Pharmacodynamics – What drug does to the body

Pharmacokinetics – what body does to drug

Mechanism of drug action – drugs achieve their therapeutic effects by acting primarily on either
 Receptors
 Enzymes
 Ion channels
 Carrier molecules
Receptors
 Proteins found on surface of cell membranes or inside cells
 Binding sites for chemicals which are produced naturally in body
o Neurotransmitters
o Steroids
o Prostaglandins
o Hormones
o Cytokines
o Peptides
 These chemicals produce their effects in the body by binding their specific receptors
 Examples of receptors
o Acetylcholine (NT) stimulates cholinergic receptors (nicotine receptors – contraction of skeletal
muscle, muscarinic receptors – slowing of heart)
o Adrenaline stimulates adrenergic receptors
 Alpha receptors (vasoconstriction)
 Beta 1 receptors (cardiac stimulation)
 Beta 2 receptors (bronchodilation)
o Endorphins and enkephalins stimulate opioid receptors
o Histamine stimulates histamine receptors
o Naturally occurring NTs, cytokines, hormones only bond their specific receptors (acetylcholine only
binds and stimulates cholinergic receptors)
o Many of the drugs used clinically bind receptors and either mimic the effects or block the effects
of naturally occurring substances
Mechanism of drug action
 Many drugs exert their actions by combining with (binding to) and activating (stimulating) receptors
normally stimulated by naturally occurring substances in the body
 Drug receptor complex: when a naturally occurring substance or a drug combines with a receptor
 Affinity: ability of natural substance or drug to form a drug receptor complex
 If a drug is capable of forming a drug receptor complex (affinity) this does not on its own result in a response
being produced —> must also set up series of actions within cell hush results in a response being produced
 Efficacy or intrinsic activity: when formation of a drug-receptor complex activates the receptor and an overt
response occurs
 Agonist: any natural substance or drug which can combine with and activate a receptor
 Therefore, agonist exhibits (has) affinity and efficacy/intrinsic activity
 Key and lock analogy
o Key goes into lock (affinity)
o Key is turned and door opens (efficacy or intrinsic activity)
 E.g. agonists are adrenaline, acetylcholine, histamine, GABA, morphine
 Each agonist only binds to its one specific receptor type(s)
 In most instances bond between agonist and a receptor (drug receptor complex) is relatively weak and easily
reversible, usually consists of ionic bonds, H binding, Van der Waals forces
 Each agonist acts on its own specific receptor type(s)
 Structure activity relationship: similar drugs can act on the same receptors
Agonist log dose response curve
 Graded response
 The magnitude of response directly related to number of receptors activated by the agonist (up to the max
response)
 Max response to an agonist often obtained when the agonist is bound to less than 100% of the receptors
 Max response can in some cases be obtained with a low receptor occupancy
  Reserve capacity, spare receptors
Potency and efficacy
 E.g. effects of adrenergic drugs on alpha receptors e.g. blood vessels
 Efficacy: maximum response a drug can produce
 Potency: amount of drug needed to produce given response

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 There is no response that can be achieved with drug A that cannot be achieved with Drug B – you just need
to take a larger dose of drug B
 Potency by itself does not infer superiority
Partial agonist: drug which binds to a receptor (has affinity) but even a full receipt occupancy it has left efficacy or
intrinsic activity than a full agonist

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Competitive antagonists: drug which can combine with a receptor (has affinity) but does not activate the receptor
(no efficacy or intrinsic activity)
 Competes with agonist to combine with a receptor and inhibits (blocks) the action of the agonist
 Lock and key analogy
 The effect is of a competitive agonist can be overcome by increasing the concentration of the agonist
 The inhibitory effect of the competitive antagonist is surmountable because the binds between the
competitive antagonist and the receptor, are relatively weak and easily broken
 A competitive antagonist shifts the agonist dose response curve to the right

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 Examples
o Narcotic antagonists such as naloxone which inhibit opioid mu receptors
o Antihistamines such as loratadine which inhibit histamine H1 receptors – inverses agonists?
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