Drugs 5

• PK


  what body does to a drug
• PD 


  what drug does to the body
• drug-target interaction


  the different ways drug interacts with target to produce a biological effect
• drug suffix -zumab


  antibody
• drug suffix -vir


  related to virus
• drug targets


  molecules (often proteins) the function of which can be modulated by a drug to produce a biological effect, drugs bind to
• 4 groups of proteins as drug targets

  ion channels, enzymes, transporters, receptors
• receptors in context of drugs


  proteins that recognise (sense/detect external chemical signals) and respond to endogenous chemical signals (transduce signal into change in activity)
• agonists


  endogenous or exogenous molecules that have affinity for and efficacy at a receptor to elicit a biological response
• antagonists


  molecules that have affinity for a receptor to limit the effects of agonists but lack intrinsic activity
• 4 receptor super families

  nuclear receptors, enzyme linked receptors, GPCRs, ligand gated ion channels
• ligand gated ion channel example and location

  GABAa receptor on cell membrane (respond in milliseconds)
• GPCR example and location

  adrenoreceptor, cell membrane (respond in s)
• drug affinity 


  binding strength of a drug to a target
• Kd 


  the conc of ligand at which 50% of the receptors are ligand bound, used to compare affinity of drug
• low Kd


  high affinity
• fraction of receptors bound by ligand


  (conc ligand) / (Kd) + (conc ligand)
• what do differences in Kd explain

  differences in potency and selectivity
• adrenoreceptor affinity

  high affinity for B-adrenoreceptor, low for a-adrenoreceptor
• drug efficacy


  ability of a drug to elicit a response once bound to a drug target
• agonist binding receptor leads to a biological effect that requires a number of steps
• full agonist 


  high efficacy, high level of receptor activation = large effect
• partial agonist


  agonist with low efficacy (between 0 and 1), low level of receptor activation = small effect
• antagonist 


  no efficacy, bind to target but don't elicit response
• magnitude of agonist induced effect - drug related factors

  conc, affinity, efficacy
• magnitude of agonist induced effect - cell factors

  receptor density, capacity of cell to convert receptor activation into change in cellular activity
• receptor density and max agonist induced effect

  as decreases, max effect decrease
• signal amplification effect on agonist induced effect

  as decrease effect max of agonist decreases
• dose/conc - response relationship 


  relationship between dose or conc of drug and magnitude of response produced
• drug potency


  amount of drug (conc or dose) needed to produce a defined effect
• antagonist potency


  conc that reduce the response to an agonist
• agonist potency 


  measured as the effective conc/dose required to produce 50% of the max response (EC/ED50) to agonist
• what does agonist potency depend on

  affinity, efficacy, cell factors
• lower EC/ED 50 means

  higher potency
• drug selectivity 


  ability of a drug to discriminate between drug targets (depends on preferential affinity for a target over another)
• what happens to drug selectivity at higher concs

  apparent selectivity of drug may be lost
• drugs that are agonists

  form receptor-ligand complex, conformational change to initiate signal transduction
• example of a drug that is an agonist

  morphine (mimic endorphin), binds GPCR