concepts and calculations Flashcards
define pharmacology
the study of the effect of drugs on the function of living systems
define pharmacodynamics
the effects of the drug on the body
Example: Paracetamol- mechanism of action is dependent on the inhibition of prostaglandin synthesis.
define pharmacokinetics
the effects of the body on the drug
(relates to Absorption, Distribution, Metabolism, Excretion (ADME))
define drug
A biologically active compound (other than a nutrient or essential dietary ingredient) taken with the intent to produce a change in the body.
define medicine
A chemical preparation which usually contains one or more drugs administered with the purpose of producing a therapeutic effect. Medicines usually contain other substances to make them more convenient to use.
who pioneered the treatment of syphilis?
Paul Ehrlich
how long did it take Ehrlich to produce ‘salvarsan’
It took him three years’ and three hundred syntheses
who proposed the magic bullet theory?
Ehrlich
what is the magic bullet theory?
- Whereby a drug would have selectively toxicity e.g. against a microbial agent or cancer cell.
- Ideally with little action on the host cell even at high doses = therapy without toxicity.
who described drug action (at the neuromuscular junction)?
Langley
how did Langley describe drug action (at the neuromuscular junction)?
in terms of interaction with a “receptor” substance.
what does receptor represent in a drug?
the major target of a drug (the ‘bullets’)
why are there multiple drug classes?
Drugs cannot be classified according to a single rational system because of the need of chemists, pharmacologists, doctors differ.
Any drug may have names in _ different classes.
3
what are the 3 drug classes?
- chemical class
- IUPAC name
- drug name
define target in terms of drugs
the molecular recognition site to which a drug will bind.
what are the majority of targets?
proteins
what percentage of drug targets are human?
73%
what percentage of drug targets are microbial, viral?
16%
what percentage of drug targets are miscellaneous?
11%
how are drug targets identified?
- exploring disease mechanisms (classical)
- analysing genetic basis or susceptibility to disease (post-genomic)
how many drugs were FDA approved in 2021?
50
what are the 2 conventional routes of identifying drug targets?
- Analysis pathophysiology
- Analysis of mechanism of action of existing therapeutic drugs.
what is the 1 novel route of identifying drug targets?
trawl the genome
what is the logical starting point for drug discovery?
to understand the mechanisms of disease.
who were the pioneers of understanding the mechanisms of disease?
Hitchings and Elion (1944) and their unravelling of the synthesis of DNA.
what are disease genes?
Genes, mutations of which cause or predispose to the development of human disease
what are disease modifying genes?
Genes whose altered expression may be involved in the development of the disease state OR genes that encode functional proteins, whose activity is altered in disease state
what is an example of sucess from trawling the genome?
Imatinib, highly specific tyrosine kinase inhibitor. Treats chronic myeloid leukaemia
what is an example of a frustration from trawling the genome?
Alzheimer’s disease
what are transgenic models?
Genetically engineered animal models encompass transgenic or knockout model groups where the mice are genetically engineered to overexpress or lack the gene of interest.
define molarity
How much of the substance is available in a given volume.
what are the units for molarity?
mol/l or M
what is the equation for molarity?
Mass (g) = Concentration (mol/L) x Volume (L) x Formula Weight (g/mol)
what is a mole?
The mole is the unit that defines the amount of a given substance
one mole contains __________ molecules of a substance
6x10 ^23
what is the mass of one mole in grams?
the molecular weight of that substance.
By definition a 1M solution of NaCl contains 1 mole (6 x1023 molecules) in 1 litre of solution. So how would you prepare 250 ml of a 0.5mM solution?
7.3mg of NaCl into 250ml
what is a biological assay?
- A method of measuring the effects of a biologically active substance using an intermediate in vivo or in vitro tissue or cell model under controlled conditions.
- For pharmacology; test the activity of a compound against a given ‘target’.
what is used to create a concentration response curve?
logarithmic scales
define logarithm
defined as the power to which a base (10) must be raised to produce a given number (e.g. Log 100 = 2)
what are theraputic concentrations?
The therapeutic range of a drug is the dosage range or blood plasma or serum concentration usually expected to achieve the desired therapeutic effect.
what is homeopathy?
an alternative medicine based on the theory of treating ‘like with like’.
- doesn’t work
what are the 4 main steps to develop a new medicine?
- discovery
- exploratory development
- full development
- registration
how much on average does it cost to develop a new medicine?
$1.3 billion
how long does it take to develop a new medicine?
12-15 years
what are the 7 steps for drug discovery?
- target discovery
- target validation
- screen development
- hit discovery
- lead development
- candidate identification
- candidate drug development
what are the 4 pharmacology principles?
- active ingredient (drug molecule)
- Selectively bind to certain molecular targets (e.g proteins) and
- Exerts cellular effect
- Exerts effect on system
- Produce a therapeutic effect in a concentration-related or concentration-dependent fashion
- efficacy (usefullness) of drug is supported by clinical trials using agreed ‘outcome measures’ and statistical validation
