animicrobial drugs.pptx

ANTIMICROBIAL AGENTS
ANTIBIOTICS
ANTIFUNGALS
ANTIVIRALS

Classification of ANTIBIOTIC
Based on mode of action:
• Bacteriostatic
• Bacteriocidal
Based on their spectrum of action:
• Broad spectrum
• Narrow spectrum

BACTERICIDAL VS BACTERIOSTATIC
bactericidal bacteriostatic
inducing
cell death
preventing cell
growth or
replication
some static drugs become cidal at
higher concentrations.

Antibiotics:mechanism of actions
• They affect the viability of microorganisms by five
processes:
• (1) inhibition of cell wall synthesis.
• (2) alteration of cell membrane integrity.
• (3) inhibition of ribosomal protein synthesis.
• (4) suppression of deoxyribonucleic acid (DNA) synthesis.
• (5) inhibition of folic acid synthesis.

MICROBIAL RESISTANCE TO
ANTIBIOTICS

MICROBIAL RESISTANCE TO ANTIBIOTICS
BY:
(1)enzymatic inactivation.
(2)modification/protection of the target site.
(3)limited access of antibiotic (altered cell
membrane permeability).
(4) active drug efflux.
(5) use of alternative growth requirements.
(6) overproduction of target sites.

1.INHIBITION OF CELL WALL
SYNTHESIS
 β-Lactam Antibiotic:
- Penicillins
- cephalosporins
- carbapenems
- monobactams
- carbacephems
 Others :
o vancomycin
o Bacitracin

1.INHIBITORS OF CELL WALL
SYNTHESIS
Β-LACTAM ANTIBIOTIC

1.INHIBITORS OF CELL WALL SYNTHESIS
 Main mechanism of action is improper
formation of peptidoglycan layer induce cell
lysis and death by changing of its osmotic
pressure.

 Bacteria resist b-lactam antibiotics by
production of β-lactamases that
hydrolyze the β-lactam ring to form a
linear metabolite incapable of binding
to PBPs.
 To overcome this resistance, β-lactam
antibiotics are often given with β-
lactamase inhibitor drugs.

SYNTHESIS
- Penicillins
- cephalosporins
- carbapenems
- monobactams
- carbacephems

 All have B-lactam ring in their chemical
structure.

PENICILLIN

Penicillins
 a group of antibiotics that share the
same:
 β-lactam ring nucleus.
 adverse drug reactions.
 mechanism of action.
 differ in their:
 antibacterial spectrum.
 Pharmacokinetics.
 resistance to β-lactamase enzymes.

Penicillins
 Effective,safe,widely used.
 Bactericidal.
 More effective against gm+ve
bacteria than gm-ve.
 It’s a natural extracts from penicillium
mold ,and have semisynthetic
derivatives.

Penicillins
 inhibit bacterial growth by interfering with a
last step in bacterial cell wall
synthesis(transpeptidation).

Penicillins
 Distributed in most body fluids
(joints,pleural,pericardial fluids,and bile)
 does not pass into intraocular and blood–
brain barrier unless the meninges are
inflamed (meningitis).
 Safe during pregnancy.
 Rapidly excreted by the kidneys.
 NAFCILLIN is an exception, its excreted
by the liver.

Penicillin
 Mechanism of bacterial resistance to penicillins:
 by producing B-lactamases , which destroy the
B-lactam ring.
 altered PBPs, which have less affinity for B-
lactams.
 decreased ability of the drug to penetrate to its
site of action.

Penicillins
Adverse effects:
 Allergic reactions very common:
 Mostly maculopapular or urticarial skin
reactions.
 Range from skin rash to anaphylactis
shock.
 Penicillins are primarily associated with IgE-
mediated (type I) allergic reactions.
 may induce cytotoxic (type II) or immune
complex (type III) reactions.

Maculopapular
or urticarial
skin reactions.

Penicillins
 intramuscular>intravenous>oral.
 less common in children.
 fatal reactions may be more likely in elderly
patients with systemic diseases.
 Risk factors for penicillin allergies:
 multiple allergies to other drugs(“multiple allergy
syndrome”)
atopic disease:(asthma, allergic rhinitis, nasal
polyps).

PENICILLINS

Penicillins
 Nonallergic Adverse effects:
 Large intravenous doses of penicillins,
especially in patients with compromised
renal function, may induce
hyperexcitability, seizures,and
hallucinations.
 Pain at the site of injection.
 thrombophlebitis.

Penicillins
 Nonallergic Adverse effects:
 May interfere with oral contraceptives.
 Rare and reversible disorders :
 pancreatitis, neutropenia, aseptic meningitis,
hepatotoxicity.
 increased prothrombin time/ (INR) in patients
taking oral anticoagulants either through
impaired platelet function or altered
gastrointestinal microbial flora.

Penicillins
• Can be divided into four groups:
1. penicillin G and penicillin V.
2. antistaphylococcal penicillins.
3. Aminopenicillins.
4. Extended –spectrum penicillins
(Antipseudomonal).

Penicillins
Penicillin G:
 Benzylpenicillin.
 Natural penicillin.
 Narrow spectrum (active mainly against
gm+ve organisms).
 Short duration of action.
 poor gastric absorption (acid-liable).
 Destroyed by penicillinase enzyme.
 Given IM or IV.

Penicillins
Penicillin V:
 Phenoxymethylpenicillin.
 Semisynthetic penicillin Derived from
penicillin G and have the same
antibacterial spectrum.
 Acid resistant.
 Given only by oral rout.

PENICILLIN
PenicillinG Penicillin V
 Natural  Semisynthetic
 Destroyed by gastric
acid
 Resist gastric Acid
 Given IM or IV  Given ORALLY

Penicillins
2. antistaphylococcal penicillins (penicillinase-
resistant):
 Methicillin (no longer used clinically)
 Nafcillin and derivatives:
 (Oxacillin, Cloxacillin, and Dicloxacillin) (ORALLY,
I.M ,I.V).
o It is resistant to degradation by penicillinase.
o is useful against penicillinase producing by Staph aureus.
o Narrow spectrum
o Elimination occurs mainly by kidney and partly by liver.

Penicillins
3. Aminopenicillins:
 Ampicillin and Amoxicillin.
 Extended-spectrum penicillins.
 Bactericidal for many Gm+ve and Gm-ve
 acid-stable.
 Given (orally, I.V , I.M)

Penicillins
3. Aminopenicillins:
 Ampicillin:
 not destroyed by gastric acid.
 penicillinase susceptible.
 incompletely absorbed orally and food
interferes with its absorption.
 It is excreted in urine in unchanged form
and high amount is also present in the bile.

Penicillins
3.Aminopenicillins:
 Amoxicillin:
 Semisynthetic.
 Its completely absorbed by oral
administration.
 It is eliminated in urine in unchanged
form.

AMINOPENICILLINS
Ampicillin Amoxicillin
incompletely absorbed orally Completely absorbed orally
food interferes
with its absorption
Food does not interfere with
its absorption
Excreted in urine, high
amount in bile.
Excreted completely in urine.

Penicillins
4. Extended –spectrum penicillins (Antipseudomonal):
 CARBENICILLIN.
 PIPERACILLIN.
 TICARCILLIN.
o indicated mainly to treat Gm-ve bacilli infection by
pseudomonas, proteus and enterobacter.
o Adverse effects: platelet dysfunction, hypokalemia
and hypersensitivity reaction.

B-LACTAMASE INHIBITOR
Clavulanic acid.
Sulbactam.
Tazobactam.
Avibactam.
four agents are available to bind
irreversibly to the catalytic site of
susceptible β-lactamases to prevent
hydrolysis of β-lactam antibiotics:

B-LACTAMASE INHIBITOR
 Penicillins/B-lactamase inhibitor
combinations:
 B-lactamase inhibitor protect penicillin
from degradation by B-lactamase
enzymes.
 amoxycillin with clavulanic acid.
 Ampicillin with sulbactam.
 Piperacillin with tazobactam.

CEPHALOSPORINS

CEPHALOSPORINES
 Derived from a fungus.
 Bactericidal.
 broad spectrum antibiotic.
 They are widely distributed after administration
throughout body fluids.
 Active against Gm+ve and Gm-ve bacteria but
more active against Gm-ve ones.
 Mechanism of action is identical to penicillins.

CEPHALOSPORINES
 Therapeutic uses in dentistry:
 have good activity against many orofacial
pathogens.
 limited activity against oral anaerobes.
 some cephalosporins are choices for prophylaxis
during dental procedures.
 not indicated in acute dental infections unless
culture and sensitivity testing indicate otherwise.

CEPHALOSPORINES
 Adverse effects:
 Major concern :cross-allergenicity with
penicillins.
 transient increases in liver enzymes.
 Nephrotoxicity.
 Reversible :neutropenia, eosinophilia and
thrombocytopenia.
 Anaphylactic reactions are rare.

CEPHALOSPORINES
Contraindications:
 patients with a positive penicillin skin
test or a history of local or systemic
penicillin anaphylaxis.
 Penicillin-allergic individuals may have
a fourfold greater risk of allergy to
cephalosporins.

CEPHALOSPORINES
 classified according to their generations from 1st
generation to 5th generation.
 Each bacterial species may have different
PBPs.
 Most cephalosporins bind to PBP1 and PBP3 of
Gm-ve organisms.
 The major mechanism of resistance to
cephalosporins is the microbial β-lactamases
(cephalosporinases).

CEPHALOSPORINES
 1st generation agents are very sensitive to
β-lactamase hydrolysis.
 From 2nd to 5th generations more resistant
to β-lactamases.
 Cephalosporins are well absorbed orally.
 Safe during pregnancy.
 Excretion of most cephalosporins in kidney.
 Exceptions include cefoperazone:in bile
and ceftriaxone:in both bile and kidney.

CEPHALOSPORINES
Each newer generation of
cephalosporines has significantly
greater G–ve antimicrobial
proerties than prevous one

CEPHALOSPORINES
o First generation:
 Cefadroxil (orally)
 Cefazolin (I.M, I.V)
 Cephalexin (orally)
 Cephalothin (I.M)
 Cephapirin (I.M)
 Cephradine (orally, I.V , I.M)

CEPHALOSPORINES
o First generation:
 Highly active against gram positive but
weaker against gram negative bacteria.
 Can works against Klebsiella pneumoniae,
Proteus mirabilis, Escherichia coli.
 Dental prophylaxis (cephalexin,cefazolin)

CEPHALOSPORINES
o Second generation:
 Cefaclor (orally)
 Cefamandole (I.M , I.V)
 Cefonicid (I.M , I.V)
 Cefotetan (I.M)
 Cefoxitin (I.M , I.V)
 Cefprozil (orally)
 Cefuroxime (orally, I.M , I.V)

CEPHALOSPORINES
o Second generation:
 Greater effect against some gram-negative
organisms than first-generation drugs.
 cefotetan and cefoxitin have activity
against anaerobes.
 Effective against : H-influenzae, klebsiella
species, E.coli ,some strains of proteus.

CEPHALOSPORINES
o Third generation:
 Cefdinir (orally)
 Cefixime (orally)
 Cefoperazone (I.M , I.V)
 Cefotaxime (I.M , I.V)
 Cefpodoxime (orally)
 Ceftazidime (I.M, I.V)

CEPHALOSPORINES
o Third generation:
 Ceftazidime/avibactam (I.M ,I.V)
 Ceftibuten (orally)
 Cefditoren (orally)
 Ceftizoxime ( I.M ,I.V)
 Ceftriaxone ( I.M ,I.V)

CEPHALOSPORINES
o Third generation:
 Indicated for: Penicillin-resistant S. pneumoniae,
multidrug-resistant S. pneumoniae, enterococci
some β-lactamase–producing organisms.
 Ceftazidime/avibactam is effective against
Enterobacteriaceae, Pseudomonas aeruginosa,
and organisms producing extended-spectrum β-
lactamases.

CEPHALOSPORINES
oFourth generation:
 Cefepime (Maxipime) (I.V)
 Cefpirome (I.M , I.V)

CEPHALOSPORINES
o Fourth generation:
 More active against Gm-ve bacteria than 3rd
generation
 Have a greater stability against breakdown by
many β-lactamases compared with 3rd generation.
 Retains activity against strains of Enterobacteria
and P.aeruginosa.
 Not active against MRSA.

CEPHALOSPORINES
oFifth generation:
 Ceftolozane/tazobactam
 Ceftaroline

CEPHALOSPORINES
oFifth generation:
 Similar to forth generation drugs,
but more extended-spectrum
against β-lactamases.
 Effective against Methicillin
resistant S. aureus (MRSA)

CARBAPENEMS

CARBAPENEMS
 Imipenem
 Meropenem
 Ertapenem
 Doripenem
 very wide spectrum antibiotic.
 bactericidal
 have a high specificity for PBP2 of Gm+ve and Gm-ve
microorganisms.
 Resist most β-lactamases.
 Used parenterally.

CARBAPENEMS
 Microbial resistance to carbapenems via:
 the loss of an outer membrane protein, resulting in
retarding cell wall penetration of the drugs.
 altered PBPs in Enterococcus and MRSA.
Safety data about using during pregnancy are very
limited.
Have cross-allergenicity with other β-lactams.
 may associated with (CNS) toxicity and seizures.

MONOBACTAMS

MONOBACTAMS
 Aztreonam.
 its spectrum is limited to aerobic
Gm-ve species.
 Not the first drug of choice for any
infection.
 Not indicated in dental infections.
 Safe during pregnancy

CARBACEPHEMS

CARBACEPHEMS
LORACARBEF
New class of B-lactam antibiotics.
similar in structure to cephalosporins.
Potent broad-spectrum.
Inactive against MRSA.
Given ORALLY.

OTHERS: VANCOMYCIN
 inhibits gram-positive bacterial cell wall
synthesis.
 inhibit the transglycosylase reaction in
peptidoglycan synthesis (second step of
bacterial cell wall synthesis).
 Affect bacteria cytoplasmic membrane
permeability and RNA synthesis.

OTHERS : VANCOMYCIN
 it requires active cell replication.
 Bactericidal.
 Its activity is exclusively against aerobic
and anaerobic Gm+ve species.
 administered intravenously.
 Excreted through kidney.

OTHERS: VANCOMYCIN
 Its active against methicillin-resistant
staphylococci (MRSA) and S.
pneumoniae.
 Its useful against non-vancomycin-resistant
enterococcal infections.
 Has No use in the management of acute or
chronic orofacial infections unless dictated
by laboratory culture and sensitivity tests.

OTHERS: VANCOMYCIN
 Resistance in vancomycin-intermediate S.
aureus and glycopeptide-intermediate S.
aureus may be due to the production of
abnormal peptides (“false binding sites”) in
the cell wall that bind vancomycin and
prevent its attachment to its receptor.
 Vancomycin resistance s.aureus (VRSA) is
developed !!!

OTHERS: VANCOMYCIN
 Nephrotoxicity.
 auditory toxicity(dose dependent)
 Hypotension.
 reversible neutropenia.
 Ototoxicity.
 Red man syndrome: skin flushing occure with rapid
infusion of I.V vancomycin.

SYNTHESIS
- Penicillins
- cephalosporins
- carbapenems
- monobactams
- carbacephems
 Others :
 vancomycin
Bacitracin

OTHERS: BACITRACIN
 block cell wall formation by interfering with the
dephosphorylation of the lipid compound that
carries peptidoglycans to the growing microbial cell
wall
 Effictive against gram positive includes
staphylococci, streptococci,Corynebacterium, and
Clostridium, with rare resistance seen in
staphylococci.
 Used topically.

(2) ALTERATION OF CELL MEMBRANE INTEGRITY
Polymyxin B.
Daptomycin.
Mechanism of action:by disruption the
integrity of the cell membrane by displacing
Ca2+ and Mg++ from membrane lipid
phosphate groups.
that literally puts holes in the wall or
membrane

(2) ALTERATION OF CELL MEMBRANE INTEGRITY
POLYMYXIN B
 Its spectrum is gram negative, and it is
particularly useful against P. aeruginosa.
 Used topically.
 Not used parenterally because of its side
effects:
 Paresthesias
 Ataxia
 slurred speech

(2) ALTERATION OF CELL MEMBRANE INTEGRITY :
DAPTOMYCIN
 bacteriocidal antibiotic.
 Its causes depolarization of sensitive gram-positive
bacteria after binding to their cell membranes.
 Its spectrum includes MRSA, enterococci,
S.Pyogenes, and Peptostreptococcus
 Given intravenously.
 excreted unchanged by the kidney.
 Adverse effects : skeletal muscle damage and
peripheral neuropathy.

(3) INHIBITION OF RIBOSOMAL
PROTEIN SYNTHESIS.
Macrolides.
Aminglycosides
Tetracyclin
Clindamycin
chloramphinicol

(3) INHIBITION OF RIBOSOMAL
PROTEIN SYNTHESIS.
MACROLIDES

(3) INHIBITION OF RIBOSOMAL PROTEIN SYNTHESIS
MACROLIDES
Erythromycin
Azithromycin
Clarithromycin
Troleandomycin
Dirithromycin
telithromycin

MACROLIDES
Mechanism of action:
 bind reversibly to the P site of the 50S
ribosomal subunit and inhibit RNA-
dependent protein.
 The spectrum of activity depends on the
concentration of drug.
 low concentration are bacteriostatic high
concentrations are bactericidal

MACROLIDES
Therapeutic uses :
 Macrolides are often indicated for treating
community-acquired bacterial pneumonia .
 Erythromycin has a long and successful history
of use against acute orofacial infections
 Clarithromycin and azithromycin are more
active against some organisms than is
erythromycin.

MACROLIDES
 Therapeutic uses:
Clarithromycin is most active against
gram-positive anaerobes.
Azithromycin has the best activity
against gram-negative anaerobes and
has much less possibility for drug
interactions.

MACROLIDES
 Epigastric pain.
 ototoxicity (deafness).
 Acute pancreatitis.
 Mania.
 cholestatic hepatitis.
 hypersensitivity syndrome.
 Stevens-Johnson syndrome (erythema
multiforme) may occur with erythromycin.

MACROLIDES
 Drug interactions:
 Bacteriostatic macrolides may interfere
with the bactericidal effect of cell wall
inhibitors.
 macrolides may seriously reduce digoxin
metabolism in the GIT.
 Macrolides may potentiate the
anticoagulant effect of oral anticoagulants.

MACROLIDES
 Azithromycin and erythromycin are
SAFER than clarithromycin during
pregnancy.
 Erythromycin is metabolized in liver and
excreted in bile.
 Azithromycin is excreted in bile.
 Clarithromycin is metabolised in the liver
and excreted in urine.

MACROLIDES
erythromycin clarithromycin azithromycin
source natural semisynthetic semisynthetic
Antibacterial
spectrum
Narrow-
spectrum
Broad-spectrum Broad-spectrum
Duration of
action
Short acting Long acting Long acting
Effictive more
against:
Gm+ve Gm+ve gm_-ve
Stability in
stomach
acidity
The least stable
on acid
The most stable in
acid
Stable on acid

(3) INHIBITION OF RIBOSOMAL PROTEIN SYNTHESIS.
AMINGLYCOSIDES
 streptomycin
 gentamicin
 tobramycin
 Amikacin
 Neomycin
o Mechanism of action:
o Aminoglycosides bind irreversibly to the 30S
ribosome to interfere with the reading of the
microbial genetic code and to inhibit protein
synthesis.

AMINGLYCOSIDES
Aminoglycosides are bactericidal.
Its activity directed toward Gm-ve bacilli and
mycobacteria.
are poorly absorbed orally and do not penetrate
well into the CNS.
Have NO uses in orofacial infections unless
dictated by culture and sensitivity tests.
Not safe during pregnancy.
are excreted primarily by KIDNEY.

AMINGLYCOSIDES
Gentamicin is the most commonly
used.
Streptomycin :is one of the first line
drugs for T.B
Amikacin has the broadest spectrum
and used for T.B
Neomycin is highly nephrotoxic and
often used topically.

AMINGLYCOSIDES
most common bacterial resistance
mechanisim is, plasmid-mediated
aminoglycoside- modifying
enzymes.
Adverse effects:
 Renal toxicity.
 Eighth cranial nerve toxicity (auditory
and vestibular ototoxicity).

TETRACYCLIN
 Tetracycline
 Tetracyn, Tetracap
 Doxycycline
 Minocycline
Mechanism of action: interfere with
attachment of t-RNA to m-RNA ribosome
complex.

TETRACYCLIN
Broad-spectrum.
Bacteriostatic.
Used in:
 treatment of and prevention of peptic ulcers .
 Multidrug-resistant
 Community-acquired pneumonia in penicillin-
resistant and macrolide-resistant strains.
Doxycycline is the most commonly used.

TETRACYCLIN
Tetracyclines induce microbial resistance
not only to themselves but also other
antibiotics.
are metabolized in the liver.
Given orally.
used oral and topical preparations in the
treatment of acne.
deposited in calcifying teeth, bone, and
cartilage.

TETRACYCLIN
Contraindicated in pregnancy and lactation
because of staining of teeth and potential
hepatotoxicity.
Minocycline is also able to impart a grayish
discoloration of teeth, even after tooth
formation and eruption.
Tetracycline staining is not permanent in bone
and cartilage, but it is permanent in teeth
should not be used in children younger than 8
years.

CLINDAMYCINE
Mechanism of action: inhibition of
microbial protein synthesis by binding to
23S subunit of the 50S bacterial
ribosome.
Bacteriostatic.
active against many Gm+ve and Gm-ve
anaerobic and facultative/aerobic
microorganisms.

CLINDAMYCINE
Bacterial resistance:
1.ribosomal protection.
2.receptor alteration
3.drug inactivation by a nucleotidyl transferase.
 well absorbed orally.
 penetrates well into bone but not cerebrospinal
fluid.
 Safe in pregnancy.
 Excreted into milk,best avoided during lactation.
 metabolized in the liver

CLINDAMYCINE
 indicated in the treatment of:
 bone infections.
 female genital tract infections.
 pelvic infections.
 abdominal penetrating wounds .
 acute orofacial infections because ,the
oral microbial resistance to β-lactams
continues to increase.

CLINDAMYCINE
 adverse effect:
 Major concern:antibiotic-induced diarrhea
and colitis.
 Reversible increase in serum transaminase
levels.
 Reversible myelosuppression.
 Metallic taste.
 Allergy and maculopapular rash.

CHLORAMPHINICOL
 Chloromycetin
 Broad-spectrum antibiotic.
 Bacteriostatic.
 inhibits bacterial protein synthesis by
reversible binding to the 50S ribosomal
subunit.
 no indications for management of orofacial
infections

CHLORAMPHINICOL
 Adverse effects:
 reversible and irreversible bone marrow
depression seen with oral, parenteral, and
even topical use.
 gray baby syndrome: inability of the
immature liver of neonates to detoxify the
drug.
 Rarely used

• They affect the viability of microorganisms by five
processes:
• (2) alteration of cell membrane integrity.
• (3) inhibition of ribosomal protein synthesis.
• (4) suppression of (DNA) synthesis.
• (5) inhibition of folic acid synthesis.

4) SUPPRESSION OF (DNA) SYNTHESIS
Inhibit DNA gyrase Interfere with DNA
function
 Fluoroquinolones:  Metronidazole
Ciprofloxacin  Rifampicin
Ofloxacin
Levofloxacin
Moxifloxacin

(4) SUPPRESSION OF (DNA) SYNTHESIS
FLUOROQUINOLONES
Inhibit DNA gyrase and preventing DNA supercoiling.
Bactericidal
Indications for use:
 Urinary tract infections.
 Bacterial gastroenteritis.
 Typhoid fever.
 septicemia.
 otitis media.
 Respiratory infections pneumonia.
 Ocular infections.

FLUOROQUINOLONES
Bacterial resistance:
 mutations in DNA gyrase.
 drug efflux pumps
 Reduction in microbial outer membrane
permeability.
well absorbed orally.

FLUOROQUINOLONES
Adverse effects:
 mild neuropathy
 Dermatologic toxicity.
 Chondrotoxicity
 Phototoxicity may occur on skin areas
exposed to sunlight.

FLUOROQUINOLONES
 are NOT indicated for any acute orofacial
infections unless dictated by culture and
sensitivity tests.
 Ciprofloxacin should be used with caution
during pregnancy and in children.
 Others fluoroquinolones are contraindicated
in children younger than 18 year.
 Excreted by kidney.

METRONIDAZOLE
 metronidazole requires entry into the cell and affect
DNA by 3 methods:
 causing inhibition of DNA replication
 fragmentation of existing DNA
 mutation of the bacterial genome.
 active only against anaerobes.
 Bactericidal
 Microbial resistance to metronidazole is limited.

METRONIDAZOLE
 the drug of choice for various protozoal infections
 The combination of metronidazole with amoxicillin
may significantly enhance its activity for serious
acute orofacial infections. and in the management
of aggressive periodontitis..
 has a wide volume of distribution, has excellent
CNS penetration
 Given orally or I.V
 Metabolised in the liver

METRONIDAZOLE
 Reversible neutropenia, metallic taste, dark or red-
brown urine, skin rash, urethral or vaginal burning
sensation,nausea and vomiting.
 Rare major adverse reactions with prolonged
doses: pancreatitis, seizures, encephalopathy,
cerebellar dysfunction, paresthesias, mental
confusion, and depression.
 Best avoided during 1st trimester in pregnancy.

RIFAMPICIN
 Inhibit DNA dependent -RNA polymerase.
 effective against numerous gram-positive and gram-
negative.
 Well absorbed orally.
 Elimination occurs by liver
 excretion in the urine and feces.
 Decreased effectiveness of oral anticoagulants, oral
contraceptives.

(5) INHIBITION OF FOLIC
ACID SYNTHESIS
SULFONAMIDE

(5) INHIBITION OF FOLIC ACID SYNTHESIS
SULFONAMIDE:
 Sulfisoxazole (oral)
 Trimethoprim/sulfamethoxazole (oral)
 Mafenide (topical/burns)
 Silver sulfadiazine (topical/burns)
 inhibit the enzyme folic acid synthetase
which is involved in the conversion of PABA
(para-amino benzoic Acid) to folic acid.

SULFONAMIDE:
Bacterostatic
Broad spectrum.
General therapeutic uses
 genitourinary tract infections
 otitis media, acute bronchitis,
community-acquired pneumonia, and
traveler’s diarrhea.

SULFONAMIDE:
Bacterial resistance:
 increased cell permeability barriers
and efflux proteins.
 decreased sensitivity or alterations in
target enzymes .
 Create new target enzymes.

SULFONAMIDE:
 Given orally or topically.
 Penetration into all fluids and tissues in the body
including the CNS.
 Metabolized in liver and excreted in urine.
 nausea and vomiting, blood dyscrasias, and
skin rash and pruritus .
 Stevens-Johnson syndrome (with long acting
sulfonamide), epidermal necrolysis, exfoliative
dermatitis, photosensitivity ,anaphylaxis.

ANTIVIRAL AGENTS
antiviral agents are classified according their
specific Infections
Anti-Influenza Viral Agents.
Anti-Herpetic Agents.
Anti-Respiratory Syncytial Virus Agents.
Antiviral Hepatitis Agents.
Antihuman Immunodeficiency (HIV)
Agents.

REPLICATIVE CYCLES OF
INFLUENZA VIRUS
Penetrating into the
cytoplasm of cells
through endocytosis
the viral M2 protein
induces an influx of
hydrogen ion into the
virion from the cytoplasm
of the infected cells
uncoating of
virion
release of
viral
ribonucleopro
tein (RNP)
complex into
the cytoplasm
viral RNAs
(vRNAs) enter
nuclei of cells
and began to
replicate
progeny vRNAs
and expressing
mRNAs for
making
structural and
nonstructural
proteins of the
virus
Produce
virions
released
from the
infected cell

ANTI-INFLUENZA VIRAL AGENTS
Amantadine
Rimantadine
Oseltamivir
zanamivir
Peramivir

 Amantadine
 Rimantadine
 inhibit the function of M2 protein, and in
doing so, they prevent the uncoating
process of the virus.
 Antiviral Spectrum:Prophylaxis of
influenza A infection

 Oseltamivir
 zanamivir
 Peramivir
 Inhibit the activity of viral neuraminidase,
resulting in blocking the release of progeny
virus from the infected cells.
 Antiviral Spectrum:Prophylaxis and
treatment of influenza A and B virus
infection

 influenza vaccines:
1. trivalent inactivated vaccine
2. live-attenuated intranasal vaccine.
 are recommended for:
 pregnant women.
 individuals over 50 years old.
 persons over 5 years old with chronic medical conditions.
 caregivers of children under 6 years old.
 health care workers.

 influenza vaccines:
 two weeks after immunization, antibodies
against influenza virus will reach a
protective level and persist for 6 months.
 A significant proportion of individuals
receiving the live-attenuated vaccine will
shed vaccine-strain viruses, but the peak
titer is below the infectious dose.

ANTI-HERPETIC AGENTS
Acyclovir vs Valacyclovir:
 Both drugs target the same viruses and same
mechanism of action.
 Valacyclovir provides longer duration of action
than Acyclovir, so doses can be taken fewer
times (3 times daily), while (5 times daily) for
Acyclovir.
 Using topical acyclovir for symptomatic relief of
recurrent herpes labialis in patients with normal
immune systems doesn’t providing real benefits.

Acyclovir Valacyclovir
Both are similar drug, valocyclovir is converted to acyclovir in
body
They both treat same infection : HSV1, Herps zozter, varicella
Short duration of action
5 times daily
Longer duration of action
2,3 times daily
Dosage formed
Oral tablets & topical
Oral tablets
Drug interaction
Probenecid, phenytoin, valporic
acid
No significant drug interaction
Both have little difference in effectiveness
Both need to be used with caution in elderly patient & those
with renal impairment

Bioavailability of acyclovir is less than valacyclovir
Valacyclovir is more compliance than acyclovir >>
so its more expensive
Mechanism of action:
Inhibit viral tyhmidine enyme >> only destroy cells
they have it.
(very specific)
(Very safe)
Note: in human cell there is thymidine enzyme, but
not destroyed by drug

More effective
in early stage
of replication
( burning
sensation)
to prevent
synthesis of
virus

ANTI-HERPETIC VACCINE
o Live-attenuated varicella zoster
vaccine for prevention of shingles.
o vaccine enhances VZV-specific cell-
mediated immunity to inhibits the
reactivation of latent VZV.
o The vaccine reduces the severity and
duration of discomfort and pain
caused by herpes zoster.

ANTI-RESPIRATORY SYNCYTIAL
VIRUS AGENTS

ANTI-RESPIRATORY SYNCYTIAL VIRUS AGENTS
Ribavirin:
 mechanism of action: interferes with viral
m-RNA synthesis and its metabolites.
clinical uses:
 aerosolization to hospitalized infants and
young children with respiratory syncytial
virus infections as a result of Winter
outbreaks of respiratory tract illness.

ANTIVIRAL HEPATITIS AGENTS
 hepatitis viruses are A, B, C,
D,E.
 antiviral agents are accessible for
treatment (HBV) and (HCV)
infections.
 Therapeutic strategies for HBV
and HCV are different from each
other.

AGAINST HBV
 lamivudine (3 TC)
 Entecavir
 Adefovir
 Telbivudine
 Clevudine
 ALL the above have the same mechanism of Action:
Inhibits DNA polymerase
 Tenofovir: (Reverse transcriptase inhibitor)
 Side effects: Fatigue, nausea, headache, lactic
acidosis with fatty liver.

AGAINST HCV
 Interferons
 Ribavirin
 Sofosbuvir
 telaprevir,
 Boceprevir
 Simeprevir
 Mechanism of action: Protease inhibitor.
 Sides effects:Headache, dysgeusia, GI
symptoms, anemia, neutropenia, pancytopenia.

INTERFERONS
 glycoproteins secreted by virus-infected
cells that promote the establishment of an
antiviral state in uninfected cells.
 regulate cellular functions dealing with cell
proliferation and immunologic responses.
 all tissues appear to be capable of
synthesizing interferons.
 ALL VIRUSES ARE SENSITIVE TO
INTERFERON

INTERFERONS
 are produced by induction of synthesis in human
leukocytes, fibroblasts, or lymphoblastoid
cells and, in larger amounts, by recombinant
DNA techniques in bacteria.
 Interferons can be classified according to three
major groups: α, β, γ
 PEG is a protein modification by which
polyethylene glycol (PEG) molecules are added to
interferons.
 PEG makes interferon last longer in the body,
allowing less frequent dosing.

INTERFERONS
 Interferon α and interferon α2b: are use against:
 chronic hepatitis B and C infections
 condyloma acuminata (anogenital warts)
 multiple sclerosis
 Kaposi sarcoma
 Interferons β1a and β1b: for multiple sclerosis.
 Interferon γ1b :for chronic granulomatous disease.
 Sides effects:
 increases in pulse rate and temperature.
 decreases in WBC counts.
 headache, somnolence, and malaise.

ANTIHUMAN IMMUNODEFICIENCY
VIRUS (HIV) AGENTS

ANTIHUMAN IMMUNODEFICIENCY VIRUS
(HIV) AGENTS
Nucleoside/nucleotide reverse transcriptase
inhibitors (NRTIs)
Non-nucleoside reverse transcriptase
inhibitors (NNRTIs)
Protease inhibitors (PIs)
Integrase strand transfer inhibitors (INSTIs)
Entry inhibitors (CCR5 antagonist)
Fusion inhibitors.

(HIV) AGENTS
Nucleoside/nucleotide reverse transcriptase inhibitors
(NRTIs): block the enzymatic function of reverse
transcriptase and prevent completion of viral DNA
synthesis and multiplication.
Non-nucleoside reverse transcriptase inhibitors
(NNRTIs):noncompetitive inhibition of the reverse
transcriptase enzyme, thereby preventing cells from
being infected.
protease inhibitor: HIV protease is a viral enzyme
responsible for the cleavage of the Gag and Gag-Pol
polyproteins into the enzymes and structural proteins
that are required for the final assembly of new
infectious virions

(HIV) AGENTS
Integrase strand transfer inhibitors (INSTIs): Block
Integration of the virally produced DNA into the host
DNA, it’s a critical step in the pathogenesis of HIV.
Entry inhibitors (CCR5 antagonist) : interfere with
virus binding to receptors on the outer surface of the
cell as it tries to enter.
Fusion inhibitors :drug binds to a viral envelope
glycoprotein, which prevents the fusion between the
viral envelope with host plasma membrane,
blocking HIV from entering the cell.

(HIV) AGENTS
Highly active antiretroviral therapy (HAART):
combines drugs from at least two different classes To
prevent strains of HIV from becoming drug resistant .
Sides effect of ANTI-HIV agents :
 Mitochondrial damage
 lactic acidosis with fatty liver
 peripheral neuropathy
 Anemia
 myopathy
 pancreatitis.

ANTIVIRAL THERAPY IN THE ORAL
CAVITY
 HSV-associated viral lesions are routinely treated
by oral acyclovir.
 Acyclovir is best used as soon as the symptoms
begin to appear
 intravenous dosage is based on body weight and
the type of the lesion.
 Generally, 5 to 10 mg/kg of body weight is
administered intravenously for a 1-hour period
and repeated every 8 hours for 5 to 10 days.

ANTIVIRAL THERAPY IN THE ORAL
CAVITY
 Treatment of oral hairy leukoplakia is
rendered only in symptomatic patients and
usually involves topical application of a
solution of podophyllin resin 25% and
acyclovir 800 mg four times daily.
 normally recurs when the medication is
discontinued.

ANTIFUNGAL AGENTS
 POLYENE  AZOLE  ECHINOCANDIN
 Amphotericin-
B
 Imidazoles  Caspofungin
 nystatin  triazoles  Micafungin
 Anidulafungin

ANTIFUNGAL AGENTS: POLYENE
Amphotericin B: Either fungistatic or fungicidal
activity depending on:
 Its concentration.
 the pH.
 the fungus involved.
 Peak activity is occurs at a pH between 6.0 and 7.5
 broad spectrum antifungal activity.
 Active against: Candida species, Histoplasma
capsulatum, Cryptococcus neoformans,
Blastomyces dermatitidis, and Coccidioides
immitis.

Amphotericin B:
o absorbed from the skin or mucous membranes.
o poorly absorbed from the gastrointestinal tract.
o For systemic infections, amphotericin B is
administered by slow intravenous infusion.
o slowly excreted by the kidney over the next 2
months
o applied topically as a 3% cream, ointment, or
lotion.
o useful in the treatment of superficial Candida
infections

Amphotericin B:
o adverse effects:
o In topical application or oral administration: local irritation and mild
GIT disturbances if swallowed.
o As an intravenous agent, amphotericin B is the most toxic antifungal in
current use:
 hypotension and delirium
 fever, nausea, vomiting, abdominal pain
 anorexia, headache, and thrombophlebitis
 Hypochromic, normocytic anemia.
 RARELY:leukopenia and thrombocytopenia .
 Allergic reactions
 nephrotoxicity, may lead to discontinuation of therapy.
 Permanent damage of the kidneys during high doses
 hypokalemia

Nystatin: spectrum of activity slightly narrower than
that of amphotericin B.
 active against :Candida,Histoplasma,
Cryptococcus, Blastomyces, and the
dermatophytes Epidermophyton, Trichophyton,
and Microsporum.
 NOT absorbed very well from the skin, mucous
membranes, or GIT.
 the bulk of the administered dose appears
unchanged in the feces.

o Nystatin:
o Because of unacceptable systemic toxicity,
nystatin is not used parenterally.
o is used primarily to treat candidal infections
of the mucosa, skin, intestinal tract, and
vagina.
o topical nystatin remains a drug of choice for
the treatment of candidal infections of the
oral cavity (oral moniliasis, thrush, denture
stomatitis).

 Nystatin:
o used prophylactically in immunocompromised
patients.
o treatment of oral candidiasis : 2 to 3 mL of a
suspension containing 100,000 units/mL of nystatin
are placed in each side of the mouth, swished, and
held for at least 5 minutes before swallowing.
o This regimen is repeated every 6 hours for at least
10 days or for 48 hours after remission of
symptoms.
o Alternatively, one to two lozenges (200,000 units
per each) may be used four to five times per day.

 Nystatin:
o For denture stomatitis, nystatin ointment (100,000
units/g) can be applied topically every 6 hours to
the tissue surface of the denture.
o Nystatin is well tolerated.
o mild and transient gastrointestinal disturbances
such as nausea, vomiting, and diarrhea may
occure.
o The major complaint associated with nystatin is its
bitter, foul taste.

one of the nitrogen atoms of the azole ring binds to the heme moiety of the
fungal cytochrome P450 enzyme lanosterol14-α-demethylase, thereby
inhibiting the conversion of lanosterol to ergosterol.

ANTIFUNGAL AGENTS: AZOLE
Triazoles are more selective for the
fungal cytochrome P450 enzymes than
the imidazoles.
Triazoles have lower toxicity and fewer
drug–drug interactions.
Acquired resistance to the imidazoles is
becoming more common.

ANTIFUNGAL AGENTS: IMIDAZOLES
Ketoconazole:
 Its used topically .
 its not often used for systemic purposes because it
has several adverse effects:
 Inhibit the synthesis of testosterone leads to
gynecomastia in males.
 Inhibit estradiol leads to menstrual irregularities in
women.
 inhibits the metabolism of several other drugs with
potentially serious drug–drug interactions. Its topical
uses.

Clotrimazole:
 used for various mucosal and cutaneous
infections.
 For the treatment of oral candidiasis,
clotrimazole is available as a 10-mg troche
 Slow dissolution in the mouth results in the
binding of clotrimazole to the oral mucosa, and
gradually released to maintain at least
fungistatic concentrations for several hours.
 It is metabolized in the liver and eliminated in
the feces

Clotrimazole:
 standard regimen for oropharyngeal candidiasis:
One troche dissolved in the mouth five times a day
for 2 weeks.
 more pleasant taste than nystatin
 highly effective and is the drug of choice for the
treatment of oral candidiasis in patients with AIDS.
 Adverse oral effects associated with topical
clotrimazole: oral burning, altered taste, and
xerostomia, minor gastrointestinal upset may follow
oral ingestion of the drug.

Miconazole:
 Useful against cutaneous candidiasis and vulvovaginitis
caused by C. albicans.
 Available as 2% miconazole nitrate cream.
 A buccal tablet is available for treatment of oral
candidiasis.
 The tablet is pressed on the gingiva in the canine fossa.
 It adheres there and releases the drug over a period of
about 6 hours.
 Adverse oral effects are similar to those of clotrimazole,
with the additional :possibility of gingival irritation and
pain at the application site

ANTIFUNGAL AGENTS: TRIAZOLE
Itraconazole:
 broad spectrum of antifungal activity.
 is well absorbed from the gastrointestinal tract when it
is given with meals.
 Its metabolized in the liver and partially eliminated in
the bile.
 Can be used systemically for more severe
candidiasis.
 Adverse effects include: hypokalemia, liver
dysfunction, rarely heart failure, and some drug–drug
interactions.

ANTIFUNGAL AGENTS:TRIAZOLE
Fluconazole:
 more selective antifungal actions than
ketoconazole.
 It is well absorbed from the gastrointestinal tract.
 also available for intravenous injection.
 well distributed throughout the body.
 Its ability to penetrate the blood–brain barrier in
the treatment of fungal meningitis
 Fluconazole is excreted in kidney.

Fluconazole:
 Fluconazole is active in suppressive therapy and
primary treatment of cryptococcal meningitis,
which may occur in patients with AIDS.
 It is effective in the treatment of mucosal
candidiasis, including oropharyngeal and
esophageal candidiasis.
 Adverse effects :liver dysfunction, hypokalemia,
cardiac QT elongation, and some drug–drug
interactions.

Voriconazole:
 used orally for systemic fungal infections.
 active against Aspergillus species and Candida
species.
 broad-spectrum fungicidal activity against molds
and fungistatic activity against Candida and other
yeast.
 the drug of choice for the treatment of invasive
aspergillosis.

Voriconazole:
 is also effective against dimorphic fungi.
 is considered a safer alternative to other
antifungals such as amphotericin B for patients at
risk of renal dysfunction.
 Adverse side include :
 erythematous rash
 visual disturbances
 Hepatotoxicity
 headache

Posaconazole:
 a newer addition to the antifungal triazoles that
structurally resemble itraconazole.
 it has activity against Mucorales.
 as effective as fluconazole for the treatment of
oropharyngeal candidiasis in patients infected with
HIV.
 has usefulness as an alternative drug in severe
candidiasis.

Posaconazole:
 Sides effect:
 Fatigue.
 Nausea.
 Diarrhea.
 hepatic toxicity.
 prolongation of the QT interval.

ANTIFUNGAL AGENTS : ECHINOCANDIN

 Caspofungin
 Micafungin
 anidulafungin.
 The echinocandins are especially useful for
candidal esophagitis and candidemia,
Aspergillus infections,empirical treatments
of febrile neutropenia, and for antifungal
prophylaxis in hematopoietic stem cell
transplant (HSCT) recipients.

 Caspofungin:
 importance in patients with life-threatening systemic
fungal infection who cannot tolerate amphotericin B
or azole therapy;
 well tolerated when administered parenterally.
 its used intravenously.
 adverse effects :resemble histamine-mediated
symptoms, such as rash, facial swelling, and
pruritus.
 Hepatic toxicity and hypokalemia .

Micafungin:
 The same indication with
fluconazole with fewer adverse
effects.
 is given at a daily infusion dose of
150 mg for esophageal candidiasis
and of 50 mg for antifungal
prophylaxis.

 Anidulafungin:
 It is the newest addition to the echinocandin
antifungals.
 Has potent and broad antifungal activity against
Candida and Aspergillus spp., including those
resistant to fluconazole.
 more effective than caspofungin against Aspergillus.
 given by intravenous infusion with 100-mg daily
maintenance dose for invasive candidiasis and 50-
mg daily dose for esophageal candidiasis.

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