Chapter 6 in the syllabus principles of pharmacology
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CHAPTER 6 IN THE SYLLABUS: Principles of Pharmacology. Dr. Robert L. Patrick Department of Neuroscience Brown University [email protected] Biomed 370: January 12, 2005. PURPOSE OF TODAY’S LECTURE. To provide a basic introduction to pharmacological principles

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CHAPTER 6 IN THE SYLLABUS: Principles of Pharmacology

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Chapter 6 in the syllabus principles of pharmacology

CHAPTER 6 IN THE SYLLABUS:Principles of Pharmacology

Dr. Robert L. Patrick

Department of Neuroscience

Brown University

[email protected]

Biomed 370: January 12, 2005

Purpose of today s lecture


  • To provide a basic introduction to pharmacological principles

  • To use these principles to help appreciate the approaches taken in the use of drugs to alter the activity of brain neurotransmitters

What is pharmacology


  • Pharmacology is the science that deals with the mechanism of action, uses, and adverse effects of drugs

  • The word ‘pharmacology’ comes from the Greek word for drug: pharmakon



  • Most common description: A substance used as a medicine for the treatment of disease.

  • In a larger context: A substance taken because of its biologically active properties. This would include substances such as caffeine, nicotine, alcohol, cannabis, heroin and cocaine.

Source of drugs

Source of Drugs

  • Natural: Plants, fungi, microrganisms

  • Semi-synthetic (making a chemical derivative of a natural product)

  • Synthetic

Chapter 6 in the syllabus principles of pharmacology

Source of atropine: Atropabelladonna (deadly nightshade)

Source of Digitalis: Digitalis Purpurea (foxglove)

Drug names using antidepressants as examples






  • Q: Which are easier to remember?

How can drugs alter brain neurotransmitter activity

How Can Drugs Alter Brain Neurotransmitter Activity?

  • By altering some aspect of the Life Cycleof the transmitter:

  • Synthesis

  • Storage

  • Release

  • Receptor Interaction

  • Transmitter Inactivation

What are the common drug targets

What Are The Common Drug Targets?

  • Most common targets are body proteins:

  • Receptors: Can alter transmitter signaling

  • Example: Using risperidone to block dopamine receptors in schizophrenic patients

  • Enzymes: Can alter transmitter synthesis

  • Example: Using L-DOPA, a substrate for DOPA decarboxylase,to increase dopamine synthesis in the brains of patients with Parkinson’s Disease

Drug targets con t

Drug Targets (con’t)

  • Transporters: Can alter transmitter inactivation

  • Example: Using fluoxetine (Prozac) to inhibit serotonin reuptake in depressed patients

  • Ion Channels: Can alter neuronal excitability

  • Example: Using phenytoin to block sodium channels in epileptic patients

3 types of neurotransmitters

3 Types of Neurotransmitters

  • Biogenic Amines: Acetylcholine, Dopamine,Norepinephrine, Epinephrine, Serotonin (can have either excitatory or inhibitory actions)

  • Amino Acids: Glutamatic acid (excitatory) GABA and Glycine (inhibitory)

  • Peptides: Enkephalins, Endorphins, Substance P (can be either excitatory or inhibitory)

Drug action

Drug Action

  • The degree of drug action at a target site will, in general, depend upon the drug concentration at that site

And what determines drug concentration

And What Determines Drug Concentration?

  • Route of administration

  • Absorption and distribution

  • Binding

  • Inactivation

  • Excretion

Entry into the brain

Entry Into The Brain

  • The brain can pose a problem for drug entry, due to the blood-brain barrier

  • A drug can gain entry into the brain if:

  • A. It is lipophilic, and can diffuse across membranes, or

  • B. A specific transport system exists that can carry (transport) the drug across membranes

Drug effects

Drug Effects

  • What does a curve look like when you plot drug effect on the y-axis and dosage administered on the x-axis?

  • In words: You generate a dose-responsecurve!

  • In pictures: The shape of the curve depends upon whether you plot dosage or log of the dosage on the x-axis

Points on the curve

Points on the Curve

  • The maximal effect is called the efficacy

  • The amount of drug that produces 50% of the maximal effect is called the potency

  • The potency is often expressed as the ED50

  • This means that the lower the ED50 the greater the potency (important point to remember!)

Agonists and antagonists

Agonists and Antagonists

  • Agonist: An agent producing a cellular effect (e.g., norepinephrine stimulating the heart or acetylcholine inhibiting the heart)

  • Partial Agonist: Does not produce as great an efficacy as a full agonist (e.g., buprenorphine at opiate receptors)

  • Antagonist: An agent which blocks the effect of the agonist (e.g., atropine preventing acetylcholine action at the heart)

Therapeutic index


  • Therapeutic Index (TI) = TD50 / ED50

  • True or False?: If Drug A has a higher TD50 compared to Drug B, then Drug A must also have a higher therapeutic index.

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