Study guides -
Here are some questions to consider as you work through the reading and videos:
What is the difference between pharmacology, pharmacodynamics (PD), and pharmacokinetics (PK)?
What happens with pharmacology drug-receptor interactions on a molecular level?
What are the various types of agonists and antagonists?
What are the four basic concepts of pharmacokinetics? How would I use these when prescribing?
What are the physicochemical properties for drug transfer?
What factors modify drug absorption in relation to the method of drug administration and what is the
associated effect on bioavailability?
What factors modify drug distribution and what is the relationship to elimination?
What factors affect metabolism?
What is the difference between Phase I and Phase II metabolism?
What are the basic parameters of clearance pharmacokinetics?
How does pharmacokinetics impact therapeutic dosing?
What are mechanisms of drug toxicity?
Trivia Sorter: Generic
The mechanism of action for the class of drug.
Properties or effects that are common to all drugs in the class.
Is (are) the drug(s) the drug of choice for some disorder or symptom?
Name recognition—what drugs are in this class?
Unique features about single drugs in the class.
Are there any side effects (rare or not) that may be fatal?
Drug interactions.
Rare side effects or actions that are common to all drugs in the class.
Rare side effects or actions for single drugs in the class.
Percentage of drug that is metabolized versus renal excretion.
Half-life of each drug in the class.
Teratogenicity of each drug in the class.
Structure of each drug in the class.
,Week 1
Chapter 1:
However, most drugs have molecular weights between 100 and 1000. The lower limit of this narrow range is probably set by the
requirements for specificity of action. To have a good “fit” to only one type of receptor, a drug molecule must be sufficiently unique in
shape, charge, and other properties to prevent its binding to other receptors. To achieve such selective binding, it appears that a
molecule should in most cases be at least 100 MW units in size. The upper limit in molecular weight is determined primarily by the
requirement that most drugs must be able to move within the body (eg, from the site of administration to the site of action and then
to the site of elimination). Drugs much larger than MW 1000 do not diffuse readily between compartments of the body (discussed
under Permeation, in following text). Therefore, very large drugs (usually proteins) must often be administered directly into the
compartment where they have their effect. In the case of alteplase, a clot-dissolving enzyme, the drug is administered directly into the
vascular compartment by intravenous or intra-arterial infusion.
Drugs that bind to the same receptor molecule but do not prevent binding of the agonist are said to act allosterically and may
enhance or inhibit the action of the agonist molecule. Allosteric inhibition is not usually overcome by increasing the dose of agonist.
Pharmacodynamics – what drug does to body
Pharmacokinetics – what body does to the drug (metabolism)
ADME – absorption, distribution, metabolism, excretion
4 types of chemical bonds – if no shell, atoms can add/lose or share electrons
Covalent – strongest, share electrons
Hydrogen bond – 3rd strongest bond type, the addition of the hydrogen atom creates a more positively charged particle
Ionic bond – 2nd strongest bond type, atoms with excess of electrons are attracted to atoms with a deficiency of electron.
Vanderwall interaction – weakest bond
Hydrophilic versus hydrophobic
Hydrophilic – water loving. Typically, renally excreted. Form hydrogen bonds. Needs transport mechanisms to cross blood brand
barrier.
Hydrophobic – non-polar. Diffuse across BBB easily. Not usually ionized.
Lipid-soluable drugs easily cross BBB.
Chapter 2:
RECEPTOR Signaling Mechanisms & Drug Actions
Agonists versus antagonists –
Agonist activates a receptor. It mimics the action of signal ligand by binding to & activating a receptor.
An antagonist blocks/inhibits the function of an agonist (prevents agonist activity). It binds to a receptor without activating
them & decreases a receptor’s ability to be activated by another agonist.
Full agonist – binds and causes maximal effect of medication when bound.
Partial agonist – activation at receptor without maximal efficacy
Inverse agonist – stabilizes response in case of receptor change. Ex: allergic type response.
Competitive antagonist – Narcan, blocks morphine to decrease effect or morphine.
Non-competitive antagonist – reduces only efficacy, not potency. Adding more drug will not produce a greater effect. Ketamine,
atropine
, Osmosis vid:
Okay, now the maximal effect or response an agonist can produce, abbreviated as E max, is determined both by the number of
receptors bound to the agonist, which depends mainly on the amount of the agonist given, also known as dose, as well as its intrinsic
activity, which is the ability of the agonist to fully or partially activate its receptors. Let’s plot all this into a nice graph to show the
relationship between the dose given, on the x axis, usually on a logarithmic scale, and the response produced, on the y axis. So full
agonists, upon binding to the receptor at high doses, are capable of producing a maximal response of 100% Emax on the y axis. This
represents the point where all available receptors are bound to an agonist. In contrast, partial agonists, even at very high doses, when
they occupy all of the receptors, result in a smaller response, so their Emax will be lower. For example, a 70% response would shift the
curve downwards.
Now, let’s say a partial agonist is used at the same time with a full agonist and they compete for the same receptors. If we increase
the dose of the full agonist, it will displace the partial agonist from the receptor, and the maximal response will still be achieved. So,
the dose-response curve will shift to the right, without affecting Emax, but the dose required to achieve 50% of the maximum effect,
also known as effective dose ED50, will be increased. In other words, when a partial antagonist and a full agonist of the same receptor
are present together, then the full agonist’s potency, which is the dose of agonist needed to elicit a maximal response, will be
decreased, but the full agonist’s efficacy, which is the maximal effect that an agonist can produce, will stay the same.
Alright, at the other end of the spectrum, antagonists can be divided into competitive antagonists, and non-competitive antagonists.
Now, a competitive antagonist is a medication that reversibly binds to the same receptor site where an agonist binds, but it does not
activate it. Competitive antagonists usually bind to the receptor in a reversible way, meaning that they bind and dissociate from it
pretty fast. So when they unbind, it’s more likely for one of the ligands to bind. So the inhibition caused can be overcome when there
are more ligands floating around. This is sometimes referred to as surmountability. Now, on the graph, competitive antagonists
typically shift the curve to the right without affecting Emax, but increase the effective dose ED50. So, competitive antagonists
decrease the agonist potency, but do not affect the agonist efficacy.
On the other hand, non-competitive antagonists don’t bind to the same site as an agonist. They bind to a spot called an “allosteric
site”. When they bind, it causes the shape of the receptor to alter in such a way that the ligand can no longer recognize it as a binding
site. And even if it does manage to bind, it won’t be able to produce the agonist effect. Now, binding of a noncompetitive antagonist
to the receptor is either irreversible or it dissociates very slowly. This means that the receptor will not activate, no matter how many
agonists are around. In other words, this type of antagonism is not surmountable.
What we see on a graph is that the dose-response curve won’t shift, so the ED50 won’t change, but the slope and peak, and thus the
maximal effect Emax that can be achieved by any dose of an agonist would be reduced. In other words, non-competitive antagonists
reduce agonist efficacy without affecting agonist potency.
All right, as a quick recap, agonists activate receptors and can be divided into full agonists, which can produce a maximal response,
and partial agonists, which can only produce a submaximal response. Antagonists prevent receptor activation and can be competitive,
meaning they bind reversibly to the same agonist binding site; and noncompetitive, meaning they bind irreversibly to the same
agonist binding site or to a different allosteric site. Competitive antagonism can be overcome by adding more of the agonist, while
noncompetitive antagonism cannot.
On the cell membrane are cell-surface receptors, which are embedded into the plasma membrane and bind to ligands too large or
hydrophilic, meaning water- loving, to pass through.
Based on their structure and properties, cell- surface receptors fall into three main types.
First are ligand- gated ion channels, which form channels or pores that are generally closed, but then open up once they bind a
specific ligand.
They allow ions like chloride, calcium, sodium, and potassium to passively flow into the cell, down their gradient, and trigger the
signaling pathway.
Next are the G-protein coupled receptors, also known as seven- pass transmembrane receptors, which means they are really long
proteins that have one end that sits outside the cell, and then the snake- like protein dips in and out of the cell membrane seven times,
and finally ends on the inside of the cell.
Here are some questions to consider as you work through the reading and videos:
What is the difference between pharmacology, pharmacodynamics (PD), and pharmacokinetics (PK)?
What happens with pharmacology drug-receptor interactions on a molecular level?
What are the various types of agonists and antagonists?
What are the four basic concepts of pharmacokinetics? How would I use these when prescribing?
What are the physicochemical properties for drug transfer?
What factors modify drug absorption in relation to the method of drug administration and what is the
associated effect on bioavailability?
What factors modify drug distribution and what is the relationship to elimination?
What factors affect metabolism?
What is the difference between Phase I and Phase II metabolism?
What are the basic parameters of clearance pharmacokinetics?
How does pharmacokinetics impact therapeutic dosing?
What are mechanisms of drug toxicity?
Trivia Sorter: Generic
The mechanism of action for the class of drug.
Properties or effects that are common to all drugs in the class.
Is (are) the drug(s) the drug of choice for some disorder or symptom?
Name recognition—what drugs are in this class?
Unique features about single drugs in the class.
Are there any side effects (rare or not) that may be fatal?
Drug interactions.
Rare side effects or actions that are common to all drugs in the class.
Rare side effects or actions for single drugs in the class.
Percentage of drug that is metabolized versus renal excretion.
Half-life of each drug in the class.
Teratogenicity of each drug in the class.
Structure of each drug in the class.
,Week 1
Chapter 1:
However, most drugs have molecular weights between 100 and 1000. The lower limit of this narrow range is probably set by the
requirements for specificity of action. To have a good “fit” to only one type of receptor, a drug molecule must be sufficiently unique in
shape, charge, and other properties to prevent its binding to other receptors. To achieve such selective binding, it appears that a
molecule should in most cases be at least 100 MW units in size. The upper limit in molecular weight is determined primarily by the
requirement that most drugs must be able to move within the body (eg, from the site of administration to the site of action and then
to the site of elimination). Drugs much larger than MW 1000 do not diffuse readily between compartments of the body (discussed
under Permeation, in following text). Therefore, very large drugs (usually proteins) must often be administered directly into the
compartment where they have their effect. In the case of alteplase, a clot-dissolving enzyme, the drug is administered directly into the
vascular compartment by intravenous or intra-arterial infusion.
Drugs that bind to the same receptor molecule but do not prevent binding of the agonist are said to act allosterically and may
enhance or inhibit the action of the agonist molecule. Allosteric inhibition is not usually overcome by increasing the dose of agonist.
Pharmacodynamics – what drug does to body
Pharmacokinetics – what body does to the drug (metabolism)
ADME – absorption, distribution, metabolism, excretion
4 types of chemical bonds – if no shell, atoms can add/lose or share electrons
Covalent – strongest, share electrons
Hydrogen bond – 3rd strongest bond type, the addition of the hydrogen atom creates a more positively charged particle
Ionic bond – 2nd strongest bond type, atoms with excess of electrons are attracted to atoms with a deficiency of electron.
Vanderwall interaction – weakest bond
Hydrophilic versus hydrophobic
Hydrophilic – water loving. Typically, renally excreted. Form hydrogen bonds. Needs transport mechanisms to cross blood brand
barrier.
Hydrophobic – non-polar. Diffuse across BBB easily. Not usually ionized.
Lipid-soluable drugs easily cross BBB.
Chapter 2:
RECEPTOR Signaling Mechanisms & Drug Actions
Agonists versus antagonists –
Agonist activates a receptor. It mimics the action of signal ligand by binding to & activating a receptor.
An antagonist blocks/inhibits the function of an agonist (prevents agonist activity). It binds to a receptor without activating
them & decreases a receptor’s ability to be activated by another agonist.
Full agonist – binds and causes maximal effect of medication when bound.
Partial agonist – activation at receptor without maximal efficacy
Inverse agonist – stabilizes response in case of receptor change. Ex: allergic type response.
Competitive antagonist – Narcan, blocks morphine to decrease effect or morphine.
Non-competitive antagonist – reduces only efficacy, not potency. Adding more drug will not produce a greater effect. Ketamine,
atropine
, Osmosis vid:
Okay, now the maximal effect or response an agonist can produce, abbreviated as E max, is determined both by the number of
receptors bound to the agonist, which depends mainly on the amount of the agonist given, also known as dose, as well as its intrinsic
activity, which is the ability of the agonist to fully or partially activate its receptors. Let’s plot all this into a nice graph to show the
relationship between the dose given, on the x axis, usually on a logarithmic scale, and the response produced, on the y axis. So full
agonists, upon binding to the receptor at high doses, are capable of producing a maximal response of 100% Emax on the y axis. This
represents the point where all available receptors are bound to an agonist. In contrast, partial agonists, even at very high doses, when
they occupy all of the receptors, result in a smaller response, so their Emax will be lower. For example, a 70% response would shift the
curve downwards.
Now, let’s say a partial agonist is used at the same time with a full agonist and they compete for the same receptors. If we increase
the dose of the full agonist, it will displace the partial agonist from the receptor, and the maximal response will still be achieved. So,
the dose-response curve will shift to the right, without affecting Emax, but the dose required to achieve 50% of the maximum effect,
also known as effective dose ED50, will be increased. In other words, when a partial antagonist and a full agonist of the same receptor
are present together, then the full agonist’s potency, which is the dose of agonist needed to elicit a maximal response, will be
decreased, but the full agonist’s efficacy, which is the maximal effect that an agonist can produce, will stay the same.
Alright, at the other end of the spectrum, antagonists can be divided into competitive antagonists, and non-competitive antagonists.
Now, a competitive antagonist is a medication that reversibly binds to the same receptor site where an agonist binds, but it does not
activate it. Competitive antagonists usually bind to the receptor in a reversible way, meaning that they bind and dissociate from it
pretty fast. So when they unbind, it’s more likely for one of the ligands to bind. So the inhibition caused can be overcome when there
are more ligands floating around. This is sometimes referred to as surmountability. Now, on the graph, competitive antagonists
typically shift the curve to the right without affecting Emax, but increase the effective dose ED50. So, competitive antagonists
decrease the agonist potency, but do not affect the agonist efficacy.
On the other hand, non-competitive antagonists don’t bind to the same site as an agonist. They bind to a spot called an “allosteric
site”. When they bind, it causes the shape of the receptor to alter in such a way that the ligand can no longer recognize it as a binding
site. And even if it does manage to bind, it won’t be able to produce the agonist effect. Now, binding of a noncompetitive antagonist
to the receptor is either irreversible or it dissociates very slowly. This means that the receptor will not activate, no matter how many
agonists are around. In other words, this type of antagonism is not surmountable.
What we see on a graph is that the dose-response curve won’t shift, so the ED50 won’t change, but the slope and peak, and thus the
maximal effect Emax that can be achieved by any dose of an agonist would be reduced. In other words, non-competitive antagonists
reduce agonist efficacy without affecting agonist potency.
All right, as a quick recap, agonists activate receptors and can be divided into full agonists, which can produce a maximal response,
and partial agonists, which can only produce a submaximal response. Antagonists prevent receptor activation and can be competitive,
meaning they bind reversibly to the same agonist binding site; and noncompetitive, meaning they bind irreversibly to the same
agonist binding site or to a different allosteric site. Competitive antagonism can be overcome by adding more of the agonist, while
noncompetitive antagonism cannot.
On the cell membrane are cell-surface receptors, which are embedded into the plasma membrane and bind to ligands too large or
hydrophilic, meaning water- loving, to pass through.
Based on their structure and properties, cell- surface receptors fall into three main types.
First are ligand- gated ion channels, which form channels or pores that are generally closed, but then open up once they bind a
specific ligand.
They allow ions like chloride, calcium, sodium, and potassium to passively flow into the cell, down their gradient, and trigger the
signaling pathway.
Next are the G-protein coupled receptors, also known as seven- pass transmembrane receptors, which means they are really long
proteins that have one end that sits outside the cell, and then the snake- like protein dips in and out of the cell membrane seven times,
and finally ends on the inside of the cell.
