INTRODUCTION TO PHARMACOLOGY Flashcards
Define Pharmacokinetics, Pharmacodynamics and Pharmacotherapeutics and explain how they are related
- Kinetics: How the body metabolises the drug
- Dynamics: The changes the drug causes in the body
- Therapeutics: The use of drugs to treat and prevent disease
- Kinetics+Dynamics=Therapeutics
When a drug produces a response, what is it dependent on?
- The type of target and what the target is linked to:
- Affinity - degree of attraction
- Efficacy (intrinsic activity) ability to change target in a way that produces an effect
What is the definition of potency?
The quantity of drug required to achieve a desired effect
What are the 3 types of agonist?
Full, partial and inverse
What do agonists do?
Agonists have affinity and efficacy – they are attracted to a target and produce a response
What do full agonist do?
Produce maximal response - they have maximal efficacy and affinity
What do partial agonist do and how do they behave when full agonists are present?
- only PARTIALLY respond, irrespective of drug concentration
- possesses a lower intrinsic activity than a full agonist
- a partial agonist acts as an antagonist in the presence of a full agonist (if they compete for the same receptors)
What do inverse agonist do?
Binds to the same receptor as an agonist but induces a pharmacological response opposite to that of the agonist
- they only have an effect when the target is continually stimulated by an agonist, this is because inverse agonists suppresses the receptor signalling
Name the 3 types of allosteric modulators
Positive - increases affinity, increases efficacy
Negative - decreases affinity, decreases efficacy
Neutral - has no effect on the binding of the agonist
What do allosteric modulators do and how do they do it?
Increases (or decreases) the binding of the agonist while having no effect on its own binding (binds to a different site on the receptor - allosteric site)
What do antagonists do?
Prevent agonist from binding
Name the different types of antagonist?
Competitive - reversible
Non-competitive - binds to allosteric site (irreversible)
What are the four different receptor drug targets?
G protein-coupled receptors
Ion channels
Nuclear hormone receptors Protein kinases
Opening of Na+ or Ca2+ ion channel causes…
the opening of Na+/Ca2+ channels cause further depolarisation
Ca2+ channels open
Increase in Ca2+
Hence increase in cellular activity
Opening of K+ channels causes…
Cause hyperpolarisation (more negative)
Ca2+ channels close
Decrease in Ca2+
Hence decrease in cellular activity
What is an example of a ligand-gated ion channel?
Nicotinic acetylcholine receptor
Nicotine is an agonist = causes the Na+ movement (depolarization)
What does GTP stand for?
Guanosine triphosphate
How many lipophilic membrane domains does a GTP receptor have?
7 α -helices
How many subunits does GTP proteins have?
Three subunits (α, β, γ)
G alpha – largest and binds to GTP or GDP
G beta & G gamma which is permanently bond together
Describe how GTP coupled receptors work
- Receptor forms complex with alpha-GDP complex
- GDP exchanged for GTP
- Alpha-GTP dissociates from G protein and binds to a target protein in the cell (causes changes)
- GTP is hydrolysed (by GTPase)
- Alpha subunit rejoins the other subunits of the G protein
Describe the activation of adenylyl cyclase by Gs proteins (e.g. b adrenoreceptors)
- The first messengers bind to the receptor, activating Gs protein
- The G protein releases the alpha subunit, which binds to and activates the adenylyl cyclase
- Gi-GTP inhibits adenylyl cyclase e.g. opioid receptors
- this catalyse the conversion of ATP to cAMP
- cAMP activates protein kinase A
- protein kinase A catalyses the transfer of a phosphate group from ATP to a protein OR changes the Ca2+ conc
- The altered protein activity causes a response in the cell
Differentiate Gs-GTP and Gi-GTP
Gs-GTP = stimulatory (activates adenylyl cyclase) Gi-GTP = inhibitory (inhibits adenylyl cyclase)
Describe the activation of phospholipase C by Gq proteins
- The messenger binds to the receptor, activating a G protein
- The G protein releases the alpha subunit, which binds to and activates the phospholipase C
- Phospholipase C catalyses the conversion of PIP2 to DAG and IP3.
- DAG remains in the membrane and activates the enzyme protein kinase C.
- Protein kinase C catalyses the phosphorylation of a protein (leads to a biological response)
- At the same time:
- IP3 moves into the cytosol
- IP3 triggers the release of calcium from the endoplasmic reticulum. (change in Ca2+ conc cause a biological response)
Give an example of a Gq-GTP receptors
muscarnic receptors and alpha-adrenoceptors
What kind of drug is digoxin?
cardiotonic
used in heart failure
How does digoxin work?
- Digoxin inhibits the Na+/K+-ATPase
- To reduce the increased Na+, the Na+/Ca2+ exchanger is stimulated,
- Increase in Ca2+
- Increase in force of contractions
Give an example of a tyrosine kinase receptor
Insulin receptor
How does a tyrosine kinase receptor work?
- Signal molecule binds
- Dimerisation of receptor
- Activate of tyrosine-kinase regions and phosphorylation of the dimer.
- Dimer goes on to phosphorylate tyrosine molecules and activate inactive relay proteins via this mechanism
- the phosphorylation of the protein changes its activity, bringing cellular response
Give examples of nuclear receptor drugs
steroids and thyroid hormones (lipophilic drugs)
Name some illnesses associated with malfunctioning nuclear receptors
Inflammation, cancer, diabetes, cardiovascular disease, obesity and reproductive disorders
How does a nuclear receptor work?
- If a receptor is in the nucleus, the hormone diffuses into the nucleus (through cytoplasm) and binds to it, forming a hormone-receptor complex.
- Inside the nucleus, the hormone-receptor complex functions as a transcription factor by binding to a region of DNA called the hormone response element (HRE), which is located at the beginning of a specific gene.
- Binding of the complex to the HRE activates or deactivates the gene, which affects transcription of mRNA and ultimately increases or decreases synthesis of the protein coded by the gene.
- The mRNA moves into the cytosol
- The mRNA is translated by ribosomes to yield proteins.
Describe speed of:
- Ligand gated ion channels
- G protein coupled receptors
- Kinase-linked receptors
- Nuclear receptors
Milliseconds
seconds
hours
hours-days
