Drug receptors Flashcards
What is a Drug Receptor?
Protein or protein complex on a cell membrane or within a cell = binding site of a cell to endogenous and exogenous compounds
Most drugs exert their effect by binding to and activating a receptor
Drug binds to receptor = change cellular function
Receptor on its outer surface, the cell is able to differentiate and respond to specific substances that approach the cell = the receptor ‘decides’ if the substance can enter the cell
Drug receptor and fit
poor receptor fit = no pharmacologic effect
some drug receptor fit = slight therapeutic response possible
agonist = excellent receptor fit = therapeutic response
RECEPTOR LOCATION
Outer surface of the cell membrane = recognizes endogenous (hormones) and exogenous compounds (drugs)
Receptor transmits a message through the cell membrane to create a change in activity of the cell
Transmembrane proteins – span the width of the cell membrane
Receptors affect cell function with the following mechanisms:
1) Acting as an ion channel = directly alter membrane permeability: Ligand Gated Ion Channel
2) Linked to regulatory proteins = coupled receptor: G Protein Coupled Receptor
3) Acting enzymatically = directly influence cellular function: Enzyme Linked Receptor
4) Within the cell = Intracellular Receptor
Receptors-Classification
Ligand gated Ion channel
G Protein Coupled Receptor
Enzyme linked receptors
Intracellular receptors
Ligand gated Ion channel:
Nicotinic Ach receptor & GABA receptor = binding site for GABA & Valium-Diazepam
Movement of ions = change in membrane potential
G Protein Coupled Receptor:
Muscarinic Ach receptor = vision, smell, taste, and pain = mediate responses
Membrane permeability influenced = linking of an
Intermediate regulatory protein located on the inner
Surface of the cell membrane
intermediate regulatory protein – this protein must bind with the effector substance and receptor in order to influence membrane permeability or enzyme activity
Surface receptor activated = attaches to a G Protein = G Protein activated = altered enzyme activity or ion channel = change In cell function
Example: morphine = opioid receptor = agonist = pain killer
Enzyme linked receptors:
insulin = extracellular activation translates to intracellular enzymatic activity
Transmembrane receptor = extracellular receptor site and intracellular enzymatic component
Drugs that bind to the extracellular receptor site can change the action of the intracellular catalytic component = Change to physiologic function
Intracellular receptors:
steroid = highly lipid soluble drugs
Receptors located inside the cell membrane = cell’s Cytoplasm and nucleus
Endogenous example: Hormones
Exogenous example: Steroids
Steroid/hormone forms a complex with the intracellular
Receptor = moves from cytoplasm to nucleus =
Change of function
Acetylcholine Receptor
ligand gated ion channel receptor
Located on the postsynaptic membrane of the neuromuscular junction
Acetylcholine molecule = activation of channel = increase in sodium permeability into muscle = cellular depolarization = muscle contraction
Gamma-Aminobutyric Acid (GABA) Benzodiazepine-Chloride Ion Channel
ligand gated ion channel receptor
Chloride permeability increases = binding of GABA and benzodiazepine (Valium)
GABA = endogenous
Benzodiazapines (Valium) = exogenous
In the presence of benzodiazepines = GABA effects are enhanced
Response: sedative, hypnotic, anti-anxiety, anticonvulsant, muscle relaxant
Valium is an agonist drug to GABA
G Protein Receptor Modulation
Drugs that links to a G Protein and activates the effector system = open an ion channel or activates a specific enzyme
Drugs that links to a G Protein and inhibits the effector system = close an ion channel or inhibits intracellular enzymatic activity
Therefore, the same drug can bind with two different surface receptors and G Proteins = two very different results
Insulin
Insulin acts through an enzyme linked receptor
Insulin binds to receptor = initiates enzymatic activity on the inner = Surface of the cell membrane = changes in cell function
Results in increased uptake of plasma glucose
DRUG-RECEPTOR INTERACTIONS
Ability to bind: size and shape dependent
Affinity: amount of attraction between drug & receptor = high-affinity drugs bind with low concentration, low affinity drugs need higher concentration
Receptors exist in various affinity states:
super-high, high, moderate, low
minimum effective concentration =
certain level of drug must be present in the body to produce an effect at all
strength of response to a drug =
increases proportionately as more drug is given
potency =
amount of a drug that must be given in order to produce a particular response
efficacy =
how well a drug produces its desired effect
related to its intrinsic activity
Drug Selectivity:
degree to which a drug acts on a specific site relative to other sites
Drug is selective if it affects only 1 type of cell or tissue
Function of its ability to Interact with specific receptors on the target tissue
Drug selectivity is a relative term = no drug produces only one effect
PHARMACODYNAMICS:
study of a drugs effect on a body
Bring down activity when a receptor is overstimulated
agonist =
drug that occupy receptors and activate them
antagonist =
drugs that occupy receptors but do not activate them
block receptor activation by agonists
agonist alone =
agonist & antagonist =
antagonist alone =
agonist alone = full activation
agonist & antagonist = less activation
antagonist alone = no activation
