Pharma information to remember - module 1 Flashcards
Since when did the most growth in medicines approvals occur?
since 1930
What are pharmacodynamics?
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.
What are pharmacokinetics?
What the body does to the drug. Extending from absorption, distribution through bloodstream to body tissues, metabolism within liver and eventual excretion.
What is a xenobiotic?
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.
How do “small molecule” drugs compare to “biologic” drugs in function?
“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)
How are drugs named?
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)
Why are drug names so confusing?
No international body imposes uniform names
Same drug can be known by many names across national boundaries
What are some common stems in drug names?
- cillin (antibiotics)
- olol (beta blockers)
- pril (ACE inhibitors)
- sartan (AtII receptor blockers)
How are new drugs discovered?
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
What is bioprospecting?
Systematic testing of
naturally‐procured materials for
pharmacological activity
What is disease-model screening?
Screening sets of chemicals on a model organism (Often an animal)
What is “Me-Too” Drug optimisation?
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
What is astute clinical observation?
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)
What is rational drug design?
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
What is irrational drug discovery?
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
Is potency important in determining which drug is selected for use?
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).
What do drugs bind to to exert their effects?
Receptors
What is an NME?
New Molecular Entities are molecules that have been approved by an official drug regulatory agency such as the US Food and Drug Administration [FDA]).
How many receptors are associated with currently approved drugs?
667 drug receptors that mediate the effects of currently approved drugs.
What are the classes of receptors for drugs?
Four broad protein classes, namely G-protein coupled receptors (GPCRs) [33%], ion channels [18%], kinases, and nuclear receptors.
How large are “small molecule” medicines?
Molecular mass of 500 g/mol or less
Why small molecules?
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.
Small molecule drug advantages vs disadvantages:
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
Advantages and disadvantages of large molecule drugs:
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
What are the 3 main stages of pharmaceutical innovation?
Discovery phase
Developmental phase
Commercialisation phase
What is lexisenatide?
An anti diabetes drug produced in the gila monster lizard
Marine organisms were the sources for which important medicines?
Ziconitide
Vincristine
Which drug is used in the treatment of glaucoma and was invented using rational design strategies?
Dorzolamide
In 2017, how many new drugs were approved by the US Food and Drug Administration?
46
