Wk4 Challenging Dogma Flashcards
What is pharmacology?
The study of the mechanism of drug action
What is a drug?
– The active ingredient of a medicine
– Any substance which interacts with a biological system and changes it.
What names do drugs have?
Generic name and trade/brand names
Drugs which produce their effects not by binding to a receptor (protein)
but due to their physicochemical properties
Antacids (stomach)
– sodium bicarbonate
Laxatives
– methylcellulose (bulk)
– magnesium sulfate (osmotic)
Heavy metal antidotes ‐ EDTA (chetalor)
Osmotic diuretics – mannitol
General anesthetics – halothane
Alcohol
Effects are rather non‐specific
Tend to need rather high concentrations
Drug characteristics
The effects of most drugs
‐ occur at very low concentrations
– high potency
Can be very specific
– Biological specificity (receptor‐wise)
– Chemical specificity (drug‐wise)
Stereo‐selectivity
– Competition
Thalidomide
then marketed as Contergan S = active formin vivo razemisation
How are drugs classified?
- Chemical nature of drugglycoside, alkaloid, steroid
- Symptoms or diseases in which they are usedanti‐hypertensive, anti‐ malarial, anti‐tubercular, or anti‐epileptic agents
•Organ system affectedAlimentary, cardiovascular, respiratory, nervous, etc. •ReceptorCholinoreceptor agents, adrenoceptor agents, serotonin receptor
agents, dopamine receptor agents, etc.
- Duration of actionfrom ultra‐short acting up to ultra‐long acting agents
- GenerationsAnti‐microbials such as cephalosporins and oral hypoglycemic agents such as sulfonylureas and H1 anti‐histaminic drugs
- Route of administrationInhaled beta‐agonists, inhaled steroids, oral hypoglycemic agents, etc.
What are dirty drugs?
One drug – many targets = “dirty drugs” “wanted side effects”
Aspirin – would never be approved today…
… inhibiting COX1 and COX2 (and doing other stuff)
Highly selective cyclooxygenase‐2‐inhibitors
problems due to their very selectivity ‐ tipping the balance of pro‐ and antithrombotic mediators in an unfavourable way
Steroid hormones act by binding to intracellular “nuclear receptors” [textbook knowledge] but also activate membrane‐bound GPCRs!!! [very recent findings]
The effects of steroids often result from the interplay of the two mechanisms
Quetiapine
‐ an atypical antipsychotic
‐ with the following pharmacological actions:
• Dopamine D1, D2, D3, D4, and D5 receptor antagonist
• Serotonin 5‐HT1A receptor partial agonist, 5‐HT2A, 5‐HT2B, 5‐HT2C, 5‐HT3, 5‐HT6,
and 5‐HT7 receptor antagonist, and 5‐HT1B, 5‐HT1D, 5‐HT1E, and 5‐HT1F receptor ligand
• α1‐ and α2‐adrenergic receptor antagonist
• Histamine H1 receptor antagonist
• Muscarinic acetylcholine receptor antagonist
that means two different dosings of the same drug are actually equivalent to TWO different drugs
How does asparaginase act?
As a medication, L‐asparaginase is used to treat acute lymphoblastic leukemia, acute myeloid leukemia, and non‐Hodgkin’s lymphoma. It is
given by injection into a vein, muscle, or under the skin.
What is pharmacology good for?
Knowing what drugs exist and what their benefits, but also their side effects are.
How to manage a vast number of drugs?Categorisation
‐ receptor (classes) & ligands
‐ agonists & antagonists
‐ etc. (maybe a bit boring)
Quantifying drug action
‐ binding constants
‐ first‐pass metabolism
‐ pharmacokinetics
What is endocrinology?
For a hormone a receptor is a biomolecule they have to bind to
to exert their biological function
Crystallographic structure of Tumor Necrosis Factor (TNF) and it’s receptor
What is the nature of drug receptors? Overview
ANYTHING that causes a physiological effect, when interacting with a drug is a receptor
(in pharmacology).
way broader concept than in endocrinology
More pragmatically, just look at the receptors that known drugs bind to.
There are several larger categories of receptors (such as GPCRs) that we will discuss soon.
The nature of drug receptors specific
Enzymes –cyclooxygenase; the aspirin receptor Ion channels –Ca2+ channels blocked by nifedipine Transporters (pumps, transport proteins) – noradrenaline transporter blocked by cocaine “Physiological” receptors – receptors for hormones, neurotransmitters etc – acetylcholine, histamine, insulin etc, etc, etc...
Substrates, metabolites and proteins - asparagine (degraded by asparaginase)
DNA/RNA and the ribosome - cisplatin, many antibiotics, DNAse (in Cystic Fibrosis)
Various physicochemical mechanisms
Targets of monoclonal antibodies EGFR (targeted e.g. by cetuximab)
Unknown mechanism of action many drugs!
What is a receptor?
‐ testosterone ‐ androgen receptor ‐ endocrinology/pharmacology
‐ sildenafil – phospho‐di‐esterase 5 and 6
‐ aspirin ‐ mainly cyclooxygenase (but also other proteins)
‐ DNase (highly purified DNA‐cleaving human DNase I enzyme) ‐ nebuliser solution
Quantitive pharmacology
“Quantitative pharmacology is based on the assumption that drugs act by entering into a simple chemical relation with certain receptors in cells and that there is a simple relation between the amount of drug fixed by these receptors and the action produced”
The relationship between drug concentration and response
Relationship is
–continuous, even linear at the beginning
–Saturating
–Exhibits threshold
What are organoids used for?
1) monitoring the development of a disease
2) drug testing
organoid ‐ small and simplified version of an organ
