Lecture 1: Introduction to Pharmacology Flashcards
What is pharmacology?
drugs exert their effects by binding to receptors in our bodies and triggering a functional change
the mechanism of action of common drug classes
what are the receptors involved in a response? what is the mechanism that translates drug binding to a receptor, into some physiological change? what are the different ways that a drug can influence its receptor?
How is pharmacology different than physiology and biochemistry?
we will focus on drugs, including therapeutic and illicit/recreational drugs; that is, compounds that are ingested in order to alter function
to understand drug effects on an organism, we will often discuss the underlying physiology of a system that is targeted
drugs act on some molecular entity called a receptor and we will often discuss biochemistry concepts to understand the underlying molecular mechanism of drug effects
What are receptors?
the molecular target of a drug
we think of the actions of drugs as being the result of their interaction with a target receptor
in this case, the target receptor was the H1 histamine receptor
What is a prodrug?
a compound which is not intrinsically active, and is activated by some metabolic step after administration
terfenadine is metabolized quickly in the liver by something called “first pass metabolism”
How are drugs altered in the body?
more generally, most drugs are altered by our bodies in some way (they can become activated or inactivated)
how this happens is usually distinct from their actions on their target receptors
How does the mechanism of how the body alters Terfenadine add complexity to its biological effects?
if metabolism of terfenadine to fexofenadine is inhibited somehow, the inactive form can circulate in the body and influence undesired targets
Terfenadine is a very powerful blocker of certain proteins (hERG ion channels) that control electrical activity and beating of the heart
if the liver doesn’t completely process the drug, unprocessed drugs are in the body
this “off-target” effect of terfenadine can lead to a potentially lethal cardiac arrhythmia called “torsades de pointes”
so some people died from taking a little bit of medication to stop a runny nose or hay fever
What are off-target effects?
drugs are usually not perfectly specific for one receptor type
sometimes they will influence closely related receptors (H1 vs. H2 receptors)
sometimes they influence completely unrelated receptors (H1 receptors vs. potassium channels in the heart)
What are adverse effects?
undesirable drug effects can vary in severity
some off-target effects are mild/benign; some are very serious or lethal; some are common; some are rare
sometimes they are related to the mechanism of action of the drug (“on-target” effect)
sometimes adverse events arise due to effects that are unrelated to the desired mechanism of action of the drug (“off-target” effects)
In what ways are most therapeutic drugs not perfect?
they might not work well in some/most patients
they also carry the risk of certain undesired effects
we will learn about the benefits and the risks (and the mechanisms) about many common drugs
What is pharmacogenetics?
the genetic background of a patient can significantly affect how they respond to the drug
it is becoming more common to investigate how genetics influence susceptibility to both the benefits and harmful effects of a drug
What are drug interactions?
it is very common for one drug/substance to adversely affect the response to another
the effects of terfenadine highlight the importance of understanding how ingesting multiple drugs at once can have unexpected consequences
What are the levels of complexity of pharmacology?
we will study how drug classes interact with their target receptors, and mechanisms of action
we will learn about adverse effects and their underlying mechanisms
we will learn the basics of how drugs are handled (absorbed and eliminated) by our bodies, and how this affects drug design and safety
