Receptors Flashcards
____ ____ ____ is still the central dogma
of receptor activation
Lock and Key
The 4 superfamilies of receptors:
- Ligand-gated channels
- G protein coupled receptors (GPCRs)
- Enzyme/cytokine receptors
- Ligand-activated transcription factors
KNOW
What are:
- located on cell surface
- act by opening pores in the plasma membrane to allow ions to enter
- usually composed of multiple subunits
- usually multiple binding sites
Ligand-gated ion channels
In skeletal muscle, target of succinylcholine is a nicotinic acetylcholine receptor is an example of what type of receptor?
ligand-gated ion channel
This receptor is located on cell surface.
- Incredibly diverse array of activators; largest mammalian gene family
- Targets for high percentage of prescription drugs
- Signal transduction involves small _____ ______
- Probably operate as monomers, with some exceptions
G protein coupled receptors
second messengers
These molecules can bind to G protein receptors: (7)
autocoids
light
tastants
odorants
neurotransmitters
hormones
B-adrenergic receptor in heart is an example of:
G protein coupled receptor
Located on cell surface, activated by growth factors or cytokines
i. single polypeptide with intrinsic enzymatic activity
ii. usually tyrosine kinases or guanylate cyclase
iii. sometimes receptor lacks enzyme activity but has
docking sites for another enzymes
iv. often dimerizes on activation to cross-phosphorylate and initiate intracellular signal
Enzyme/cytokine receptors
What can bind to enzyme/cytokine receptors? (2)
Growth Factors
Cytokines
What are enzyme growth factor inhibitors? (2)
Monoclonal antibodies
Small molecule tyrosine kinase inhibitors
What receptor is located in cell nucleus, usually activated by steroids or other hydrophobic molecules
i. fairly common drug targets
ii. dimerize on binding agonist
ii. Agonist occupied dimers bind to DNA and alter gene
transcription
nuclear receptors
These receptors blocks chain of activity to follow:
nuclear receptors
What inhibitors are important in the treatment of cancer?
EGFR inhibitors
Progestin receptor is an example of:
Intracellular protein, binds estrogen, dimerizes, translocates to nucleus and alters transcription of particular genes
nuclear receptor
Sub-classification receptor types: (2)
Note: Within each super-family, receptors are classified based on the endogenous compound that binds to and activates them.
Adrenergic receptors: epinephrine and norepinephrine
Cholinergic receptors: acetylcholine
______ receptors were historically divided into alpha and beta subtypes, but pharmacologic and genome advancements show alpha-1, alpha-2, and beta receptors each have three. For a total of 9 adrenergic receptor subtypes!
What receptor is “fast”? “Slow”?
Adrenergic
alpha
beta
One would expect a ____ agonist to maximize the response curve.
full
One would expect a ____ agonist to somewhat increase the response curve.
partial
Binding of a drug to its receptor is usually a _______equilibrium
reversible
The amount of drug receptor complex formed is related to drug ______.
concentration or dose
Agonists have structural features that trigger a conformational change in receptor resulting in 2nd equilibrium leading ultimately to a cellular response. True or false?
true
At equilibrium, rate of association = rate of dissociation is known as:
Mass Action Law
What is the equilibrium dissociate constant?
Kd
How do you solve for affinity? Give formula.
Kd
k-1/k1
[D] * [R] / [DR]
Know units for:
k1
k-1
kd
M-1*min-1
min-1
M
The KD value is expressed in concentration units and is unique for a drug/receptor pair. It is a numerical value describing the sum of chemical bonding forces between the two. True or false?
true
Fractional occupancy equation (2 forms)
[DR] / [Rtotal]
[D] / ( [D] + Kd)
High Kd tells us ___ affinity.
low
and vice-versa
Kd tells us:
- the affinity between a drug and receptor
- reflective of the chemical bonding forces
- a unique chemical fingerprint for a drug-receptor pair
- approximate concentration of drug that occupies 50% of receptors in a preparation
- allows you to predict receptor occupancy for any drug concentration without knowing anything more about the receptor
Which is false and why?
tells us exact concentration of drug that occupies 50% of receptors
The concentratrion of drug that occupies 50% of receptors in a preparation is___.
Kd
They fully activate only a fraction of the receptors they occupy.
partial agonists
When spare receptors are present the preparation is much more sensitive to agonists, and the EC50 for an agonist may be much _____ than its Kd would predict.
lower (more potent)
Often a maximal response can be achieved at less than full occupancy; other times, full occupancy is necessary for a full maximal response.
This is known as the ____ _____ ____.
spare receptor concept
EC50 is equal to Kd. True or false?
false
EC50 is not equal to Kd because (4)
spare receptors
the receptor activation equilibrium (for agonists)
competition with endogenous activators
impaired drug access to receptor
Factors affecting drug distribution: Cellular reservoirs (3)
- Fat
- lipid-soluble drugs
- Bones/teeth
- metals form insoluble phosphates
- Increased Vd, biological half-life
The rapidity of anesthesia into the brain depends on 2 factors:
- Blood flow
- Crosses bbb easily
Propofol has termination due to distribution out of brain and blood. True or false?
true
Three phases of propofol PK
Redistribution phase (~\_\_\_ min) Rapid metabolic clearance (~\_\_\_ min) Slow phase (\_\_\_\_-\_\_\_hr) elimination from poorly perfused tissues
3
45
3-4
Amount of drug excreted =
glomerular filtration \+ \_\_\_\_\_\_ \_\_\_\_\_\_ - \_\_\_\_\_\_ \_\_\_\_\_\_
tubular secretion
tubular reabsorption
____ ______ (units of ml/min) is volume of plasma from which drug is fully removed per unit time.
Renal clearance
GFR depends on (3)
plasma protein binding
volume of distribution
blood pressure and blood flow
Only _____ drug (both non-ionized and ionized) is filtered.
free
Tubular reabsorption of sodium, water, creates a _______ gradient of drug in the urine, which is also concentrated, in the ____ tubule.
concentration
proximal
Drug reabsorption occurs via _______ diffusion, primarily in ____ _____ and ____ ____
passive
distal tubule
collecting duct
Lipid soluble, ____ polar drugs (unmetabolized) are reabsorbed
less
______ drug is ______ in urine
Ionized
excreted
Therapeutic modulation of pH of the renal filtrate in drug overdose toxicity acidic drugs: enhanced excretion in ______ urine (NaHCO3)
alkaline
