Pharmacodynamics

This is the term for the actions of a drug on the body.

Pharmacodynamics

This is the term for molecules to which drugs bind and cause response.

Receptors

What are the 2 general receptor types?

Membrane receptors, intracellular receptors

Drug-receptor interactions involve formation of _____________________.

Chemical bonds

Are most drug-receptor interaction bonds reversible or irreversible?

Reversible

Which drug-receptor interaction bonds are irreversible?

Covalent bonds of organophosphates

This receptor interaction requires a precise fit. The opening of the item reflects the activation of the receptor.

Lock and Key

This receptor interaction is marked by the receptor undergoing a conformational change after the drug binds

Induced Fit Model

Formation of the drug-receptor complex leads to a ______________ response.

Biologic

What are the 4 main types of receptors?

Ligand-gated ion channels, G protein-coupled, Enzyme-linked, intracellular

This channel works by the drug binding to it and it then regulates the activity of the ion channel.

Ligand-gated

Nicotinic receptor stimulation by ACh is an example of what type of receptor?

Ligand-gated

BZD binding to GABA receptors to cause Cl- influx is an example of what type of recptor?

Ligand-gated

The response of a ligand-gated channel lasts how log?

Milliseconds

In this receptor type, the receptors are linked to a structure with 3 subunits (a, b, y).

G-protein

Binding of a drug to this receptor type will lead to a conformational change in the protein. This will cause a GDP for GTP exchange with dissociation to interact with an effector protein

G-protein

What are the 3 major effector proteins of G-protein receptors?

cAMP, Phospholipase C, Ion channel proteins

The response of the G-protein coupled channel lasts how long?

Several seconds to minutes

The binding of a drug to an extracellular receptor of this type activates or inhibits enzymes.

Enzyme-linked Receptors

Insulin and it's activation of tyrosine kinase is an example of what type of receptor type?

Enzyme-linked Receptors

The response to enzyme-linked receptors lasts how long?

Minutes to Hours

In order to activate this receptor type, the drug must be lipid soluble.

Intracellular Receptors

Steroid hormones are an example of what type of receptor type?

Intracellular Receptors

The response to Intracellular receptors lasts how long?

Hours to Days

How long does it take before the onset of intracellular receptors?

> 30 minutes

These amplify signal duration or intensity for receptors.

Spare receptors

This is the term for repeated administration of a drug resulting in diminished effect.

Tachyphylaxis

This is the term for when receptors undergo endocytosis and is sequestered in the cell. This results in less receptors available on the cell surface.

Down Regulation

If too few drug molecules occupy receptors, we will see what?

Minimal or no effect

Once all the receptors are occupied, will increasing the dose have any effect?

No

If you increase the concentration of the drug, what happens to the effects?

They increase

This is the term for response is continuous and gradual.

Graded Effect

Graded dose response curve allows for the determination of what 2 items?

Potency, Efficacy

Efficacy can also be referred to as what?

Intrinsic Activity

Which is more important? Maximal potency or maximal efficacy?

Maximal Efficacy

This is the term for the amount of drug required to produce a given effect.

Potency

The concentration that produces 50% of the maximum effect (EC50) is used to determine what?

Potency

What is an important contributing factor when thinking about potency?

Affinity

In comparing potency, Drug A is 4 mg, while Drug B is 75 mg. Which is more potent?

Drug A

The smaller the EC50, the more or less potent the drug is?

More Potent

This is the term for the ability of the drug to illicit a physiologic response when it interacts with the receptor.

Efficacy

What is dependent on the number of drug receptor complexes and the efficiency of the interaction to cause a response?

Efficacy

Efficacy is represented by what?

Maximal Response (Emax)

Which is more clinically useful? Potency or efficacy?

Efficacy

Which drug is more therapeutically beneficial? One with a greater potency or one with a greater efficacy?

Greater Efficacy

When looking at the graph, how do you tell if one drug is more efficacious than another?

The most efficacious drug reaches 100 (It's taller).

If Drug A has an EC50 of 10, and Drug B has an EC50 of 25, what does that mean?

Drug A is more potent

If Drug B reaches 100, and Drug C reaches 50 on the biological effect, what does that mean?

Drug B is more efficacious

This is the term for a drug that stimulates a receptor, provoking a maximal biologic response.

Full Agonist

These types of drugs have a strong affinity for receptor and good efficacy.

Full Agonist

This is the term for a drug that stimulates a receptor, provoking a sub-maximal response.

Partial Agonist

These types of drugs have efficacy less than a full agonist. Even if all the receptors are bound, this will not produce the same magnitude as a full agonist.

Partial Agonist

Which has a higher affinity? Full or Partial Agonist?

Depends

This is the term for a drug that interacts with a receptor but does not result in a biologic response.

Antagonist

This is the term for drugs that bind to the same site as the agonist, but do not produce a biological response.

Competitive Antagonist

This is the term for a drug that binds covalently or binds at a different (allosteric) site that reduces the number of receptors available to the agonist.

Irreversible Antagonist

Are irreversible antagonists considered competitive or non-competitive antagonists?

Non-competitive

On the graph, how will you know if a drug is an irreversible antagonist?

Downward shift of Emax, with no shift of EC50

Can you overcome an irreversible antagonist by adding more agonist?

No

This is the term for the antagonist that causes opposing actions.

Functional Antagonist

This is also called physical antagonism.

Functional Antagonist

What is an example of Functional Antagonist?

Epinephrine ro histamine-induced bronchoconstriction

This is the term for the antagonist may bind with the agonist, which makes the agonist unavailable to bind to the receptor.

Chemical Antagonist

What is an example of chemical antagonist?

Protamine binds to heparin and renders it inactive

This is the term for the influence of the magnitude of a dose on the proportion of a population that responds. It is "all or none".

Quantal Dose-Response

This is the term for the effective dose for 50% of the population.

ED50

This is the term for the dose that produces toxic effects in 50% of the population.

TD50

This is the term for the lethal dose in 50% of the population?

LD50

This is also called the therapeutic window

Therapeutic Index

This is a measurement of the drugs safety.

Therapeutic Index

A larger value of this indicates wide margins between doses that are effective and those that are toxic.

Therapeutic Index

What is the equation for TI?

TI = TD50/ED50

Does Warfarin have a large or small TI?

Small

Does Digoxin have a large or small TI?

Small

Does Penicillin have a large or small TI?

Large

This is the term for the blood concentration of a drug needed to produce a response.

Minimum Effective Concentration (MEC)

This is the term for the time at which MEC is reached & the response begins.

Onset of Action

This is the term for the time between the onset of action and the time when the minimum effective concentration is reached by declining blood concentrations.

Duration of Action

This is the term for 2 drugs with similar pharmacologic actions.

Additive Effects

This is the term for 2 drugs with different mechanisms given together produce greater effects than either does when taking alone.

Synergism/Potentiation

This is the term for something given to block or decrease toxic effects of a drug.

Antidote

This is the term for drugs that combine to produce less-absorbable compounds.

Decreased Intestinal Absorption

How can drug-drug interactions alter Absorption?

Bind to Gi tract and alter environment (GI motility, pH)

How can Drug-Drug interactions affect distribution?

Displacement from protein binding sites

How can Drug-Drug interactions affect metabolism?

Enzyme induction/inhibition

How can Drug-Drug interactions affect excretion?

Drugs can compete for the same transport mechanism, influenced by pH

If a drug interaction takes 2 weeks to occur, but the patient will only be on the interacting medication for 5 days, are the results likely clinically significant?

No

A patient is given 100 mg of an anticonvulsant medication. The resulting plasma concentration is 5 mg/L. A therapeutic concentration is 10 mg/L. This drug follows first order kinetics and has an elimination rate constant of 0.12 hr-1. What additional dose would be needed to reach a therapeutic concentration?

100 mg

A patient is given 100 mg of an anticonvulsant medication. The resulting plasma concentration is 5 mg/L. A therapeutic concentration is 10 mg/L. This drug follows first order kinetics and has an elimination rate constant of 0.12 hr-1. What is the half life of this drug?

5.8 hours

A patient is given 100 mg of an anticonvulsant medication. The resulting plasma concentration is 5 mg/L. A therapeutic concentration is 10 mg/L. This drug follows first order kinetics and has an elimination rate constant of 0.12 hr-1. Calculate the expected clearance for this drug in ml/min.

40 mL/min

A patient is given 100 mg of an anticonvulsant medication. The resulting plasma concentration is 5 mg/L. A therapeutic concentration is 10 mg/L. This drug follows first order kinetics and has an elimination rate constant of 0.12 hr-1. If a continuous IV infusion is started with this anticonvulsant, how long would it take to reach SS?

23.2 hours

A 75 year old female with an IBW of 121 lb requires an antibiotic to treat an infection that requires dose adjustment based on renal function. Her most recent serum creatinine (SrCr) is 1.5. The dose is 1 gram IV, but the dosing interval is according to the chart below:CrCl ≥ 60 ml/min - every 6 hoursCrCl 40-59 ml/min - every 8 hoursCrCl 20-39 ml/min - every 12 hoursCrCl < 20 ml/min - every 24 hours. What is the most appropriate dosing?

Every 12 hours

Which of the following is correct? A) In selecting a drug, potency is usually more important than efficacy

B) Variation in response to a drug among different individuals is most likely to occur with a drug showing a large therapeutic index

C) If 10 mg of Drug A produces the same response as 100 mg of Drug B, Drug A is more efficacious than Drug B

D) The greater the efficacy, the greater the potency of a drug

E) A competitive antagonist increases the ED50

E

Drug X produces maximal contraction of cardiac muscle in a manner similar to epinephrine. Drug X is considered to be a(n):

A) Competitive Antagonist

B) Irreversible Antagonist

C) Agonist

D) Partial Agonist

E) Inverse Agonist

C

Variation in the sensitivity of a population of individuals to increasing doses of a drug is best determined by which of the following?

A) Quantal dose-response curve

B) Potency

C) Efficacy

D) Graded dose-response curve

E) Therapeutic Index

A

Based on the values below, which of the following drugs has the widest margin of safety?

Drug; TD50; ED50

A) Drug A; 3.75 mg/L; 2.5 mg/L

B) Drug B; 20 mg/L; 4 mg/L

C) Drug C; 10 mg/L; 1 mg/L

D) Drug D; 25 mg/L; 0.5 mg/L

D