Cano content L6-9 Flashcards
Define enzyme inhibitors
Enzyme inhibitors are molecules that interact in some way with the enzyme and decrease their activity
What do reversible inhibitors do and what are the two type
Bind to the enzyme using weak bond
- competitive
- non-competitive
What do irreversible inhibitors do
Bind to the enzyme using a strong, usually covalent bond
Describe reversible inhibitors
Reversible inhibitors bind to enzymes with non-covalent interactions such as hydrogen bonds, hydrophobic interactions and electrostatic bonds. Multiple weak bonds between the inhibitor and the active site combine to produce strong and specific binding
Describe competitive inhibition
In competitive inhibition the inhibitor binds to the substrate binding site, preventing the substrate binding.
Describe non-competitive inhibition
A non-competitive inhibitor may be bonded at, near, or remote from the active site. The basic structure of the enzyme is modified to the degree that is ceases to work
Describe irreversible inhibitors
Irreversible inhibitors usually covalently modify an enzyme and inhibition cannot be reversed.
Define co-enzymes
Co-enzymes are organic molecules or metal ions that bind to the active site to allow the catalytic action. They do not form a permanent part of the enzymes’ structures
What are co-enzymes
co-enzymes function act as intermediate carriers of electrons, specific atoms or functional groups that are transferred in the overall reaction
What must a drug be in order for it to be truly bioavailable
for a drug to be truly bioavailable it must not only be soluble but must also cross the phospholipid bilayer membrane surrounding cells
What is importance of solubility
- many drugs are given in solid dosage forms and must dissolve before absorption can take place
- If absorption is slow relative to dissolution then solubility is not
an issue - However, if dissolution is slow, then the factors affecting
dissolution are important
What happens as solubility increases
as solubility increases so does the rate of dissolution
List the Physicochemical properties of drugs
ionisation constants
Aqueous solubility
Lipophilicity
Partition coefficient as a measure of lipophilicity
Distribution coefficient
What is important in determining the ionisation state
The pH and drug pKa are important in determining the ionisation state and will influence significantly the transport
What is pKa and what does it help to determine
The pKa or ‘Dissociation Constant’ is a measure of the strength of an acid or a base. Allows you to determine the charge on a molecule at any given pH
What sort of Ka does a strong and weak acid have
strong acids have a high Ka and weak acids have a low Ka
Describe drugs that have ionisable groups
many drugs have ionisable groups and need to be in a particular ionisation state in order to act, to be absorbed they may need tot be in a different ionisation state
What does amphipathic mean
having both hydrophilic and lipophilic parts
Why is a weak acid at acid pH more lipid soluble
because it is uncharged, a weak acid at acid pH will pick up a proton and become uncharged
Why is a weak base at alkaline pH more lipid soluble
because it is uncharged, a weak base at alkaline pH will lose a proton and become uncharged
What is the partition coefficient p
is a measure of the relative solubitlity of a molecule in the aqueous phases vs the organic phase in the absence of ionisation
What does it mean if logP = 1
10:1 ratio of organic:aqueous
What does is mean if log P = 0
1:1 ration of organic:aqueous
What does log P = -1 mean
1:10 ration of organic: aqueous
