Pharmacodynamics

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Pharmacodynamics

• Pharmacology 49.222
• Bill Diehl-Jones RN, PhD
• Faculty of Nursing and Department of Zoology

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Agenda

• Definitions
• Receptors, ligands, agonists and antagonists
• Receptors types
• Alpha and beta adrenoreceptors
• Receptor Up- and Down-Regulation
• Partial agonists, competitive/non-competitive
  antagonists
• Therapeutic Index

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Pharmacodynamics
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Major ConceptDrugs ultimately work at the
cellular level
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Major Concepts

• Drugs often work by binding to a receptor
• Receptors are found in the cell membrane, in the
  cytoplasm, and in the nucleus
• Anything that binds to a receptor is a ligand

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Once a ligand binds to a receptor, stuff
happens...
Ligand
Y
Receptor
? Cai
X
Z
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Not all drugs work on receptors

• Eg many anaesthetics affect the stability of the
  plasma membrane
• Others (such as caffeine!) affect the
  biochemistry of cells

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Drug Receptors

• Agonists and antagonists
• Functions
• Receptor numbers and response

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So, what is a receptor agonist?

• Any drug that binds to a receptor and stimulates
  the functional activities
• eg adrenaline (epinephrine)

Some Effect
A Cell
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Types of Receptors

• Are they specific?
• usually, but not always
• Are there subtypes?
• sometimes
• example
• there are several types of epinephrine receptors

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There can be several types of receptors
Epinephrine
?1 Receptors in Heart
?2 Receptors in Bronchioles
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Some Questions

• 1. What is the effect of Beta receptor activation
  in the heart?2. What is the effect of Beta
  receptor activation in the lungs?Hint They
  produce different effects. Why?

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A Problem

• Epinephrine is a non-specific drug it is an
  agonist for BOTH ?1 and ?2 receptors
• Why might this be a problem for someone with
  asthma?

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A Solution

• More specific agonists have been developed
• eg terbutaline is a more specific ?2 agonist
  that is used for treating people with asthma

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So, what is a receptor antagonist?

• Any drug that prevents the binding of an agonist
• eg propranolol (a beta blocker)

Propranolol
Dude, youre in my way!
Epinephrine
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Still More Problems

• Propranolol is a non-specific antagonist
• Giving propranolol can cause asthma
• Why?

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Any Solutions?
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Receptor Numbers and Responses

• The NUMBER and AFFINITY of receptors may change
• An increase in receptor number is called
  UPREGULATION
• A decrease in receptor number is called
  DOWNREGULATION

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Eg Thyroid Hormone and Beta1 Receptors

• Eg Upregulation
• Thyroid hormone increases the number of cardiac
  ?1 receptors
• Clinical relevance
• During thyrotoxicosis, Propranolol can be used
  for treating tachycardia
• why? Because propranolol will have enough ?1
  receptors

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Eg Thyroid Hormone and Beta1 Receptors

• Eg Downregulation
• prolonged use of propranolol can DECREASE the
  number of ?1 receptors
• Clinical relevance
• A patients response to drug therapy may change
  over time

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Receptor Numbers and Responses

• The NUMBER and AFFINITY of receptors may change
• An increase in receptor number is called
  UPREGULATION
• A decrease in receptor number is called
  DOWNREGULATION

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Eg Thyroid Hormone and Beta1 Receptors

• Eg Upregulation
• Thyroid hormone increases the number of cardiac
  ?1 receptors
• Clinical relevance
• During thyrotoxicosis, Propranolol can be used
  for treating tachycardia
• why? Because propranolol will have enough ?1
  receptors

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Eg Thyroid Hormone and Beta1 Receptors

• Eg Downregulation
• prolonged use of propranolol can DECREASE the
  number of ?1 receptors
• Clinical relevance
• A patients response to drug therapy may change
  over time

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New Concepts

• Competitive Antagonist
• both the drug and its antagonist compete for the
  same receptor
• Non-competitive Antagonist
• the drug and its antagonist do not compete for
  the same receptor
• Partial Agonist
• a drug which blocks the agonist site by causing a
  lesser response
• STAY TUNED!

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Bringing Pharmacodynamics and Pharmacokinetics
Together
Drug Non-competitive Antagonist
Drug Competitive Antagonist
Drug PartialAgonist
Drug Alone
Effective Dose
Biological Effect
Drug Concentration
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Some Homework

• Be familiar with the following terms
• Bioavailability
• Therapeutic Index