drug discovery

Question 1

What are small molecule drugs?

Answer 1

natural compounds, normally produced by organsims. e.g penicillin, rapamycin (mTOR inhibitor)

(Semi) synthetic chemistry: modified nautural compounds, libaries of chemically sysnthesised compounds

Question 2

What are some deriviatives of morphine?

Answer 2

heroin. made by boiling morphine with acetic acid.

codeine.

Question 3

what is methadone?

Answer 3

is a synthetic drug made to fill the gap of morphine in germany at the end of the first world war. Has analgesic properties. can still cause respiratory depression but lacks the euphoric effects of morphine and heroin. Still additive.

Question 4

what is the aim of phase 1 clinical studies?

Answer 4

to define the pharmacology, route and metabolic fate in humans. tends to have a fraction of the effective dose in animals.

small number study.

Question 5

What is the purpose of phase 2?

Answer 5

to define the therapeutic profile and dose regimen,

there is lots of dose ranging so there are lots of data at sub optimal doses.

larger study with more patients.

there is a limited number of clinical centres involved.

Start to look at the pharacokinetic aspects of the the drugs metabolism

Question 6

what occurs in phase 3 studies?

Answer 6

Determination of the clinical efficacy compared to placebo / comparators.

there is a greater duration of treatment and there are larger numbers studied.

multiple clinical centres are used and often multiple indications are investigated.

there is a close monitoring of compliance and other drugs and side effects.

Question 7

Phase 4 studies do what?

Answer 7

there is less controlled clinical practice than in phase 3 and large numbers and more diverse paitents are treated

Adverse drug reactions (ADRs) are reported by practitioners.

black triangle drugs- all ADRs and events should be reported. (drugs that are monitored more heavily as they are new )

Question 8

what reasons might a drug fail to get to market?

Answer 8

lack efficay at target
lack of target linkage
no testable model
lack of suitable biomarker

Question 9

what is the purpose of a biomarker?

Answer 9

to measure the effect of your drug in vivo. it is best when can actually mesure the correct tissue

Question 10

What are reasons to modify a lead drug target?

Answer 10

to generate new specicifities
to increase target selectivity 
to increase the bioactivty 
increase efficay and potency
to change the ADME profiles

Question 11

why is compartmetn pH important in absorbtion and elimination of drugs?

Answer 11

absorption of acidic drugs are better in teh stomach but basic drugs are better in the ileum.

renal excretion leads to acidic drugs being more rapidly excreted by the kidneys if the pH of the urine is more alakaline. alakaline drugs are more protonated so their urirnary excretion is faster if the urine is more acicic.

Question 12

what are isosteres?

Answer 12

where the atoms or groups of atoms or molecules or compounds have the same arrangement and or same number of electrons but have a change in an atom. e.g a carbon to a nitrogen.