Pharmacology Flashcards
Definition of pharmacology
Study of effects of drugs on function of living systems
What is a drug?
Chemical substance with biological effects
What are receptors?
Proteins that recognise and respond to a chemical signal with a binding and functional site
What is a ligand?
A chemical that binds to a receptor. Can be endogenous (hormone) or exogenous (applied drug)
Agonist vs Antagonist
Agonist: ligand that activates a receptor
Antagonist: ligand that blocks an agonist and doesn’t activate a receptor
Specificity
Receptors that are only activated by one endogenous agonist
Potency
Amount of agonist needed to induce a given response. Expressed as a dose or concentration
Affinity
How effective a ligand binds to its receptor
Efficacy
How effective a ligand activates its receptor
Size of response is proportional to…
Number of receptors occupied by an agonist
What is the strength of ligand-receptor determined by?
Electrical charge interactions, hydrogen bonding and hydrophobic interactions
Law of mass action
Rate of chemical reaction is proportional to the product of concentrations of reactants
What does acute mean?
Single drug that induces immediate response due to direct action to receptor
What does chronic mean?
Repeated drug treatment that induces a delayed response due to indirect action on receptor
Tolerance
- Gradual decrease in effectiveness of drug
- Chronic treatment can cause tolerance
- Tolerance occurs because the drug has an effect on homeostasis which minimises drug effects
Downregulation vs Upregulation
Downregulation: decrease in the number of receptors on a cell surface
Upregulation: increase in the number of receptors on a cell surface
Desensitisation vs Super sensitivity
Desensitisation: reduction in functional response with binding to receptors
Super sensitivity: increase in functional response with binding to receptors
Withdrawal
Avoiding drugs completely leading to adverse effects. Avoided by removing drugs gradually
Receptor classification
Classified based on differences in how functional responses are induced when drug binds to receptors
Signal transduction
Mechanism involved in translating signal to a response
What are receptor subtypes?
Endogenous agonists that can bind to and activate more than one receptor
What do ion channels do?
Mediate very fast synaptic transmission in nervous system and communicate between neurones or between a neuron and a muscle cell
How does agonist binding effect ion channels?
Allows ions to pass through using proteins to prevent the membrane being hydrophobic
What is ion movement based on?
Electrochemical gradient where concentration of ions on either side determines movement
Name the 3 ion channels
Cation channels (positive), anion channels (negative) and ion specific (sodium and potassium)
What do G-protein-coupled receptors (GPCRs) do?
Involved in fast synaptic transmission. Agonist binding to receptor induces functional response indirectly through G-proteins present in membrane
Why are they called G-proteins?
Association with guanine nucleotides GTP and GDP and are comprised of a trimetric structure with three units (α, β, and γ)
GPCR structure
Long third cytoplasmic loop of receptor coupled to G-proteins
GPCR activation
- GDP binds with alpha
- GDP is converted to GTP causing dissociation with complex
- Resulting in α-GTP with βγ complex
- These are active forms of G-protein and bind to various effectors in membrane
GPCR inactivation
Reverse reaction
Kinase-linked receptors
Mediate slow forms of communication by altering gene transcription and target peptides and hormones
What is kinase?
An enzyme that phosphorylates proteins
What is phosphatase?
An enzyme which de-phosphorylates proteins
Kinase-linked receptors structure
Single large polypeptide chain with one transmembrane domain and large extracellular ligand-binding domain and an intracellular catalytic domain
What is dimerization?
Two receptors become associated together in membrane
Auto-phosphorylation
Two receptors phosphorylating themselves
Kinase-linked receptors activation
Dimerization results in auto-phosphorylation of tyrosine which serves as a binding site for other enzymes
Nuclear receptors
Mediate very slow forms of communication by altering gene transcription which target hormones and fat-soluble vitamins
Orphan receptors
Receptors with an unknown ligand
How many classes of nuclear receptors are there?
2
Homodimers vs Heterodimers
Homodimers: two identical receptors associate and function together and act outside nucleus
Heterodimers: two different receptors associate and function together and act inside nucleus
Class 1 of nuclear receptors
Located in cytosol and form homodimers
Class 2 of nuclear receptors
Located in nucleus and form heterodimers
Structure of nuclear receptors
- N-terminal domain (contains co-activator region that binds to transcription factors)
- DNA binding domain (binds to specific DNA sequences known as hormone response element to alter gene transcription)
- Hinge region (binding site for two nuclear receptors during dimerization)
- Ligand binding domain (binding site for ligand that is specific for different receptors).
