigational or marketing
renal impairment experience or studies in humans, but
Significant interactions potential benefits may warrant use of
the drug in pregnant women despite
 Probenecid potential risks
 Antibiotic antagonism (erythromycin,
tetracyclines, chloramphenicol) Category X

BETA-LACTAMASE INHIBITORS  Studies in animals or humans have

 structurally related to the beta-lactam
ring of penicillin
 do not have significant antibacterial
activity
 Instead, they bind to and inactivate
beta-lactamases
 clavulanic acid, sulbactam, tazobactam
FDA PREGNANCY CATEGORIES
Category A
 Adequate and well-controlled studies
have failed to demonstrate a risk to the
fetus in the first trimester of pregnancy
(and there is no evidence of risk in later
trimesters).
Category B
demonstrated fetal abnormalities
 There is positive evidence of human
fetal risk based on adverse reaction
data from investigational or marketing
experience
 The risks involved in use of the drug in
pregnant women clearly outweigh
potential benefits.
Category N
 FDA has not classified the drug.
1.1.2. Cephalosporins
 beta-lactam attached to dihydrothiazine ring
 nucleus: 7-aminocephalosporanic acid
 Cross-sensitivity with Penicillin

 Animal reproduction studies have failed

to demonstrate a risk to the fetus T
Gen Gram (+) Gram (-)

1st +++ +
There are no adequate and well-controlled
studies in pregnant women 2nd +++ ++
Category C
3rd + +++
 Animal reproduction studies have
shown an adverse effect on the fetus 4th ++ ++++

Suzette B. Sagun, RPh, MD 2

 ANTI-INFECTIVES
rd
Penetrate CSF→meningitis
3
1st Cefadroxil Cephapirin Sepsis of unknown organism
Gen
Cefalexin Cephradine Empiric therapy of life-threatening
Cefazoline conditions

2nd *Cefaclor Cefoxitin, Cefoxitin,

th
Cefuroxime, Empiric in febrile neutropenic patients
4
*Cefamandole Cefpodoxime, Cefprozil UTI, pneumonia, skin infections
Gen
3rd *Cefoperazone Ceftriaxone Ceftibuten
*Cefotaxime
Ceftazidime (Tazicef, Tazidime) 1.1.3. Monobactam
 the beta-lactam ring is not fused to another ring
4th Cefepime, Cefpirome Aztreonam

 bactericidal
 active against many gram negative organisms,
SPECTRUM OF ACTIVITY including Enterobacter and P. aeruginosa
First Generation (fa/pha)
1.1.4. Carbapenems
 Pen G substitute  Broadest in activity
 Resistant to staphylococcal penicillinases  Resistant to beta-lactamases
Second generation Imipenem
Third Generation (T)  undergoes cleavage/inactivation by
 Inferior activity againsts (G+) dihydropeptidase
 Enhanced activity against (G-)  Cilastatin (inhibits dihydropeptidase)
 Ceftriaxone and Cefotaxime : DOC for Meropenem
meningitis
 Ceftazidime: active againsts P.aeruginosa  Both have anti-Pseudomonas coverage

Fourth Generation Ertapenem

 Enhanced activity against G (+) and G (-) Therapeutic Uses:

 Empiric therapy
1
st
Gram (+) and (-) infections in patients  Severe infection caused by drug-resistant
with mild allergy organisms
Gen
Serious Klebsiella infections 1.1.5. Polypeptide

nd Vancomycin
UTI (E.coli)
2
Cefaclor-- otitis media and sinusitis  effective against methicillin-resistant
Gen
Cefoxitin—mixed aerobic and anaerobic staphylococci
infections  used for potentially life-threatening antibiotic-
Cefuroxime--CAP associated colitis due to Clostridium difficile
(Pseudomembranous colitis)

Suzette B. Sagun, RPh, MD 3

 ANTI-INFECTIVES
 slow intravenous infusion is employed for  phototoxicity (demeclocycline)
treatment of systemic infections  vestibular problems (minocycline)
 adverse effect: flushing (red man syndrome)
Doxycycline
Bacitracin (Bacillus subtilis)
 Leptospirosis prophylaxis
 Cyclic peptide or a mixture of polypeptide  STI: Chlamydia
 Poorly absorbed  Skin infections
 Active against a wide variety of Gram (+)  Acne
organisms
1.2.3. Chloramphenicol
Polymyxin (Bacillus polymyxa) – effective primarily
 MOA: inhibits protein synthesis at the 50s
against gram (+) organisms
ribosomal subunit
Gramicidin (Bacillus brevis) – useful against gram (-)  drug of choice for typhoid fever
organisms  adverse effects:
o Gray baby syndrome
1.2. Protein Synthesis Inhibitors
o aplastic anemia
1.2.1. Aminoglycosides
“MYCIN” – derived from Streptomyces
1.2.4. Macrolides
“MICIN” – derived from Micromonospora
 MOA: inhibit protein synthesis at the
50s ribosomal subunit
MOA: inhibit protein synthesis at the 30s
 spectrum of activity resembles pen G
ribosomal subunit
but also effective against mycoplasma,
 synergistic with beta-lactam antibiotics
Chlamydia, campylobacter, legionella
 bactericidal
 adverse effects:
 the highly polar structure of
o epigastric distress
aminoglycosides prevents adequate
o cholestatic jaundice (estolate
absorption after oral administration
form of erythromycin)
 all must be given parenterally to achieve
adequate serum levels except neomycin Erythromycin
(topical and oral only)
 formerly Ilotycin
 adverse effects: nephrotoxicity and
 alternative to penicillin
ototoxicity
 esters of erythromycin base (e.g., stearate,
estolate, and ethylsuccinate) have improved
1.2.2. Tetracycline
acid stability, and their absorption is less altered
 broadest spectrum antibiotic
by food
 has activity against gram (+), gram (-),
 Preferred drug for
spirochetes, mycoplasma, rickettsia and
o Legionnaire’s disease
chlamydia
o Mycoplasma pneumoniae
 MOA: inhibit protein synthesis at the
o Campylobacter
30s ribosomal subunit
o Chlamydial infections
 gastric discomfort
o Diphtheria
 deposition in the bones and primary o Pertussis
dentition causing discoloration and
hypoplasia of the teeth and a Clarithromycin
temporary stunting of growth
 more potent than erythromycin against
 hepatotoxicity
streptococci and staphylococci
Suzette B. Sagun, RPh, MD 4
 ANTI-INFECTIVES
 Used with Omeprazole or Lanzoprazole for H.  Headache
pylori eradication  dizziness
 CAP  Nephrotoxicity
 Phototoxicity
Azithromycin

 unique pharmacokinetic properties: 1.3.2. Nitrofurantoin

 extensive tissue distribution  used as a urinary antiseptic
 high drug concentrations within cells  Pregnancy category B; contraindicated at
(including phagocytes), resulting in much term
greater concentrations of drugs in tissue or  Lactation: enters the breastmilk,
secretions compared to simultaneous discontinue drug or do not nurse
serum concentrations
 once a day dosing 1.3.3. Metronidazole
 the elimination half-life, 40 to 68 hours, is  drug of choice for infections:
prolonged because of extensive tissue  Entamoeba histolytica
sequestration and binding  Giardia lamblia
 Used for:  Trichomonas vaginalis
o nongonococcal urethritis caused by  an unpleasant metallic taste is often
chlamydia experienced
o LRTI  if taken with alcohol, a disulfiram-like effect
o PID occurs
o Pharyngitis
o Legionnaire’s disease
1.3.4.Sulfonamides
 MOA:
1.2.5. Lincosamides o Structural analog of PABA
Clindamycin o Compete with this substrate for the
 one of the most potent agents available enzyme dihydropteroate
against non-spore forming anaerobic synthetase, thus preventing the
bacteria (Bacteroides fragilis) synthesis of bacterial folic acid
 adverse effect: pseudomembranous  Adverse effects:
colitis (caused by C. difficile) o Crystalluria
o SJS
1.3. Synthetic Antibacterials o Kernicterus
1.3.1.Quinolones  Usually combined with folate reductase
 patterned after nalidixic acid inhibitors
 the introduction of FLUORINE atom forming  Uses:
fluoroquinolones enhances antibacterial o First attack of UTI (Cotrimoxazole)
activity o In burn as antibacterial(Silver
 Ciprofloxacin Is the most potent Sulfadiazine and Mafenide)
fluoroquinolone o ConjunctivitisSodium
 MOA: inhibition of DNA synthesis due to sulfacetamide)
the inhibition of DNA GYRASE o Malaria (quinine, pyrimethamine
(TOPOISOMERASE II) and sulfadoxime)
 adverse effects: o P.carinii pneumonia
 Diarrhea (Cotrimoxazole)
 Nausea
Suzette B. Sagun, RPh, MD 5
 ANTI-INFECTIVES
2. ANTIFUNGALS o Impotence
2.1. Echinocandins o Menstrual irregularities
Interferes with cell wall synthesis/permeability Itraconzole
via inhibition of β-(1,3)-D-glucan synthesis
effective against most species of Candida but  Lacks endocrinologic effects of
not Cryptococcus ketoconazole

Fluconazole
Examples:
Caspofungin  administered orally and intravenously
Micafungin  it has excellent penetrability into the
Anidulafungin CSF
 Drug of choice for CRYPTOCOCCAL
2.2. Polyene Antifungals MENINGITIS (Cryptococcus
neoformans)
2.2.1.Amophotericin B
Ketoconazole, Itraconazole, Fluconazole
 MOA: binds to ERGOSTEROL present in the
cell membrane disrupting membrane  for SUBCUTANEOUS and SYSTEMIC
function, allowing electrolytes to leak out mycoses
from the cell, resulting in cell death
 drug of choice for systemic mycoses Clotrimazole, Miconazole, Econazole
 Adverse effects:  for SUPERFICIAL mycoses
o Renal toxicity
o Acute febrile reaction 2.4. Allylamines and Benzylamines
o Anemia  Allylamines—Naftifine, Terbinafine
o Inflammation of vein (phlebitis)  Benzylamines—Butenafine

2.2.2.Nystatin 2.5. Griseofulvin

 used for the treatment of Candida  obtained from the mold Penicillium
infections griseofulvum
 administered as an oral agent for the  MOA: interacts with the
treatment of oral candidiasis MICROTUBULES within the fungus to
 negligibly absorbed from the GI tract so disrupt the mitotic spindle and inhibit
adverse effects are rare mitosis (arrests cell division in
metaphase)
2.3. Azoles  absorption is increased by FATTY ACIDS
 MOA: interacts with C-14 Α-DEMETHYLASE
to block demethylation of lanosterol to 2.6. Flucytosine
ergosterol, the principal sterol of fungal  used only in combination with
membranes. AMPHOTERICIN B for the treatment of
Ketoconazole systemic mycoses and meningitis caused by
Cryptococcus neoformans and Candida
 Inhibits androgen and adrenal steroid  the combination is SYNERGISTIC
synthesis
 Endocrine effects: 2.7. Other Agents
o Gynecomastia 2.7.1.Ciclopirox olamine
o Decreased libido

Suzette B. Sagun, RPh, MD 6

 ANTI-INFECTIVES
 MOA: interrupts with active membrane
transport of trivalent cations (essential 4.2. Pediculicides
cellular precursors)  Used to eliminate head, body, and crab lice
 Anti-inflammatory  Pyrethrin
2.7.2.Tolnaftate o derived from chrysanthemum plants
2.7.3.Undecylenic acid o MOA: nerve posioning
 Piperonyl butoxide
3. ANTI-TUBERCULAR AGENTS  Permethrin
3.1. Isoniazid  Lindane
 MOA: inhibits the synthesis of mycolic acid
 Principal adverse effects: 5. ANTIMALARIALS
 Peripheral neuritis 5.1. Cinchona alkaloid
 Prevention: Pyridoxine 5.1.1.Quinine
3.2. Pyrazinamide  reserved for malarial strains resistant to
 first line drug for short term treatment other agents
 adverse effect: HEPATOTOXICITY  major adverse effect: CINCHONISM (a
 must be enzymatically hydrolyzed to syndrome causing nausea, vomiting,
pyrazinoic acid (active form) tinnitus and vertigo)
3.3. Ethambutol
 adverse effect: OPTIC NEURITIS (eyes) 5.2. Chloroquine
 loss of ability to discriminate between red  drug of choice in the treatment of
and green erythrocytic falcifarum malaria
3.4. Clofazimine  Extraintestinal amebiasis
 basic red dye used in the treatment of
leprosy, including dapsone-resistant forms 5.3. Hydroxychloroquine
3.5. Rifampicin  Anti-inflammatory
 the most active agent
 Enzyme INDUCER 5.4. Primaquine
 adverse effect: hepatotoxicity, REDDISH effective only against the EXOERYTHROCYTIC
COLOR OF BODY SECRETIONS STAGES of malaria
3.6. Streptomycin only agent that can lead to RADICAL CURES of
 ONLY aminoglycoside used for tuberculosis the Plasmodium vivax and Plasmodium ovale
 the first antibiotic effective in the treatment gametocidal for all 4 plasmodia species,
of tuberculosis (1944 by Waksman) transmission of the disease can be prevented

5.5. Quinacrine
4. SCABICIDES AND ANTI-PEDICULAR AGENTS
 primarily used in the treatment of
4.1. Scabicides – compounds used to control the
GIARDIASIS
mite Sarcoptes scabei, an organism that thrives
 also effective against tapeworm and
under conditions of poor personal hygiene
malaria, and topically, against
 Permethrin
leishmaniasis.
 Benzyl benzoate
 should not be given with primaquine
 Obtained from peru balsam and other resins
because of increased toxicity
 Immediate relief from itching
 Crotaminon 5.6. Mefloquine
 Ivermectin

Suzette B. Sagun, RPh, MD 7

 ANTI-INFECTIVES
 effective single agent for suppressing and  Allergy and hypersensitivity rxns
curing multidrug-resistant forms of  Hemolytic anemia
Plamodium falciparum
Ivermectin
6. ANTI-HELMINTHICS  DOC for Onchocerca volvulus (river
6.1. Chemotherapy for Nematodes blindness)
INTESTINAL INFECTIONS  MOA: targets GABA receptors→paralysis of
 Ancylostoma duodenale worms
 Necator americanus
 Ascaris lumbricoides Thiabendazole
 Enterobius vermicularis  Strongyloidiasis (threadworm)
 Strongyloides stercolaris  MOA:
 Trichuris trichuria  also affects microtubular aggregation
 Trichinella spiralis  Adverse effects:
TISSUE INFECTIONS o Common—dizziness, anorexia,
nausea, vomiting
 Wuchereria bancrofti
o Rarely—erythema multiforme and
 Brugia malayi
Stevens-Johnson syndrome (fatal)
Albendazole
Diethylcarbamazine
• broad spectrum antihelmintic
 immobilized microfilariae by an unknown
• Mechanism of action-
mechanism
• inhibits microtubule synthesis thus irreversibly
impairing glucose uptake formation of ATP  drug of choice for filariasis
 Chemotherapy for Trematodes
Mebendazole
 MOA same as albendazole 6.2 Chemotherapy for trematodes
 drug of choice for ascaris, enterobius and Trematodes
trichuris infections  Flukes
 alternative for Taenia saginata infections  Characterized by the tissues they infect
and hydatid disease  Ex. lung, liver, blood
 Flat, Leaf-shaped flatworms
Pyrantel Pamoate  Snail—intermediate host
 for ascaris, hookworm and enterobius  Chlonorchis chinensis (Chinese or Oriental
infestations liver fluke)
 MOA: depolarizing neuromuscular agent,  Schistosoma mansoni (Blood fluke)
causing persistent activation of the nicotinic  Schistosoma haematobium (Blood fluke)
receptors  Paragonimus westermani (Lung fluke)

Praziquantel
Piperazine
 For Ascaris and pinworm  MOA: increases membrane permeability to
MOA: calcium, causing marked contraction
 Flaccid paralysis of helminth initially and then paralysis of trematode
 Blocks response of helminth muscle to Ach muscles; this is followed by vacuolization
 Pyrantel + Piperazine →Antagonistic effect and parasite death
 Adverse effects:
6.3 Chemotherapy for Cestodes
 GI and neurotoxicity (most common)
Suzette B. Sagun, RPh, MD 8
 ANTI-INFECTIVES
Tapeworms
a. Ribbon-like segmented worms that are
primarily intestinal parasites.
b. Live in the intestines of their hosts
c. Lack true digestive tract
d. Hermaphrodites
Taenia solium
Taenia saginata
Diphyllobothrium latum
Hymenolepsis nana
Echinococcus granulosus

Niclosamide
 MOA:
 Inhibits oxidative phosphorylation in
mitochondria of cestodes
 For intestinal cestodes only
o T.saginata
o D.latum
o H.nana

Suzette B. Sagun, RPh, MD 9