1. PLANT ALKALOIDS Prof.Dr.,NASHAAT LOTFY
PREPARED BY:
ALIAA KHALID SALMA SADEK
SHAIMAA ADEL MARWA SHAABAN MONA AHMED
SUPERVISED BY:
Prof.Dr.,NASHAAT LOTFY

2. INTRODUCTION
Plant alkaloid chemotherapeutic agents, as the name suggests, are plant derivatives.
They are cell-cycle specific chemotherapeutic agents. However, the phase affected is based on the drug used for the treatment.

3. CLASSIFICATION OF PLANT ALKALOIDS

4. PLANT ALKALOIDS,cont’d.
VINCA ALKALOIDS
TAXANES
CAMPTOTHECINS
PODOPHYLLOTOXIN

5. A)VINCA ALKALOIDS The vinca alkaloids are also called
antimitotic or antimicrotubule agents,
or mitotic inhibitors.
Vinca alkaloids are derived from the periwinkle plant, Vinca rosea (Catharanthus roseus)
Include vinblastine, vincristine, vindesine and vinorelbine(semi-synthetic)

6. VINCA ALKALOIDS,cont’d.
MECHANISM OF ACTION:
They are cell-cycle specific and phase specific, because they block mitosis in metaphase (M phase).
They block the ability of tubulin to polymerize to form microtubules.
The resulting dysfunctional spindle apparatus, frozen in metaphase, preventing chromosomal segregation and cell proliferation.

7. VINCA ALKALOIDS,cont’d.
PHARMACOKINETICS:
METHOD OF ADMINISTRARTION:
For I.V use only through free flowing I.V. line to avoid extravasation
FATAL if given by other routes.
Intrathecal (IT) route is nearly always fatal and is a medical emergency.
Exception: vinorelbine can be taken both orally and I.V.
DILUTION:
All can be diluted with either Glucose 5% or saline 0.9% except for vinblastine which is diluted only with saline 0.9%.
Poorly & erratically absorbed by oral route, except for vinorelbine which is absorbed also orally.
ABSORPTION
Rapid and extensive binding to tissue
DISTRIBUTION
Hepatic cytochrome P-450
METABOLISM
Primarily bilary/fecal
Some renal excretion
EXCRETION
Doses must be modified in patients with impaired hepatic function or biliary obstruction.

8. VINCA ALKALOIDS,cont’d
ORGAN SITE
SIDE EFFECT
Blood/bone marrow
Leukopenia, granulocytopenia, anemia ,thrombocytopenia
Neurological
Variable
Cardiovascular
Hypertension, stroke, MI,
Raynaud’s phenomenon esp. when combined with bleomycin.
Dermatology/skin
Extravasations, vesicant ,alopecia ,injection site pain ,phlebitis
Gastrointestinal
Constipation , nausea, vomiting , anorexia.
Infection
Pneumonia
pulmonary
Acute shortness of breath and bronchospasm dyspnea ,pulmonary edema
Auditory
Ototoxicity partial or total, temporary or permanent
Miscellaneous
Tumour lysis syndrome,tiredness, weakness, loss of fertility.
CAUTION with opioid analgesics due to the risk of additive autonomic neuropathy
which may result in severe constipation.
CAUTION Patients with preexisting ischemic cardiovascular disease .
A bowel regimen including high fiber diet and a stool softner should be initiated
CAUTION Patients with preexisting pulmonary dysfunction
CAUTION with other ototoxic medications such as
platinum-containing antineoplastics,

9. VINCA ALKALOIDS,cont’d
MECHANISM OF RESISTANCE:
Resistant cells have been shown to have
an enhanced efflux of vinca alkaloids
via P-glycoprotein in the cell membrane.
Alterations in tubulin structure may
also affect binding of the vinca alkaloids.
CONTRAINDICATIONS:
Hypersensitivity to any component
Pregnancy : Category D
Breast feeding

10. COMPARISON

11. VINBLASTINE VINCRISTINE VINORELBINE VINDESINE INDICATION HALF-LIFE
SYNONYMS
VBL, VLB
LCR, VCR, VX
VRB,VRL,VNL, NVB
DAVA, DVA, VDS
TRADE NAMES
Vilban® Velbe®
Cytoblastin®
Velbastine ®
Oncovin® Vinacrine® Vincristine® Cytocristin®
Navelbine®
Eldisine ®
INDICATION
-Hodgkin’s and
non-Hodgkin’s
lymphoma
-Testicular cancer
-Kaposi’s sarcoma
-Breast cancer
-ALL &MM
-Hodgkin’s and non-
Hodgkin’s lymphoma
-Chronic leukemias
-Non-small cell lung cancer
-Breast cancer.
-Testicular cancers.
-Ovarian cancers.
-ALL & CML.
-Lung carcinomas.
-Colorectal cancer.
HALF-LIFE
25 hrs
23-85 h
adults: h
children: 14.7 h
t½ α 3 minutes
t½ β hr
t½ γ hr
DOSE &
PROTOCOLS
Hodgkin’s disease:
(ABVD)
6 mg/m2 IV on day 1 and 15
Testicular cancer:
(PVB)
0.15 mg/Kg IV on day 1 and 2
-Doses vary between 0.5 and 1.4 mg/m2.
-The total individual dose should be limited to 2 mg to avoid neurotoxicity.
Multiple myeloma
(VAD)
Continous infusion:
0.4 mg/day for 4 days.
Leukemia [POMP]
Orally:
60-80 mg/m2 once weekly for three weeks, MAXIMUM 160 mg once weekly
By I.V. infusion:
As a single agent: 30 mg/m2 weekly,given by intravenous infusion only over 6-10 minutes.
As combination with
cisplatin: 25mg/m2 weekly.
Adults:
2-4 mg/m2
q1-2w
1.5 mg/m2/day x 5-7 days q3-4w
Adriamycin
Bleomycin Vinblastine
Dacarbazine
Vincristine
Adriamycin
Dexamethasone
Cisplastin
Vinblastin
Bleomycin
6-MP(Purinethol), Oncovin,
MTX
Prednisone

12. -Autonomic neuropathy
TOXICITY
VINBLASTINE
VINCRISTINE
VINORELBINE
VINDESINE
NEUROTOXICITY:
mostly mild parasthesia much less common and less
severe than vincristine
MYELOSUPPRESSION
leukopenia;
dose-related
nadir 4-10 days
CBC should be monitored.
-1ry and dose-limiting.
-reversible, but can persist for months after stopping therapy .
-Peripheral neuropathy
loss of deep tendon
reflexes,parasthesi,pain in
almost all patients
-Autonomic neuropathy
Resulting in constipation
Central neuropathy headache, malaise, dizziness, seizures, depression, SIADH
Mild and much less significant than with vinblastine
less neurotoxicity than other vinca alaka
GRANULOCYTOPENIA
-dose-limiting.
-nadirs occur between
7 -10 days
-CBC with differentials
should be performed&
results reviewed prior to
administering each dose
-should not be
administered to patients
with granulocyte counts
< 1,000 cells/mm3
Mostly severe
-usually severe.
- CBC with differentials
with granulocyte counts < 1,000 cells/mm3
NEUROTOXICITY:
Careful baseline
neurologic evaluation
should be performed
before starting therapy
and at the start
of each cycle.
Granulocytopenia :

13. DRUG-DRUG INTERACTIONS
MANAGEMNET
MECHANISM
EFFECT
AGENT
-Avoid combination
-Decrease dose & monitor for toxicity
Inhibition of metabolism via CYP450
Toxicity
Cyclosporin
Erythromycin
Cimetidine &
Azole antifungals
-Observe clinical response when starting or stopping carbamazepine
Enhance metabolism via CYP450
Efficacy
Carbamazepine
Monitor phenytoin serum levels observe development of siezures.
Decrease absorption &/or increase metabolism of phenytoin
Efficacy of phenytoin
Phenytoin
Monitor for signs of reduction in digoxin efficacy.
Decrease absorption
Efficacy of digoxin
Digoxin
Use bronchodilators, corticosteroids and/or oxygen for symptomatic relief
Unknown
-Acute dyspnea& bronchospasm
Mitomycin
Monitor for signs and symptoms of neuropathy
Additive effect
Neurotoxicity
Cisplatin
Paclitaxel