Pharmacology Flashcards
What is pharmacology?
A branch of science that deals with the study of drugs and their actions on living systems
What are the integral branches of pharmacology?
Pharmacodynamics
Pharmacokinetics
What is pharmacodynamics?
What the drug does to the body
Drug action and mechanism
What is pharmacokinetics?
What the body does to the drug
Barriers (ADME)
What are the key drug binding sites?
Dugs as enzyme inhibitors or substrates
Drugs targeting transporters
Drug targeting voltage gated ion channels
Drugs targeting receptors
What are the general characteristics of receptors?
Selectivity of ligands
Molecular switch
Amplification of signal
What is specificity in biology?
Right target
What is specificity in chemistry?
Right target binding site
What assessment is more critical risk or benefit?
Risk
Out of affinity and efficacy what traits do agonists and antagonists have ?
Agonists have affinity and efficacy
Antagonists only have affinity
What is affinity?
The ability of drug binding to receptor
What is efficacy?
The ability of drug to activate the receptor
What is the concentration required to occupy 50% at equilibrium of receptor called?
kD
What is an empirical measurement of antagonist potency?
EC50
Effective Concentration of agonist for 50% response
Why is potency often lower than affinity?
spare receptors/ receptor reserves
what is a drug?
chemical with a selective therapeutic agent
what does it mean when a drug targetting enzyem is reversable?
leaves enzyme without changes the active site
what does it mean when a drug targetting enzyme is irreversible?
stays on enzyme longer changing the active site
what is compettive binding?
drug compeats for active site on enzyme
what is noncompetitive binding?
drug binds to a different site on the enzyme which leads to the substrate bot being able to bind
what happens when transpotrters are in a normal state and then what happens when a drug has targeted the transporters?
transporters take back the neurotransmitters released from the presynaptic cleft after a stimulation of receptors
a drug blocks transporters which leads to no more neurotransmission to be taken back to the pre synaptic cleft
what happens when there is an ion channel blocking drug?
block sodium channel to stop depolarisation
what are the types of receptors that drugs target?
nuclear
ligand gated ion channels
catalytic receptors
g-protein coupled receptors
what happens when an inactive receptors binds with a drug?
becomes active and releases a signal
what are the general characteristics of receptors?
amplification of signals
what is relativity in terms of drug?
everything is poisonus, nothing is poisonus it is all a question of dose
what is an agonist?
deactivates the receptor but produces a similar response that would have already be given
what is an antagonist?
block the receptor
reduce the response
oppose the agonist function
what are the stages of drug receptor binding?
drug+receptor(inactive)
drug/receptor (inactive)
drug/receptor(active)
what stages of drug receptor binding show affinity?
drug+receptor(inactive)
drug/receptor(inactive)
what stages of drug receptor binding show efficacy?
drug/receptor(inactive)
drug/receptor (active)
what is a full agonist?
produces 100% response
has a receptor reserve
what is a partial agonist?
produces less than 100% max response with maximal receptor occupation
what does a competitive antagonist do?
block binding by occupying the binding site
what does a non-competitive antagonist do?
blocks response by binding different binding site from the agonist
what are the possible types of drug antagonisms?
decreased absorption/altered distribution
increased metabolism
increased renal excretion
different physcological mechanism
what does low kD mean in terms of deug affinity?
higher drug affinity?
when doing the graph how do you change the units for ease of use to see what 50% is?
change concentration to log(M)
what does 100% on the conc/potency mean?
efficacy of drug concentration
receptor max
in what shape should the conc/potency graph be?
sigmoid curve
what is the result of a full agonist?
100% response with 50% occupation (can be different for each receptors)
what is the result of a partial agonist?
1005 receptor occupancy but produces less than 100% response
what is endogenus?
inside the body
what does a reversable antagonist do?
dissociate from receptor
increase against conc can lead to more response against can achieve max with more conc
what is the general structure of catalytic receptors?
outside: N terminal and binding site
cell membrane site
inside: enzyme domains and C terminal
what is receptor tyrosine kinase used for?
receptor for growth factors
Epidermal growth factor- EGF
Vascular endothelial growth factor-VEGF
Insulin
Neurotrophins
Insulin-like growth factor- IGF
Platelet-derived growth factor- PDGF
& many others
what are the characteristics of receptor tyrosine kinase?
Growth factor binding RTK, leads
dimerization and autophosphorylation
One tyrosine kinase activate
autophosphorylation of its partner and
vice versa
Signalling proteins recruited to RTK
Signalling proteins contains SH2 domain
to sense and bind specific RTK (specificity)
what are SH2 domain proteins?
Some SH2 domain proteins are enzymes
They directly produce signals: e.g.
phospholipase C- activation leads intracellular
calcium release and PK C activation
Some SH2 domain proteins are adaptors
They link the RTK with the signalling protein
-e.g. Grb2 links between EGF receptor and
SOS, a regulator of the Ras-MAP kinase
pathway (
what are the characteristics of guanynyl cyclase receptors?
Limited membrane bound
e.g- atrial natriuretic peptide
(recollect CVS lecture 5)
-released from atria, promotes
vasodilation and urinary sodium
excretion
GTP–> cGMP–>PK G–> vasodilation
what ions are most abundant in the body?
cations: sodium, potassium, calcium
anions: chloride, phosphate, fluoride
what are the key features and properties of ion channels?
- selective membrane pore
- types of sensors or molecular switch
- specific sensor for gating (open and close)
- regulatory mechanisms
what is a p-loop in an ion channel?
selectively filter/molecular sieve- alogn together to form a transmembrane
what is a S4-voltage sensor in a ion channel?
contains positively charged aminoacids- can move up and down in response to changes in membrane potential
what can voltage gated ion channels be influenced by?
other inorganic ions
neurotoxins
drugs
what is use dependany of sodium ion channel?
the ion bockade is dependant on the rate of action potential discharge
what are the differengt types of calcium ion channels?
t-type
n-type
l-type
what process does potassium ion channel go through?
repolarisation and hyperpolarisation
what are the characteristics of ligand gated ion channels?
- N & C terminus are located extracellular
- Extracellular ligand binding site
- S2 transmembrane domain forms the pore lining
- 5 different subunits attach to form a pentamer
what is the process in ligand-gated cation channels?
Cation channels (Na+) – nicotinic Ach, glutamate, 5HT, P2X > Depolarisation»_space; Excitatory
what is the process in ligand-gated anion channels?
Anion channel (Cl-): GABA»_space; GABAA ICl »_space; Hyperpolarisation»_space; Inhibitory
what are the advantages of allosteric drugs?
*offers a novel pharmacological options of “fine-tuning”
receptor function
*
*intensify a weakened hormone/ NT signal caused by localised
deficit
*
*Clinically safer drugs with enhanced selectivity and reduced
liability for receptor tolerance and/or desensitation
