BMS II Definitions/Abbreviations

what the body does to the drug

pharmacokinetics

what the drug does to the body

pharmacodynamics

What is this the definition of?

Chemical substances found within an organism that are not naturally produced or recognized within the organism.

xenobiotics

Why does the human body restrict access to xenobiotics?

body doesn’t know if drugs are good or bad for us

Cmax is the max ________ in the blood

concentration

Tmax is the time it takes to reach _______.

Cmax

During which of the ADME processes can drug interactions occur?

ALL

How do

• solubility

• sterics

• electronics

pertain to biological barriers?

solubility- “goldilocks” not to hydrophobic/phillic

sterics- size can’t be too big

electronics- nonpolar molecules cross membranes easier

What does the following equation represent?

F= amount of drug that reaches circulation/ amount of drug that is administered

bioavailability

If a drug passes all of Lipinski’s rules, would it likely be inactive or active drug?

active

True or False: Lipinski’s rule states that a drug-like molecule cannot have more than 10 hydrogen bond acceptors

True

What are the four parameters for Lipinski’s rule?

1. how many H-bond donors?

2. how many H-bond acceptors?

3. What molecular weight?

4. What Log P?

≤5 H-bond donors

≤ 10 H-bond acceptors

< 500 molecular weight

≤ 5 Log P

a semipermeable membrane in the brain that is characterized by tight junctions and astrocytes.

(a lot less permeable compared to a normal capillary)

Blood-Brain Barrier (BBB)

_____________ are pharmacologically inactive compounds that are converted to their active forms by metabolism.

Prodrug

What is the correlation between the amount of substance administered and amount of substance in systemic circulation?

Volume of distribution

creatinine definition

A waste product produced by muscles from the breakdown of creatine phosphate. It is filtered by the kidneys and excreted in urine. Elevated levels indicate kidney dysfunction.

p-glycoprotein definition

A protein found in cell membranes that acts as a pump to remove foreign substances, like drugs, from cells. It plays a role in drug resistance and limiting the absorption of certain medications in the body.

Isozyme definition

enzymes that differ in amino acid sequence but catalyze the same chemical reaction

ligand definition

molecule that binds to the receptor

Therapeutic Window definition

reflects a concentration range that provides efficacy without unacceptable toxicity

therapeutic index defintion

a measure of a drug's safety and effectiveness. It is the ratio between the dose that produces therapeutic effects and the dose that causes toxic effects.

A (higher/lower) therapeutic index indicates a safer drug.

Higher

Area under the curve Abbreviation

AUC

Clearance (abbr and definition)

• Cl

• a measure of the body’s efficiency in eliminating drug from the systemic circulation

bioavailability (abbr and definition)

• F

• the fraction of drug absorbed into the systemic circulation

What are the 3 ways drugs can be eliminated using the renal system?

1. filtration

2. secretion

3. reabsorption

CYPs (abbr and defintion)

cytochrome P450 enzymes

• responsible for 75% of drug metabolism

• first pass metabolism

Vd abbreviation

volume of distribution

GCPR

G protein-coupled receptor

What is the kidney blood flow per minute?

1.2-1.5 L

NF-kB

nuclear factor-κB

• Transcription factor involved in immune response and inflammation.

MAPK abbr

mitogen-activated protein kinase

Kd

acid dissociation constant

ED50

half-maximally effective dose

TD50

half-maximally toxic dose

LD 50

half-maximal lethal dose

The larger the volume of distribution indicates what about the drug molecule?

More hydrophobic

Calculate the volume of distribution for the following drug:

• Dose= 400 mg

• Cmax= 0.06 mg/L

Vd=

6667

(increased/decreased) clearance indicates that more was removed from the body.

increased

What is based upon the max response to the ligand?

efficacy

____________ has positive efficacy

____________ has zero efficacy

____________ has negative efficacy

agonist, antagonist, inverse

The greater the potency, the smaller the dose at which ______ occurs.

a. EC50

b. TC50

c. LC50

a (EC50)

According to the graph, which drug is the most potent? which drug is the more effective?

Most potent- 1

More effective- 2&3 are equal

What kind of agonist is able to produce the maximum response?

full agonist

What kind of agonist is able to produce a sub-maximal response?

partial agonist

What kind of agonist binds to the same site on the receptor as the endogenous ligand?

orthosteric

What kind of agonist binds to a different site on the receptor as the endogenous ligand?

allosteric

Drugs that occupy receptors and activate them are ___________.

While drugs that occupy receptors but do not activate them are __________.

agonists, antagonists

What is the measure of strength of drug-receptor binding and how do we measure that strength?

affinity, Kd

If a drug has an affinity of 80%, if we wanted to find the ED50, what percent would we be looking at?

40%

More affinity = ______ potent

more

What term is used to describe your baseline? This is what the body attempts to restore after the effects of drugs.

Status Quo

___________ is the reduced effects/ reaction to drug following repeated use.

a. dependence

b. tolerance

c. tachyphylaxis

d. attenuation

tolerance

How can tolerance be overcome?

a. increasing # of receptors

b. increasing dose

c. decreasing dose

d. stopping drug use immediately

b

____________ can be physiological and/or psychological. It is when your baseline functionality needs a drug.

Alternative defintion:

Physiological effect: need drug in order to achieve baseline state Psychological effect: fear of not having the drug due to withdrawal/subtherapeutic situation

Dependence

Can you be addicted to redbull?

Can you be dependent on redbull?

addicted- no

dependent- yes

What is the main difference between addiction and dependence?

the psychocomponent. in addiction you seek drug in order to achieve pleasure associated with taking drug

What term describes the following?

Short-term tolerance to a drug or treatment. Repeated exposure leads to diminished response.

a. fade

b. resistance

c. tachyphylaxis

d. attenuation

c

True or False: Tachyphylaxis is non-reversible

FALSE

______________: drug binds, decreased response

______________: # of receptors decreases

desensitization, downregulation

True of False: Feedback Regulation may occur at cellular or system level, and be delayed or immediate.

TRUE

Attenuation is the decrease of response at the __________ level.

receptor

An increased response to a drug with prolonged use is:

a. sensitization

b. desensitization

c. reverse tolerance

d. tolerance

SATA

a,c

Abrupt removal of what causes supersensitivity?

antagonist

How does supersensitivity differ from sensitization?

sensitization- increase response to a drug with prolonged use

supersensitivity- abrupt antagonist removal results in increased receptor activity.

Monica is a 62-year-old woman with diabetes. She takes Lantus, and over the next couple months her cells express fewer insulin receptors. This is an example of:

a. upregulation

b. tachyphylaxis

c. dependence

d. downregulation

d

What is a type A (ADR)?

a. based on the mechanism of action

b. idiopathic, causes something else

c. based on the physiochemical properties

d. idiopathic, causes it’s intended action

a

What is a type B (ADR)?

a. based on the mechanism of action

b. idiopathic, causes something else

c. based on the physiochemical properties

d. idiopathic, causes it’s intended action

b

What do the following abbreviations stand for:

1. FDA

2. ISMP

3. WHO

And which ones, are ADRs reported to?

1. food and drug administration

2. Institute for Safe Medication Practices

3. World Health Organization

ADRS reported to all 3 organizations

Why do ADRs happen? We are changing ____________.

homeostasis

1. ___________ __________ range of efficacy without toxicity/lethality

2. ___________ __________ ratio of toxicity/lethality to efficacy

1. therapeutic window

2. therapeutic index

What is the Therapeutic Index when 400 mg of Drug A causes LD50 and 50mg of Drug A causes ED50?

8

What type of receptor is a protein that binds endogenous ligands?

physiological receptor

A receptor is acting without a ligand binding to it and producing activity.

What does this describe?

constitutive activity

What/ Who makes endogenous ligands?

your body

Drugs that mimic the effects of endogenous ligands are ____________.

agonists

__________-receptor binding will create/enhance biological effect

agonist

Does the concentration of agonist have anything to do with efficacy?

Yes

Where do primary agonists bind?

Where do allosteric agonists bind?

• same site as endogenous ligand (orthosteric site)

• different site as endogenous ligand

A ______________ enhances the effect of a drug by binding to another substance.

potentiator

What do antagonists do to the actions of agonists?

SATA

a. reduce

b. induce

c. block

d. release

a, c

When an agonist and antagonist compete for the same binding site.

a. competitive

b. allosteric

c. chemical

d. physiological

a

Binds to a different site on the receptor

a. competitive

b. allosteric

c. chemical

d. physiological

b

Binds to the agonist and prevents agonist from binding

a. competitive

b. allosteric

c. chemical

d. physiological

c

A drug that counters the effects of another by binding to a different receptor and causing opposing effects

a. competitive

b. allosteric

c. chemical

d. physiological

d

A graph of increasing response to increasing drug concentration or dose is a

__________-_______ response curve

graded-dose response curve

A graph of the fraction of a population that shows a specified response at progressively increasing doses is a __________-_______ response curve.

quantal dose

A competitive antagonist binds to the ___________ site.

orthosteric

With an uncompetitive antagonist, the antagonist binds to the ____________ site. Additionally, inhibition requires binding of the ___________.

allosteric, agonist

With inverse agonists, what is the key consideration?

constitutive activity

What binds to the allosteric site and enhances agonist activity?

allosteric potentiator

What can antagonists effect?

a. potency

b. efficacy

c. both

c

Why might chemical antagonists decrease affinity of agonists?

Chemical antagonists bind to agonist, so less binding/affinity to form the drug-receptor complex

competitive antagonists _______________ the potency of agonists

a. increase

b. decrease

b

Allosteric and Pseudoirreversible antagonists do what to potency?

decrease

Allosteric and irreversible antagonists do what to efficacy?

decrease

Allosteric potentiators impact the dose-response curve how?

increase potency

occupancy in terms of pharmacology is defined as

when a drug binds to the receptor, the receptor is occupied

What term is used to describe the % of receptors that are occupied by a drug

fractional occupancy

If a receptor has no constitutive activity, what will be the effect of an inverse agonist on that receptor?

decrease potency