Receptors Flashcards
Receptors and ligands
ligand is a chemical, substance that binds to receptor
Receptor Protein intra or exta cellular component ligand/drug bind to start chain of bio actions by drugs effect
Receptor concepts
Determing quantiitvative info, drug dose, effect.
Drug respone=#of drug receptor complexes
Selective
Bilion of yr old
Drug 100y
Medicate action of drug agonist or antagonist
Types of drug receptors
Proteins- Reg proteins, enymes, transport, structall cell components
DNA, RNA
Ribosomes, synthetic?
Enantiomers and receptor binding
?
Law of mass action and drug receptor binding
Theory-Kon Koff rates controls Assumes- all receptors are equally accessible to drug Partial binding not accounted Drug is not altered by bind Binding reversilbe
Drug + Receptor__Drug-Receptor contration. More subtrates dissoactes to product. vice versa
Potency vs efficacy
Efficacy- maximal response a drug produces. More important when selecting drug.
Potent- amt of drug (EC50) req. to produce 50% of max effect, determine Pt dose.
More potent= less drug concentration in o/t reach efficacy
Quantal dose response curve
inc. fraction of a pop. that shaw a specif respon at progressing inc does.
Sigmoid shape
Digital respons-yes, no, “HA gone yes”
ED, LD
ED50, TD50 LD50 , Kd
median effective dose- “Yes pain gone”
Toxic does
Lethal does
Grade dose, concentration of dose that cause 50% of max effect or toxicity.
Quantal- concentration or dose that cause effect in 50% population
Kd- concentration of drug that bind to 50% of avail receptors
Receptor effector coupling
transduction of drug+recptor= biological response
cascade of events
Spare receptors concept
Max effect produced but not all receptors filled Kd>ED50
If Ed50
Receptor conformation , Ri and Ra
Drugs that shift to Ractive to R inactive receptor pool, Low intrsicic efficacy
Inverse agonist
Drug+receptor= biological response by altering cell state, tips toward inactive, decrease effect
Bind to Ri, drives pool toward Ri
Benzodiaepines at GABBA receptor-inc. flow of Cl to shut down neuron
Types of antagonists
Competitive response by blocking, but can get kicked off
Epinephrine kicks off propranolol aftr exercises
Noncompetivie- no matter how much agonist, recepter remained blocked
Many sites to block
Keep Ra and Ri proportion in balance
Chemical vs physicological antagonism vs pharmoclolgical
chemical- blocks other drug, use drug to kill other drug binding
Phys- drug that encounters another drug, bind to diff site for opposite effect. hcortisone inc gluclose levels, insulin to stop
Rx-drug that binds with no acitvation
Receptor desensitization
Receptor down and up regulation
no response on some or over time
Receptors less receptors
Changes in concentration endogenous receptor ligand
Change in components of response distal to receptor
Alteration in drug concentration wen it reaches receptor
Therapeutic index
measure of drugs toxicity
TD(LD):ED ratio
Death ultimate toxic
quantal dose based- population animals only
Therapeutic range/windo
range of concentration of drug in the blood that will have max effect
Anything below {} will not work
Anything above {} will be toxin
Small range helpful but kill many
Large ranges very available bbut side effects
Lipid soluble, intracellular
drug diffuses thru membrane to bind to intracelluar receptor- STEROID- allow transciption to initate Take hrs for effect 2d duration Highly lipid soluble drugs
Activate IC enzyme domain
Ligand regulatd transmembrane
28% of drugs
w/in membrane.
outer layer- provides receptor fx
IC layer- l/t regulate IC enzyme A to B, product
Insulin-binds l/t IC enzyme activation
Sugar-so much in system, receptors desensitzed when it binds, overworked. insulin resistance
Activate IC tyrosine kinase (cytokine receptor)
bind IC tyrosine kinase enzymes (JAKs-STAT receptors
transcription regulators
Growth hormone
Ligand Ion gated channel
5%
protein opens or closes by drug-receptor binding
ACh, GABA
G Protein coupled receptor, serpentine
MOST drugs 45%**
stimulates G-protein, which produces 2nd messenger
INC. IC calcium or cAMP
1- extracelluar receptor
2- G-protein on inner face
3- activates enzyme or open/close ion gate
Agonist
Drug+receptor= biological response
Partial agonist
Drug+receptor= but biological response not 100% even with high dose
Buprenorphine- partial to opiod, safe less respirtory response than morphine
