ANTI-LEPROSY DRUGS CLOFAZIMINE

Leprosy: General information

a systemic infection a complex dye
primarily affecting skin and peripheral nerves mechanism of action is unknown
caused by Mycobacterium leprae administered orally
may be divided in 2 types according to the severity Medical uses
of mycobacterium leprae infection treatment of multibacillary leprosy with dapsone
1. PAUCIBACILLARY LEPROSY aka tuberculoid and rifampicin
leprosy Side effects
due to moderate mycobacterium leprae red discoloration of skin and urine
infection dark blue discoloration of leprous skin lesions
2. MULTIBACILLARY LEPROSY aka lepromatous headache, vertigo
leprosy nausea and vomiting
due to severe mycobacterium leprae
infection RIFAMPICIN
a first-choice antituberculotic drug
FIRST-CHOICE ANTI-LEPROSY DRUGS like first-choice antituberculotic drugs,
first-choice anti-leprosy drugs are the first-choice anti-leprosy drugs are never
preferred drugs administered against used alone, but in combinations with each
mycobacterium leprae other due to high incidence of resistance in
DAPSONE the mycobacteria
chemically related to sulfonamides the administration of first-choice anti-leprosy drug
inhibits dihydropteroate synthetase, combinations are divided in 2 according to the
thus inhibiting folate synthesis and type of leprosy:
following inhibition of bacterial DNA- and 1. PAUCIBACILLARY LEPROSY
RNA synthesis thus is bacteriostatic 6 months
bacteria may develop resistance by Combination
increased displacement (increased PABA Dapsone
synthesis) Rifampicin
administered orally 2. MULTIBACILLARY LEPROSY
Medical uses 2 years
treatment of paucibacillary leprosy then with Combination
rifampicin, Dapsone
treatment of multibacillary leprosy then with Rifampicin
rifampicin and clofazimine, Clofazimine
treatment of malaria due to Plasmodium
falciparum and/or Plasmodium malariae SECOND-CHOICE ANTI-LEPROSY DRUGS
treatment of malaria due to Plasmodium vivax second-choice anti-leprosy drugs are drugs
and/or Plasmodium ovale infection then administered against Mycobacterium leprae
administered in conjunction infections if the mycobacteria exhibit resistance to
Side effects the first-choice anti-leprosy drugs
hypersensitivity reactions leading to fever and/or 2 types
skin rashes 1. OFLOXACIN
nausea and vomiting a fluoroquinolone
hemolysis 2. AZITHROMYCIN
methemoglobinemia a macrolide
peripheral neuropathies
 ANTIFUNGAL DRUGS
Fungi
diverse kingdom of unicellular- and multicellular
eukaryotic organisms
replicate either by simple mitosis or by spore
formation
Fungal cells consist of 4 parts (listed from innermost to
outermost)
1. CYTOPLASM
contains membrane-bound organelles
including a nucleus-bound genetic material
(in opposition to bacterial cytoplasm that
neither contains membrane-bound
organelles nor a nucleus)
2. CELL MEMBRANE
consists of a lipoprotein membrane
containing ergosterol that stabilizes the
lipoprotein membrane (in opposition to
human cell membranes that contain
cholesterol, and bacterial cell membranes A. MACROLIDES
that do not contain any sterols whatsoever
(except mycoplasma))
3. CELL WALL
composed of beta-D-glucan and chitin (in
opposition to bacterial cell walls that are
composed of peptidoglycan, and human
cells that do not have a cell wall
whatsoever)
4. CAPSULE
a polysaccaride coat
present only in some fungal species
Ergosterol of the fungal cell membrane is synthesized from
squalene by an extremely complicated biochemical
pathway
however, this pathway is extremely important
pharmacologically (!)
fungal infections (mycoses) occur in subjects 1. AMPHOTERICIN B
with a decreased defense against fungal
colonization, including decreased immune defense Medical uses
system and decreased normal bacterial flora
Fungal infections may be divided in 2 groups
1. SUPERFICIAL FUNGAL INFECTIONS
Local Fungal Infections
2 groups
A. CANDIDIASIS
caused by candida albicans
Affected Sites
dermal candidiasis, oral candidiasis
vaginal candidiasis
1. DERMATOMYCOSIS AKA DERMATOPHYTOSIS
General information
caused by
1. Epidermopyhton
2. Trichophyton
3. Microsporium
(collectively known as dermatophytes)
Affected Sites
tinea corporis (affects any skin site except
the ones listed immediately below)
tinea capitis (affects the scalp)
tinea cruris (affects the groin)
tinea pedis (affects the feet)
tinea unguium (affects the nails)
2. DEEP FUNGAL INFECTIONS
Systemic Fungal Infections
may affect any internal tissue or organ
NATURAL ANTIFUNGAL DRUGS
macrolides used in treatment of fungal infections
have a different mechanism of action than those
used to treat bacterial infections
they bind to ergosterol of the fungal cell
membrane where insert themselves to form cell
membrane pores
the cell membrane pores cause severe
dysregulation of ion homeostasis, particularly
potassium homeostasis,
thus leading to disruption of several vital fungal
metabolic pathways thus macrolides are
fungicidal
the macrolides used in treatment of fungal
infections are found in the streptomyces
bacterium
2 types
administered orally, dermally and/or IV
treatment of superficial fungal infections (then
administered orally and/or dermally)
treatment of deep fungal infections (then
administered IV)
treatment of visceral leishmaniasis due to
leishmanial protozoal infection and primary
amebic meningoencephalitis
 Oral preparations
used to treat thrush
virtually nontoxic, in contrast to typical
intravenous therapy (IV) doses.
One of the main intravenous uses is in treating
various systemic fungal infections (e.g., in critically
ill, comorbidly infected
or immunocompromised patients),
including cryptococcal meningitis.
Amphotericin B is well known for its severe and
potentially lethal side-effects. Very often, a serious
acute reaction after the infusion (1 to 3 hours
later) is noted, consisting of:
high fever
shaking
chills
hypotension
anorexia
nausea
vomiting
headache
dyspnea and tachypnea
drowsiness
generalized weakness
This reaction sometimes subsides with later
applications of the drug, and may in part be due to
histamine liberation.
Nephrotoxicity
hepatotoxicity
cardiac failure
2. NYSTATIN
administered orally and/or dermally
a polyene antifungal medication to which
many molds and yeast infections are sensitive,
including Candida.
Due to its toxicity profile, there are currently no
injectable formulations of this drug on the US
market.
nystatin may be safely given orally as well as
applied topically due to its minimal absorption
through mucocutaneous membranes such as the
gut and the skin
Cryptococcus is also sensitive to nystatin.
In the UK its license for treating neonatal
oral thrush is restricted to those over the age of
one month (MICONAZOLE) is an appropriate
alternative for younger babies)
It is prescribed in units, with doses varying from
100,000 (for oral infections) to 1 million (for
intestinal ones). As it is not absorbed from the gut,
it is safe for oral use and does not have problems
of drug interactions.
Medical uses
treatment of superficial fungal infections (originally
named Fungicidin)
Cutaneous, vaginal, mucosal and esophageal Candi
da infections usually respond well to treatment
with nystatin.
Nystatin is often used as prophylaxis in patients
who are at risk for fungal infections, such
as AIDS patients with a low CD4+ count and
patients receiving chemotherapy.
B. GRISEOFULVIN
Griseofulvin is naturally found in the penicillium
griseofulvum fungus
Griseofulvin binds to microtubules in the fungal
cytoplasm, thus inhibiting mitosis thus
griseofulvin is fungistatic
It binds to keratin in keratin precursor cells and
makes them resistant to fungal infections. It is only
when hair or skin is replaced by the keratin-
griseofulvin complex that the drug reaches its site
of action. Griseofulvin will then enter the
dermatophyte through energy dependent
transport processes and bind to
fungal microtubules.
Griseofulvin is used orally only
for dermatophytosis.
It is ineffective topically.
Griseofulvin is reserved for cases with nail, hair or
large body surface involvement.
Potential for cancer treatment
Laboratory experiments at the German
Cancer Research Center show that
griseofulvin causes cancer cells to fail to
divide the chromosomes correctly, which
eventually leads to tumor cell death.
Side effects
headache
nausea, vomiting and/or diarrhea
photosensitivity
hypersensitivity reactions leading to fever and/or
skin rashes
can reduce the effectiveness of oral contraceptives
as it is a cytochrome P450 inducer
 SYNTHETIC ANTIFUNGAL DRUGS
A. ECHINOCANDINS
synthetic derivatives of echinocandin B normally
found in the aspergillus nidulans fungus
inhibit beta-D-glucan synthesis, thus inhibiting cell
wall synthesis
this leads to decreased stability and protection of
the fungal cell membrane and following osmotic
lysis of the fungithus echinocandins are
fungicidal
lipopeptide by nature
It works by inhibiting the enzyme (1,3)-D-Glucan
synthase and thereby disturbing the integrity of
the fungal cell wall.
Caspofungin was the first inhibitor of fungal -1,3
glucan synthesis to be approved by the United
States Food and Drug Administration.
CASPOFUNGIN and MICAFUNGIN
administered IV
Medical uses
treatment of deep fungal infections
Side effects
increase in the level of liver enzymes
headache
nausea, vomiting and/or diarrhea
hypersensitivity reactions leading to fever, skin
rashes and/or pruritus
B. AZOLES
inhibit ergosterol synthesis, thus leading to
decreased stability of the fungal cell membrane
however, the fungi retain the protection of their
cell wall thus azoles are fungistatic
KETOCONAZOLE
administered orally
may cross the blood-brain barrier (but only if
administered in high doses)
very lipophilic, which leads to accumulation in fatty
tissues.
The less toxic and more effective triazole
compounds fluconazole and itraconazole are
sometimes preferred for internal use.
Ketoconazole is best absorbed at
highly acidic levels, so antacids or other causes of
decreased stomach acid levels will lower the drug's
absorption when taken orally.
Ketoconazole is usually prescribed for topical
infections such as:
athletes foot
ringworm
candidiasis(yeast infection or thrush)
jock itch
The over-the-counter shampoo version can also be
used as a body wash for the treatment of tinea
versicol0r.
The side effects of ketoconazole are sometimes
used to treat nonfungal problems.
The decrease in testosterone caused by
the drug makes it useful for
treating prostate cancer and for
preventing postoperative
erections following penile surgery.
Another use is the suppression
of glucocorticoid synthesis, where it is
used in the treatment of Cushing's
syndrome.
Ketoconazole is also used in combination with
other drugs such as zinc pyrithione in rinse-off
products. The antidandruff shampoo is designed
for people who have a more serious case of
dandruff where symptoms include, but are not
limited to constant, nonstop flaking, and severe
itchiness.
Preliminary research suggests
ketoconazole shampoo may be beneficial
in men suffering from androgenic alopecia.
Support for this comes from a study in
1998 that compared ketoconazole 2% to
the proven hair loss drug minoxidil 2% in
men with androgenic alopecia
FLUCONAZOLE
administered orally and/or IV
Fluconazole is primarily fungistatic; however, it
may be fungicidal against certain organisms in a
dose-dependent manner,specifically Cryptococcus
Fluconazole is indicated for the treatment
and prophylaxis of fungal infections where other
antifungals have failed or are not tolerated (e.g.,
due to adverse effects), including:
Candidiasis caused by susceptible strains
of Candida
Tinea corporis, tinea cruris or tinea pedis
Onychomycosis
Cryptococcal meningitis
Medical uses
treatment of deep fungal infections
Side effects
headache, nausea, abdominal pain
hepatotoxicity
hypersensitivity reactions leading to fever, skin
rashes and/or stevens-johnson syndrome
MOA:
Fluconazole inhibits the fungal cytochrome
P450 enzyme 14-demethylase. Mammalian
demethylase activity is much less sensitive to
fluconazole than fungal demethylase. This
inhibition prevents the conversion
of lanosterol to ergosterol, an essential component
of the fungal cytoplasmic membrane, and
subsequent accumulation of 14-methyl sterols.
ITRACONAZOLE
administered orally and/or IV
Itraconazole has a broader spectrum of activity
than fluconazole .
In particular, it is active against Aspergillus, which
fluconazole is not.
It is also licensed for use in blastomycosis,
histoplasmosis, and onychomycosis.
Itraconazole is over 99% protein-bound and has
virtually no penetration into cerebrospinal fluid.
It is also prescribed for systemic infections, such
as aspergillosis, candidiasis, and cryptococcosis,
where other antifungal drugs are inappropriate or
ineffective.
Itraconazole is currently being explored as an
anticancer agent for patients with basal cell
carcinoma, non-small cell lung cancer,
and prostate cancer.
MICONAZOLE
an imidazole antifungal agent
commonly applied topically to the skin or to mucus
membranes to cure fungal infections.
It works by inhibiting the synthesis of ergosterol, a
critical component of fungal cell membranes.
It can also be used against certain species of
Leishmania protozoa which are a type of
unicellular parasite that also contain ergosterol in
their cell membranes.
In addition to its antifungal and antiparasitic
actions, it also has some
limited antibacterial properties.
It is mainly used externally:
Tx of athlete's foot
Tx of ringworm
Tx of jock itch
Internal application
used for oral or vaginal thrush (yeast
infection)
Oral gel
used for the lip disorder angular cheilitis.
In the UK miconazole may be used to
treat neonatal oral thrush, while the
alternative nystatin is only licensed for patients
over the age of one month; but drug interactions
are possible.
Unlike nystatin, some miconazole is absorbed by
the intestinal tract when used orally (and possibly
if used vaginally); this may lead to drug
interactions.
Interactions are possible with:
anticoagulants
Phenytoin
Terbinafine
some newer atypical antipsychotics
ciclosporin
some statins used to treat
hypercholesterolemia
C. TERBINAFINE
Terbinafine inhibits ergosterol synthesis, thus
leading to decreased stability of the fungal cell
membrane
However, the fungi retain the protection of their
cell wall thus terbinafine is fungistatic
Keratinophilic
Administered orally and/or dermally
Is synthetic allylamine antifungal
It is highly lipophilic in nature and tends to
accumulate in skin, nails, and fatty tissues.
Terbinafine is mainly effective on the
dermatophytes group of fungi.
As a 1% cream or powder it is used for superficial
skin infections such as jock itch (Tinea
cruris), athlete's foot (Tinea pedis) and other types
of ringworm (Tinea corporis).
Studies have shown that terbinafine cream works
in about half the time required by other
antifungals.
Oral 250 mg tablets are often prescribed for the
treatment of onychomycosis of the toenail or
 fingernail due to the dermatophyte Tinea ANTIVIRAL AGENTS
unguium.
Viruses are obligate intracellular parasites
Side effects
their replication depends primarily on synthetic
headache
processes of the host cell.
vertigo
Viral replication consists of several steps:
nausea, vomiting and/or diarrhea
1. Adsorption to and penetration into
myalgias
susceptible host cells;
arthralgias
2. Uncoating of viral nucleic acid;
hepatotoxicity
3. Synthesis of early, regulatory proteins, eg,
sensory problems: loss of sense of taste
nucleic acid polymerases;
immune system problems
4. Synthesis of rna/ dna;
hypersenstitivity reactions
5. Synthesis of late, structural proteins;
6. Assembly (maturation) of viral particles; and
D. FLUCYTOSINE
7. Release from the cell.
fluorinated pyrimidine analogue
Antiviral agents can potentially target any of
flucytosine is a prodrug that is converted to 5-
these steps. Most of the antiviral agents
fluorouracil in fungi
currently available act on synthesis of
human cells have little or no ablility to convert
purines and pyrimidines (step 4); reverse
flucytosine to 5- fluorouracil, thus leaving them
transcriptase inhibitors block transcription of
more or less untouched
the HIV RNA genome into DNA, thereby
5-fluorouracil is an antimetabolite that inhibits
preventing synthesis of viral mRNA and
thymidylate synthetease, thus inhibiting DNA
protein
synthesis flucytozine is fungistatic
The protease inhibitors act on synthesis of
Flucytosine is active in vitro as well as in
late proteins and packaging (steps 5 and 6).
vivo against some strains of Candida and
In this section drugs used in the treatment of herpes,
Cryptococcus. Limited studies demonstrate that
human immunodeficiency virus and anti influenza agents
flucytosine may be of value against infections with
will be discussed.
Sporothrix, Aspergillus, Cladosporium, Exophila,
and Phialophora
3 basic approaches to control viral diseases:
All patients receiving flucytosine should be under strict 1. vaccination
medical supervision. 2. chemotherapy
3. stimulation of the hosts natural resistance
Hematological, renal and liver function studies
mechanisms (immunomodulators)
should be done frequently during therapy (initially
most of the drug now block specific viral proteins
daily, twice a week for the rest of treatment).
that are involved in synthesis of viral components
Patients with pre-existing bone marrow depression
within the host cell
and liver impairment should be treated with
caution.
Anti HIV drugs
Patients treated with drugs compromising bone
reverse transcriptase inhibitors and proteases
marrow function (e.g. cytostatics) should be
inhibitors
treated carefully. Blood cell counts should be taken
Reverse transcriptase:
very frequently.
found in the RNA retroviruses
Patients with renal disease should receive
inhibition of the formation of viral DNA and RNA
flucytosine cautiously and in reduced doses.
Protease inhibitors:
Guidelines for proper dosing exist. Serum level
interfere with processing of the viral proteins
determinations are mandatory in these patients.
preventing the formation of new viral particles
Hypersensitivity to flucytosine is an absolute Combination of 2 RTI and 1 protease Inhibitor best
contraindication. combination
Use of 2 RTI:
slows the emergence of resistant virus; since
mutation of the RT is very rapid
Drugs for Influenza
Mainstay: vaccination ( trivalent or quadrivalent); every
year
Amantadine
prevention and treatment of influenza
shortens the duration of symptoms by about half
problems: resistance; adverse effects
Rimantadine
Neuraminidase Inhibitors: Oseltamivir, Zanamivir
block the release of influenza virus from infected
cells
neuraminidase is an enzyme located on the surface Ganciclovir
of the virusrelease of virus from infected cells
may stop the release of virus limit viral spread
very active in types A and B influenza
shorten the duration of symptoms if started within
30 hours of the onset of symptoms
Traditional flu vaccines offer protection against
three different flu viruses that are expected to
circulate throughout flu season. These strains
include one type B and two type A strains.
Trivalent flu vaccines are the traditional flu
vaccines administered in prior flu seasons.
Quadrivalent flu vaccines protect against four
strains of influenza viruses. The quadrivalent
vaccine now targets a fourth strain, which is a
second type B strain, in addition to the other three
strains.
Antiherpes Agents
Acyclovir
Acyclovir triphosphate inhibits viral DNA synthesis Adverse Reactions:
by two mechanisms:
1. competitive inhibition of the viral DNA
polymerase
2. by binding to the DNA template as an
irreversible complex
Acyclovir is available in oral, intravenous, and
topical formulations.
Acyclovir diffuses into most tissues and body fluids
to produce concentrations that are 50-100% of
those in serum. Cerebrospinal fluid concentrations
are 50% of serum values.
Clinical Uses:
Oral acyclovir is effective for treatment of primary
infection and recurrences of genital and labial
herpes.
Intravenous acyclovir is the treatment of choice for
herpes simplex encephalitis, neonatal HSV
infection and for severe primary, recurrent HSV
genital and labial infections and for those who
cannot ingest oral pills
Adverse Reactions:
Acyclovir is generally well tolerated.
Nausea, diarrhea, and headache have
occasionally been reported.
IV infusion may be associated with renal
insufficiency or neurologic toxicity
The activated compound competitively inhibits
viral DNA polymerase, causing an unstable
complex, but does not result in chain termination.
Ganciclovir has activity against CMV, HSV, VZV, and
EBV; its activity against CMV is up to 100 times
greater than that of acyclovir.
Clinical Uses:
Intravenous ganciclovir is indicated for the
treatment of CMV retinitis in patients with AIDS.
The drug also reduces the incidence of
symptomatic CMV disease if administered before
organ transplantation.
Administration of intravenous ganciclovir to treat
CMV pneumonitis in immunocompromised
patients is often beneficial, particularly in
combination with intravenous cytomegalovirus
immunoglobulin.
Intravenous ganciclovir has also been used to treat
CMV colitis and esophagitis
The most common side effect of treatment with
ganciclovir is myelosuppression, particularly
neutropenia.
Myelosuppression may be additive in patients
receiving both ganciclovir and zidovudine.
Central nervous system toxicity (changes in mental
status, seizures) has been rarely reported.
Foscarnet
an inorganic pyrophosphate compound that
inhibits viral DNA polymerase, RNA polymerase, or
HIV reverse transcriptase directly.
It has in vitro activity against HSV, VZV, CMV, EBV,
HHV-6, HBV, and HIV.
The drug is available in an intravenous formulation
only.
Cerebrospinal fluid concentrations are
approximately two-thirds of steady state serum
concentrations. Clearance of foscarnet is primarily
by the kidney.
Clinical Uses:
patients with CMV retinitis and acyclovir-resistant
HSV infections
for CMV colitis and esophagitis and acyclovir-
resistant VZV infections
Adverse Reactions:
Potential adverse effects:
renal insufficiency
hypocalcemia or hypercalcemia
hypo- or hyperphosphatemia.
Genital ulcerations associated with foscarnet
therapy may be due to high levels of ionized drug
in the urine.
Central nervous system toxicities
Hallucinations
seizures.
Idoxuridine (IDU, IUDR)
substituted pyrimidine analog
first antiviral agent to be approved
It is used topically in the treatment of herpes
keratitis (0.1% solution), but because of its lack of
selectivity it is too toxic for systemic
administration.
Vidarabine
Vidarabine as a 3% ointment is effective treatment
for acute keratoconjunctivitis, superficial keratitis,
and recurrent epithelial keratitis due to HSV.
Intravenous vidarabine (10-15 mg/kg
daily) is effective for treatment of HSV
encephalitis, neonatal herpes, and VZV infection in
immunocompromised patients.
The drug is eliminated primarily by renal
mechanisms as the hypoxanthine metabolite.
Potential toxicities:
gastrointestinal intolerance
neurologic manifestations (confusion,
myoclonus, seizures)
and myelosuppression.
RSV virus: Ribavirin inhalational drug
treatment of RSV (respiratory syncytial virus) in
infants and young children; antimetabolite;
DOC for RSV (croup)
tx for Lassa fever: hemorrhagic fever
Dengue virus vaccine: 2 doses given 6 months
apart: 9 yo and above only
Interferons (IFNs)
natural proteins produced by the cells of the
immune system of most vertebrates in response to
challenges by foreign agents such as viruses,
bacteria, parasites and tumor cells
They are antiviral and possess anti-oncogenic
properties, very important in fighting RNA virus
infections;
Using recombinant DNA technology can prevent
and treat hepatitis C and B: INTERFERON a
Antiprotozoal Drugs
Antiamebic drugs:
Metronidazole:
effective in the treatment of vaginal
trichomoniasis, giardiasis, and all forms of
amebiasis
also effective for anaerobic bacteria
cant enter mammalian cells but can enter
protozoal and bacterial cells
inhibits DNA replication by causing breaks and
preventing repairs
SE:
n/v
diarrhea
urine dark or red brown
metallic taste in the mouth
disulfiram reaction if taken with alcohol
abdominal cramping
vomiting
flushing
head ache
for luminal and systemic liver amebic abscess
Other drugs for amebiasis: week prior to entry into malaria endemic areas and
Diloxanide furoate: cyst passers continued for 4 weeks after leaving
Paromomycin ( amino glycoside) MOA:
Chloroquine: similar to chloroquine; PO but can be given IV
anti malarial but given with metro in pxs with
amebic liver abscess Drug of choice for malarial prophylaxis?
Chloroquine:
Antimalarial Drugs for long trips (once a week)
Malaria: safe for pregnant women
caused by single cell protozoa: the plasmodium Doxycycline:
only 4 are infectious to humans: last 2 days prior to travel
malariae least expensive
vivax: Mefloquine
most prevalent Primaquine:
ovale Good choice for shorter trips because you only
falciparum: have to take the medicine for 7 days after traveling
most serious and lethal form rather than 4 weeks
blackwater fever Good for last-minute travelers because the drug is
Complication of malaria in which red blood started 1-2 days before traveling to an area where
cells burst in the bloodstream (hemolysis), malaria transmission occurs
releasing hemoglobin directly into the blood
vessels and into the urine, frequently leading
to kidney failure. Antihelminthic drugs
Primaquine:
effective against the liver forms (exoerythrocytic) Helminths Drug of choice
kills the gametocytes Cestodes (flatworms and
Praziquantel
due to its effectivity on the liver forms DOC for tapeworms)
prophylaxis Trematodes (Flukes and
Praziquantel
may cause hemolytic anemia in G6PD deficient schistosome)
patients Nematodes
Mebendazole
Chloroquine Rounndworms (whip, pin,
Pyrantel
used for the erythrocytic forms hookworm)
Diethylcarbamazine
cause lysis of the RBC and IC parasites Filariasis
Ivermectin
inhibits parasites protesases that digest
hemoglobin
Praziquantel:
not effective for parasites outside of the RBC
unknown MOA
given PO; given IM if there is severe nausea
alter membrane function and increases membrane
oto and retinopathy prolonged and high dose
permeability
therapy;
orally active
not toxic in low doses; may be given for pregnant
Mebendazole:
women
inhibits protein function in the worms
Quinine:
binds to tubulin and inhibits glucose uptake; orally;
from bark oh cinchona tree from S. America
very little is absorbed from the GIT
Mefloquine
Pyrantel:
only successful derivative;
paralysis of the worms
prevent malaria (malaria prophylaxis) and also in
the treatment of chloroquine-resistant falciparum
malaria. taken once a week starting at least one
DEC: Anticancer drugs kill a constant fraction of cells instead of
drug of choice for lymphatic filariasis an absolute number:
alter the surface of the filarial more susceptible log kill ( act by first order kinetics)
to phagocytosis by the host immune system ex: dose 1 kills 50% of the tumor cells second
Ivermectin: dose kills 50% of what is left after the first dose
in veterinary medicinie reduction of how much??? after the second
treatment of onchocerciasis dose ANSWER: 75%
block GABA mediated transmission in the parasite a drug which reduces the tumor cell load from 10 8 to
without effect on the host 105 is said to have achieved a 3 log kill.

Anticancer Drugs Drug resistance to anticancer drugs is analogous to

anticancer therapy is aimed at killing dividing cells; resistance to antimicrobials
there are normal host cells that are also dividing; cancer cells already contain a mutation
effects on these cells cause side effects. that allows unrestricted growth they
Cancers Cells: are basically host cells that have can also mutate resistance
lost control of cell division combination of drugs are frequently
cells in the body that are actively dividing: used in the treatment of cancer this
epithelium of the GIT, hair follicles and bone reduces the incidence of drug resistance
marrow SE are often seen drugs used together often target different
phases of the cell cycle MOPP, VAMP or
CELL DIVISION CYCLE POMP
There are a number of strategies in the administration of
chemotherapeutic drugs used today. Chemotherapy may
be given with a curative intent or it may aim to prolong life
or to palliate symptoms.
Combined modality chemotherapy
use of drugs with other cancer treatments, such
as radiation therapy or surgery
G1 and G2 gaps; nothing occurs in the nucleus, Most cancers are now treated in this way.
preparation for division Combination chemotherapy is a similar practice
Ssynthesis: DNA replication which involves treating a patient with a number
Mmitosis: divides into 2 daughter cells of different drugs simultaneously.
The drugs differ in their mechanism and side
Biological basis of chemotherapy: effects. The biggest advantage is minimizing the
Cell cycle-active , phase specific chances of resistance developing to any one
Active in S phase: agent.
Antimetabolites Neoadjuvant chemotherapy (preoperative treatment)
purines initial chemotherapy is aimed for shrinking the
pyrimidines primary tumour, thereby rendering local therapy
Active in M phase: (surgery or radiotherapy) less destructive or more
vinca alkaloids effective.
taxols Adjuvant chemotherapy (postoperative treatment)
taxane (paclitaxel) used when there is little evidence of cancer
Phase nonspecific agents present, but there is risk of recurrence.
alkylators Can help reduce chances of resistance developing
antitumor antibiotics (anthracyclines, if the tumor does develop.
actinomycin and mitomycin) It is also useful in killing any cancerous cells which
have spread to other parts of the body.
 This is often effective as the newly growing Alkylating agents:
tumours are fast-dividing, and therefore very Nitrogen Mustards:
susceptible. Chlorambucil
Palliative chemotherapy is given without curative intent, Cyclophosphamide
but simply to decrease tumor load and increase life Melphalan
expectancy. For these regimens, a better toxicity profile is Mechlorethamine ( hodgkins lymphoma)
generally expected. Nitrosoureas:
All chemotherapy regimens require that the patient be Carmustine
capable of undergoing the treatment. Performance status Lomustine ( brain tumors; lipid soluble)
is often used as a measure to determine whether a patient Others:
can receive chemotherapy, or whether dose reduction is Busulphan
required. Thiotepa
Act by: adding an alkyl group to the DNA
Side effects: CYTOTOXICITY not cycle specific prone to develop tissue
due to their effects on the proliferating cells in the body necrosis and damage
1. Bone marrow:
destruction of the proliferating hematopoietic Antimetabolites:
stem cells decreases in all blood elements compete for binding sites on enzymes or can be
including WBCs and platelets incorporated into DNA or RNA
infections and bleeding: major concern Methotrexate:
not seen with bleomycin and asparaginase competitively inhibits dihydrofolate
tx: growth factors: granulocyte colony reductaseinhibits DNA synthesis
stimulating factor granulocyte macrophage resistance to methotrexate: due to transport
colony stimulating factor and erythropoietin problems solution give higher doses
2. GIT: used for the treatment of psoriasis and severe
nausea and vomiting central effect stimulate rheumatoid arthritis;
the chemoreceptor trigger zone treated with admin intrathecally; renal as route of elimination
phenothiazines like chlorpromazine; also with Leucovorin:
serotonin antagonist: ondansetron and dolasetron provides reduced folate to rescue normal cells
directly damage the proliferating mucosa of the from the action of methotrexate
GIT ulcer formation anywhere in the GIT from
mouth to esophagus and stomach Purine Analogues:
3. hair follicles Thioguanine and Mercaptopurine ;
especially true with cyclophosphamide, they have to activated for leukemia and
doxorubicin, vincristine, methotrexate and lymphoma
dactinomycin
4. local tissue necrosis: Pryimidine Analogues:
most are given IV extravasation injury Cytarabine and Fluorouracil
5. renal tubular damage:
cisplatin and high dose methotrexate Antibiotics and other natural products:
cyclophosphamide: hemorrhagic cystitis Antibiotics: all disrupt DNA function
6. cardiotoxicity: Anthracyclines: cardiac toxicity
doxorubicin and daunorubicin ; known as the D rubicins: leukemias and other tumors
d-rubicins Idarubicins: lymphomas
7. pulmonary fibrosis: Mycins:
fatal: bleomycin Bleomycin ( pulmonay fibrosis)
8. nervous system toxicity: Plicamycin:
vincristine: dose limiting used to treat life-threatening hypercalcemia
associated with malignancy
Vinca alkaloids:
bind to tubulin and disrupt the spindle apparatus
during cell division
Vincristine
for leukemias
Vinblastine
Vinorelbine
Paclitaxel:
newer agent;
prevents depolymerization of the microtubules
Etoposide and Teniposide:
dont act on mictotubules
inhibit topoisomerase