Pharma information to remember - module 1

Question 1

Since when did the most growth in medicines approvals occur?

Answer 1

since 1930

Question 2

What are pharmacodynamics?

Answer 2

What the drug does to the body. From interactions of drugs with target cell receptors, effects on cell signalling pathways, cell and tissue responses, and changes in the functions of whole organ and body systems.

Question 3

What are pharmacokinetics?

Answer 3

What the body does to the drug. Extending from absorption, distribution through bloodstream to body tissues, metabolism within liver and eventual excretion.

Question 4

What is a xenobiotic?

Answer 4

This handy word refers to any molecule that enters the body from a foreign or external source. While the term covers drugs and medicines, it also embraces many other molecules that are encountered in modern societies, including cleaning agents, pesticides, herbicides, fuel additives, environmental pollutants, industrial reagents, workplace chemicals and naturally-occurring food constituents.

Question 5

How do “small molecule” drugs compare to “biologic” drugs in function?

Answer 5

“small molecule” drugs access body readily via oral route, are often subject to drug-drug interactions and have problems with toxicity.

“Biologic” drugs are expensive to make, hard to get into the body, rarely subject to drug-drug interactions and can be immunogenic (triggering allergies)

Question 6

How are drugs named?

Answer 6

In general, a given marketed drug will be known by 3 names:

Chemical name (Describes chemical structure of drugs)

Generic name (Used in most pharmacology courses and is a simplified drug name)

Brand name (Invented by marketing division of drug companies)

Question 7

Why are drug names so confusing?

Answer 7

No international body imposes uniform names

Same drug can be known by many names across national boundaries

Question 8

What are some common stems in drug names?

Answer 8

• cillin (antibiotics)
• olol (beta blockers)
• pril (ACE inhibitors)
• sartan (AtII receptor blockers)

Question 9

How are new drugs discovered?

Answer 9

6 main discovery paradigms:

1) “Bioprospecting” based exploration
2) Disease-Model Screening
3) “Me-Too” Drug optimisation
4) Astute Clinical observation
5) Rational drug design
6) Irrational high-throughput discovery

Question 10

What is bioprospecting?

Answer 10

Systematic testing of
naturally‐procured materials for
pharmacological activity

Question 11

What is disease-model screening?

Answer 11

Screening sets of chemicals on a model organism (Often an animal)

Question 12

What is “Me-Too” Drug optimisation?

Answer 12

Companies sought new molecules within a given therapeutic class with better properties
than existing medicines from rival labs.

A better version of the original drug

Question 13

What is astute clinical observation?

Answer 13

Sometimes unexpected drug effects occur when
testing new molecules in humans.

Such “serendipitous” clinical observations
can lead to new drugs

Note: (Less common nowadays due to better
technologies for testing pharmacology of
new molecules)

Question 14

What is rational drug design?

Answer 14

Due to advances in X‐ray crystallography, NMR
and structural biology, detailed knowledge of
drug receptor structures is available.

Using computer‐aided docking software, possible to
“design” molecules that “fit” potential drug‐binding
sites

Question 15

What is irrational drug discovery?

Answer 15

Late 20th century saw advances in computing,
bioassay complexity and robotics permit mechanisation of lab processes (24/7/365 operations) allowed quicker screening of compounds for pharmacological
activity (“high‐throughput screening” (HTS)) expectation that massive libraries will, on law of averages, contain
some compounds that “hit” protein target of interest

Question 16

Is potency important in determining which drug is selected for use?

Answer 16

Rarely.

A more potent drug is useful when there is limited capacity to administer a large amount of drug, for example:
• transdermal patches,
• anaesthetic darts to
elephants (etorphine,
aka Immobilon or M99,
is 3000 times more potent
than morphine).

Question 17

What do drugs bind to to exert their effects?

Answer 17

Receptors

Question 18

What is an NME?

Answer 18

New Molecular Entities are molecules that have been approved by an official drug regulatory agency such as the US Food and Drug Administration [FDA]).

Question 19

How many receptors are associated with currently approved drugs?

Answer 19

667 drug receptors that mediate the effects of currently approved drugs.

Question 20

What are the classes of receptors for drugs?

Answer 20

Four broad protein classes, namely G-protein coupled receptors (GPCRs) [33%], ion channels [18%], kinases, and nuclear receptors.

Question 21

How large are “small molecule” medicines?

Answer 21

Molecular mass of 500 g/mol or less

Question 22

Why small molecules?

Answer 22

two great advantages of small molecules are their relative affordability and above all, the ability to administer them orally with little more than a glass of water.

Question 23

Small molecule drug advantages vs disadvantages:

Answer 23

Advantages:

Cheap, easy to make

Easy to confirm chemical purity

Easy for generic companies to copy upon patent expiry

Access the body easily

Easily supplied by pharmacies

Disadvantages:

Target multiple receptors causing side effects

Often compete for relatively few enzymes or transporters in the liver of kidneys (causes drug-drug interactions)

Can undergo metabolism to form toxic metabolites, causing organ injury

Question 24

Advantages and disadvantages of large molecule drugs:

Answer 24

Usually target a single receptor (few side effects)

Can pinpoint specific aberrant pathways (good against cancer)

Rarely cause drug-drug interactions

Profitable for companies

Disadvantages:

Hard to make (complex)

Hard to test for purity

Hard to get into the body

Expensive to consumers and healthcare

Cost hundreds or millions per annum

Can be immunogenic

Question 25

What are the 3 main stages of pharmaceutical innovation?

Answer 25

Discovery phase

Developmental phase

Commercialisation phase

Question 26

What is lexisenatide?

Answer 26

An anti diabetes drug produced in the gila monster lizard

Question 27

Marine organisms were the sources for which important medicines?

Answer 27

Ziconitide

Vincristine

Question 28

Which drug is used in the treatment of glaucoma and was invented using rational design strategies?

Answer 28

Dorzolamide

Question 29

In 2017, how many new drugs were approved by the US Food and Drug Administration?

Answer 29

46