Pharmacodynamics- Receptors Flashcards
Define Pharmacodynamics
What a drug does to the body when it enters.
The 2 effects of drugs are:
- Systemic effect of drugs
2. Local effect of drugs
Systemic effect of drugs means…
Effect is made throughout the body. The drug has impact of entire body.
Give 2 examples of drugs that have a systemic effect.
Antihypertensive drugs - Lisinopril and Captopril
Local effect of drugs means…
Effect is limited to the area of the body, where it’s administered.
An example of a local effect of drugs:
Topical application of drugs
What 2 things affect the onset of the effect of drug action?
- Route of administration
2. Drug dosage
Give the 4 factors that affects the duration of drug action.
- Drug dosage
- Rate of redistribution
- Rate of metabolism
- Rate of excretion
The 3 sites of drug action are:
- Extracellular
- Cellular
- Intracellular
5 Types of Drug action are…
- Stimulation
- Inhibition/Depression
- Replacement
- Irritation
- Cytotoxic action
The 4 Mechanisms of action of a drug are:
- Physical action
- Chemical action
- Through enzymes
- Through receptors
The 4 Targets of drug action are:
- Enzymes
- Channels
- Transporters
- Receptors
Give 4 ways drugs produce effects in the body.
- acting on RECEPTORS.
- inhibiting ENZYMES.
- modulating or blocking ION CHANNELS.
- inhibiting CARRIER MOLECULES (TRANSPORTERS)
Explain the Lock & Key Model of Ligand-Receptor Interaction.
A ligand (hormone or neurotransmitter - ‘key’) bind to specific receptors (‘lock’).
This binding then unlocks the cell’s response.
Explain Agonists in terms of lock & key model.
Drugs that cause the receptor to respond in the same way as the naturally occurring substance.
- Activates the receptor = ‘pick the lock’.
Explain Antagonists in terms of lock & key model.
Drugs that bind to the receptor, but don’t produce a response.
This results in an inhibitory effect on the naturally occurring substance.
- Prevents activation of receptor
Drugs _______ enzyme mediated reactions.
increases/decreases
2 kinds of Enzyme inhibition
- Reversible inhibition
- Irreversible inhibition
Explain Reversible inhibition.
Process where reversible inhibitors bind to enzyme with only non-covalent interactions (weak bonds).
What happens when a reversible inhibitor binds to an enzyme?
No reaction occurs - dynamic equilibrium
How is a reversible inhibitor removed?
Easily removed by dilution or dialysis.
3 types of Reversible inhibition
- Competitive inhibition
- Non-competitive inhibition
- Uncompetitive inhibition
Explain Competitive inhibition
Process where competitive inhibitors bind only to enzymes (not enzyme-Substrate complex = ES) and inhibits enzyme to function.
Action of Competitive inhibitors
Competitive inhibitor has a similar structure to substrate so therefore competes with substrate to bind to the active site of enzyme
(forming an Enzyme-inhibitor complex = EI)
Examples of Competitive inhibitors
- Sulfonamides
- Methotrexate
- Penicillin
Explain Irreversible inhibition
Process where Irreversible inhibitors bind to enzyme via covalent bonds (strong bonds = permanent) and prevents enzyme catalytic acts.
Irreversible inhibitors act on _____
Some selected group of enzymes (not all).
Examples of Irreversible inhibitors.
Heavy metals
- Cadmium (Cd)
- Arsenic (As)
- Lead (Pb)
Explain Non-competitive inhibition
Process where non-competitive inhibitors bind to both the Enzyme and Enzyme-Substrate complex (ES), hence inhibiting the enzyme to function.
Action of Non-competitive inhibitors
They have no resemblance to normal substrate, therefore will:
- work either to slow down the rate of reaction
- or block the active site altogether and prevent enzyme function.
Why can Non-competitive inhibitors become toxic?
Because they are non-selective in their actions and will destroy all enzymes.
Examples of Non-competitive inhibitors
- Mercury
- Arsenic
- Copper
Drugs also target channels - mainly on 3 types which are…
- Ligand gated channels
- G-protein channels
- Direct action on channels.
How are substrates translocated across membrane?
By binding to specific transporters (carriers) = Solute Carrier Proteins (SLC)
Many drugs don’t bind directly but act through ____.
receptors
What is a receptor?
Specific molecule, usually a protein that interacts with a specific chemical, that then causes a change in the specific molecule, causing a change in regulatory function.
Receptors are present either on: (3)
- Cell surface
- Cytoplasm
- Nucleus
Examples of Receptors
- Muscarinic receptors
- Nicotinic receptors
What are Ligands?
Naturally occurring substances:
- Hormones
- Neurotransmitters (NT)
- Mediators
2 essential functions of Receptors
- Recognition of specific ligand molecules
(Ligand binding domain) - Transduction of signal into response
(Effector domain)
Drugs target receptors that are…
expressed to respond to endogenous ligands.
Characteristics of drug-receptor interaction
- Affinity bonds: Vander Waals
- Specific and Selective
- Competitive and Non-competitive
What are the 3 different properties of drug that decide the effect of drug?
- Affinity
- Intrinsic activity (IA) / Efficacy
- Selectivity
What is Intrinsic activity / Efficacy?
Ability of drug receptor complex to produce a maximum functional response.
What is efficacy dependent on?
- Number of drug receptor complexes formed
- Efficacy of the coupling receptor activation to cellular responses.
What is a Competitive Antagonist?
Any antagonist that competes with the binding of AGONIST at the binding site.
What is a Non-competitive Antagonist?
Any antagonist that binds to a site on the receptor other than the AGONIST binding site.
It deactivates the receptor, preventing AGONIST from activating the receptor.
What is Partial agonist?
A drug that has full affinity to receptor but with low intrinsic activity.
Unique feature of Partial agonist drugs
Under appropriate conditions, partial agonists may act as an Antagonist of a full Agonist.
What is Inverse agonist?
A drug that has full affinity towards the receptor, but intrinsic activity is 0 to -1 (produced effect is opposite to that of agonist).
Action of receptor
Initial combination of drug with its receptors, resulting in or prevention of conformational change later on.
Effect of receptor
Ultimate change in biological function as a consequence of drug action. Done through a series of intermediate steps.
What is Receptor regulation?
Ongoing activity that determines density and efficacy of receptors.
Define Supersensitive
- Up regulation of receptors
- Increase in the number of receptors to a molecule (hormone or NT)
Supersensitive can be caused by…
Prolonged occupation of receptors by a blocker (antagonist).
Define Desensitize
- Down regulation of receptors
- Decrease in the number of receptors to a molecule (hormone or NT)
Desensitize can be caused by…
Prolonged exposure to higher conc. of an agonist.
4 types of Drug receptors
- Ligand-gated ion channels
- Enzyme-linked receptors
- G-protein coupled receptors
- Nuclear (gene) receptors
Ligand-gated ion channels are responsible for…
regulation of the flow of ions across cell membranes.
Activity of Ligand-gated ion channels is regulated…
by binding of a ligand to the channel.
Duration of response to Ligand-gated ion channels
Few milliseconds
Important examples of Ligand-gated receptors
- Nicotinic receptor
- Gamma-aminobutyric acid (GABA)
Explain Ligand-gated ion channels/receptors - Cell surface receptors
- Cell membrane requires specific ligand-gated channels for the movement of hydrophilic molecules through it.
- Ligand binds to the receptor, then the receptor gate opens.
