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 Robert\[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

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
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.