ANTIMYCOBACTERIALS FOR LEPROSY

Drug
Dapsone
CLOFAZIMINE

Use
PABA antagonist, against M. leprae, effective for
pneumocystis and brown recluse spider bites
-

activity against M. lepraiand MAI

Side effects
Erythema nodosum leprosum
peripheral neuropathy
methemoglobinemia
GI upset
red/purple discoloration of skin and body fluids

Others
-

Acetylated in liver
structurally related to sulfonamides
eliminated in urine
wide distribution, does not penetrate CSF
partially metabolized
excreted in bile
synthetic phenazinedye
binds DNA and inhibits replication and transcription

ANTIFUNGALS

Undecylenic Acid

Drug avail
Desenex, Cruex

NUCLEOSIDE ANTIFUNGALS
FLUCYTOSINE
Ancobon

SAR
A fatty acid that resembles like sebum which
augments antifungal properties. It has reactive
double bonds.

Dose
Apply TOPICALLY to affected areas 2 times
daily for 2-4 weeks

Deamination converts to 5-FU, which is the

active metabolite.

USE
-

10% for topical prep.

Traditionally used for Tinea pedis
Applied to mucous membranes (severe irritant)

It inhibits fungal protein synthesis by replacing uracil with 5-flurouracil in fungal

RNA.
inhibits thymidylate synthetase via 5-fluorodeoxy-uridine monophosphate and thus
interferes with fungal DNA synthesis

POLYENES
AMPHOTERICIN B

Fungizone

NYSTATIN

Mycostatin

Streptomyces nodosus is used to produce

amphotericin B
(Streptomyces noursei)

NATAMYCIN

Pimaricin, Natacyn

(Streptomyces natalensis)

GRISEOFULVIN

Grisovin

(Penicillium griseofulvum)

ALLYLAMINES
TERBINAFINE HCl
TOLNAFTATE
NAFTIFINE HCl
AZOLE
CLOTRIMOXAZOLE
TIOCONAZOLE
MICONAZOLENO3
ITRACONAZOLE
FLUCONAZOLE
KETOCONAZOLE

Pkinetics: Poor oral bioavailablity.

Advice: Take the drug with a fatty meal.

Lamisil
Quadriderm
Naftin
Canesten
Trosyd
Daktarin
Sporanox
Diflucan
Nizoral, ketovid

synthetic antibacterial agents

mainstay antifungal agent for treatment of life-threatening mycoses and for most
other mycoses, with the possible exception of the dermatophytoses.
first successful antifungal antibiotic to be developed
broad-spectrum antifungal activity
it has activity against yeasts
treat superficial mycotic infections of the eye.
active against both yeasts and moulds.
- Mitotic spindle poison.( in fungi)
-Dissolution of mitotic spindle apparatus.

DRUG
USE
Patterned after nalidixic acid; aka 1-4-dihydro-4-oxo-3-pyridinecarboxylic acid

QUINOLONES
NITROFURANS
NITROFURAZONE
FURAZOLIDONE

OTHERS

Furacin
Furoxone

Nitrofurantoin
NIFURTIMOX
METHENAMINE SALTS

Applied topically in the tx of burns

Oral treatment of bacterial or protozoal diarrhea caused by susceptible organisms (S. Aureus, E.
coli, Salmonella, Shigella, Proteus, Enterobacter, V. Cholerae)
Macrodantin)
Used as urinary antiseptic
(Lampit)
Used in the treatment of Trypanosomiasis infection (Chagas disease)
Antibacterial property is due to liberation or conversion to formaldehyde.

CI: alcohol

ANTIPROTOZOAL DRUGS
DISEASE

DRUG
1.Pentamidine

BRAND NAME
Nebupent, Pentam 300)

2.Suramin
3.Melarsoprolol

USE
1. treatment of pneumonia by P. carinii.
2. Treatment of african trypanosomiasis

OTHERS

Drug of choice for the treatment of trypanosomiasis

Pkinetics: excellent penetration into the CNS (thus effective against meningoencephalic forms of
T.gambiense and T. rhodiense)
Trivalent arsenicals tend to be more toxic to the host than the corresponding pentavalent compounds.
SAR:
Bonding of arsenic to sulfur atoms reduces host toxicity, increase chemical stability
Myelosupressive:Complete blood count must be monitored
SAR: Decarboxylation and release of fluorine only the (-)isomer is active
MoA: irreversible inactivation of ornithin decarboxylase
SIDE EFFECTS: Peripheral neuropathy, bone marrow depression, Hypersensitivity

TRYPANOSOMIASIS

4.Eflornithine

Treatment of west african sleeping sickness

Specifically indicated for meningoencephalic stage
of the disease
treatment of chagas disease
Antibacterial, Antifungal, Antiprotozoal
USE: acute and chronic form of South American
Trypanosomiasis.

5.Benzinedazole
6.Nitrofurtimox/Nifurtimox

Metronidazole

Flagyl

most useful group of antiprotozoal nitroimidazole derivatives that have been synthesized.
Effective only against anaerobic bacteria!
2-Methyl-5-nitroimidazole-1-ethanol
reduction of the 5-nitro group
binds to the DNA of microorganism = lethal.
Potential reactive intermediates:
nitroxide, nitroso, hydroxylamine and amine
ability to acts as a radiosensitizing agent is related to its reduction to its reduction potential.

Giardia lamblia

2.Tinidazole
3.Mepacrine
4.Albendazole
Diloxamide
8-hydroxyquinoline

Furamide, eutamide
oxine, quinophenolor
oxyquinoline

IDOQUINOL

Other drugs:

EMETINE &
DEHYDROEMETINE
ATOVAQUONE

Mepron)

Tx of asymptomatic carriers of E. hystolytica.

1.Derivative with ability tochelate metals = activity
2.Solutions of acid salts of oxine (SO4) used as topical
antiinfectives.
Acute & chronic amebiasis
direct amebicidal action:
protoplasmic poisons
alternative to TMP-SMX for the tx of & prophylaxis
of PCP

SAR: Hydrolysis of the amide is required for the amebicidal effect.

SAR: Substitution of an iodine atom at the 7thpostion of 8-hydroxyquinolines = broad spec amebicide.

recommended for acute intestinal amebiasis but is not effective in extraintestinal disease.
High incidence of atopic neuropathy therefore it should not be routinely used for travelers diarrhea.
Occur as levorotatory form
inhibits protein synthesis by preventing protein elongation.
SAR: *similar with ubiquinone
but may act as an antimetabolite for it.

SODIUM
STIBOGLUCONATE

sodium antimony
gluconate.
Pentostam
BAL

DIMERCAPROL

= interfere with the funtion of electron transport enzymes

PCEUTICS: aq. Susp = better absorption
fat content = absorption
SI: GI intolerance
SIDE: could cause heavy metal poisoning

tx of leishmaniasis

2,3-Dimercapto 1-propanol
Dithioglycerol
MoA: chelation = formation of ring compounds= excretable =)

ANTIHELMINTHS
The word helminth is a general term meaning worm
Types:
platy-helminths for flat-worms
Cestodes (tapeworms)
Trematodes (flukes)
nemat-helminths for round-worms
drug
PIPERAZINE
DIETHYLCARBAMAZINE CITRATE
PYRANTEL PAMOATE

Hexahydropyrazineor diethylenediamine(Arthriticine, Dispermin)

Hetrazan
Antiminth

THIABENDAZOLE

2-(4-Thiazolyl)benzimidazole
Mintezol

MEBENDAZOLE

Vermox)

Use
Txfor pinworm and roundworm
Tx for filariasis
pinworms and roundworms

ALBENDAZOLE

New and Old world hookworm

Praziquantel

drug of choice for schistosomiasis

(blood flukes)
tx of Onchocerciasis (river blindess) Oncocerca volvulus

Ivermectin
ANTISCABIOUS & ANTIPEDULAR AGENTS
BENZYL BENZOATE

local anesthetic effect.

effective when applied topically

Immediate relief from itching by local anesthetic effect.
25% emulsion = single application = cure!

MoA: blocks response of Ach = flaccid paralysis

MoA: depolarizing neuromuscular blocking agent =
spastic paralysis
Forms complexes with metal ions
MoA:
1. inhibit fumarate reductase
2. Arrest cell division by inhibit microtubule assembly.
( coz it has affinity to tubulin)
MoA:
1.Irreversibly blocks uptake = glycogen stores
2.Inhibits cell division
SAR: Sulfoxide conjugate = active form
Pkinetics: absorption with fatty meals
MoA: Spastic paralysis
MoA: Stimulate GABA = inhibitory effect

LINDANE

SAR: isomer 10-13% is responsible for the insecticidal activity.

MoA:
1.Direct contact poison
2.Fumigant effect
3.Acts as stomachic poison
racemic cis-isomer form is responsible for the activity.
treatment of headlice.
has lethal action against lice, ticks, mites and fleas.

PERMETHRIN

ANTIBACTERIAL SULFONAMIDES
Name
LEAD COMPOUND
SULFONAMIDES

PRODRUG
SULFANILAMIDE

para-Amino group is essential (R1=H)

para-Amido groups (R1=acyl) are allowed
inactive in vitro, but active in vivo
act as prodrugs
Aromatic ring is essential
para-Substitution is essential
Sulfonamide group is essential
Sulfonamide nitrogen must be primary or secondary
R2 can be varied
Amide group lowers the polarity of the sulfonamide
Amide cannot ionise
Alkyl group increases the hydrophobic character
Crosses the gut wall more easily
Metabolised by enzymes (e.g. peptidases) in vivo
Metabolism generates the primary amine
Primary amine ionizes and can form ionic interactions
Ionised primary amine also acts as a strong HBD

METABOLISM
Sulfonamides are metabolised by N-acetylation
N-Acetylation increases hydrophobic character
Reduces aqueous solubility
May lead to toxic side effects
SULFONAMIDES WITH REDUCED ACTIVITY
Notes
Thiazole ring is replaced with a pyrimidine ring

Use

Mechanism of action

others

Treatment of urinary tract infections

Eye lotions
Treatment of gut infections
Treatment of mucous membrane infections

MECHANISM OF ACTION
Target enzyme
Dihydropteroate synthetase -bacterial
enzyme
Not present in human cells
Important in the biosynthesis of the
tetrahydrofolate cofactor
Cofactor is crucial to pyrimidine and DNA
biosynthesis
Crucial to cell growth and division

Sulfonamides
Competitive enzyme inhibitors
Bacteriostatic agents
Not ideal for patients with weakened
immune systems
Mimic the enzyme substrate -paraaminobenzoic acid (PABA)
Bind to the active site and block access to
PABA
Reversible inhibition
Resistant strains produce more PABA

Pyrimidine ring is more electron-withdrawing

Sulfonamide NH proton is more acidic and ionizable
Sulfadiazine and its metabolite are more water soluble
Reduced toxicity
Silver sulfadiazine is used topically to prevent infection of burns
SULFADOXIME
Belongs to a new generation of sulfonamides
Long lasting antibacterial agent
Once weekly dosing regime
Sulfadoxine + pyrimethamine = Fanisdar
Used for the treatment of malaria
SUCCINYL SULFATHIAZOLE
Acts as a prodrug of sulfathiazole
Ionized in the alkaline conditions of the intestine
Too polar to cross the gut wall
Concentrated in the gut
Slowly hydrolysed by enzymes in the gut
Used for gut infections
BENZOYLE PRODRUGS
-

Too hydrophobic to cross gut wall

Slowly hydrolyzed by enzymes in gut

Used for gut infections
Sulfamethoxazole + trimethoprim = co-trimoxazole
Agents inhibit different enzymes in same biosynthetic pathway
Strategy of sequential blocking
Allows lower, safer dose levels of each agent