Antimicrobial Therapy

Chemotherapeutic agent (drug): any chemical substance used in

medical practice.
Fleming observation 1928!

Antibiotic: chemical substances produced by microorganisms

that inhibits & destroys other microorganisms when used at
low concentration. (synthetic drug or semisynthetic)


1.

2.

Properties that an AB should have (ideal drug):

Selective toxicity: the drug should harm the microbe without
significant harm on the host. This means the toxic dosage level
(the dose that causes damage to the host) should be much higher
than the therapeutic dosage level (the dose needed to destroy the
microbe).
To evaluate toxicity of the drug, chemotherapeutic index is used: the ratio
between the conc. at which the drug causes harm to the host (toxic
dose) & that at which it is required to be clinically effective (therapeutic
dose)
Soluble in body fluids in order to penetrate body tissues

3.

Should not be metabolized so quickly so that they are excreted before

having time to exert their effect

4.

Minimal side effects e.g allergy

5.

Long shelf life with convenient storage conditions requirement & low cost

6.

Stable in body fluids to have therapeutic activity over long hours.e.g oral
drugs should withstand acidic environment of the stomach.

7.

Has no significant effect on normal microflora

8.
Resistance to it not easily acquired

Broad spectrum Vs narrow spectrum antibiotics

Broad spectrum AB: effective against a wide range of
microorganisms of different taxonomic groups including G+ve & Gve bacteria. e.g tetracycline
Narrow spectrum AB: effective against small no. of microorganisms
or single group e.g Penicillin
If the microorganism is identified, use narrow spectrum AB, because
narrow spectrum reduce the possibility of producing resistance in
microorganism, also using broad spectrum will destroy microflora
(normal flora). Normal flora is the indigenous microbes that live in/on
the host & prevent the growth of infectious microbes.
If the patient is seriously ill & the microbe is not identified, broad
spectrum AB is useful in this case.

Modes of action
Antibiotics could have bactericidal effect (killing effect) or bacteriostatic
effect (inhibit bacterial growth) where in this case the host immune
response destroys & eliminate the microbe.
5 major modes of action through which antibiotics act on microbes

1.
2.
3.
4.
5.

Inhibition of Cell wall synthesis

Inhibition of protein synthesis
Disruption of cell membrane
Inhibition of nucleic acid synthesis
Action as antimetabolite

Cell wall inhibitors:

Many bacteria & fungi have external rigid cell walls, while
animal cells dont, therefore antibiotics that disrupt cell
wall synthesis will cause the bacteria cells to burst when
present in low osmotic pressure in body fluids.
The main group of AB that act on cell wall is the beta
lactams. So called due to presence of -lactam ring. It
includes penicillins, cephalosporins & others.

 -lactams are analogues to D-alanyl-D-alanine residue

of the peptidoglycan chain which is the substrate for the
enzyme transpeptidase. They bind irreversibly to
transpeptidase & inhibit it from cross linking the
peptidoglycan chains,
so the cell wall continues to form but become
weaker, then the cell swells & lyses.

https://www.youtube.com/watch?v=qBdYnRhdWcQ

Penicillins
The 1st naturally isolated AB was benzyl
penicillin or penicillin-G. Isolated from mold
Penicillium notatum. It is administered
parenterally (IV or IM) because it is degraded
by stomach acids. It is effective against G+ve
bacteria only because it is unable to penetrate
G-ve cell wall.

 Penicillin-V is naturally occurring, similar to

Penicillin-G but is less acid labile i.e can be taken
orally.
Semisynthetic penicillins: they have the same
nucleus of penicillin but with side chains added
chemically.

Ampicillin: acid stable with broader spectrum of activity

than Penicillin-G, i.e acts on G-ve bacteria.
Amoxicillin: acid stable, broad spectrum.
Carbenicillin, ticarcillin, Pipercillin: broad spectrum,
especially useful against Pseuodomonas infections.
Used parenterally.

 A problem that faces penicillins is that they are

degraded by naturally occurring bacterial blactamase enzyme (a group of it called
penicillinase) which breaks b-lactam ring &
inactivates the drug.
Some drugs are resistant to penicillinase:
Methicillin: semisynthetic, narrow spectrum (G+ve)used
for bacteria that are resistant to penicillin. In the past it
was the ultimate solution for treating resistant bacteria
mainly Staphylococcus aureus, until Methicillin Resistant
Staph. aureus emerged (MRSA).

Oxacillin: semisynthetic, narrow spectrum, G+ve,

antistaphylococcal drug.
Nafcillin: G+ve , Antistaphylococcal drug

 To overcome the inactivation caused by -lactamase,

inhibitors to -lactamase are given in combination with the
drug e.g Clavulanic acid (Amoxicillin/Clavulanic acid=
Augmentin )& tazobactam (Tazobactam/ piperacillin)
effective against G+ve &G-ve including Pseudomonas).
These inhibitors have no antimicrobial activity but increase
the activity of antibiotics.
Procaine penicillin is long acting, procaine slows excretion &
prolongs duration.
Penicillins generally are non toxic, but 1-5% of adults are
allergic to them (penicillin allergy is rare among children), in
extreme cases death may result from anaphylactic shock.
Penicillins may be used prophylactically (to prevent
infections) before surgeries.

 Cephalosporins

Naturally occurring ones produced from fungus Cephalosporium, have

little antimicrobial action. Cephalosporins have broader specificity than
penicillins & more resistance to -lactamase. But still cephalosporins are
degraded by cephalosporinase enzymes (a group of b-lactamases)
Semisynthetic cephalosporins differ by their side chains. They are
divided into generations (1st, 2nd, 3rd, 4thgeneration). When resistance
appeared to old generations new generation was produced. The aim of
these generations was to broaden spectrum of activity & to include many
G-ve bacteria.
In general, 1st generation have better activity against G+ve bacteria,
2nd generation: more active on G-ve, some G+ve, more resistant to lactamase
3rd generation (with some exceptions) more G-ve activity,
4th generation have both G+ve & G-ve activity (used for hospital
acquired infections)

Antibiotic

Route

1st generation

Spectrum
G +ve

Cephalexin (Keflex)

Oral

Cephradine

Oral

Cefadroxil (Duricef)

Oral

Cefazolin

Parenteral

2nd generation

Broad spectrum (mainly G-ve)

Cefaclor (Ceclor)

Oral

Cefuroxime (Zinnat)

Oral

3rd generation
Cefixime (Suprax)

Oral

Cefdinir

Oral

Cefpodoxime (Cefodox)

Oral

Cefotaxime (Claforan)

Very good G-ve, some G+ve

Ceftriaxone (Rocephin)

Very good G-ve, some G+ve

Ceftazidime (Fortum)

G-ve including Pseudomonas

4th generation
Cefpirome, cefepime

G+ve, G-ve, Pseudomonas

P

5th generation ?

Ceftaroline

Skin & soft tissue infections, MRSA, Gram +ve, G -ve

P

 Ceftaroline : 5th generation??, active against MRSA for skin & soft
tissue infections.
Cephalosporins usually are not the first drugs considered in
treatment of an infection, they are used when toxicity or allergy
prevents the use of other drugs.
Since Cephalosporins are structurally similar to penicillins, 4-15% of
patients who are allergic to penicillins are also allergic to
cephalosporins.
Penicillins & cephalosporions exert their activity against growing
bacteria
Other cell wall inhibitors

Monobactam includes the drug Aztreonam

The -lactam ring is alone not fused with other ring. It resists lactamases, effective against G-ve bacteria including Pseudomonas
aeruginosa, used for meningitis, UTI & kidney infections

 Carbapenems
A group of -lactams that are resistant to -lactamase. e.g
Imipenem, meropenem (Meronem).
Imipenem: active against G+ve & G-ve bacteria including
Pseudomonas aerogenosa & Enterococcus. Usually coadministered
with Cilastatin (Tynam), (a compound which inhibits imipinem
degradation in kidneys, not needed with meropenem).

Bacitracin: a mixture of polypeptide produced by Bacillus bacteria,

has bactericidal activity. It inhibits cell wall synthesis by interfering
with the molecules that carry peptidoglycan subunits across cell
membrane to their site in the cell wall. It is highly effective against
G+ve bacteria, but with high toxicity, therefore used topically (skin,
mucus membranes)

 Vancomycin (administered only IV in hospitals)

A large complex glycopeptide
produced by soil actinomycetes.
Its large size prevents its penetration
through G-ve pores in the outer membrane,
therefore, it is not effective against most
G-ve bacteria.
It acts by binding to the D-alanyl-D-alanine residue & forming a
complex with it which inhibits peptidoglycan synthesis. It is effective
against streptococci & Staphylococci & due to its toxicity used as
last resort for organisms resistant to methicillin & cephalosporins e.g
MRSA & enterococci.
It was used for 40yrs without having resistance against it until strains
of Vancomycin resistant Staphylococcus aureus (VRSA) emerged.

It is the drug of choice for treating pseudomembranous colitis

(enteritis with formation of false membranes on stool), an
infection (super infection) by Clostridium difficile that results
from the use of broad spectrum antibiotics
It is given IV. It is fairly toxic, causes hearing loss, kidney
damage.

Protein synthesis inhibitors

These drugs act on bacterial ribosomes. Since bacterial ribosomes
are (30S+50S= 70S) while animal ribosomes are (60S+40S =80S),
these antibiotics act selectively on 70S ribosomes.

mRNA translation
(protein synthesis)

 These drugs include many groups:

Aminoglycosides: obtained from different species of

Streptomyces & Micromonospora. They act on 30S subunit &
interferes with mRNA translation.
Aminoglycosides act synergistically with other drugs e.g
cephalosporins, penicillins. Therefore in most cases are used in
combination with other drugs.
They have varying degree of toxicity to kidneys (damage kidney
cells causing protein excretion) & (ototoxicity) inner ear (damaging
8th cranial nerve).
They are active against G+ve & G-ve bacteria including
Pseudomonas & Enterobacter.
Due to their toxicity ,they are used in treating complicated infections
(urinary tract infections, peritonitis -infection of the lining of
abdomen-, joint & bone infections) or to treat bacteria resistant to
other drugs

 They are not absorbed in GIT, administered IV or IM or

topically
They include:
Streptomycin: v. toxic causes damages to the kidneys & ringing
in the ear. Usually used in combination with other drugs to treat
TB & plague.
Neomycin
Kanamycin
Tobramycin
Gentamicin
Netilmicin
Amikacin: for hospital acquired infections resistant to other drugs


Tetracyclines: produced from Streptomyces species & some are

semisynthetic. They act on 30S ribosomal subunit. They are
absorbed from GIT.

They have the widest spectrum of activity (G+ve, G-ve,

mycoplasma)& can enter the cell host, therefore useful for
intracellular infections (ricketssia & Chlamydia).
Because of their wide spectrum, they destroy the intestinal normal
flora causing severe GI disorders. Superinfections by
Staphylococcus & Pseudomonas & yeast also occur.
Tetracycline form complexes with calcium & become inactive,
therefore milk & dairy product should not be taken. Due to reaction
with Ca, they cause coloration to the teeth (under age of 5 or by
mother during last half of pregnancy)& abnormal bone formation
(abnormal skull of infants) if taken by pregnant women.
Tetracyclines include
Tetracycline
Chlortetracycline
Minocycline
doxycycline

tetracycline

macrolide

 Tigecycline (approved 2005): belongs to new class of drugs,

glycylcycline (a derivative of minocycline) inhibits proteins
synthesis by binding to 30S ribosome. Has broad spectrum
activity (Except Pseudomonas), mainly used against MRSA
Chloramphenicol: it is bacteriostatic agent. Acts on 50S ribosomal
subunit in a way to prevent amino acid assembly in a chain.
Nowadays produced synthetically.
It is broad spectrum (G+ve & G-ve excluding pseudomonas &
enterococcus), but has serious side effect that it damages bone
marrow which could be fatal. therefore, its use is considered as last
choice when other effective agents are available. Its main use is to
treat typhoid fever & to treat meningitis for patients with allergy to
cephalosporins & penicillins.

Macrolides:
A group of compounds have macrolide ring. They are bacteriostatic
agents. Act on 50S ribosomal subunit in a way to prevent amino acid
assembly in a chain (elongation). They are readily absorbed.

They are active against most G+ve bacteria: streptococci, pneumococci,

staphylococci, corynebacteria & also mycoplasma. Macrolides have variable
activity against G-ve bacteria.

Macrolides include:
Erythromycin: one of the safest commonly used drugs.
Roxithromycin
Azithromycin
Clarithromycin: a member of the triple therapy used to treat Helicobacter
pylori responsible for stomach & duodenal ulcers.

Macrolides main use: for penicillin resistant infections & as alternative to

penicillin for patients allergic to them.

Very important for treating Legionnaires disease (pneumonia like disease)

caused by Legionella pneumophila

Lincosamides

Bacteriostatic agents, bind to 50S ribosomal subunit & inhibit polypeptide

elongation.

Include Clindamycin & lincomycin. Clindamycin is less toxic than lincomycin.

 Clindamycin is used to treat Bacteroids & other anaerobic

bacteria except Clostridium defficile. Also used for G+ve cocci
(except enterococci), in topical preparations for acne.
Long term use of clindamycin causes pseudomembranous colitis
due to toxins from Clostridium difficile

Streptogramins
Relatively new drugs. A group of macromolecules produced by
streptomyces sp., includes Streptogramin A & B.
Quinopristin/Dalfopristin (30/70 ratio): derivatives of
Streptogramin B (Quinopristin) & Streptogramin A (Dalfopristin).
Both interact with the ribosome at different sites & act
synergistically to inhibit protein synthesis. Dalfopristin inhibits
early stages of protein synthesis while quinopristin prevents
polypeptide elongation & causes early release of the polypeptide
chain.

 Given IV. They are effective against G+ve bacteria resistant to other
antibiotics including vancomycin.
Used for life threatening infections caused by vancomycin resistant
Enterococcus faecium (G+ve bacteria that cause skin, blood
&abdominal infections), MRSA, & Streptococcus pyogenes.

 Disrupters of cell membrane

Animal cells have cell membranes that differ than bacterial or fungal
membranes, this allows for selective action of antibiotics.
These drugs include:
Polyenes
Cyclic lipopeptides (polymyxins & Daptomycin)

Polyenes:
e.g amphotericin B & Nystatin: they bind to certain sterols present in the
fungal membrane, but their therapeutic index is low.


Cyclic lipopeptides
Polymyxins:
designated A, B, C, D, E: are polypeptides act as detergent.
(Polymexin E= colistin). They bind to the membrane
phospholipids & cause distortion to it, thus, the cytoplasm & cell
contents are lost. Since G-ve bacteria has outer membrane
which is rich in phospholipids, polymyxins are especially effective
against them.
Causes serious side effects if taken systemically ( administered by
injection & needs monitoring).
Generally, they are used topically for skin infections caused by G-ve
bacteria like Pseudomonas, wounds & burns.

Daptomycin:
It is inserted into the cell membrane forming aggregates which
results in membrane disruption and depolarization

Active against G+ve bacteria (including multidrug-resistant

strains such as VRE and MRSA). Given parenterally, but
induce serious side effects

Nucleic acid synthesis inhibitors

DNA synthesis inhibitors
Quinolones: a group of synthetic AB, They act by inhibiting DNA gyrase,
the enzyme which unwinds DNA double helix preparing it to replication,
thus inhibiting DNA synthesis.
The basic drug of this group is Nalidixic acid, the majority of drugs in
clinical use belong to the subgroup, fluoroquinolones, e.g ciprofloxacin,
norfloxacin, enoxacin.
They are active against G+ve & G-ve bacteria including Pseudomonas
aeuroginosa. Used mainly for travelers diarrhea & urinary tract
infections caused by multipley resistant bacteria
Levofloxacin: new generation (3rd generation). Used mainly for
community acquired pneumonia, sinusitis & acute exacerbations of
chronic bronchitis

 Inhibitors of nucleic acid synthesis

Rifampin/Rifampicin: a semisynthetic drug belongs to
Rifamycins (produced by Streptomyces sp).
Rifampin binds to RNA polymerase & blocks mRNA
synthesis. It penetrates tissues therefore used against
Mycobacteria to treat TB as part of the cocktail treatment.
Unlike other antibiotics, it interacts with other drugs reducing
or nullifying their effect like oral contraceptives,
anticoagulants & the reason is that it stimulates liver
enzymes that metabolize these drugs.
At high doses it turns the secretions like tears, sweat, saliva,
breast milk & urine to orange red color, even the skin, this is
called red man syndrome. Also high doses result in liver
damage.

Antimetabolites
A group of compounds that are structurally similar to
normal microbial metabolites, therefore they interfere
with microbial metabolic reactions. They act by 2 ways:
Competitive inhibition to the enzyme. They resemble the
substarte of metabolic enzyme, thus they bind to the
active site of the enzyme & prevent the substrate of the
enzyme from binding, this slows or ceases the metabolic
reaction.
By being incorporated into important molecules (e.g
nucleic acids), thus inhibiting their function.

Antimetabolites include:
Antifolates (sulfa drugs & trimethoprim)
Purines analogues
Pyrimidines analogues

 Sulfonamides (sulfa drugs): a group of synthetic

compounds that are bacteriostatic, the first one known
Sulfanilamide.
They act by competitive inhibition to the enzymes that acts on
Para amino benzoic acid needed for folic acid, which is
important for synthesizing nucleic acids & other metabolic
products. Sulfonamides are chemically similar to (PABA).
When sulfonamides rather than PABA bind to the enzyme, the bacterium
can not make folic acid. Animal cells can not produce folic acids & should
obtain it from diet, on the other hand, bacteria can not use folic acid from
diet & should synthesize it, thus sulfonamides are selective in activity.

NH2

NH2

SO2NH2

COOH

sulfanilamide

PABA

Used to treat some kinds of meningitis as they pass cerebrospinal

fluid easily.
e.g sulfamethoxazole & sulfadiazine. These are usually given in
combination with Trimethoprim (sulfa powder used in world war II).
Cotrimoxazole is a combination of sulfamethoxazole &
Trimethoprim. Trimethoprim inhibits another enzyme in the
pathway of synthesizing folic acid.

 Cotrimoxazole (Bactrim,
Septrin ):
used for urinary tract infections
& considered drug of choice for
Pnemocystis pneumonia
(fungal complication of AIDS
patients). Both drugs are toxic
to bone marrow .
Trimethoprim-sulfonamides are broad spectrum effective against most
G-ve bacteria & skin Staphylococci.

Isoniazid: also called isonicotinyl hydrazine (INH) antimetabolite for 2

vitamins nicotinamide (niacin) & Vit B6 (pyridoxal). It binds to the
enzymes that converts the vitamins to other molecules. This results in
inhibiting the synthesis of mycolic acid a component of Mycobacteria
cell wall (responsible for acid fastness).

 Isoniazid is absorbed from GIT & reaches all body tissue &fluids. It is
effective against Mycobacteria & has little effect on other bacteria. As
such it is inactive (prodrug) & should be transformed by bacterial
enzyme to the active form.
Resistant mycobacteria does not produce the activating enzyme thus
INH remains inactive. Since resistance to INH is high, it is usually given
in combination with other 2 or 3 drugs e.g Rifampin & ethambutol.

Nitrofurans: synthetic drug. Interferes with bacterial

respiration. Nitrofurantoin, used for UTI,
Ethambutol:
It inhibits cell wall synthesis of mycobacteria. Since
resistance to it emerges rapidly, it is used in combination
with other drugs for TB treatment

Antifungal agents
Since fungi & human cells are eukaryotes, these drugs cause toxic
side effects. Their use is increasing due to emergence of resistant
strains & to the increase in immunosuppressed patients, especially
AIDS patients.

Imidazoles & triazoles

N N
N
N

imidazole

triazole

These form a large group of fungicides. Imidazoles (e.g clotrimazole,

ketoconazole, miconazole) & Triazoles e.g fluconazole,
voriconazole.
These drugs interfere with plasma membrane of the fungus by
disrupting the synthesis of membrane sterols.
Ketoconazole & fluconazole are used orally to treat systemic fungal
infections.

 Voriconazole (new drug given orally & IV) activity is compared

to amphotericin B used for aspergillosis & candidemia
(candida in blood).
Imidazoles & triazoles are used topically to control skin
infections (dermatomycoses) & Candida skin infections.

Polyenes: family of antifungal agents that has at least

2 double bonds, e.g Amphotericin B & Nystatin.

Amphotericin B: derived from Streptomyces sp., it binds to a

sterol (ergosterol) present in fungal plasma membrane & some
protozoa but not humans. Amphotericin B thus increases
permeability of plasma membrane & causes leak of glucose,
potassium & other substances from the cell.
It is the drug of choice to treat most systemic fungal infections like
aspergillosis, coccidioidomycosis & cryptococcosis (fatal fungal

infection)

 Amphotericin B has poor absorption so it is given IV. It has

many side effects some are severe like kidney damage,
depression anemia & blindness.

Nystatin:

same mode of action like amphotericin B, but

also used topically to treat Candida yeast skin infections.
Since it is not absorbed from intestines, it is given orally to
treat fungal superinfection in intestines.

Griseofulvin: it interferes with fungal mitosis by disrupting

the mitotic spindle used in cell division. It is given orally to
treat skin, nails & scalp infections. Treatment may take from
4wks to 1year if the infection was recalcitrant associated with
fingernails or toenails.
it is not effective against most systemic fungal infections.
Due to its mode of action could be potential drug for cancer.

 Flucytosine: in the body it is transformed to fluorouracil, an

analogue of uracil, therefore it interferes with nucleic acid & protein
synthesis. It is less toxic than Amphotericin B & its use should be
considered instead of Amphotericin B whenever possible.

Tolnaftate: a topical fungicide, available OTC. Used for fungal skin

infections like athletes foot (flaking, itching & scaling).

Terbinafine: relatively new fungicide for topical infections &

cutaneous candidiasis. It is absorbed through skin & reaches
therapeutic levels faster than the orally administered griseofulvin

Antiviral agents
The difficulty in finding antiviral drugs is that the drug should attack
viruses inside cells without affecting host cell.
Antiviral agents act by interfering on some phase of viral
replication but they dont kill viruses.
 Purines & pyrimidines analogues
These agents are considered antimetabolites because they are
similar to purines & pyrimidines
of nucleic acids so the virus
incorporate wrong information
(the analogue) into nucleic acid
leading to incorrect base pairing thus,
interfering with its replication.

 Pyrimidines analogues: Idoxuridine & trifluridine.

Both drugs are analogues of thymine, used in eye

drops to treat infection of the cornea by herpesvirus.
Not used internally due to toxicity (suppress bone
marrow).
Azidothymidine =Zidovudine (AZT): analogue of thymine.
It interferes with reverse transcriptase the enzyme which
synthesizes DNA from RNA e.g HIV virus. It is one of the
first drugs approved for treating HIV.

 Purines analogues include Vidarabine, Ribavirin, Acyclovir, Ganciclovir.

Vidarabine: Analogue of adenine. Used to treat viral encephalitis

(inflammation of the brain) caused by herpesviruses or
cytomegaloviruses.
Ribavirin: analogue of guanine. Blocks viral replication. Has activity
against wide range of unrelated viruses which makes it potential broad
spectrum antiviral drug. Used in aerosol for influenza viruses, in
ointments to heal herpes lesions. Also used with interferons to treat
Hepatitis C. Has low toxicity but may induce birth defects.
Acyclovir: analogue of guanine. Used topically, orally & IV. It is most
commonly used to treat herpes simplex virus infections, HV 1, 2 (cold
sores, genital herpes) & herpes zoster virus (shingles). Effective in
reducing pain & promoting healing of genital herpes lesions.
It doesnt prevent establishment of latent virus in the nerve cells
It is more effective than vidarabine against herpes encephalitis.

Shingles

Shingles

Cold sores

 Acyclovir has 100 times more affinity to viral DNA polymerase than to the
human one (therefore it is less toxic than other analogues), so it interacts
with the virus DNA polymerase & blocks its action.

Ganciclovir: analogue to guanine, similar to acyclovir. Active against

several herpes viruses mainly cytomegalovirus eye infections in AIDS
patient.

 Amantadine: tricyclic amine, it is used to treat Parkinson disease in

addition to its antiviral activity although mechanism of actions are not
related.
Amantadine prevents Influenza A virus from entering the host cell by
interfering with viral protein. It is given orally & should be given days to
a week earlier before the exposure to the virus. It has many side
effects.
 Rimantadine: similar to amantadine but with less side effects.

Antiprotozoan agents
Drugs used to treat infections caused by protozoa. Protozoa are
unicellular animal like organisms.
Examples: giardia, amoeba, plasmodium, leishmania, toxoplasma
Giradiasis: (transmission by fecal-oral route); caused by Giardia lamblia;
complications: gastrointestinal disorders (irritable bowel syndrome,
biliary tract dysfunction).
Amoebiasis: (transmission: fecal-oral route); caused by Entamoeba
histolytica; severe form is amoebic dysentery characterized by severe
diarrhea, abdominal pain, loss of appetite, wt loss. May reach the liver &
form abscess.
Malaria (caused by plasmodium)
Leishmaniasis: (transmitted by sand fly) caused by Leishmania. It results
in skin lesions& ulcers (cutaneous form), mucucutaneous forms causes
deformation to the affected region, visceral form leads to death.

 Antimalarial drugs
Malaria is caused by Plasmoidum vivax,
P. ovale, P. malariae;
P. falciparum (the most deadly one)
Occurs in more than 100 countries
throughout Africa, Asia, Latin America.
2-3 billion inhabitants at risk
300-500 million clinical cases
1-2 million per year
It affects cardiovascular system (hypotension,
tachycardia, P falciparum causes blocking in
heart capillaries), Anemia; GI: nausea vomiting;
pulmonary system; blood; kidneys, enlargement
of liver& spleen & other serious effects.

 Quinine: from the bark of cinchona trees. The first effective

drug for malaria, used for centuries. Nowadays used to treat
malaria resistant to other drugs.
Chloroquine & Primaquine: synthetic drugs, most widely
used antimalarial drugs.
Chloroquine:
it enters red blood cells & accumulates in the parasite
vacuole & interferes with protozoan enzyme that convert
heme (toxic to the parasite) to nontoxic molecule, thus,
toxic heme will accumulate in the parasite.
Primaquine: is essential co-drug with chloroquine. It is
effective against dormant forms in tissue. It is given in
combination with chloroquine as prophylaxis to people

visiting places where malaria occurs.

 Mefloquine: antimalarial drug, effective against resistant

strains of parasite (falciparum malaria).

Pyrimethamine: interferes with folic acid synthesis needed for

purines & pyrimidine synthesis. Used in combination with sulfa
drugs (2 step blockage of folic acid synthesis) to treat some
resistant forms of malaria & for some protozoan infections like
toxoplasmosis.
___________________________