Introduction to Pharmacology Flashcards
Learning outcomes • Define the term pharmacodynamics • Identify molecular targets for drug action including receptors, ion channels, enzymes and transporters • Identify cellular mechanisms of action including excitation, contraction and secretion and describe how these actions translate into responses at the tissue and organ level • Explain the relationship between drug dose and response
What is pharmacology?
The science of drugs and their effect on living systems.
What is pharmacodynamics?
The mechanism of action of a drug to the body.
What is pharmacokinetics?
What the body does to the drug (E.g. absorbed, metabolised, excreted).
How do drugs work?
- By identifying molecular targets for drug action.
- By identifying cellular mechanisms of action.
What are molecular targets for drug action?
Receptors, ion channels, enzymes and transporters.
What are cellular mechanisms of action?
Excitation, contraction and secretion.
What is an agonist?
A substance that mimics the actions of a neurotransmitter or hormone to produce a response when it binds to a specific receptor in the brain.
Agonists have affinity and efficacy.
What are antagonists?
Chemical substances that bind to and block the activation of certain receptors on cells, preventing a biological response.
What is drug affinity?
The ability to bind to the target receptor.
What is efficacy?
The ability to change receptor activity to produce a response/effect.
What is potency?
The amount of the drug/ concentration of the drug required to produced a defined effect.
What is salbutamol?
- An agonist drug.
- Causes bronchodilation
- Mimics the action of adrenaline from adrenal glands
- Binds and activates adrenergic receptors on smooth muscle surface - intracellular signals via G proteins which leads to muscle relaxation
What are antihistamines?
- Antagonist drugs that oppose the action of histamine
- Pollen stimulates mast cells to release histamine which activates histamine receptors and leads to swelling, fluid exudation (via intracellular signalling)
What are enzyme inhibitors?
Compounds which modify the catalytic properties of the enzyme and slow down the reaction rate / stop the catalysis. Block or distort the active site.
What are statins?
Enzyme Inhibitor
Compounds that inhibit cholesterol synthesis (e.g. Atorvastatin, simvastatin, lovastatin, rosuvastatin)
What is Ibuprofen?
Enzyme inhibitor
- Inhibits cyclooxygenase which produce prostaglandins that cause inflammation (swelling and pain).
What are proton pump inhibitors (PPIs)?
PPIs prevent H+/K+ ATPase from working so acid isn’t pumped into the stomach from cells in stomach lining which pump hydrogen ions into the stomach via the H+/K+ ATPase, increasing stomach pH.
What are antidepressants?
- Selective serotonin reuptake inhibitors (SSRIs) that inhibit the transporter protein that moves serotonin from synapse into cells.
What is the function of local anaesthetics?
Block sodium channels which prevents nerve conduction. Action potential cannot be generated as it requires ion channels.
What is drug selectivity ?
- The ability of a drug to bind to one receptor subtype without affecting another receptor subtype.
What is the cancer risk from replication errors?
- human body has over 10^13 cells and over an avg. lifetime undertakes 10^16 mitotic divisions occur due to turnover. Each cell contains a genome of ~ 3 billion bases to be replicated
- Cancer risks will relate to fidelity of DNA replication and recognition and replacement of errors
- Transcription mistakes are possible with ecery new cell that is formed. Ageing is a risk factor due to increased likelihood of errors and also environmental exposures
- If cancer was due to biological processes only , the incidence of cancer should be similar across different populations but vaaries between countries highlighting the importance of lifestyle and environment
What are cancer risks due to genetics?
- Only 5-10 % of all cancer risk is due to genetic inheritance, with the remainder from lifestyle and environmental factors
- Many life-style factors can be avoided and risks minimalised
q
What is the genetic epidemiology of cancer?
- Focuses on the understanding of :
- the role of genetic factors in relation to the susceptibilty to and relapse from cancer and the relationship between environmental and lifestyle exposures and genetic susceptibility
- Can involve the use of families and population-based case-control studies to:
- identify susceptibility genes
- Determine the contribution of these genes to the incidence of cancers in population
- Understand the inter-relationship between genetic susceptibility and environmental and lifestyle exposures
- Understand the timing of critical environmental and lifestyle exposures for cancer
- investigate both somatic gene changes germline genetic variation and environmental lifestyle exposures in determining risk of relapse
What are the health risks from pollutants?
~65,000 current licensed chemicals, 500-1000 new ones/year
-Recent gov report concluded that the majority of cancers are from chemical exposures
- Risk assessment of chemical exposures often rely on animal models without human exposure testign and rarely consider multiple chemical exposures
How can chemicals damage DNA?
- Increased risk of cancer drom environmental and occupational chemical exposures
- 8-Hydroxy-2’-deoxyguanosine (8-OHdG is a marker of oxidative stress damage to DNA)
What is the correlation between cancer and lifestyle?
- Susceptibility to cancer is influenced by lifestyle and environmental factors
- Fluid and can be driven by a change in these factors such as population movement
What is the viral infection risk factor for cancer?
- Possibilty of viral oncoprotein expression and/or modification of genes is a one or two step process
What is an example of the viral-induction of cancer?
- HPV
- Viral protein disrupts normal cell growth and monitoring of cell death by degrading tumour suppressors such as p53 (hpv e6 protein) and promoting cell proliferation (HPV E7 protein)
What are bacterial-related cancers?
- Example : link between chronic helicobacter pylori infection and potential driver for stomach cancer
