• ﻏﯿﺒﺖ ﻏﯿﺮ ﻣﻮﺟﮫ • ﺣﻀﻮر ﺑﮫ ﻣﻮﻗﻊ و ﺑﺪون ﺗﺎﺧﯿﺮ • ﺧﺎﻣﻮش ﮐﺮدن ﻣﻮﺑﺎﯾﻞ ھﺎ • اﻣﺘﺤﺎن از ﻣﺒﺎﺣﺚ ﮐﻼﺳﯽ و ﮐﺘﺎب رﻓﺮاﻧﺲ • ﺗﺎرﯾﺦ اﻣﺘﺤﺎن ﻣﯿﺎن ﺗﺮم روی ﻃﺮح درس
Pharmacodynamics M Rabbani Ph.D. Department of Pharmacology Isfahan University of Medical Sciences
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Lecture Objectives
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What is pharmacodynamics?
Pharmacodynamics definition Drug targets Agonists / Antagonists Affinity
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Dose
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Effect site Concentration
Effect
Pharmacokinetics
Pharmacodynamics
Absorption Distribution Metabolism Elimination Drug interactions
Tissue/organ sensitivity (target status) It is the study of biochemical and physiological effects of drug and their mechanism of action at organ level as well as cellular level.
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Drug targets
Drugs Drugs can be defined as chemical agents that uniquely interact with specific target molecules in the body, thereby producing a biological effect.
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BOUND WITH WHAT ?
Question A drug will not work unless it is bound AGREED or NOT AGREED
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PARTICULAR CONSTITUENTS OF CELLS & TISSUES IN ORDER TO PRODUCE AN EFFECT
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ARE THERE DRUGS THAT ACT WITHOUT BEING BOUND TO ANY OF THE TISSUE CONSTITUENTS?
PROTEINS LIPIDS DNA Else
YES OR
NO
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YES
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Most drugs act by binding to a target molecule
OSMOTIC DIURETICS OSMOTIC PURGATIVES ANTACIDS HEAVY METALS CHELATING AGENTS
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Drug targets: enzymes 1. In patients (Captopril Captopril,, ACE inhibitors,) 2. In microbes (Penicillins Penicillins,, inhibit transpeptidase) 3. In cancer cells (55-FU, inhibits thymidilate synthase)
TARGET BIOMOLECULES: 1. 2. 3. 4.
ENZYMES ION CHANNELS TRANSPORTERS RECEPTORS
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Drug targets: ion channels Ca: Verapamil Na: Lidocaine K : Sulfonlyurea Cl: Lubiprostone
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Drug targets: transporters
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Receptors
Na/K ATPase: cardiac glycosides
Usually a protein
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Definition: macromolecule or binding site located on cell surface or inside the effecter cell that serves to recognize the signal molecule/drug and initiate the response to it, but itself has no other function
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Receptor Families
Drug targets: receptors
Most drugs act on receptors in or on cells Form tight bonds with the ligand Size, shape, stereospecificity Can be agonists (salbutamol), or antagonists (propranolol)
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A- Ligand-gated ion channels
A
B
C
D
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B. G-protein coupled receptor systems Have three components: the recptor recptor,, G protein, effector effector..
• Specific for certain ions
•When ligand binds, channel opens allowing ions to flow either inward or outward
LigandLigand-bound domain is located in a pocket accessible from the cell surface
• Response extremely fast
Response rapid
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G protein-linked receptors
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C- Enzyme linked Span full width of membrane Ligand binding domain is external and catalytic binding region is on inside of membrane Response within seconds.
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D- Transcription Factors
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Transcription Factors
Found within the cell (on DNA in nucleus) Regulate protein synthesis through RNA synthesis Eg Eg.. steroids receptors Responses are delayed (hours to days)
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Agonists Agonists: Full Partial Inverse
Antagonist
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Agonist
Agonist
Agonist: An agent which activates a receptor to produce an effect similar to a that of the physiological signal molecule, e.g. Muscarine Increase or decrease the effect
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Agonist: molecules that activate receptors (mimicry)
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Agonist Inactivation (Depression) – decrease the rate of functional activity (ß2 in lung)
ß1 in heart
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Full vs Partial Inverse agonist: an agent which activates receptors to produce an effect in the opposite direction to that of the agonist, e.g. DMCM Ligand: any molecule which attaches selectively to particular receptors or sites (only binding or affinity)
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Intrinsic activity
Inverse agonist
Ability of a drug to activate its receptor. High intrinsic activity relates to high maximal efficacy 2 drugs can bind to same # of receptors with different intensities of response
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آﻧﺘﺎﮔﻮﻧﯿﺴﺖ
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Antagonist
ﺟﻠﻮﮔﯿﺮی از ﭘﯿﻮﻧﺪ اﮔﻮﻧﯿﺴﺖ ﯾﺎ ﻣﻮاد اﻧﺪوژن ﺑﺎ رﺳﭙﺘﻮر اﻓﯿﻨﯿﺘﯽ ﺑﺎﻻ ﺑﺮای رﺳﭙﺘﻮر اﻣﺎ ﺑﺪون اﻓﯿﮑﺎﺳﯽ ﯾﺎ ﻓﻌﺎﻟﯿﺖ زاﺗﯽ : ﺗﻘﺴﯿﻢ ﺑﻨﺪی آﻧﺘﺎﮔﻮﻧﯿﺴﺖ آﻧﺘﺎﮔﻮﻧﯿﺴﺖ ھﺎی ﻓﺎرﻣﺎﮐﻮﻟﻮژﯾﮏ آﻧﺘﺎﮔﻮﻧﯿﺴﺖ ھﺎی ﻓﯿﺰﯾﻮﻟﻮژﯾﮏ آﻧﺘﺎﮔﻮﻧﯿﺴﺖ ھﺎی ﻓﺎرﻣﺎﮐﻮﮐﯿﻨﺘﯿﮏ آﻧﺘﺎﮔﻮﻧﯿﺴﺖ ھﺎی ﺷﯿﻤﯿﺎﯾﯽ
Blocking – prevents an action or respons
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آﻧﺘﺎﮔﻮﻧﯿﺴﺖ ھﺎی ﻓﺎرﻣﺎﮐﻮﻟﻮژﯾﮏ رﻗﺎﺑﺘﯽ ﯾﺎ ﺑﺮﮔﺸﺖ ﭘﺬﯾﺮ ﻏﯿﺮ رﻗﺎﺑﺘﯽ ﯾﺎ ﺑﺮﮔﺸﺖ ﻧﺎﭘﺬﯾﺮ
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آﻧﺘﺎﮔﻮﻧﯿﺴﺖ ﻓﯿﺰﯾﻮﻟﻮژﯾﮏ
آﻧﺘﺎﮔﻮﻧﯿﺴﺖ ﻓﺎرﻣﺎﮐﻮﮐﯿﻨﺘﯿﮏ
آﺛﺎر ﻣﺘﻀﺎد دو دارو در ﺑﺪن ﺑﺎ ﺗﺎﺛﯿﺮ ﺑﺮ دو ﻧﻮع ﮔﯿﺮﻧﺪه اﺛﺮ ھﯿﺴﺘﺎﻣﯿﻦ و اﻣﭙﺮازول
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ﺑﺎ ﻣﮑﺎﻧﯿﺴﻢ ھﺎی ﻣﺘﻔﺎوت ﻏﻠﻈﺖ ﯾﮏ دارو را در ﺑﺪن ﮐﺎھﺶ ﻣﯽ دھﻨﺪ ﻓﻨﻮﺑﺎرﺑﯿﺘﺎل و وارﻓﺎرﯾﻦ
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آﻧﺘﺎﮔﻮﻧﯿﺴﺖ ﺷﯿﻤﯿﺎﺋﯽ اﺛﺮ ﺷﻼﺗﮫ ﮐﻨﻨﺪه دی ﻣﺮﮐﺎﭘﺮول ﺑﺮروی ﻓﻠﺰات ﺳﻨﮕﯿﻦ Heparin, an anticoagulant, acidic If there is too much bleeding and haemorrhaging Protamine sulfate is a base. It forms a stable inactive complex with heparin and inactivates it.
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