Understand the basic concepts of pharmacodynamics

1. PHARMACODYNAMIC
S
ALBASHIR TAHIR
+2348068440615
albashirtahir@gmail.com
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2. PHARMACODYNAMICS
 Pharmacodynamics is the study of drug effects.
 It starts with describing what the drugs do, and goes on to explain how
they do it.
 Thus, it attempts to elucidate the complete action-effect sequence and
the dose-effect relationship.
 It provides fundamental insights into biochemical and physiological
regulation.
 Modification of the action of one drug by another drug is also an aspect
of pharmacodynamics.
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3. PRINCIPLES OF DRUG ACTION
 Drugs (except those gene based) do not impart new functions
to any system, organ or cell; they only alter the pace of
ongoing activity.
 However, this alone can have profound medicinal as well as
toxicological impact. The basic types of drug action can be
broadly classed as:
 Stimulation: It refers to selective enhancement of the level of
activity of specialized cells, e.g. adrenaline stimulates heart.
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4. PRINCIPLES OF DRUG ACTION...
 Depression: It means selective diminution of activity of
specialized cells, e.g. barbiturates depress CNS, quinidine
depresses heart, omeprazole depresses gastric acid
secretion.
 Replacement: This refers to the use of natural metabolites,
hormones or their congeners in deficiency states, e.g. insulin
in diabetes mellitus, iron in anaemia.
 Cytotoxic action: Selective cytotoxic action on invading
parasites or cancer cells, attenuating them without
significantly affecting the host cells is utilized for
cure/palliation of infections and neoplasms.
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5. MECHANISM OF DRUG ACTIONS
 Majority of drugs produce their effects by interacting with a discrete target
biomolecule, which usually is a protein.
 Such mechanism confers selectivity of action to the drug.
 Functional proteins that are targets of drug action can be grouped into four
major categories, viz.
o Receptors
o Enzymes
o Ion channels and
o Transporters.
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6. RECEPTORS
 Receptors are macromolecules that serves to recognize the
signal molecule/drug and initiate the response to it, but itself has
no other function.
 May be cell surface or nuclear receptors
 The concept of drugs acting on receptors (receptive substance)
generally is credited to John Langley (1878)
 The word receptor was introduced in 1909 by Paul Ehrlich
 They are usually protein in nature, specific and have affinity
 Receptors serve two essential functions, viz, recognition of the
specific ligand molecule and transduction of the signal into a
response.
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7. Drug – Receptor Interactions
 The following terms are used in describing drug-receptor interaction:
 Agonist: An agent which activates a receptor to produce an effect similar
to that of the physiological signal molecule.
 Partial agonist: An agent which activates a receptor to produce
submaximal effect but antagonizes the action of a full agonist.
 Inverse agonist: An agent which activates a receptor to produce an effect
in the opposite direction to that of the agonist.
 Antagonist: An agent which prevents the action of an agonist on a
receptor or the subsequent response, but does not have any effect of its
own.
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8. Drug – Receptor Interactions...
Characteristics
 Chemical bond: ionic, hydrogen, Van der Waals, and
covalent.
 Saturable
 Competitive
 Specific and Selective
 Structure-activity relationships
 Transduction mechanisms
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Receptor activities

9. [D] (concentration units)
%
Maximal
Effect
0.01 0.10 1.00 10.00 100.00 1000.00
0.0
0.2
0.4
0.6
0.8
1.0
Partial agonist
Full Agonist
Partial agonist
Types of Agonists
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10. Examples
Receptor Agonist Antagonist
Adenoceptors Epinephrine (β and α)
Phenylephrine (α1)
Salbutamol (β2)
Atenolol (β1)
Prazosin (α1)
Phentolamine (α)
Cholinoceptors Acetylcholine (M & N)
Carbachol (M & N)
Nicotine (N)
Atropine (M)
Scopolamine (M)
Tubocurarine (N)
H-receptors - Promethazine (H1)
Cimetidine (H2)
Opioid receptors Morphine, Heroin
Codeine
Naloxone,
Naltrexone
5-HT receptors Buspirone (5-HT1A)
Triptans (5-HT1B & 5-HT1D)
Ketanserin,
Oandansetron
D-Receptors Bromocriptine
Pramipexole
Chlorpromazine
Fluphenazine
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11. Enzymes
Common drug target, next to receptors
Enzymes are involve in biosynthesis
Some drugs bind to enzymes and inhibit their
activities.
Loss of product due to the inhibition mediates
the effects of the drug
Few drugs also activate enzymes
 Nitroglycerin (Guanylyl cyclase)
 Pralidoxime (cholinesterase)
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12. Active Enzyme
Substrate Product
Cellular Function
Inactive Enzyme
Substrate
Bound Enzyme
Inhibitor (Drug)
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13. Enzyme Inhibitors
Enzyme Inhibitors (Drugs)
Acetylcholinesterase Neostigmine, physostigmine
Dihydrofolate reductase Trimethoprim, methotrexate
Dihydropteroate synthase Sulphonamides
Aldehyde dehydrogenase Disulfiram, metronidazole
Cyclooxygenase (COX) Aspirin, ibuprofen
HMG CoA reductase Statins
Angiotensin Converting
Enzyme
Captopril, enalapril
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14. Ion Channels
 Proteins which act as ion selective channels participate in
transmembrane signalling and regulate intracellular ionic
composition.
 Thus, certain drugs modulate opening and closing of the
channels.
 This makes them a common target of drug action.
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15. Examples
Channel Drug
Ca channel blocker Verapamil
Amlodipine
Diltiazem
Na channel blocker Lidocaine
Amiodarone
K Channel activator Minoxidil
Cl channel activator alprazolam
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16. Transporters
 Several substrates are translocated across membranes by
binding to specific transporters (carriers) which either facilitate
diffusion in the direction of the concentration gradient or pump
the metabolite/ion against the concentration gradient using
metabolic.
 Many drugs produce their action by directly interacting with
the solute carrier (SLC) class of transporter proteins to inhibit
the ongoing physiological transport of the metabolite/ion.
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17. Examples
Transporter Ligand Drug
SERT Serotonin Fluoxetine
Paroxetin
Na-Cl-K symporter Na
Cl
Furosemide
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18. Unconventional Mechanisms
 Being nutrients e.g. vitamins and minerals
 Being antigens e.g. vaccines
 Being Enzymes e.g. streptokinase for thrombolysis
 Reacting chemically with small molecules e.g. antacids
 Disruption of structural proteins e.g. vinca alkaloids for cancer,
colchicine for gout
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