# Viva C(v)a

This viva is relevant to the objectives of Section C(v)  of the 2017 CICM Primary Syllabus, which asks the exam candidate to "describe affinity and dissociation constants".

###### What are the rate constants of drug and receptor binding?
• kon  and koff are rate constants for association and dissociation: • The population of drug molecules and receptor molecules combine at a certain rate kon,  and then separate again at another (possibly different) rate koff.
• When the system is allowed to rest for an infinitely long time these reactions will run to an equilibrium, where there will be a constant concentration of free drug, unbound receptor and drug/receptor complexes.
• In this equilibrium state, kon = koff.
• Units used to describe rate constants are usually are units of [D] multiplied by the units of [R] over time, i.e. it is usually expressed in moles per second

(Lower case "k" is used to denote rate constants such as kon and koff, whereas uppercase K is used for equilibrium constants (such as Kd). To be precise, kon and koff are actually not the official terms - the IUPAC would prefer you to use k+1 for the association reaction and k-1 for the dissociation of drug from receptor)

###### What is the dissociation constant?
• Kd is the dissociation constant. This is the constant which describes the drug / receptor interactions at equilibrium.
• Kd = koff / kon
• The units for Kd are mol/L , i.e. units of concentration.
###### What is the association constant?
• It is the opposite of Kd; i.e. when a drug has a low Kd it has a high Ka(i.e. it binds avidly to the receptor).
• The colloquial term "affinity" is often used interchangeably with Ka; however affinity as a chemical definition is actually something slightly different.
###### What is meant by "affinity", with regards to drug-receptor interactions?
• Affinity is usually used to describe how avidly a drug binds to its receptor.
• This concept is borrowed from chemical physics and physical chemistry, where affinity is defined as the quantifiable representation of the tendency of dissimilar chemical species to form chemical compounds.
###### What are the determinants of affinity?
• The major factors which affect affinity and dissociation constant are
• Temperature
• Presence of a catalyst.
• The presence of a catalyst affects the activation energy for the reaction (Ea)
• In general, the rate of any reaction is determined by the Arrhenius equation, in which most factors are fixed constants (eg. the universal gas constant). 