Week 3 & 4 Antimicrobials
Week 3 & 4 Antimicrobials
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.
1.Toxicity
2.Hypersensitivity reactions
3.Drug resistance
4.Superinfection
5.Nutrirional Deficiencies
6. Masking an action
CHOICE OF AN ANTIMICROBIAL AGENT-
CLASSIFICATION-
• Short acting- Sulphadiazine
• Intermediate acting- Sulphamethoxazole
• long acting- Sulphadoxine
• Special purpose- Mafenide, Silver
sulphadiazine
Antibacterial Spectrum
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
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.
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.
• 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
2.Anti-retrovirus
Zidovudine,Dianosine
3.Anti-influenza virus
Amantadine,Rimantadine
• 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:
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:
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 Clinical Features
Borderline Tuberculoid Leprosy Characterized by small and
numerous skin lesions The disease
goes back to the tuberculoid stage
or progresses to the next stage
Borderline Borderline Leprosy 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
Borderline Lepromatous Leprosy 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)
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