Chem test 4 Erin's Flashcards by Rae Perry

this is the study of the interactions between a drug and
organism

pharmacology

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the study of how a drug affects the
organism

Pharmacodynamics

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the study of how the organism affects the drug

Pharmacokinetics

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What is included in pharmacodynamics?

-Site of Action
-Mechanism of Action
-Receptor Binding
-Postreceptor Effects
-Chemical Interactions

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What can affect pharmacodynamics?

Disease or Disorder
Age
Drug–Drug interactions

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What are the three receptor subtypes?

Enzymes
Ion Channels
Membrane receptors

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What are the ways that drugs bind due to chemical interactions (4 total)?

Electrostatic interactions (intermolecular forces)
Hydrophobic interactions
Covalent bonds
Stereospecific interactions (enantiomers)

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how well the drug binds to the receptor

affinity

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how well the drug produces its desired effect

efficacy

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term used to compare the relative affinity of competing drugs

potency

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These concepts help us gain a better understanding of how we are going to administer the drug

absorption, distribution, metabolism, and excretion of drugs from the body

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What is the most common type of intermolecular force with drugs?

hydrogen bonding

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LD50

lethal dosage to kill 50% of the population given that drug - not done on humans

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This method of drug administration is other than the intestine

parenteral

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Examples of parenteral drug administration

-intramuscular
-Subcutaneous
-Intravenously
-Inhalation

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This determines time to maximal concentration at the receptor to produce peak effect.

Absorption rate

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This is how much of the administered drug is actually
absorbed. (typically used for oral administration)

bioavailability

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8 factors effecting bioavailability

Molecular weight of the drug
Drug formulation
Drug stability (especially pH sensitivity)
First pass metabolism (typically in the liver)
Blood flow
Gastric emptying (food slows this process)
Intestinal motility
Drug interactions

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This is the effectiveness of the movement of the drug throughout the body

distribution

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What influences distribution? (6 things)

Blood
Total body water
Extracellular fluids
Lymphatic fluids
Cerebrospinal fluids
Protein-binding

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What type of properties help determine ability of drug to be
distributed to the desired receptor site.

drug solubility

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This is the breakdown of drugs into metabolites

metabolism

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What happens to prodrugs during metabolism?

They are converted from inactive form to active form

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Cytochrome p450 enzymes like to use this type of reaction to metabolize drugs

REDOX reactions

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Common metabolism processes

REDOX reactions, hydrolysis

What things are metabolized via hydrolysis?

esters, amides, and nitriles

What is a downside to metabolism?

Has the potential to lead to the formation of toxic metabolites

Main routes for excretion:

* Kidneys (majority of drugs) * Feces (unabsorbed drug or metabolites from bile) * Lungs (inhaled anesthetic drugs) * Sweat (not very common)

Most drugs fail during the _____ phase

discovery

___% of all drugs fail in clinical testing

90%

Lipinski Rule of 5

-describes drug potential for a new chemical entity (NCE) -Used as a tool to measure a NCE’s potential bioavailability

Ionized drugs are more ___ soluble

water

Lipinski rule of 5 with drug development is based on

*Hydrogen bond donors (typically amines and alcohols) * Hydrogen bond acceptors (total number of N, O, and F) * Molecular weight (MW) * Calculated Partition Coefficient (cLogP)

Violation of more than one “rule” predicts a NCE is ______

non-orally available

We try to limit molecular weight at

500

Ratio of the solubility of a drug in oil vs water (so it mirrors the cellular membrane)

cLogP

Try to keep the cLogP under __

We try to limit the amount of hydrogen bond acceptors (N and O) to __ or less

This is where the binding has to occur to elicit a response

active site

Is it easy for low MW drugs with a low cLogP to cross membranes?

Yes

Potential drug compounds must have a mix of ________ and ______ groups

hydrophilic, lipophilic

Structural alerts – certain functional groups that have been linked to increased toxicity due to their metabolites (5 total) :

* Aromatic anilines * Nitroaromatics * Aliphatic halides * Polycyclic aromatic hydrocarbons * Thiophenes

Drug efficacy is directly related to ____________

the concentration of the drug at its site of action.

True or false Drugs must cross membranes throughout the entirety of ADME

true

Absorption of drugs into the bloodstream is dependent on the _____ properties of the drug and the ___ at the site of absorption

acid/base, pH

Why does transport plateau at high drug concentrations?

due to limited number of transport proteins available

Daltons is shorthand for

g/mol

Extremely Small Drugs (< 50 Da)

Bulk Flow (passive transport)

Lipophilic Drugs (50 – 500 Da)

Passive transport

Lewis acid

electron acceptor

Lewis base

electron donor

Bronsted base

proton acceptor

Anything less than 500 g/mol will diffuse by

passive transport

Bronsted acid

proton donor

These acids completely ionize (break apart into ions) when dissolved in water

strong acids

Strong acid examples

HCl, HBr, HI, HNO3, HClO4, H2SO4

These acids partially ionize when dissolved in water

weak acids

Examples of weak acids

HF, H2CO3, H3PO4, organic acids (carboxylic acids, protonated drugs, etc)

Strong Acids have ____ conjugate bases

weak

Weak Acids have _____ conjugate bases

strong

When we calculate pH we focus on the ____ definition of acid and bases. Why?

Bronsted-Lowry, we are looking at the protons

Conjugate acid and bases are shown on the ___ side of an equation

product

Water can act as

either an acid or base How it acts depends on what it is being mixed with

Think of acidity as

a sliding scale You can take two acids and they react together, one will react as an acid one as a base because one is more acidic than the other.

This is the substance formed by the removal of a proton from an acid

conjugate base

This is a chemical compound formed when an acid gives a proton to a base

conjugate acid

When talking about strength of acids we are referring to

if it completely ionizes (strong) or not (weak)

What does ionize mean?

break apart into ions

All of the drugs we are dealing with will be

a weak acid or weak base

These bases completely ionize (break apart into ions) when dissolved in water

strong base

What does the double arrow "equilibrium" represent

The rate of the forward reaction is equal to the rate of the backwards reaction

Strong base examples

LiOH, NaOH, KOH, Sr(OH)2, Ca(OH)2, Ba(OH)2

These bases partially ionize when dissolved in water

weak bases

What is the Water Constant (KW)? (definition)

measure of the self ionization of water

What is the water constant (#)?

1.00 x 10^-14

The higher the pH the more ___ something is

basic

The higher the pOH the more ___ something is

acidic

The lower the pOH the more ___ something is

basic

When dealing with a strong acid it produces

H3O+

When dealing with a strong base it produces

OH-

When solving for a pH of a base solve for ___ initially then ___

pOH, then subtract it from 14 to get pH

If you get a pH for a base it should always be

>7.0

if you get a pH for an acid it should always be

<7.0

pH + pOH =

pH of 7 =

neutral

Acid strength is actually relative and depends on the ability of the group to _________

give up a proton.

The larger the KA = the easier it is to ______

remove the proton (more acidic)

The lower the pKA the more ___ something is

acidic

Note the pH scale is logarithmic so a change of 1 actually scales to a change by a _____

factor of 10 So when you go to a pH of 6 --> 7 you are actually changing it by a factor of 10

If the exponent is negative move your decimal place

to the left

Calculate the pH of the following solution: 1.50 x 10^-3 M HCl

2.82 Steps: -log [1.50 x 10^-3] = 2.82

Calculate the pH of the following solution: 3.51 x 10^-2 M NaOH

12.55 Steps: -log[3.51 x 10^-2] = pOH = 1.45 pH = 14 - 1.45 = 12.55

pKA of H2O

Water is amphoteric, what does this mean?

can act as either an acid or a base