PHM304: Microbiology and

Parasitology
Week 3 & 4: Antimicrobials

Hadassah Reyes-Cendaña
October 2021
ANTIMICROBIALS
 What are Antimicrobials?
An antimicrobial is a substance that either
kills or inhibits the growth of microorganisms
such as bacteria, fungi, or protozoan's.

History
The history of antimicrobials begins with the
observations of Pasteur and Joubert, who
discovered that one type of bacteria could
prevent the growth of another.
INFECTION- An infection is the invasion of
body tissues by disease causing
microorganisms.
MICROBIOCIDAL- kills the microbes.

MICROBIOSTATIC- inhibits the growth of microbes

DISINFECTANT- used on non-living objects or outside

the body.

ANTISEPTIC- substances that are applied to

living tissue/skin to reduce the possibility
infection.

CHEMOTHERAPY- Treatment of systemic infection

with specific drug without affecting the host.
 Classification on the basis of:
1. CHEMICAL STRUCTURE
2. MECHANISM OF ACTION
3. TYPE OF ORGANISM
4. SPECTRUM OF ACTIVITY
5. TYPE OF ACTION
6. ANTIBIOTICS OBTAINING FROM
1.ON THE BASIS OF CHEMICAL STRUCTURE
1.Sulphonamide and related drugs- Dapson(DDS), Para
aminosalisylic acid
2.Diaminopyridines- Trimethoprim, Pyrimethamin
3.Quinolones- nalidixic acid
4.B-lactum antibiotics- penicilines,
cephalosporin
5.Tetracycline- oxytetracyclin,
doxytetracyclin
6.Nitrobenzene derivative-
chloramphenicol
7.Amino glycosides- streptomycin,
gentamicin
1.ON THE BASIS OF CHEMICAL STRUCTURE

8.Macrolide antibiotics- erythromycin, clarithromycin

9.Lincosamide antibiotic- lincomycin, clindamycin
10.Glycopeptide antibiotics- vancomycin
11.Nitrofuran derivative- nitrofurantoin derivatives
12.Nitroimidazoles- metronidazoles
13.Polyene antibiotics- Nystatin, Amphoterecin-B
14.Azole derivatives- Ketoconazole, fluconazole
 2. ON THE BASIS OF MECHANISM OF
ACTION:
1. Inhibit cell wall synthesi penicillin, cephalosporin
2. Cause leakage from cell membrane- Amphoterecin-b Nystatin
3. Inhibit protein synthesis- tetracycline,
chloramphenicol, erythromycin
4. Cause misreading of m-RNA code and affect permeability-
streptomycin, gentamycin
5. Inhibit DNA gyrase- Fluroquinolones, ciprofloxacin
6. Interfere with DNA function- Rifampin, metronidazole.
7. Interfere with DNA synthesis- Acyclovir, Zidovudine
8. Interfere with intermediary metabolism- Sulphonamides,
sulphones, ethambutol
 3. ON THE BASIS OF TYPES OF ORGANISM AGAINST
WHICH PRIMARILY ACTIVE-
1. Antibacterial- Penicillin's, amino glycosides
2. Antifungal- Griseofulvin, Amphoterecin-b, ketoconazol
3. Antiviral-Acyclovir, Amantidin, Zidovudin
4. Antiprotozoal- Chloroquine, Pyrimethamine
5. Anthelmentic- Mebendazole, pyrantel

4. ON THE BASIS OF SPECTRUM OF ACTIVITY-

6. Narrow Spectrum- Penicillin-G, Erythromycin
7. Broad Spectrum- tetracycline, Chloramphenicol

5. ON THE BASIS OF TYPE OF ACTION-

8. Primarily bacteriostatic- Sulphonamide, Erythromycin, ethambutol
9. Primarily bactericidal- Rifampin, isoniazide, penicillin
PROBLEMS THAT ARISE WITH THE USE
OF AMAs

1.Toxicity
2.Hypersensitivity reactions
3.Drug resistance
4.Superinfection
5.Nutrirional Deficiencies
6. Masking an action
CHOICE OF AN ANTIMICROBIAL AGENT-

PATIENT RELATED FACTORS

1. Age
2. Renal & hepatic function
3. Drug allergy
4. Impaired host defense
5. Pregnancy
6. Genetic factors

DRUG RELATED FACTORS

7. Spectrum of activity
8. Type of activity
9. Sensitivity of organism
10. Relative toxicity
11. Pharmacokinetic profile
12. Route of administration
13. Cost
 COMBINED USE OF ANTIMICROBIALS
1. To achieve synergism
2. To reduce adverse effects
3. To prevent emergence of resistance
4. To broaden the spectrum of antimicrobial action

PROPHYLACTIC USE OF ANTIMICROBIALS-

5. Prophylaxis against Specific organism-
E.g.. Rheumatic fever, T.B , HIV infection, Cholera, Plague

2. Prevention of infection in high risk situation-

E.g.. Dental extraction, Catheterization, Chronic obstructive lung
disease.

3. Prevention of infection in general –

E.g. Neonates, Viral upper respiratory tract infection.
 Combined-Use of Antimicrobials

•To achieve synergism

•To reduce adverse effects
•To prevent resistance
•To broaden the spectrum
of antimicrobial action
 SULFONAMIDES
 They are the first antimicrobial agents
 Because of rapid emergence of bacterial resistance
and availability their current utility is limited.

CLASSIFICATION-
• Short acting- Sulphadiazine
• Intermediate acting- Sulphamethoxazole
• long acting- Sulphadoxine
• Special purpose- Mafenide, Silver
sulphadiazine
 Antibacterial Spectrum

It is primarily Bacteriostatic against Gram-positive

and Gram-negative bacteria.

[Gram-positive: Gram-positive bacteria retain the

color of the crystal violet stain in the Gram stain.]
[Gram-negative: Gram-negative bacteria lose the
crystal violet stain in Gram's method of
staining]
 MECHANISM OF ACTION:

 Certain microbes require p-aminobenzoic acid

(PABA) in order to synthesize dihydrofolic acid
which is required to produce purines and ultimately
nucleic acids.
 Sulfonamides,chemical analogs of PABA, are
competitive inhibitors of dihydropteroate
synthetase.

Sulfonamides therefore are reversible
inhibitors of folic acid synthesis and
bacterostatic not bacteriocidal.
USES:

 In treating urinary tract infections

 Combination of Trimethoprime and
Sulphamethoxazole is used in many bacterial
infections
 Also used in treatment of Malaria and
Toxoplasmosis
Adverse effects-
 Fever, rash
 Photosensitivity
 Nausea, vomiting,diarrhea
 Urinary tract problems
 Stevens-Johnson syndrome
 Hemopoietic disturbances
 Granulocytopenia
COTRIMOXAZOLE
The fixed dose combination of Trimethorim and
Sulphamethoxazole is called as
COTRIMOXAZOLE
Concentration ratio of Sulfamethoxazole and
Trimethoprim is 20:1
Spectrum of action- Salmonella typhi, Klebsiella,
Enterobacter, Shigella
 Uses
 Urinary tract infection
 Respiratory tract infection
 Typhoid
 Dysentery

Adverse effect
 Patients with renal disease may cause Uremia
 bone marrow toxicity due to Cotrimoxazole
 Thrombocytopenia
 Megaloblastic anemia
QUINOLONES-
 These are synthetic antimicrobials having a Quinolone
structure.
 Active against Gram negative Bactria.

Classification-
1. Nalidixic Acid
2. Fluro- quinolones-
a.First generation quinolones- Norfloxacin,
ofloxacin, Ciprofloxacin
b.Second generation quinolones-
levofloxacin, Moxifloxacin.
Mechanism of action
Quinolones and fluoroquinolones are chemotherapeutic
bactericidal drugs, eradicating bacteria by interfering
with DNA replication
Uses
 In treatment of serious bacterial infections
 Hospital-acquired infections
 Pneumonia
 Genitourinary infections
 Ciprofloxacin used in Typhoid
 Respiratory infection
 Tuberculosis
Adverse effect:
Cardiac arrhythmias
Convulsions
Tendon Rupture
Phototoxicity
 ANTIBIOTICS
An antibiotic is a selective poison.
 It has been chosen so that it will kill the desired
bacteria, but not the cells in your body. Each
different type of antibiotic affects different
bacteria in different ways.
 For example, an antibiotic might inhibit a
bacteria's ability to turn glucose into energy,
or the bacteria's ability to construct its cell
wall.
 Therefore the bacteria dies
instead of reproducing.
 Beta-lactam Antibiotics
 Antibiotics have a bactericidal effect.
 Those antibiotics having a B-lactum ring in their structure
are called as the Beta-lactam Antibiotics
 Penicilline was the first antibiotic to be used
clinically.
 It was obtained from the fungus penicillium notatum.
 Mechanism of action-
 All b-lactam antibiotics interfere with the
synthesis of bacterial cell wall

Rapid cell wall synhesis occurs when the
organisms are actively multiplying; B-lactam
antibiotics are more lethal in this phase.
 PENICILLIN
Mechanism of action-
 All penicillin like antibiotics inhibit synthesis of
peptidoglycan, an essential part of the cell wall.
 They do not interfere with the synthesis of other
intracellular components. The continuing buildup of
materials inside the cell exerts ever greater pressure on
the membrane, which is no longer properly supported by
peptidoglycan.
 The membrane gives way, the cell contents leak out,
and the bacterium dies. These antibiotics do not affect
human cells because human cells do not have cell walls
 Classification
 Natural penicillins
 PenG, PenV, Benzathine Pen, Procaine Pen
2.Aminopenicillins
 Ampicillin, Amoxicillin
3.Penicillinase resistant penicilline
 Oxacillin, Dicloxacillin
4.Extended - Spectrum Penicillins
 Carbenicillin , Mezlocillin, Piperacillin,
Ticarcillin,
Adverse effects-
 Local irritancy and direct toxicity
 Hyper sensitivity

Uses-
 Streptococcal infections
 Meningococcal infections
 Syphilis
 Tetanus
 Gas gangrene.
CEPHALOSPORIN-
 These are a group of semi-synthetic antibiotics derived
from cephalosporin-c obtained from a fungus
Cephalosporium.
 Chemically related to penicillin

Classification-
First generation - Cefazolin, Cephalexin,
Cephadroxil
Second generation - Cefuroxime, Cefaclor
Third generation- Cefixime, ceftibuten.
Fourth generation- Cefepime
Mechanism of action-
 All Cephalosporin are bactericidal
 They have the same mechanism of action as
penicillin. i.e. inhibition of bacterial cell wall
synthesis.
 They bind to different proteins than those which
bind to penicillin.
 Resistance is developed.
 Adverse effects:
 Pain after IM injection
 Hypersensitivity
 Nephrotoxicity
 Bleeding occurs
 Neutropenia and thrombocytopenia
 Disulfiram like interactions

Uses
 Alternative to penicillin-G
 Respiratory, urinary and soft tissue infections
 Meningitis
 Typhoid
 Infections in cancer
TETRACYCLINE-
 These are the class of antibiotics having a nucleus of
four cyclic rings.

Mechanism of action-
 The tetracycline's are primarily bacteriostatic.
 They easily enters into microbes because of their high
lipid solubility.
 Inhibit protein synthesis by binding to 30s
ribosomes in susceptible organism.
 Tetracycline antibiotics are protein synthesis inhibitors,
inhibiting the binding of aminoacyl- tRNA to the
mRNA-ribosome complex.
Antimicrobial spectrum

 All types of Gram-positive and negative cocci

are sensitive
 Most gram positive bacilli
 Enterobacteria are now largley resistant.

Administration
 Oral capsules are mostley used
 Capsule should be taken ½ hr before or the 2
hrs before meal.
 IM route is painful.
Adverse effects
 Irritative effects
 Dose related toxicity like liver damage, kidney
damage, photo toxicity
 Increase intracranial pressure
 Hypersensitivity
 Super infection

Precautions
 Tetracycline's should not be used during
pregnancy, lactation
 Should be used cautiously in renal or hepatic
insufficiency
Uses
 used in the treatment of infections of the
urinary tract and the intestines
 especially in patients allergic to β-lactams
and macrolides
 current use is in the treatment of
moderately severe acne
 it is also used in veterinary medicine on
pigs
 They may have a role in reducing the
duration and severity of cholera
 for the treatment of certain
inflammatory disorders.
Chloramphenicol-
 It was initially obtained from the Streptomyces
venezuelae.
 excellent BBB penetration
 It has antibacterial activity because of nitrobenzene
substitution in their chemical structure.

Mechanism of action-
 Chloramphenicol is a bacteriostatic drug that stops
bacterial growth by inhibiting protein synthesis.
 It directly interferes with substrate binding.
Antimicrobial spectrum-
 Gram positive and negative bacteria,
rickettsia.
 Highly active against the Salmonella typhi.

 Adverse effects-
 Major adverse effect -Bone marrow
depression
 Hypersensitivity reaction
 Irritative effects like nausea, vomiting, pain
on injection
 Gray baby syndrome
Uses
 Meningitis
 variety of bacterial infections, including gram
positive, gram negative and anaerobic bacteria.
 Mainly for eye infections

CHLORAMPHENICOL WARNINGS
 People with eyesight problems
 People who are sensitive to light (photophobia)
 People who have inflamed eyes and a rash on
the scalp or face
 People with glaucoma
 Antifungal

Drugs
An antifungal drug is a medication used to treat
fungal infections such as athlete's foot,
ringworm, candidiasis (thrush), serious systemic
infections such as cryptococcal meningitis, and
others
 These are the drugs used for superficial & deep
fungal infections.
 Fungal infections occur when the
resistance of host is poor.
 Fungi easily invade living tissues
 2 Classes of antifungals

a)Polyenes – Amphotericin B,
Nystatin,Hamycin, Natamy cin.

b)Heterocyclic – Griseofulvin,
Benzofuran.
 AMPHOTERICIN B (AMB)
• It is obtained from Streptomyces nodosus.
• Antifungal Spectrum: active against wide range of yeasts & fungi.
• Uses: can be used for Otomycosis, Systemic mycosis, Oral
Vaginal & cutaneous candidiasis.
• Reserve drug for resistant cases

Properties:
They are all insoluble in water and unstable in aqueous medium;
Fungicidal at high conc.; Have high affinity for ergosterol present in
fungal cell membrane; Resistance is rarely noted; Not effective
against Dermatophytes.
 AMPHOTERICIN B (AMB)
They are all insoluble in water and unstable in
aqueous medium.

• Fungicidal at high conc.

• Have high affinity for ergosterol present in

fungal cell membrane.

• Resistance is rarely noted.

• Not effective against Dermatophytes.

Griseofulvin

 Mechanism of action :
 Mechanism of action binds to
microtubules comprising the spindles
and inhibits mitosis. incorporates
into keratin and protects newly
formed skin.
• Active against most most
Dermatophytes but not candida.

• Gets deposited in keratin forming cells of

skin,hair & nails

• Ineffective topically.
 Griseofulvin
 Extracted from Penicillium
griseofulvum.
 Uses: used systemically for
dermatophytosis.
 Adverse Effects: Headache, G.I.T.
disturbance, peripheral
neuritis, rashes, transiant
leukopenia & albuminuria.
 Dose: 125-250mg with meals.
 Adverse Effects:
-Acute reaction; consists of
chills, fever, aches, nausea, dys
pnoea & pain all over.
-Long term Nephrotoxicity.
- C.N.S. Toxicity.
 Aminoglycosides
Aminoglycosides are a group of antibiotics that are
used to treat certain bacterial infections. This group
of antibiotics includes at least eight drugs:
• Amikacin, gentamicin, kanamycin, neomycin,
netilmicin, paromomycin, streptomycin, and
tobramycin.
• All of these drugs have the same basic chemical
structure.
 History
Aminoglycoside Year Source organism
streptomycin 1944 Streptomyces griseus
neomycin 1949 Streptomyces fradiae
kanamycin 1957 Streptomyces kanamyceticus
paromomycin 1959 Streptomyces rimosus
spectinomycin 1962 Streptomyces spectabilis
gentamicin 1963 Micromonospora purpurea
tobramycin 1968 Streptomyces tenebrarius
sisomicin 1972 Micromonospora inyoensis
amikacin 1972 semisynthetic derivative of
kanamycin
netilmicin 1975 semisynthetic derivative of
sisomicin
 Classification
 Micromonospora actinomyctes
 Gentamicin (gentamicin and netilmicin)

 Streptomyces spp.
 Streptomycin (streptomycin and
dihydrostreptomycin)
 Kanamycin (kanamycin, amikacin, and tobramycin)
 Neomycin (neomycin) groups
 Apramycin
 Amikacin
 Broadest spectrum of activity
• Resistant to aminoglycoside-inactivating enzymes
• Less active against enterococci
 Similar dosing interval and monitoring

 Peak

• Life-threatening infection 25-30 mcg/ml

• Serious infection 20-25 mcg/ml
 Tobramycin
 Antimicrobial activity and PK properties
very similar to Gentamicin
• Superior activity against P. aeruginosa
• Less active than gentamicin against enterococci
Some commonly used aminoglycosides include:
amikacin (Amikin®)
apramycin
capreomycin
gentamicin (Garamycin®)
kanamycin (Kantrex®)
neomycin (Mycifradin®)
netilmicin (Netromycin®)
paromomycin (Humatin®)
streptomycin
tobramycin (TOBI
Solution®, TobraDex®,
Nebcin®)
Mode of Excretion:
 Aminglycoside antibiotics are eliminated
unchanged by the kidney by glomerular
filtration.
 Wide inter-patient variability in elimination
occurs even in patients with normal creatinine
clearances.

Other Factors influencing Kinetics of

Aminoglycosides:
Age, Fever, Body Weight, Gender, Obstetric
Patients, Patient who suffered from burns,
Pediatric Patients, Ascites
 Anti-viral drugs
A class of medication used specifically
for treating viral infections.
 Viruses have no cell wall and made up
of nucleic acid components.
 Viruses are obligate intracellular
parasite
 Anti-viral drugs
• Certain viruses multiply in the cytoplasm
but others do in the nucleus
• Most multiplication take place before diagnosis is
made
• Effective host immune response remains
essential for the recovery from the viral
infection
 Anti-viral drugs
1.Anti-herpes virus agents
 Acyclovir / Ganciclovir

2.Anti-retrovirus
Zidovudine,Dianosine

3.Anti-influenza virus
Amantadine,Rimantadine

4.Nonselective antiviral Drugs

Ribavirin,Lamivudine
Anti-viral drugs
Acyclovir & Congeners :
 Valacyclovir is a prodrug of Acyclovir with
better bioavailability.
 Famciclovir is hydrolyzed to Penciclovir and
has greatest bioavailability.
 Penciclovir is used only topically
whereas Famciclovir can be
administered orally.
 Anti-viral drugs
Mechanism of action of Acyclovir :
 All drugs are phosphorylated by a viral
thymidine-kinase, then metabolized by host cell
kinases to nucleotide analogs.
 The analog inhibits viral DNA
polymerase
 Only actively replicating viruses are inhibited
 Aciclovir targets virus-infected cells quite
specifically, and this explains the drug`s
relatively low toxicity.
 Acyclovir
Therapeutic Uses:

 Chicken pox: Acyclovir is the drug of

choice :reduces fever,eruption & prevents
viceral complication.
 Herpes simplex infections of skin,
mucous membranes and cornea.
 Zidovudine (AZT)
Mode of action
 HIV virus is an RNA virus capable of
including the synthesis of a DNA transcript
of its genome, which can then become
integrated into the host cell`s DNA, thereby
allowing viral
replication.
 Synthesis of the initial DNA transcript
involves the enzyme reverse transcriptase.
 Zidovudine
Mode of action
 Zidovudine is a potent inhibitor of
reverse transcriptase.
 It has relatively specific toxicity for the virus.
 Adverse Effects:
Acyclovir / Zidovudine

 Nausea, vomiting and diarrhea

 Nephrotoxicity: crystalluria, haematuria,
renal insufficiency
 Rashes,sweating,emesis and fall in BP occur only in
few patients.
 What are antimalarial drugs?
Antimalarial: a medicinal drug used to prevent or
treat malaria.
Most antimalarial drugs target the erythrocytic
stage of malaria infection, which is the phase of
infection that causes symptomatic illness.
The extent of pre-erythrocytic (hepatic stage)
activity for most antimalarial drugs is not well
characterized. Treatment of the acute blood stage
infection is necessary for malaria caused by all
malaria species. In addition, for infection due to
Plasmodium ovale or P. vivax.
72
TYPES OF MALARIA AND
THEIR CAUSES
MALARIA IS CAUSED BY 4 SPECIES OF
PROTOZOAL PARASITES:

• PLASMODIUM VIVAX

• PLASMODIUM OVALE

• PLASMODIUM FALCIPARUM

• PLASMODIUM MALARIAE

73
74
 MALARIAL PARASITES EXHIBIT A
COMPLEX LIFE CYCLE
 THEY HAVE ALTERNATING CYCLE
OF ASEXUAL DIVISION (SCHIZONY)
IN HUMANS

 SEXUAL DEVELOPMENT
(SPOROGONY) OCCURS IN
FEMALE MOSQUITOES.

75
 OBJECTIVES AND USE OF
ANTIMALARIAL DRUGS
MALARIAL INFECTION ARE:

(a)TO PREVENT AND TREAT CLINICAL

ATTACK OF MALARIA
(b)TO COMPLETELY ERADICATE
THE PARASITES FROM THE
PATIENTS BODY

(c)TO REDUCE THE HUMAN RESER

76
 2 Classifications of
Antimalarial Drugs
4-aminoquinolones: Cinchona Alkaloids:
Chloroquine Quinine
CHLOROQUINE
 CHLOROQUINE IS A RAPIDLY ACTING SCHIZONTOCIDE.
 Most effective drug and widely
 MECHANISM OF ACTION
 LIKE CHLOROQUINE IT RAISES THE
INTRAVASCULAR PH.
 IT BINDS TO THE HAEM AND THE COMPLEX
DAMAGES MEMBERANES OF THE PARASITE.
 RESISTANT ORGANISMS ACCUMULATE
LESS MEFLOQUINE
 Exact mechanism is unknown. Probably it blocks the
enzymatic system responsible for DNA and RNS
synthesis. So it inhibits transcription.

78
 Quinine
 It is the oldest drug, being used
from 1633
 Can be used orally and
parenterally.
 Mechanism of action is not clear.
(Many mechanisms are
proposed)
 Adverse Effects: bitter in taste,
nausea, vomiting, diarrhea,
dizziness, abdominal pain and
sinus bradycardia.

79
Proposed Mechanisms:
1st mechanism—it may depress many enzymatic
system
2nd mechanism—it may produce H- bonding between
the DNA strands. So there is no separation, no
synthesis of mRNA and no transcription.
3rd mechanism—it may poison the protoplasmic
parasitic
 Quinine Indications
 Malaria
 Cerebra Malaria
 Nocturnal Muscle Cramps
 Diagnosis of Myasthenia gravis
 Spermicidal in vaginal creams

82
Anti-TB Drugs
 General Considerations:
Pulmonary Tuberculosis
• Tuberculosis is a chronic infection potentially of
lifelong duration, caused by two species of
mycobacteria M. tuberculosis and rarely, M. bovis.
• It was isolated by Robert Koch in 1882.
• The morbidity and mortality of tuberculosis are
high in developing countries.
• The disease is confined to the lungs in most patients
but may spread to almost any part of the body
Etiology • The tubercle bacillus
(M. tuberculosis) is
aerobic, non-motil,non-
spore-forming, high in
lipid content, and acid
and alcohol-fast
• It grows slowly.
• It can’t tolerate heat, but
It can live in humid or
dry or cold
surroundings.
 Epidemiology
A key link of epidemic existence of
tuberculosis are:

 The source of contagiousness

 The route of spread
 People who are easily affected
 Tuberculosis is transmitted
by airborne droplet nuclei
(containing tubercle bacilli).
Many droplet nuclei are
capable of floating in the
immediate environment for
several hours.
Large particles may be
inhaled by a person breathing
the same air and impact
trachea or wall of the upper
airway.
How is transmission being determined?
• The probability of contact with a case of TB.
• The intimacy and duration of that contact.
• The degree of infectiousness of case.
• The shared environment of the contact.
Pathogenesis of Tuberculosis
Antituberculosis drugs

First-line drugs
Isoniazid, rifampin, pyrazinamide, eth ambutol
and streptomycin

Second-line drugs
Aminosalicylic acid/Para-aminosalysylic
acid(PAS), kanamycin
Isoniazid
• In 1952, it is the most active drug for treatment of
tuberculosis.
• MOA: Isoniazid inhibits the synthesis of mycolic
acid which is essential components of mycobacterial
cell walls.
• Antimicrobial activity: High activity against both
intracellular and extracellular tubercle bacilli.
• Pharmacokinetics: Diffuse readily into all body fluids
and tissues; Metabolyzed by acetylation.
• Clinical uses: First choice for all types of TB.
Isoniazid
• ADR: Peripheral neuropathy, CNS Toxicity
(memory loss, pychosis, seizures), hepatotoxicity:
the most frequent, increase in aminotransferase,
hepatitis, allergic reactions.
Rifampicin
• Antimicrobial activity: Active against mycobacteria,
some G+ and G- cocci, chlamydia, and some virus.
• MOA: Binds to β-subunit of bacterial DNA-
dependent RNA polymerase and inhibit RNA
synthesis.
• Clinical uses: Tuberculosis and leprosy, infections
caused by staphylococci and other rifampicin-
susceptible bacteria.
• ADR: Gastrointestinal disturbance, liver toxicity
(cholestatic jaundice, hepatitis).
Ethambutol
• MOA: Interferes with the synthesis of RNA by
combination with Mg²⁺
• Clinical Uses: Used in combination with INH or
rifampicin.
• ADR: Loss of visual disturbance, optical neuritis,
red-green colorblindness.
 Rationale for the use of
Antituberculosis drugs
 Use as early as possible
 Drug combination
 Appropriate doses
 Use regularly and enough time
Leprosy
(Hansen’s Disease)
Antileprotic drugs
 Classifications of AL Drugs
 Sulfone - Dapsone (DDS)
 Phenazine derivative - Clofazimine,
 Antitubercular drugs -Rifampicin,
Ethionamide,
 Solapsone
 Other antibiotics - Oflaxacin,
Minocycline, Clarithromycin.
Leprosy
• Leprosy –one of the few diseases which can be
eliminated.
Leprosy meets the demanding criteria for
elimination
 Practical and simple diagnostic tools
 It can be diagnosed on clinical signs alone
 The availability of an effective
intervention to interrupt its transmission
by multidrug therapy
 A single significant reservoir of
infection: humans.
 Leprosy-integrated General
Health Services
• Integration scopes:
• to provide comprehensive‖ essential services
from one service point to improve patients’
access to leprosy services and thereby ensure
timely treatment;
• to remove the special‖ status of leprosy as a
complicated and terrible disease;
• to consolidate substantial gains made;
• to ensure that all future cases receive timely and
correct treatment and to ensure that leprosy is
treated as a simple disease
 Diagnosis of Leprosy:
 Examine skin
 Check for patches
 Test for sensation
 Count the number of patches
 Look for damage to nerves
Signs of Leprosy
Pale or slightly reddish patch
Definite loss of sensation in the patch
Signs of damage to nerves
 definite loss of sensation in hands/feet
 weakness of muscles of hands/feet/face
 visible deformity of hands/feet/face
 Classification of Leprosy
Disease Clinical Features
Intermediate Leprosy They are the first type of skin lesions
characterized by hypo-pigmented spots. The
lesions undergo healing spontaneously.
Paucibacillary A large red patch with well-defined raised
(Tuberculoid Leprosy) borders or a large hypopigmented asymmetrical
lesions. Lesions is dry and hairless. Infectivity is
minimal at this stage.
Loss of sensation is seen Nerves become thick
followed by loss of function It either progresses
to the borderline stage or spontaneously get
cured
 Classification of Leprosy
Disease
Borderline Tuberculoid Leprosy
Borderline Borderline Leprosy
Borderline Lepromatous Leprosy
Clinical Features
Characterized by small and
numerous skin lesions The disease
goes back to the tuberculoid stage
or progresses to the next stage
Several small, irregular red lesions
are seen Moderate sensory loss is
seen It either goes back to the
previous stage or progresses to the
next
Several lesions such as plaques,
macules, papules, and nodules are
seen. Lesions have a characteristic
inverted saucer like appearance.
 Classification of Leprosy
Disease Clinical Features
Multibacillary Early symptoms: Several lesions such as plaques,
Hansen’s Disease macules, papules, and nodules are seen. Nasal
(Lepromatous congestion, and bleeding is seen Inflammation of the
Leprosy) leg and ankles Progressive symptoms: Thickening of
the dermis (skin) in the forehead and ear lobes Loss
of eyebrows and eyelashes Eye defects such as
glaucoma and blindness are seen Nodules in the legs
break and form ulcers Enlargement of the breast and
sterility occurs in the males Internal infection results
in the enlargement of the liver and lymph nodes
Loss of sensation in the peripheral nerves.
Deformation of the fingers and toes results due to
painless repeated trauma.
 ANTI-PROTOZOAL DRUGS
(Anti-amoebics)
• These are drugs used in infection caused by the
protozoa Entamoeba histolytica.
 Therapeutic Classification of
Anti-Amebic Drugs
I. Luminal Amebicides (Drugs effective in Luminal
Infection only)
• Dichloroacetamides: Diloxanide Furoate
• Halogenated Hydroxyquinoline: Idoquinol
(Diiodohydroxyquine)
• Antibiotics: Tetracyclines, Paromomycin
• Oral Bismuth Salt : Emetine Bismuth Iodide
 Therapeutic Classification of
Anti-Amebic Drugs
II.Extra-Luminal Amebicides
A: Systemic or Tissue Amebicides
1. Chloroquine
2. Emetines (Emetine, Dihydroemetine)

B: Mixed Amebicides - Drugs effective in systemic &

Intestinal Amebiasis
Nitroimidazoles (Metronidazole, Tinidazole, Secnidazole)
*Note (Mixed): (Not reliably effective against luminal
infections as luminal concentrations are too low for single
drug treatment)
Metronidazole (Flagyl)
 Most commonly used anti-amoebiasis.
 Mixed tissue amoebicide (Intestinal & extra
Intestinal) not reliably effective against amoeba in
the lumen as luminal concentrations are too low
for single drug treatment.
 Kills only trophozoits in intestinal wall but
not the cysts of E. histolytica.
Nitroimidazole: Metronidazole
 Metronidazole: MOA
Metronidazole kills protozoa & is bactericidal for
anaerobic bacteria
.
• Metronidazole is a pro-drug.
It requires reductive activation of the NITRO group.
• This occurs in sensitive anaerobic protozoa
& anaerobic bacteria by Ferredoxins;
which are electron transport proteins.
• These proteins can donate electrons to Metronidazole
,which serves as electron acceptor.
• The reduced product is cytotoxic, it targets
DNA & other biomolecules / proteins,
resulting in cell death.
Hence it kills the micro-organisms .
Antimicrobial Spectrum
Kills anaerobic protozoa & bacteria
• Entamoeba histolytica (Trophozoits
only)
 Trichomona vaginalis
 Giardia lamblia
 Clostridia – Clostridium difficile
 Bacillus fragilis
 Helicobacter pylori
Also toxic to hypoxic / anoxic cells
USES
1. Amebiasis:
2. Trichomoniasis
3. Giardiasis
4.Bacterial vaginosis
5.Eradication of H. pylori
6.Pseudomembranous enterocolitis
Adverse Effects
GIT:
Dry mouth, metallic taste --- most common.
Nausea, vomiting, abdominal cramps ,
Diarrhea.
Oral thrush--stomatitis
Rarely Pancreatitis.
Neurotoxicity: Headache, Insomnia, numbness
or paraesthesias, weakness , dizziness.
Rarely Ataxia, encephalopathy & seizures.
III. OTHER A/E:
1. Disulfiram like action with alcohol.
2. Dysuria ,Dark urine.
3. Mutagenic in bacteria.
4. Carcinogenic in Rodents.
5. Hypersensitivity reactions--- rash, neutropenia
Drug interactions
 Potentiate Anticoagulant effect of Warfarin.
 Metabolism of Metronidazole induced by
Phenytoin & Phenobarbitone & Cimetidine
may inhibit it.
 Metronidazole increases Lithium toxicity.
Contraindications
 Patient with active disease of the CNS.
 Hepatic Disease/Renal disease, dose adjustment
should be done.
 Pregnancy/ Nursing Mothers.
Tinidazole :
• It is a second- generation Nitroimidazole.
• Congener of Metronidazole
• It is similar to Metronidazole in spectrum of
activity, MOA , absorption , A/E & D/I.
• It is also effective against cysts of E.histolytica.
• It is longer acting –once daily dose.
• Short course– 2gm daily, single dose-- for 3 days.
•Secnidazole: Longer acting
• Single 2gm dose is given
Emetine
• It is another class of drug which acts as anti-
protozal and anti amoebic.
• Source: Alkaloid of Ipecacuanna (Ipecac)
that is pharmacologically used as anti-emetic
effective against the trophozoits of
Entamoeba histolytica.
• Dehydroemetine---Synthetic analog
Therapeutic Uses :Limited use: Only when Metronidazole
can not be used in :
 Severe Amoebic dysentry
 Hepatic Amebiasis

Dehydroemetine is preferrd– better toxic profile

Drug should be used S/C or I/M injection in a supervised
setting Never given I/V
Used only for minimum period to relieve severe symptoms.
Usually 3-5 days.
Adverse Effects
Mild when used for 3-5 days, increase with time
 Diarrhea
 Central nausea & vomiting
 Pain & tenderness at site of injection/ sterile abscess
 Muscle weakness & discomfort
 Minor ECG changes

Serious toxicity:
 Hypotension, Cardiac arrhythmias, Cardiac failure
Contraindications:
 Cardiac/Renal disease, young children , and pregnant
women
Diloxanide Furoate
(Luminal amoebicide)
• Dichloroacetamide derivative
• Pharmacokinetics: Given orally, in gut splits
into Diloxanoid & furoic acid. 90% Diloxanoid
is absorbed & conjugated to form glucuronide
-- excreted in urine
• MOA: Not understood.
• Unabsorbed Diloxanoid is directly amoebicidal
• against amoebea in lumen but not those in
intestinal wall.
Therapeutic uses
 Drug of choice for Asymptomatic Luminal
Amoebiasis (cyst passers)
 Along with tissue amoebicide in severe intestinal &
extra intestinal amoebiasis.
•Adverse effects
 Flatulence
 Nausea, abdominal cramps

 Skin rashes, rarely

 Precautions: Pregnancy
ANTIBIOTICS
 Paromomycin
 Tetracyclines
Uses: Luminal amoebicides
 Asymptomatic infection (Carriers).
 Along with extra luminal amoebicides in
serious infections.
Paromomycin sulfate
 An aminoglycoside antibiotic.
 Not significantly absorbed from the gut.
 Used as Luminal amoebicide.
 Superior to Diloxanide furoate in clearing
asyptomatic infections.
 No effect on extra-intestinal amebic infections.
 Also used in visceral leishmeniasis paenterally.
 Less toxic than other agents.
 A/E: Abd. Distress & diarrhea.
Tetracyclines
 Used as Luminal amoebicide.
 Does not kill bacteria directly but disturbs the
symbiosis between normal intestinal flora & E
histolytica .
 The amebae grow at expense of normal intestinal
flora.
 Tetracyclines are broad spectrum antibiotics & kill
these flora leading to death of E .histolytica also.
 Used in resistant cases.
Thank you!