Pharmacology for microtubles

1. MICROTUBULE
INHIBITORS

2. 1 BENZIMIDAZOLES
 are in use for the treatment of helminthic
infections
 have a broad range of activity against many
nematode and cestode parasites, including
cutaneous larva migrans, trichinosis,
disseminated strongyloidiasis, and visceral
larva migrans
 considered as the drug of choice for Fasciola
hepatica therapy

3. 1.1 Thiabendazole
 inhibits fumarate reductase and electron
transport–associated phosphorylation in helminths
 Interference with ATP generation decreases
glucose uptake and affects the energy available
for metabolism
 This inhibits microtubule assembly, which is
important in a number of helminth cellular
processes, such as mitosis, transport, and motility.
 shows a broad spectrum of activity against
different nematodas lumbricoides, N. americanus,
A. duodenale, E. vermicularis, S. stercoralis, and
Trichuris trichiura

4. Adverse drug reactions
 Anorexia
 nausea
 vomiting
 Drowsiness
 vertigo occur in upto one-third of patients
 Diarrhea, pruritus, rash, hallucinations, crystalluria,
and leukopenia are less common
 shock, hyperglycemia, lymphadenopathy, and
Stevens-Johnson syndrome are rare.
 Some patients report that their urine smells like
asparagus, a reaction related to excretion of the
metabolite asparagine.

5. 1.2 Albendazole
 cytoplasmic microtubular degeneration, which in
turn impairs vital cellular processes and leads to
parasite death
 also inhibits helminth-specific ATP generation by
fumarate reductase
 given orally and is poorly and variably absorbed
(5%) because of its poor water solubility
 Oral bioavailability is increased as much as five
times when the drug is given with a fatty meal
instead of on an empty stomach
 Has broad spectrum of activity against intestinal
nematodes and cestodes, as well as the liver
flukes

6. Adverse drug reactions

7. 2 Vinca Alkaloids (Vincristine, Vinblastine, and
Vinorelbine)
 alkaloids bind avidly to tubulin, a class of proteins that
form the mitotic spindle during cell division
 regarded as phase specific in the cell cycle, some
mammalian cells are most vulnerable in the late S-
phase
 Both vincristine and vinblastine are extensively bound
to tissues, and only small amounts of the drug are
distributed to the brain or CSF with nearly similar
pharmacokinetics
 Vincristine is an important component of the curative
combination chemotherapy for acute lymphoblastic
leukemia, Hodgkin’s disease (the MOPP regimen),
and non-Hodgkin’s lymphomas

8. Cont …
 Vinorelbine is particularly useful in the
treatment of advanced non–small cell lung
cancer and can be administered alone or in
combination with cisplatinIt
 thought to interfere with mitosis in dividing
cells through a relatively specific action on
mitotic microtubules.

9. Adverse drug reaction
 Neurological toxicity
 bone marrow toxicity
 Severe leukopenia
 potent local blistering agents and will produce
tissue necrosis if extravasated.

10. 3 Taxanes (Paclitaxel)
 highly complex, organic compound isolated from
the bark of the Pacific yewtree
 binds to tubulin dimers and microtubulin filaments,
promoting the assembly of filaments and
preventing their depolymerization
 increase in the stability of microfilaments results in
disruption of mitosis and cytotoxicity and disrupts
other normal microtubular functions, such as
axonal transport in nerve fiber
 among the most active of all anticancer drugs,
with significant efficacy against carcinomas of the
breast, ovary, lung, head, and neck

11. Adverse drug reaction
 Myelosuppression
 Alopecia
 Most patients have mild numbness and
tingling of the fingers and toes
 Mild muscle and joint aching
 Nausea is usually mild or absent
 Severe hypersensitivity reactions may occur
 Cardiovascular side effects, consisting of mild
hypotension and bradycardia, have been
noted

12. Monoclonal antibody

13. Palivizumab (Synagis)
 is a humanized monoclonal antibody directed against
the highly conserved antigenic site of the F protein on
the surface of RSV
 contains 95% human and 5% murine antibody
sequences and tends to have little immunogenicity in
humans
 is composed of the human framework region of the
IgG-1 -chain joined to the antigen-binding regions of a
mouse monoclonal antibody
 neutralizes RSV and inhibits its ability to fuse with
host cell membranes. Resistant strains of RSV have
been derived in vitro but have not been found in
clinical isolates to date.

14. Cont …
 administered prophylactically as a monthly
intramuscular injection prior to and during RSV
season
 half-life of palivizumab is approximately 20 days
 used to prevent serious lower respiratory tract
infection due to RSV
 only in high-risk children who are younger than 24
months of age and have bronchopulmonary
dysplasia or chronic lung disease that required
treatment in the previous 6 months
 is also indicated for premature infants (less than
32 weeks’ gestation)

15. Adverse drug reaction
 Serious adverse reactions are rare
 Mild erythema and pain may occur at the
injection site
 Although no anaphylactoid reactions have
been reported to date, the possibility of this
reaction exists because palivizumab is a
protein,

16. Monoclonal antibody drug for
Immunomodulating(Muromonab-(CD3))
 is a mouse monoclonal antibody that is a purified IgG
 used for the prevention of acute allograft rejection in kidney
and hepatic transplants and as prophylaxis in cardiac
transplantation
 also used to deplete T cells in marrow from donors before
bone marrow transplantation.
 alters the cell-mediated immune response by binding to the
CD3 (cluster of differentiation antigen, T3) glycoprotein on T.
 Within minutes of injection, total circulating T cells are rapidly
depleted from the blood
 later reappear devoid of CD3 and antigen recognition
complexes.

17. Adverse side effects
 include fever
 pulmonary edema,
 Vomiting
 Headache
 anaphylaxis

18. Monoclonal antibody drug for Gastrointestinal
Disorders(Infliximab)
 TNF-is an inflammatory cytokine thought to have a
contributory role in producing chronic inflammation in
various diseases, including Crohn’s disease and
rheumatoid arthritis
 is a mouse–human chimeric monoclonal neutralizing
antibody to human TNF- and is considered a
biological drug
 Specific indications are for the reduction of signs and
symptoms in patients with moderately to severely
active Crohn’s disease) and fistulizing Crohn’s
disease
 Responses occur within 2 weeks of an infusion,

19. The most common side effects
 include rash
 low blood pressure
 chills, and chest pain these symptoms are
generally temporary and often respond to a
decrease in infusion rate
 Another side effect is increased risk of
infections
 Fatal cases of tuberculosis have been
reported following infliximab therapy
 increased risk of lymphoma