Ch. 1- Intro: The nature and development of drugs.

Question 1

Two principles that the student should remember

Answer 1

1. 1. all substances can be toxic and that chemicals in botanicals “nutraceuticals” are no different from chemicals in manufactured drugs except for the much greater proportion of impurities in botanicals.
2. All dietary supplements and all therapies promoted as health enhancing should meet the same standards of efficacy and other drugs and medical therapies.

Question 2

Xenobiotics

Answer 2

substances that are foreign to the body or to an ecological system.

Question 3

Most drugs have weights between

Answer 3

100 and 1000

Question 4

To achieve such selective binding, it appears that a molecule should in most cases be at least

Answer 4

100 MW in size

Question 5

Even in the absence of an agonist, the receptor must still be in the active form sometimes. This is known as..

Answer 5

constitutive activity

Question 6

Full agonists

Answer 6

maximize the Ra configuration of receptor

Question 7

Partial agonists

Answer 7

Do not evoke a maximum response, no matter how high their concentration.

Question 8

Intrinsic efficiency

Answer 8

Drugs such as partial agonist that still hold the Ri-D configuration are said to have low intrinsic efficiency.

Question 9

A drug such as pindolol can do what?

Answer 9

If no full agonist is present, then it can act as an agonist

If full agonist is present, then it can act as an antagonist.

Think ** How it acts relative to what else is present.

Question 10

When an antagonist blocks the effect of agonist

Answer 10

neutral antagonism

Question 11

When a drug has a very high affinity for Ri-D configuration

Answer 11

Inverse agonists

Question 12

Inert binding site

Answer 12

When binding of a drug to a nonregulatory molecule results in no detectable biological change in the function of the biological system

Question 13

Prodrug

Answer 13

inactive drug that must be metabolized to active form in body

Question 14

Fick’s Law of Diffusion

Answer 14

(C1-C2) x (Area * permeability coefficient) / (Thickness)

Question 15

The more ionized a molecule that means more

Answer 15

water soluble

Question 16

Weak acid

Answer 16

neutral molecule that breaks apart into an anion and a proton

Question 17

Weak base

Answer 17

neutral molecule that can form into a cation

Question 18

HH equation

Answer 18

log(prot/unprot)=pKa-pH

Question 19

PKa pH relationship

Answer 19

The lower the pH relative to the PKa, the greater will be the fraction of drug in the protonated form.

Question 20

Because the uncharged form is the more lipid soluble …

Answer 20

more of a basic drug will be in the lipid soluble form at alkaline pH because there will be less floating protons therefore the base will less likely to form a cation

easy version: acid = neutral molecule that can break into anion, so an acidic environment can prevent ion (charges formation) therefore more lipid soluble.

more of a acidic drug will be in the lipid soluble form at at acidic pH because there will be more protons to neutralize the anions formed.

easy version: base= neutral molecule that can form cation, so in basic or alkaline pH there are less protons for it to gain to become a cation therefore more lipid soluble

Question 21

Weak acids are usually excreted faster in alkaline urine , why?

Answer 21

to be reabosorbed, the molecule must be lipid soluble. To be excreted, the molecule must be water soluble.
To be water soluble, the molecule must be charged.
To be charged, the weak acid must be in an environment where the molecule can lose protons. In an alkaline environment, there will be more OH- to capture the protons of the acid molecule, thus causing the molecule to become charged therefore the molecule will be charged and excreted faster.

Question 22

Weak bases are usually excreted faster in acidic urine why?

Answer 22

A weak base is defined as a neutral molecule that can form a cation. For the base to be excreted, the base must be charged. For the base to gain a proton, it must be in an acidic environment to become a charged cation.

Question 23

Three inorganic compounds discussed in class

Answer 23

Lithium Carbonate- neurological disorders
Silver nitrate-external antibiotic
Cisplatin-alkalizing treatment for cancer

Question 24

Smallest molecule of drug is

Answer 24

Lithium chloride with a MW of 7

Question 25

Liquid drugs discussed in class

Answer 25

ethanol , nicotine

Question 26

Heparan comes from

Answer 26

bovine lungs and pigs intestines

Question 27

The Lipinski rule of five

Answer 27

1. MW is less than 500
2. logP is less than 5
3. Number of hydrogen donors in the molecule is less than 5 (amine, hydroxyl)
4. Hydrogen acceptors of molecule are less than 10 (oxygen, nitrogen)

Question 28

The more positive the logP, the more..

Answer 28

lipophilic

Question 29

CNS drugs must have a ? logP value and why?

Answer 29

high, to cross BBB

Question 30

logP values can be detected using

Answer 30

chromatography

Question 31

What the body does to the molecule

Answer 31

Liberation
Absorption
Metabolism
Excretion

Question 32

Four ways that drugs can be transported across biological barriers

Answer 32

1. Aqueous diffusion- (passive)-small molecules
2. Lipid diffusion- (passive, small lipophilic molecules
3. Active transport-(active) for (peptides, glucose, amino acids) ((MDR1)) (MRP).
4. Endocytosis and exocytosis- (active) B12, Neurotransmitters

Question 33

Drug trial phases

Answer 33

P1: 20 -100 healthy volunteers to determine toxicity, etc, if adverse effects are seen in this phase, then participants with the disease participate in P1 trial. 63.2% move to phase 2.

P2: patients with the disease (100-200 people). 30.7% move to phase 3.

P3: similar to P2 but much larger sample. 58.1 percent move to new drug application.

Question 34

Drugs from paper and drugs talked about in class

Answer 34

1. Paclitaxel- chemo drug- isolated from the Pacific yew, Taxus brevifolia (fungus in the bark of the tree).
2. Artemisinin- malaria-derived from A. annua.
3. Ivermectin- targets nematodes-derived from Streptomyces avermitllis