Alkylating Agents Flashcards
MOA of Alkylating agents
Carbonium and immonium ion intermediates..
Linked to high electron density sites..
And transfer alkyl groups..
What are high electron density sites
Hydroxyl , Carboxyl, Sulphydryl, amino groups
Most susceptible parts of nucleobasis
Guanine - N7, O6
Adenine - N1, N3
Cytosine - N3
How immonium ion is formed and involved in mechanism
Intracellular Cyclisation of Alkylating agents - ethylene immonium ion - which either directly or through the formation of carbonium ion…
Types of Alkylating agents
SN2 - Directly react - Conc of Alkylating agents and cellular cons …..
SN1 - Reactive intermediates - Conc. Of reactive intermediates
Examples of SN1 and SN2
Nitrogen mustard
Nitrosoureas
Busulfan
What is carbomoylation
Lysine reacts with isocyanic acid to form isocyanate
Nitrosoureas MOA
Carbamoylation - Isocyanate - on single or both strands - which lead to abnormal base pairing
Effective on rapidly dividing cells
Pharmacokinetics of Alkylating agents
IV, orally, subcutaneous
Which enzyme reactive alkylating agent is created
Liver microsomal cytochrome P450 enzyme
Eg of activation of 1st alkylating agent..
Precursor - Cyclophosphamide - 4 hydroxy cyclophosphamide and aldophophamide -
End Product - phosphoramide
What is MOPP
Combination therapy
M - Mechlorethamine
O - Oncovin
P - Prednisone
P - Procarbazine
Use of MOPP therapy
Haematologic and solid Cancers.
Use of Cyclophosphamide
Burketts lymphoma
Hodgkin’s lymphoma
Breast Cancer
Use of Nitrosoureas
Preferred in brain tumors
