Lecture 1 and 2 (Part 1) Flashcards
What are the most common binding sites for drugs?
Proteins, particularly enzymes, carrier proteins, ion channels and receptors
What are the three types of ligands that are recognised by receptors?
Neurotransmitters such as noradrenalineHormones such as adrenalineLocal Hormones such as prostaglandins
What are ligands?
Chemicals that bind to a receptor
What is efficacy?
The ability to create a signal by binding to a receptor
What features must a ligand have to produce its intended effect?
Must bind to the target receptor with some selectivity, which is determined by the shape, charge and size of the ligand and the receptors binding sites
What is affinity with respect to a receptor?
The attraction of a ligand for a receptor
How is efficacy measured?
On a scale of 0 (no activity) to 1 (maximum possible activity)
What is the difference between agonists and antagonists?
Agonists are mimics which have both affinity and efficacy while antagonists are blockers which have affinity but NO efficacy
Why do side effects occur when drugs are taken?
No drug is totally specific for a receptor family which will lead to unwanted side effects
What is important about receptor structure?
Specificity for ligandVerification of receptor family subtypesStructure confers functionally important characteristics for intracellular signallingStructure is fluid
What is a family with respect to receptors?
Families all have one endogenous ligand
what is Drug action is dependant on?
Drug properties (selectivity for receptor subtypes)Tissue properties (Distribution of receptor subtypes throughout tissues)
What are the different histamine receptors?
H1= Skin, Allergic reactionsH2= Stomach and acid secretionH3= CNS, ileum and cardiac tissue often pre-synaptic and autoregulatory
What is selectivity?
Preferential binding to a certain subtype leading to a greater effect on that subtype to help avoid side effects
Why is salbutamol used as opposed to fenoterol and propranolol?
Salbutamol is selective for Beta1 receptors which affects the lungs while, fenoterol would affect both beta 1 and beta 2 receptors to cause vasodilation and slowing of the heartPropranolol affects both beta receptors to slow down the heart but will also block airways
What are the different antagonists for each of the histamine receptor subtypes?
H1= antihistamines (chloropheniramine, loratidine)H2= Inhibition of gastric acid secretion (cimetidine)H3= typically experimental but could be used for treating pain and inflammation (thioperamide)
How does the two isoforms of COX show the importance of selectivity?
COX I is used in homeostatic mechanisms while COX II is only induced in inflammationNSAIDs which universally inhibited COX therefore caused problems like ulcers and uncontrollable bleeding not seen with the more modern rofecoxib or celecoxib which are selective for COX II
What are the four receptor theories?
Receptor occupancy theory, rate theory, two state model, floating receptor model
What is the receptor occupancy theory?
The drug effect is directly proportional to the number of receptors occupied
What is the rate theory?
The drug effect is directly proportional to the rate of occupancy
What is the two state model?
Receptors exist in active or inactive form
What is the floating receptor model?
The D-R complex may interact with a variety of effectors in the membrane to produce its effect
What is the underlying principle of occupancy theory?
When a drug is present in the body there is an equilibrium present, of free receptor + unbound drug to drug-receptor complexcausing there to be a logarithmic fractional occupancy-concentration relationship
What is Ka/Kd?
The association/dissociation constantConcentration of the ligand which gives 50% occupancy
What is the two state receptor model?
Receptors can exist in two states, inactive and active which causes an equilibrium independent of agonist presence, which in the absence of agonist strongly favours the inactive positionFull agonists bind only to the active form and fix it in this positionPartial agonists bind mostly to the active form, but some to the inactive formAntagonists bind to either the inactive or active form with no preference
