BIOL2212 Chemotherapy Intro

Two types of chemotherapy

anti-infective chemotherapy

cancer chemotherapy

what is anti-infective chemotherapy

use to prev or treat disease caused by parasitic organisms or MOs

selective for target

what is cancer chemotherapy

drugs used to treat cancer

usually induce lethal cytotoxic event or apoptosis

ideally only interfer with cancerous cells

how is chemotherapy used as a treatment

prevent

treat

cure

3 sources of most drugs

MOs (soil bact)

plants

man made

what drugs have been sourced from plants

anticancer and antimalarial

drug discovery methods (4)

serendipity/chance

empirical screening of natural and sythetic mols

synthetic mod of pharmacophores followed with focused screening

target driven approaches

explain empirical screening of natural and synthetic mols

test large library of compounds against a biological system without knowning exact target or mech of action

what is a pharmacophore

essential structure (geometric arrangement of atoms or functional groups) necessary for binding/biological response

explain target driven approaches of drug discovery

known target, design entire drug around it

empirical screening vs focused screening

screen large library against nonspecific target/entire biological system

smaller library tested against specific target

3 ways chemotherapeutic drugs exploit enzymes

inhibitors

false substrate so waste resources and pot form toxic product

pro-drug given so chem mod by enzyme form active drug

define therapeutic index

ratio of the dose that prods toxicity to the dose tha prods clinically desired effect

a meaure of drug safety

is a large or small therapetutic effect better

larger

(can safely prod therapeutic effect without being near toxic dose)

when are drugs with a lower therapeutic index used

cases of more lifethreatening diseases where adverse effects tolerated for hope of treatment/cure (cancer)

what does ADME of a drug determine

speed of onset

intensity of action

duration

what is ADME

absorption

distribution

metabolism

elimination

what are the two types of administration

enteral

parenteral

what are enteral routes of administration

admin related to the intestines/GI tract

deliver drug directly across the body’s barrier defenses and used

what are parenteral routes of administration

non GI tract routes of admin

where are orally administered drugs absorbed

stomach or intestine

what effect does ingestion of a drug with food have

decrease its absorbance

by diluting drug and delaying gastric emptying so acid can destroy drug so drug unavailable for abs

what is an enteric coating on a drug

coating that protects drug from stomach acid

what process affects orally adminstered drugs that IV administered drugs avoid

first pass metabolism by the liver

how can first pass metabolism be overcome

use I.V. injection instead

give higher oral dose

benefits of parenteral routes of administration

give higher bioavailability, especially I.V.

no first pass metabolism

rapid effect

gives maximum control over circulating drug levels

3 types of parenteral administration

I.V.

S.C.

I.M

benefit of S.C. and I.M. that I.V. doesnt have

suitable for sustained release

act as drug depot/reservoir

down sides of parenteral administration

hard to self administer

pot intro bact.

cant recall drug once given (oral can make vomit or give activated charcoal to bind it)

fast admin can induce haemolysis (immune breakdown of RBC)

2 absorption methods of orally administered drugs

passive diffusion - down grad, no carrier, most common, for both lipid and water sol drugs (channel or diff thru bilayerO)

Carrier mediated active transport - drug resembles transp mol

define bioavailability

fraction of administered drug that reaches systemic circulation in a chemically unchanged form

how do you calculate bioavailability

compare plasma levels achieve with RoA to I.V. admin levels

(Area under curve of RoA/AUC I.V. x 100 on plasma drug conc vs time graph)

factors that affect bioavailability

first pass metab

solubility of drug

chemical stability

nature of drug frormulation

define drug distribution

process of drugs reversibly leaving bloodstream into extracellular fluid (intersitium) and cells

another name for extracellular fluid

intersitium

what influences drug distribution

blood flow to area and capillary perm

drug structure and physiochemical properties (charge hydrophobicity)

reversible binding to plasma proteins

what plasma protein is often bound to by drugs

albumin

how do drugs bind to plasma proteins

reversibly

nonspecific

at sites where endogenous compounds normally bind

effect of drug binding to plasma proteins

sequesters drug in nondiffusable form

can act as drug reservoir

how are drugs metabolised

biotransformation (then excreted into urine)

principal site is the liver

what is the principal site of drug metabolism

liver

2 processes of biotransformation

conv lipophilic drugs into more polar mols thru reactions cat. by cytochrome p450 system

subsequent conjugation reactions to further enhance conversion to polar, water sol metabolites

purpose of drug metabolism

convert drug into more water soluble form that is readily excreted

what is the principal route of drug elimination

thru kidney into urine

how are drugs eliminated other than the kidney

bile

intestine

lung

sweat

milk in nursing mothers