Medical pharmacology – Chapter 2 – Dose-effect relationships of
drugs; receptor theory (pharmacodynamics, the effect of drugs on
the body)
Drug effect the functions of body cells (strengthen or weaken).
Receptor; any body molecule with which a drug has an interaction. But the receptor
concept is limited to a localised cell membrane or intracellular macro-molecule with
which a body substance (neurotransmitter or hormone = endogenous chemicals) or
type of pharmaceutical compound (drug = exogenous compound) can initiate a
specific interaction that leads to change in activity in the cell.
Chelating agents; action of drugs due to a simple chemical reaction or physical
process.
Chemotherapy drugs and antibiotics; attach to pathogenic microorganism that might
be present in the body
4 levels of drug action and drug classification:
Mechanism Definition Response components
System An effect on system Integrated systems
function including linked systems
(nervous system,
cardiovascular system)
Tissue An effect on tissue Electrogenesis,
function contraction, secretion,
metabolic activity,
proliferation
Cellular Transduction The biochemicals linked
to drug target (e.g. ion
channel, enzyme, G
proteins)
Molecular Interaction with the drug’s The drug target (e.g.
molecular target receptor, ion channel,
enzyme, carrier molecule)
Targets for drug action (drugs interact
selectively with cellular proteins);
Receptors; protein that recognize
endogenous (neurotransmitter or
hormone) compounds thereby causing
a cellular effect
o Agonist; drug activates the
relevant receptors
o Antagonist; drug inhibit the
relevant receptors (no effect)
Ion channels
o Blockers; drug block ion channel (sometimes called antagonist)
o Modulators; drug don’t block ion channel. Increased or decreased
opening probability
, Enzymes
o Inhibitor; drug bind to enzyme and lowers catalytic activity of the drug
o False substrate; drug bind to enzyme but are transformed by enzyme
and to abnormal product
o Pro-drug; drug is not active but is transformed by enzyme to active drug
and active drug is produced
Transporters
o Normal transport; drug bound to transporter and it is transferred to the
other side of the membrane.
o Inhibitor; drug inhibit the transport over the membrane
o False substrate; same as by the enzyme, abnormal compound
accumulates
General structure of the 4 receptor families;
Type 1; ligand-gated ion channels, when
ligand (=drug) bind the channel opens
(ionotropic receptors) (milliseconds to
observe changes) (nicotin, ACh receptor)
Type 2; G-protein coupled receptors
(metabotropic receptors) (biggest group
of receptors for drugs) (seconds to
observe changes) (Muscarinic, ACh
receptor)
Type 3; kinase-linked receptors (enzyme
as well as receptors) (hours to observe
changes) (insulin, cytokine receptor)
Type 4; nuclear receptors; not located in cell membrane but it in cytoplasm.
When ligand bind the receptor in cytoplasm it can move to nucleus bind to
DNA and regulate gene expression (hours to observe changes) (oestrogen
receptor)
Receptor proteins show characteristic selectivity = different receptor proteins
recognize only certain endogenous chemical compounds and drugs
A drug usually does not have a specific affect, this depends on the dose.
Drug which have specific affect, selectivity depends on binding affinity for different
types of receptors at a specified (low) drug concentration -->Dose low drug will only
bind to one type of receptor and only activate other receptors at much higher doses.
Receptor theory is based on the following;
1. The drugs have affinity for the receptors (drug and receptor recognise each
other)
2. Occupancy postulate: the effect of drug depends on number of receptors
bound by the drug. Total number of receptors that is occupied by the drug-
molecules
3. Interaction between drug and receptor is reversible and take place at 1:1
ration (biomolecular reaction)
4. Drug concentration is so high compared to receptor concentration that the
drug concentration is not significantly affected by binding of drug-molecules to
the receptors
drugs; receptor theory (pharmacodynamics, the effect of drugs on
the body)
Drug effect the functions of body cells (strengthen or weaken).
Receptor; any body molecule with which a drug has an interaction. But the receptor
concept is limited to a localised cell membrane or intracellular macro-molecule with
which a body substance (neurotransmitter or hormone = endogenous chemicals) or
type of pharmaceutical compound (drug = exogenous compound) can initiate a
specific interaction that leads to change in activity in the cell.
Chelating agents; action of drugs due to a simple chemical reaction or physical
process.
Chemotherapy drugs and antibiotics; attach to pathogenic microorganism that might
be present in the body
4 levels of drug action and drug classification:
Mechanism Definition Response components
System An effect on system Integrated systems
function including linked systems
(nervous system,
cardiovascular system)
Tissue An effect on tissue Electrogenesis,
function contraction, secretion,
metabolic activity,
proliferation
Cellular Transduction The biochemicals linked
to drug target (e.g. ion
channel, enzyme, G
proteins)
Molecular Interaction with the drug’s The drug target (e.g.
molecular target receptor, ion channel,
enzyme, carrier molecule)
Targets for drug action (drugs interact
selectively with cellular proteins);
Receptors; protein that recognize
endogenous (neurotransmitter or
hormone) compounds thereby causing
a cellular effect
o Agonist; drug activates the
relevant receptors
o Antagonist; drug inhibit the
relevant receptors (no effect)
Ion channels
o Blockers; drug block ion channel (sometimes called antagonist)
o Modulators; drug don’t block ion channel. Increased or decreased
opening probability
, Enzymes
o Inhibitor; drug bind to enzyme and lowers catalytic activity of the drug
o False substrate; drug bind to enzyme but are transformed by enzyme
and to abnormal product
o Pro-drug; drug is not active but is transformed by enzyme to active drug
and active drug is produced
Transporters
o Normal transport; drug bound to transporter and it is transferred to the
other side of the membrane.
o Inhibitor; drug inhibit the transport over the membrane
o False substrate; same as by the enzyme, abnormal compound
accumulates
General structure of the 4 receptor families;
Type 1; ligand-gated ion channels, when
ligand (=drug) bind the channel opens
(ionotropic receptors) (milliseconds to
observe changes) (nicotin, ACh receptor)
Type 2; G-protein coupled receptors
(metabotropic receptors) (biggest group
of receptors for drugs) (seconds to
observe changes) (Muscarinic, ACh
receptor)
Type 3; kinase-linked receptors (enzyme
as well as receptors) (hours to observe
changes) (insulin, cytokine receptor)
Type 4; nuclear receptors; not located in cell membrane but it in cytoplasm.
When ligand bind the receptor in cytoplasm it can move to nucleus bind to
DNA and regulate gene expression (hours to observe changes) (oestrogen
receptor)
Receptor proteins show characteristic selectivity = different receptor proteins
recognize only certain endogenous chemical compounds and drugs
A drug usually does not have a specific affect, this depends on the dose.
Drug which have specific affect, selectivity depends on binding affinity for different
types of receptors at a specified (low) drug concentration -->Dose low drug will only
bind to one type of receptor and only activate other receptors at much higher doses.
Receptor theory is based on the following;
1. The drugs have affinity for the receptors (drug and receptor recognise each
other)
2. Occupancy postulate: the effect of drug depends on number of receptors
bound by the drug. Total number of receptors that is occupied by the drug-
molecules
3. Interaction between drug and receptor is reversible and take place at 1:1
ration (biomolecular reaction)
4. Drug concentration is so high compared to receptor concentration that the
drug concentration is not significantly affected by binding of drug-molecules to
the receptors
