PHARMACODYNAMICS
PAA KOFI TAWIAH ADU-GYAMFI
PHARMACODYNAMICS
“COPORA NON AGUNT
NISI FIXATA”
“A drug will not work unless it is bound”
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PHARMACODYNAMICS
• This section addresses the question: what are the effects of the
drug on the tissues?
• Drugs work as a result of the physiochemical interactions
between drug molecules and the patient’s/recipient’s molecules.
• These chemical reactions may alter the way the cells are
functioning which in turn may lead to changes in the behaviour
of tissues, organs and systems.
Pharmacodynamics
• Pharmacodynamics is the study of the mechanism of
drug action on living tissues. It is the study of what
drugs do to the body and how they do it.
Mechanisms of Drugs Actions in the Body
• Most work by interacting with endogenous proteins
a) Action through unconventional/non-receptor mechanisms
b) Action through conventional/receptor mechanisms
i. Some activate endogenous proteins via receptor
ii. Some antagonize, block or inhibit endogenous proteins via receptors
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Non-receptor Mechanisms (2)
• Actions due to physical properties
• Mannitol (osmotic diuretic), laxatives
• Working Via an Antisense Action
• Fomivirsen for CMV retininitis in AIDS
• Being Antigens
• Vaccines
• Unknown mechanisms of action
• general anesthetics
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Targets for Drug Action
• Most drugs produce their effect by one of the following
ways
• Enzymes:
• Ion channels:
• Receptors
• Carrier
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ENZYMES
Enzymes Inhibitors
Cyclo-oxygenase 1 and 2 Aspirin,ibuprofen,diclofenac
Cyclo-oxygenase 2 celecoxib
Angiotensin-converting enzyme Captopril ,lisinopril,
HIV protease Saquinavir
Reverse transcriptase zidovudine
ION CHANNEL
Ion channels Blockers Modulators
Voltage-gated sodium channels Local anaesthetics
Renal tubule sodium channels Amiloride/Triamterene Adolsterone
Voltage-gated calcium channels Divalent cations (e.g. Cd2+) Dihydropyridines eg nifedipine
CARRIERS
Carrier Inhibitor(s)
Na+/K+ pump cardiac glycosides
Na+/K+/2Cl- co-transporter frusemide
Proton pump omeprazole
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Receptors
Receptor Agonist(s) Antagonist(s)
ACh d-TC
Nicotinic ACh
nicotine a-bungarotoxin
b-adrenoceptor noradrenaline, propranolol
Histamine (H1 r eceptor) histamine mepyramine
Histamine (H2 receptor) impromidine ranitidine
Opioid (m receptor) morphine naloxone
PHARMACODYNAMICS
• Receptor
• Drugs are chemicals and the only way drugs can produce their effects
is by interacting with other chemicals. Receptors are chemicals in the
body that most drugs interact with to produce an effect.
• Receptors is therefore defined as any functional macromolecule in a
cell to which a drug binds to produce its effect
• Lock and key or induced-fit models
– drug acts as key, receptor as lock, combination yields response
– dynamic and flexible interaction
Receptors
• A receptor is a signal-transducing protein; it
changes its conformation and thereby regulates
cellular activity when it binds an agonist, but it
does not change the agonist itself.
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Receptor Characteristics
Most drugs (ligands eg substrates, inhibitors, activators and
neurotransmittersact) bind to receptors
In or on cells
Form tight bonds with the ligand
Exacting requirements (size, shape, stereospecificity)
Can be agonists (salbutamol), or antagonists propranolol)
Receptors have signal transduction methods
Receptor Types and Signal
Transduction (1)
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Receptor Types and Signal
Transduction (2)
1. Enzyme linked
(multiple actions)
2. Ion channel linked
(speedy)
3. G-protein linked
(amplifier)
4. Nuclear (gene) linked
(long lasting)
A Receptor equivalent to
receiver/switch
ON/OFF
Drug - Receptor Binding
• Covalent bonds
• Drug and receptor share a pair of electrons
• Very strong bond
• Not very common in pharmacology
• Electrostatic bonds
• Attraction due to charge differences
• Vary in strength
• Very strong (ionic bonds)
• Very weak (van der Waals forces)
• Hydrogen
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Drug-Receptor Interactions
Lock and key mechanism
Agonist Receptor
Agonist-Receptor
Interaction
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Receptor Interactions
Induced Fit
Receptor
Perfect Fit!
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Drug - Receptor Binding
D+R DR Complex
Affinity
Affinity – measure of propensity of a drug to bind receptor; the
attractiveness of drug and receptor
• Covalent bonds are stable and essentially irreversible
• Electrostatic bonds may be strong or weak, but are usually reversible
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Drug Receptor Interaction
DR Complex Effect
Efficacy (or Intrinsic Activity) – ability of a bound drug to
change the receptor in a way that produces an effect; some
drugs possess affinity but NOT efficacy
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POTENCY
• Amount of a drug needed to produce a given effect
• Determined mainly by the affinity of the receptor for
the drug
• Potency affects drug dosage
• Relatively unimportant in clinical use of drugs
•
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EFFICACY
• The maximal effect that can be produced by a drug
•
• Determined mainly by the properties of the drug
and its receptor-effector system
•
• Important clinical measure
•
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Dose-Response Curves Showing Efficacy
& Potency
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Agonist Drugs
• Drugs that interact with and activate receptors;
they possess both affinity and efficacy
• Two types
• Full Agonist – an agonist with maximal
efficacy
• Partial Agonist– an agonist with less then
maximal efficacy
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Antagonist Drug
• Antagonists interact with the receptor but do
NOT change the receptor
• they have affinity but NO efficacy
• two types
• Competitive
• Noncompetitive
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Competitive antagonist
• Competitive antagonist bind reversibly to receptors. As
their name implies, competitive antagonist produce
receptor blockade by competing with agonist for
receptor binding.
Non competitive
• Non-Competitive inhibitors bind to an allosteric site of
the enzyme (A site on the enzyme which is not the
active one). This results in a conformational change of
the protein, distorting the active site and thus is unable
to bind the substrate. So long as the non-competitive
inhibitor is bound, the enzyme remains inactive.
Competitive Receptor
Interactions
Antagonist Receptor
Antagonist-Receptor
DENIED!
Complex
Non-Competitive Receptor Interactions
Non-competitive Antagonist
Inhibition
Agonist Receptor
DENIED!
‘Inhibited’-Receptor
