Drug Target Sites: Receptors Flashcards
In which ways do drugs act?
Therapeutically to prevent disease, relieve the symptoms and (sometimes) cure the condition
What is a drug?
Chemical substance/natural product which affects body function (i.e.bioactive)
What do drugs include?
Active agents of medicines (therapeutic agents) as well as drugs of abuse
What is an exogenous agent?
Manufactured outside the body
What is an endogenous agent?
Something the body manufactures in order to carry out a specific function e.g. hormones
Give an example of a hormone that’s both an endogenous and exogenous agent?
Adrenaline
What are some examples of drugs?
Aspirin (aka acetylsalicylic acid- acetyl derivative of salicylic acid)- analgesic (pain relieving)
Diamorphine (aka diacetylmorphine, heroin)- analgesic (pain relieving) Valium (aka Diazepam)- anxiolytic (anti-anxiety)
Sildenafil (aka Viagra)- vasodilator
What are cells, tissues and organs controlled by?
Nervous system
Humoral agent
Local factors
How do drugs affect normal working cells?
By mimicking or blocking the action of the ‘endogenous’ agent at specific cellular targets
In what ways can a drug be classified?
By nature
By action
Which cell components are involved
Which of the body systems does the drug affect
How does the drug help in the disease state
In what way can drugs be classified in nature?
Where or how it is obtained (e.g. origin of the drug, chemical structure)
In what way can drugs be classified by their action?
How and where the drug acts
What do all drugs do?
Interact with some part of a cell to produce a response
In what way can drugs be classified by the components involved?
Receptors
Ion channels
Enzymes
Carrier molecules
In what way can drugs be classified by the system the drug effects?
E.g. cardiovascular, respiratory, immune, endocrine
In what ways can drugs be classified by how the drug helps in the disease state?
I.e. therapeutic/clinical effects
Where do drugs act on a cell?
Either on or inside the surface of cells
What are drugs main targets?
Receptors (MAIN)
Ion channels
Enzymes
Carrier molecules
What is a drug receptor?
A large (macromolecular) protein structure
What do drug receptors participate in?
Intracellular communication via chemical signals
What happens when some agents dock a receptor?
Trigger a series of events
What are the primary cells arranged to within the body?
Muscle
Nervous
Epithelial
Connective tissues
What happens upon recognition of an appropriate chemical signalling molecule (ligand)?
Receptor proteins transmit the signal into a biochemical change in the target cell
What do drug + receptor give?
Response
What are the types of signalling molecules?
Endocrine signals
Paracrine signals
Autocrine signals
What are endocrine signals?
Hormones produced by endocrine cells, which travel through the blood to reach all parts of the body
Give an example of endocrine signal
E.g. adrenaline released from the adrenals acting on the heart muscle cells
What are paracrine signals?
Target only cells in the vicinity of the emitting cell
Give an example of paracrine signalling
E.g. neurotransmitters released from neurone and acting on neighbouring muscle cell
What are autocrine signals?
Affect only cells that are of the same cell (type) as the emitting cell
Where are autocrine signals found?
Immune cells
Where an receptors be found?
Intracellular receptors
Cell membrane
What are intracellular receptors?
Only a few
Association with steroid hormones
Why do many receptors have to be on the cell membrane?
Many molecules are polar and can’t get through membrane
What does cell membrane receptors involve?
Active docking site outside the cell
Endogenous transmitters or drugs interact outside the cell
What happens when a drug attaches to a receptor on the cell membrane?
Cell changes shape and a cascade of events occur
What do transmembrane receptors allow?
Communication across the cell membrane
What are transmembrane receptors?
Proteins that span the thickness of the plasma membrane
What is the structure of transmembrane receptors?
One end is outside (extracellular domain) and one end inside (intracellular domain)
7-7 proteins that span the membrane
Where are the active sites for transmembrane receptors?
Outside the cell
What can transmembrane receptors bind?
Drugs (exogenous agents) or natural (endogenous) agents e.g. Na or Ach (neurorotransmitters)
What are agonists?
Binds to and activates the receptor
Through series events causes a change to occur
What are antagonists?
Binds onto receptor Doesn’t activate it Tends to block it Don’t usually see an effect Means agonists can’t bind to receptor to stimulate and cause a change
What are some common features about receptors?
Proteins (glycoproteins or lipoproteins)
One or more binding sites
Activated by binding of endogenous ligand- induces a conformation (shape) change
Saturable
How many signals do receptors generate?
One or more (second messenger signals)
What properties do receptors have?
Recognition
Transduction
What does the fraction of total membrane receptors occupied by Ligands determine?
Size of transmembrane signal transduction
I.e. More ligand greater chance of bigger signal
What are drugs features that act on receptors?
Receptor modulators
Enhance/diminish transmission or receipt of a ligand generated signal
Mimic signal (agonist)
Diminish signal (antagonist)
What are the actions of drugs on receptors?
Allosteric agonists or antagonists enhance or block the signal by binding allosteric sites that influence signal transmission
Where can other drugs block signal transduction?
Within the membrane
At intercellular signal reception points
What is the strength a signal replayed by the receptor dependent on?
Concentration of the hormone-receptor complex
What is the signal strength relayed by dependent on?
Affinity of the hormone for the receptor
Concentration of the hormone
Concentration of the receptor
What’s the equation for the drug receptor interaction?
[H] + [R] [HR]
R- receptor
H- free hormone
HR- receptor bound hormone
Why is Kd?
Dissociation constant for the binding of the drug to the receptor
Kd is reciprocal of the affinity constant- higher the affinity of the drug for the receptor the lower the Kd
High Kd= low affinity, fewer receptor complexes
How do you calculate Kd?
[Kd] = [H] x [R] / [HR]
What mechanisms does the recognition of a drug or hormone by a receptor require?
Non-covalent mechanisms
E.g. Covalent, ionic, hydrogen, hydrophobic, van dee Waals
What are most drug-receptor interactions?
Reversible
Weak chemical bonds
What are irreversible drug-receptor interactions?
Uncommon
Strong chemical bonds (covalent)
E.g. Aspirin, anti-tumour drugs
Usually undesirable
What are the major classes of receptors
Ligand gated ion channels (e.g. Acetylcholine and GABA-A receptors)
G-protein coupled receptors (e.g. Beta- adrenoceptors)
Tyrosine-kinase linked receptors (e.g. Insulin)
Ligand activated transcription factors (e.g. Thyroid and steroid hormone receptors)
What are the important steps of hormone initiated signal transduction?
Biosynthesis of a hormone
Storage and secretion of the hormone
Transport of the hormone to the target cell
Recognition by the hormone receptor protein
Relay and amplification of the signal that leads to defined biochemical reactions within the target cell
Removal of hormone
