PHL 211 Pharmacology

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PHL 211 Pharmacology
Second Lecture ByAbdelkader Ashour, Ph.D.
Phone [phone] Email aeashour_at_ksu.edu.sa
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Drug Receptors

• Receptor/Binding site
• A specific protein in either the plasma
  membrane or interior of a target cell with which
  a ligand/drug combines
• It must be selective in choosing ligands to bind
  ? To avoid constant activation of the receptor by
  promiscuous binding of many different ligands
• It must change its function upon binding in such
  a way that the function of the biologic system
  (cell, tissue, etc) is altered ? This is
  necessary for the ligand to cause a pharmacologic
  effect

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Drug Receptors

• Receptor/Binding site
• A specific protein in either the plasma
  membrane or interior of a target cell with which
  a ligand/drug combines
• It must be selective in choosing ligands/drugs to
  bind ? To avoid constant activation of the
  receptor by promiscuous binding of many different
  ligands
• It must change its function upon binding in such
  a way that the function of the biologic system
  (cell, tissue, etc) is altered ? This is
  necessary for the ligand to cause a pharmacologic
  effect

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Drug Receptors

• Receptor/Binding site
• A specific protein in either the plasma
  membrane or interior of a target cell with which
  a ligand/drug combines
• It must be selective in choosing ligands/drugs to
  bind ? To avoid constant activation of the
  receptor by promiscuous binding of many different
  ligands
• It must change its function upon binding in such
  a way that the function of the biologic system
  (cell, tissue, etc) is altered ? This is
  necessary for the ligand to cause a pharmacologic
  effect

• In order to interact chemically with its
  receptor, a drug molecule must have the
  appropriate size, electrical charge, shape, and
  atomic composition

• Orphan receptors
• Receptors for which no ligand has been
  discovered but they have a similar structure to
  other identified receptors and whose function can
  only be presumed
• If a ligand for an orphan receptor is later
  discovered, the receptor is referred to as
  "adopted orphan receptor"

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Drug Receptors, contd.

• Receptor Down-regulation
• A decrease in the total number of target-cell
  receptors for a given messenger/ligand in
  response to chronic high extracellular
  concentration of the messenger/ligand

• Desensitization
• The loss of a drugs effect, when it is given
  continuously or repeatedly, on a short
  time-scale
• Often results from receptor down-regulation

• Receptor Up-regulation
• An increase in the total number of target-cell
  receptors for a given messenger/ligand in
  response to a chronic low extracellular
  concentration of the messenger/ligand

• Supersensitivity
• The increased responsiveness of a target cell
  to a given messenger/ligand, resulting from
  receptor up-regulation

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Drug Receptor Interactions

• Agonist
• A chemical messenger (or drug) that binds to a
  receptor and triggers the cells response often
  refers to a drug that mimics a normal messengers
  action.
• For example, pilocarpine is a muscarinic receptor
  agonist because it can bind to and activate
  muscarinic receptors

• Antagonist
• "A molecule that competes for a receptor with a
  chemical messenger normally present in the body.
  The antagonist binds to the receptor but does not
  trigger the cells response
• For Example, atropine is a muscarinic receptor
  antagonist because it can bind to muscarinic
  receptors but it does not trigger the cells
  response. In this way, it prevents binding of
  acetylcholine (ACh) and similar agonist drugs to
  the ACh receptor

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Drug Receptor Interactions

• The Lock and Key Model of Signal-Receptor
  Interaction
• Ligands such as hormones, neurotransmitters or
  drugs (the "key") affect target cells by binding
  to specific receptors (the "lock), which are
  often located in the cell membrane
• This binding "unlocks" the cell's response, so
  that the hormone or neurotransmitter can exert
  its effects

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Drug Receptor Interactions
Lock and key mechanism
Agonist
Receptor
Agonist-Receptor Interaction
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Drug Receptor Interactions
Competitive Inhibition
Antagonist
Receptor
Antagonist-Receptor Complex
DENIED!
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Drug Receptor Interactions
Non-competitive Inhibition
Antagonist
Agonist
Receptor
DENIED!
Inhibited-Receptor
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Drug Receptor Interactions, contd.

• Affinity
• The extent to which the ligand/drug is capable
  of binding and remained bound to receptor
• High Affinity the ligand binds well and remains
  bound long enough to activate the receptor
• Low Affinity the ligand binds less well and may
  not remain bound long enough to activate the
  receptor

High Affinity
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Drug Receptor Interactions, contd.

• Affinity
• The extent to which the ligand/drug is capable
  of binding and remained bound to receptor.
• High Affinity the ligand binds well and remains
  bound long enough to activate the receptor
• Low Affinity the ligand binds less well and may
  not remain bound long enough to activate the
  receptor

Low Affinity