Lecture 1 - introduction Flashcards
What is pharmacology?
The study of mechanisms by which drugs affect the function of living systems
Where is morphine derived from?
Poppy - synthesis achieved in 1950s
What drug was first sold as a non-addictive form of morphine?
Heroin
What is the 4th largest product in the healthcare sector?
Aspirin
What can endorphins be referred to as?
a self-made form of pain relief
What is a drug?
a chemical (of known structure) which when administered to a living organism produces a biological effect.
What are 3 types of drugs?
- synthetic chemical (heroin)
- plant chemical (morphine from poppy)
- biopharmaceutical (generated through the biotech industry)
What is a medicine?
A chemical preparation that usually contains one or more drugs, ADMINISTERRED to produce a therapeutic effect
What else do medicines contain other than drugs?
- excipients
- stabilizers
- solvents
What impact do excipients have on a medicines’ therapeutic effect?
They don’t impact the potency of the drug and its therapeutic effect
How might you engineer proteins?
Change the properties of insulin to last longer
What is gene therapy?
The addition of genetic material to cells to prevent, alleviate or cure disease
Describe what you can use DNA technology for
- therapeutic monoclonal antibodies
- recombinant hormones
- siRNA
- mRNA
Describe an example of regenerative medicine
Engineered stem cells to replace irreparably damaged organs
Describe what occurs in the first generation in the development of biologics
Copies of endogenous proteins produced by recombinant DNA technology
Describe what occurs in the second generation in the development of biologics
‘engineered’ proteins to improve the performance
Why would you alter the amino acid sequence of insulin?
Faster-acting hormone - tackle diabetes
Why would you alter the amino acid sequence of tissue plasminogen activator analogues?
Longer circulating half-life - tackle thrombolysis
Why would you alter the amino acid sequence of interferon analogue?
for superior antiviral action
Why would you alter the amino acid sequence of Factor VIII analogue?
smaller molecule, better activity - tackle haemophilia
Why would you alter the amino acid sequence of Diphtheria toxin-interleukin-2 protein fusion protein?
Target toxin to appropriate cells - tackles T-cell lymphoma
Why would you alter the amino acid sequence of Tumour necrosis factor?
Prolongs half-life - tackles rheumatoid disease
What are larger molecules referred to as?
Biologics
What is the new biologics?
engineered humanized monoclonal antibodies
What is an example of new biologics?
Adalimumab (Humira) - biologic drug to treat rheumatoid arthritis
What are more expensive, biologics or small molecule drugs?
Biologics
What is pharmacogenetics?
the study of genetic influences on responses to drugs, usually to identify the risk of adverse reactions.
What is pharmacogenomics?
use of more complex analysis of individuals genes to guide choice of drug therapy - personalised medicine.
What is pharmacoepidemiology?
study of drug effects at a population level
What is pharmaco-economics?
Aim to quantify the cost & benefit of drugs
What are the 2 general principles underlying the interaction of drugs with living systems?
Drug molecules must exert some CHEMICAL INFLUENCE on at least 1 constituents of cells to produce a pharmacological response.
Drug molecule must be BOUND to particular cells to produce an effect.
What is the role of a receptor?
Recognise and response to endogenous chemical signals
What may be used to identify and class receptors?
Their structure, pharmacology and signaling mechanism
What is the effect on specificity when increasing dosage?
Increasing dose will cause it to affect other targets - unwanted side effects, toxicity.
What are the 3 ways a drug can interact with a receptor?
- agonists
- antagonists
- inverse agonists
Role of agonist
activation occurs and signalling occurs in cell
Role of antagonist
no activation of signalling occurs in cell
Role of inverse agonist
binds to receptor and shuts down constitutive activity. This leads to a decrease in signaling.
What is an example of receptor that shows ‘constitutive activity’?
5HT2A receptor (subtype of serotonin)
What type of receptors are Opioid receptors?
G-protein coupled receptors
What are examples of agonists of mu-opioid receptors?
- Enkephallins
- Endorphins
- Morphine
- Heroine
- Fentanyl
What is an example of an antagonist of the mu-opioid receptor?
Naloxone
What are blockers?
Drugs that act on channels that lead to permeation becoming blocked
What are modulators?
Drugs that act on channels that lead to increased or decreased opening permeability
What do local anesthetics bind to?
ion channels to prevent activation
Consequence of inhibitor?
normal reaction inhibited
Consequence of false substrate?
Abnormal metabolite produced
Consequence of prodrug?
active drug produced - prodrug is inactive drug, which when processed by enzyme, becomes activated
What 2 drugs bind to an enzyme?
Aspirin & Viagra
What is an example of a false substrate?
cocaine - transported where neurotransmitters would usually be
What are 2 drugs that bind to a transporter?
- Prozac
- Digoxin
