L1 Pharmadynamics Flashcards
The aim of drug therapy is to what?
rapidly deliver and maintain therapeutic, yet nontoxic, levels of the most appropriate drug in the target tissue so that the disease is treated without adversely affecting the patient.
How the drug is delivered will affect what?
how much of the drug reaches its target and how long it remains in the animal
In short the aim of drug therapy is?
- maximize efficacy
- minimize adverse effects
No drug are completely safe or without risks. In order to decide if to use a drug you must use?
A risk benefit analyses
There are 3 approaches when deciding what drugs to use, What are they? List them in order to most reliable to least
1) An evidence‐based approach
2) A pathophysiological approach
3) Anecdotal” approach
Describe the evidence based approach?
Where we have the
scientific evidence and clinical trials to back up our therapeutic decisions. Although this can be rare in vet med.
Describe the pathophysiological approach
information on the disease, we know the pathophysiological mechanisms, and we know certain things about the drugs we are using. Based on these things we make a rational decision but dont have clinical trials to back our decisions.
Describe the anecdotal approach
The least satisfactory option, but commonly used. Someone with status in vet med community says “in this situation I use this drug at this dose”
What is empirical therapy?
Similar to anecdotal therapy. Drug selection based on prior (historical) experience with the specific situation.
Typically used when we dont have a firm diagnosis and are treating to see a response.
What is rational therapy?
Drug selection based on detailed Risk/Cost/Benefit
Considerations. More invloved than patient has X I will treat with Y
What are the three ways to name drugs?
Brand name- many brand names for one drug, often more commonly recognized. Patented
International non‐proprietary name (INN) & generic products- identify pharmaceutical substances or active pharmaceutical ingredients. Non-patent and INN name is recognized globally.
Chemical name- long complicated and rarly used
Doe every drug have a generic name and generic product?
Generic name (what we use in the course) but not necessarily a generic product
What does label use mean?
Using drug specifically what it is approved for (disease, species and dose) . This can vary from country to country, an issue when reading textbooks.
What is extra-label use?
Any deviation for label use (i.e. species, disease, dose, or route of administration). Vets have the privilege to do this.
What are drug formulations?
The base of drugs stay the same but they have different salts, preparations, diluents, etc. The pharmadynamics stay the same but the pharmakenetics change. Therefore have different administrations, routes, doses, withdrawal times, etc
What is pharmadynamics?
What the drug does to the body and how drugs interact with and affect biological systems
What is pharmakinetics?
What the body does to the drug. The processes of absorption, distribution, metabolism and elimination.
In order to understand the pharmadynamics of a drug you must first understand?
The physiology of the system it acts on
Drugs can have different ______ but achieve the same effect
different mechanisms of action
Two drug classes used to treat gastric ulcers in horses
H2 blockers and proton pump inhibitors, even tho have different mechanism of action, they both reduce gastric acid production
Omeprazole
is a selective and irreversible proton pump inhibitor. What does the mean?
- Selective means that it acts only on the proton pump
- irreversible means that once it binds the proton pump it does not come off – to regain proton pump function a new proton pump has to be made by the cell.
What is Structure-Activity Relationship?
Structure‐activity relationship is the term for the physical interaction between a drug and its target, and the effect that has on the drug/target activity. Can have important effects on drug characteristics
What are the 8 principles of Pharmacodynamics?
- Drugs act primarily through molecular targets
- Receptor types determine response to many drugs
- Receptors can be turned “on” or “off”
- Multiple mechanisms of antagonism exist
- Efficacy and potency are not the same
- Receptors are not static
- Selectivity is important
- The body tries to maintain homeostasis
List characteristics of drug targets (ie receptors)
- Can be cell surface or intracellular
- All receptors have endogenous ligands (naturally occurring)
- Receptors can transduce and amplify signals
What is affinity?
The strength with which a drug binds to its target (ie receptor)
If two drugs with different affinities for the same target are administered concurrently, the one with the higher affinity for the target will…..
“win” and displace the other drug from the target
Covalent>ionic>hydrogen> van der waal
Are affinity and efficacy the same?
No!
Name 4 receptors types in order of speed of their response. 1= fastest
1) Ligand‐gated ion channels
2) G‐protein‐coupled receptors
3) Enzyme‐linked receptors
4) Nuclear receptors
Describe ligand‐gated ion channels. And give an example
increase or decrease the flow of ions across a membrane when bound by a drug. Not voltage gated ion channels. Ex: synaptic cleft
Describe G‐protein‐coupled receptors.
Span the cell membrane and transmit external signals to the inside of the cell via activation of G‐proteins. They amplify the response to the ligand/agonist.
Describe Enzyme‐linked receptors
Have large extracellular binding site linked to an intracellular enzyme. When ligands bind to both receptors they form a dimer. This activates an enzyme
Describe Nuclear receptors. And give an example
Very complex, when bound, they translocate to the nucleus and alter gene
transcription. This is why they have a slower response time
What is an against?
A drug when it interacts with a receptor in a way that activates the receptor
What is a competitive antagonist?
Binds to the receptor at the same place as the endogenous ligand and prevents activation while they are on the site. Compounds compete for the same binding site; increasing
the concentration of one compound (the drug or the endogenous chemical).
What is a non-competitive antagonist?
They bind to receptors at a site other than where the ligand bind. This alters the shape of so that the ligand is no longer able to bind. Therefore, its
effect cannot be out‐competed. But no irreversibly bound therefore when drug is cleared from body effect is lost
What is Irreversible antagonism?
two compounds may
compete for the same binding site (so there may be an initial competitive phase) but the antagonist irreversibly binds to the target so that it can no longer be outcompeted. Has a greater duration compared to other types.
Describe full agonists, partial agonists, inverse agonists and antagonists
- Full agonists fully activate a
receptor - Partial agonists activate their receptor, but not to it’s full effect
- Inverse agonists bind to their receptor and cause an opposite response from that of its agonist
- Antagonists prevent receptor activation, often by blocking agonists binding. They do not cause
any activation of the receptor themselves.
What is physiological antagonism?
Occurs when agents produce opposite physiological effects
What is Chemical antagonism or drug incompatibility?
An interaction in solution that occurs without directly affecting a target (eg., one drug binds up another in solution) or binds in the body (chemical antagonism)
What is Pharmacokinetic antagonism?
One drug alters the disposition of another drug or chemical in the body so that it is eliminated more quickly or prevented from entering the body
Alpha 1 adrenoreceptors have what effect?
Vasoconstriction of blood vessels
Alpha 2 adrenoreceptors have what effect?
Vasodilation (shorts) followed by vasoconstriction
Beta 1 adrenoreceptors have what effect?
Increased cardiac output
Beta 2 adrenoreceptors have what effect?
Vasodilation of sk ms and heart ms along with bronchodialtion
If under anthesis a hors has plummeting BP which do you use, a B1 against or a B1 and B2 antagonist?
B1 against, will increase cardiac output
Explain the difference between efficacy and potency
- Efficacy refers to how effective a drug is at producing a response. Efficacy is the effect
observed at saturating (or maximal) concentrations. It can be described on a molecular, systemic, or population level.
-Potency is the amount or concentration of a drug that is required to produce a
response and is usually determined by the affinity of the drug for the target
What is Ec50? And 1/Ec50?
Ec50 is the concentration of a drug that produces a 50%
maximal response
1/Ec50 is the potency
Describe dose response curves
Demonstrates the different between efficacy and potency.
Typically % biological effect on y axis with drug concentration on x- axis. Can be log transformed or not.
Describe the arrows in this picture
yellow- maximal effective concentration- all of the available receptors are bound and increasing the dose
Red- EC50- The concentration of the drug that gives a response equal to half of the maximal response
The lower the EC50…
The greater the potency
Compare the red and black drug
The red drug is more potent but less efficacious. The black drug is the reverse.
Typically we _______ influences the dose of the drug we use and _________ determines what drug we choose
potency, efficacy
Explain the difference between clinical efficacy and pharmacological efficacy
Clinical efficacy is the magnitude and percent of clinical response (size of BP response). Determined by many things.
Pharmilogical efficacy is inhibition or activation of receptor activity (most likely measured in test tube)
Explain what “receptors aren’t static” means
Receptors can be desensitized, down-regulated, up-regulated etc in response to drugs, genetics, environmental impacts. This will influence the response to drugs on a temporary or long term basis
What is tolerance?
When receptors are chronically stimulated and they become down regulated or desensitized. This can occur with many medications that are used chronically. Ex, opioid tolerance
What is selectivity _________ and ___________
response and adverse effects
What does selectivity is reciprocal mean?
individual classes of drugs bind selectively to certain targets, and individual targets (esp. receptors) recognize only certain classes of drugs
“Drugs (and endogenous ligands) vary in their selectivity” what implications does this have?
Increasing the dose of a drug will cause it to affect targets other than the principal one (i.e. selectivity is lost), and this can lead to adverse effects. However in some cases affecting more than one target is advantageous
Higher dose = more adverse effects
Are drugs specific to only one targert?
Typically no, they are selective for their
primary target, but they interact with other
targets, leading to other physiological effects. Either non important or side effects
Receptor downregulation and desensitization are mechanisms the body uses to try to…..
Maintain homeostasis
