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    Mechanisms of Drugs Action 2021 Full For MBBS

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    MARYAM ASIM
    Pharmacodynamics describes the mechanisms of action of drugs. Drugs act by interacting with receptors, which are molecules that drugs bind to produce changes in biological systems. This binding either directly activates effectors that cause a response, or triggers intracellular signaling pathways. The potency and efficacy of a drug depends on factors like what dose is needed to produce an effect and the maximum response achieved. Antagonists can block receptor activation by agonists. Understanding receptor interactions is crucial for determining how drugs produce their intended effects.

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    Mechanisms of Drugs Action 2021 Full For MBBS

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    MARYAM ASIM
    32 views80 pages
    Pharmacodynamics describes the mechanisms of action of drugs. Drugs act by interacting with receptors, which are molecules that drugs bind to produce changes in biological systems. This binding either directly activates effectors that cause a response, or triggers intracellular signaling pathways. The potency and efficacy of a drug depends on factors like what dose is needed to produce an effect and the maximum response achieved. Antagonists can block receptor activation by agonists. Understanding receptor interactions is crucial for determining how drugs produce their intended effects.

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    Mechanisms of Drugs Action 2021 full for MBBS

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    Mechanisms of Drugs Action 2021 full for MBBS

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    Pharmacodynamics describes the mechanisms of action of drugs. Drugs act by interacting with receptors, which are molecules that drugs bind to produce changes in biological systems. This binding either directly activates effectors that cause a response, or triggers intracellular signaling pathways. The potency and efficacy of a drug depends on factors like what dose is needed to produce an effect and the maximum response achieved. Antagonists can block receptor activation by agonists. Understanding receptor interactions is crucial for determining how drugs produce their intended effects.

    Copyright:

    © All Rights Reserved
    Download as PPTX, PDF, TXT or read online from Scribd
    Download as pptx, pdf, or txt
    32 views80 pages

    Mechanisms of Drugs Action 2021 Full For MBBS

    Uploaded by

    MARYAM ASIM
    Pharmacodynamics describes the mechanisms of action of drugs. Drugs act by interacting with receptors, which are molecules that drugs bind to produce changes in biological systems. This binding either directly activates effectors that cause a response, or triggers intracellular signaling pathways. The potency and efficacy of a drug depends on factors like what dose is needed to produce an effect and the maximum response achieved. Antagonists can block receptor activation by agonists. Understanding receptor interactions is crucial for determining how drugs produce their intended effects.

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    © All Rights Reserved
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    of 80

    Pharmacodynamics

    Mechanisms of Action of Drugs


    DRUG TARGET SITES
    RECEPTORS

    • Are the specific molecules in a biologic


    • system with which drugs interact to produce changes in
    the function of the system.

    • Must be selective in their ligand-binding characteristics

    • must also be modifiable when they bind a drug molecule

    The receptor site (the recognition site) for a drug


    is the specific binding region of the receptor
    macromolecule and has a relatively high and selective
    affinity for the drug molecule.

    • Many drugs are classified on the basis of their primary


    receptor affinity.
    • EFFECTORS are molecules that translate the
    drug–receptor interaction into a change in
    cellular activity.

    OR
    • Component of a system that accomplishes
    the biologic effect after the receptor is
    activated by an agonist; often a channel or
    enzyme molecule

    • The best examples of effectors are enzymes


    such as adenylyl cyclase.
    RECEPTORS SITES FOR DRUGS/LIGANDS BINDING
    EFFICACY or Emax

    • Often called maximal efficacy—is the


    greatest effect (Emax) an agonist can
    produce if the dose is taken to very high
    levels.

    • Partial agonists have lower maximal


    efficacy than full agonists .
    POTENCY

    • OR
    • The amount of drug needed to produce a
    given effect.

    • The effect/response usually chosen is 50%


    of the maximal effect and the dose causing
    this effect is called the EC50
    GRADED DOSE-RESPONSE
    RELATIONSHIPS
    • A graph of increasing response to increasing drug concentration or dose

    • When the response of a particular receptor-effector system is measured


    against increasing concentrations of a drug, the graph of the response
    versus the drug concentration or dose is called a graded dose-response
    curve

    • The efficacy (Emax ) and potency (EC50 or ED50 ) parameters are


    derived from these data..

    • The smaller the EC50 (or ED50 ), the greater the potency of the drug.
    GRADED DOSE-RESPONSE RELATIONSHIPS
    QUANTAL DOSE-RESPONSE
    RELATIONSHIPS
    • A graph of the fraction of a population that shows a specified response at
    progressively increasing doses

    • When the minimum dose required to produce a specified response is determined


    in each member of a population, the quantal dose-response relationship is
    defined

    • The median effective (ED50), median toxic (TD 50), and (in animals) median
    lethal (LD50) doses are derived from experiments carried out in this manner.

    • Quantal dose-response data provide information about the variation in sensitivity


    to the drug in a given population, and if the variation is small, the curve is steep.
    In Quantal dose-response measurements,

    ED50 (median effective dose), TD 50 (median toxic dose) and


    LD50 (median lethal dose )are also potency variables, in 50%
    of the population studied.

    • Unlike the graded dose-response determination, no attempt


    is made to determine the maximal effect of the drug.

    • Thus, potency can be determined from either Graded or


    Quantal dose-response curves, but the numbers obtained
    are not identical.
    QUANTAL DOSE-RESPONSE RELATIONSHIPS
    Therapeutic index (TI) of a Drug
    •is the ratio of the dose that produces toxicity in half the population (TD50) to the dose
    that produces a clinically desired or effective response (ED50) in half the population

    • TI = TD 50

    ED50

    •Represents an estimate of the safety of a drug, because a very safe drug might be
    expected to have a very large toxic dose and a much smaller effective dose.

    Therapeutic window:

    • A more clinically useful index of safety

    •Describes the dosage range between the minimum effective therapeutic concentration /
    dose, and the minimum toxic concentration/ dose.
    ANTAGONISTS
    Competitive Pharmacologic Antagonists
    • are the drugs that bind to, or very close to, the agonist receptor site in
    a reversible way without activating the effector system for that
    receptor.

    • In the presence of a competitive antagonist, the log dose-response


    curve for an agonist is shifted to higher doses (ie, horizontally to the
    right on the dose axis), but the same maximal effect is reached .

    • The agonist, if given in a high enough concentration, can displace the


    antagonist and fully activate the receptors.

    • Unlike the effects of a competitive antagonist, the effects of an


    irreversible antagonist cannot be overcome by adding more agonist.
    Allosteric antagonists

    • Do not bind to the agonist receptor site, they bind to some other
    region of the receptor molecule that results in inhibition of the
    response to agonists .

    • They do not prevent binding of the agonist.

    • In contrast, pharmacologic antagonists bind to the agonist site and


    prevent access of the agonist.

    • High concentrations of agonist displace or prevent the binding of a


    pharmacologic antagonist but not an allosteric antagonist.

    • A noncompetitive antagonist that acts at an allosteric site of the


    receptor may bind reversibly or irreversibly; a noncompetitive
    antagonist that acts at the receptor site binds irreversibly.
    Physiologic Antagonists
    • Binds to a different receptor molecule, producing
    an effect opposite to that produced by the drug it
    antagonizes.

    Example of a physiologic antagonist

    • The antagonism of the bronchoconstrictor action


    of histamine (mediated at histamine receptors)
    by epinephrine's bronchodilator action (mediated
    at adrenoceptors).
    Chemical Antagonists
    • Interacts directly with the drug being antagonized to
    remove it or to prevent it from binding to its target.
    • A chemical antagonist does not depend on interaction with
    the agonist's receptor (although such interaction may
    occur).

    Examples of a chemical antagonist

    • Dimercaprol, a chelator of lead and some other toxic


    metals.

    • Pralidoxime, which combines avidly with the phosphorus


    in organophosphate cholinesterase inhibitors(insecticides).
    Signaling Mechanisms and receptors
    These are the molecular mechanisms by which a drug acts and represent the classic
    drug–receptor interactions and involve signaling across the membrane.

    Types of transmembrane-signaling mechanisms for receptor-effector systems

    (1)Intracellular Receptors for Lipid-Soluble Agents

    (2)Membrane-spanning receptor- effector enzymes

    (3)Receptors Located on Membrane-Spanning Molecules That Bind Separate


    Intracellular Tyrosine Kinase Molecules (Janus kinases; JAKs)
    (4)Receptors Located on Membrane Ion Channels
    OR
    Ligand-activated or modulated membrane ion channels

    (5)Receptors Linked to Effectors via G Proteins


    Intracellular Receptors for Lipid-Soluble Agents (often steroid
    receptor-like)

    • Some drugs, especially more lipid-soluble or


    diffusible agents (eg, steroid hormones, nitric oxide),

    • may cross the membrane and combine with an


    intracellular receptor that affects an intracellular
    effector molecule.

    • The receptor and effector may or may not be the


    same molecule, but no specialized trans-membrane
    signaling device is required.
    Receptors That Are Intracellular
    Membrane-spanning receptor- effector enzymes

    • A transmembrane receptor that binds and stimulates a protein tyrosine kinase

    • Drugs that affect membrane-spanning enzymes combine with a receptor site


    on the extracellular portion of the molecule and modify its intracellular activity.

    • For example,
    Insulin acts on a tyrosine kinase that is located in the membrane.
    The insulin receptor site faces the extracellular environment, and the effector
    enzyme catalytic site is on the cytoplasmic side.

    When activated, such receptors dimerize and phosphorylate specific intracellular


    protein substrates.
    Receptors Located on Membrane-
    Spanning Enzymes,eg.Insulin receptor
    Receptors Located on Membrane-Spanning Molecules
    That Bind Separate Intracellular Tyrosine Kinase
    Molecules (Janus kinases; JAKs)
    • Also known as cytokine receptors, these receptors have
    and intracellular domains and form dimers.

    • However, after receptor activation by an appropriate drug


    (often a cytokine) at the extracellular receptor site,
    associated but separate tyrosine kinase molecules (Janus
    kinases; JAKs) are activated,

    • resulting in phosphorylation of STAT molecules (signal


    transducers and activators of transcription).

    • STAT dimers (the effectors) then travel to the nucleus,


    where they regulate transcription.
    Receptors Located on Membrane Ion Channels
    OR
    Ligand-activated or modulated membrane ion channels

    • Receptors that regulate membrane ion channels may


    directly cause the opening of the channel (eg,
    acetylcholine at the nicotinic receptor)
    or
    • Modify the ion channel's response to other agents (eg,
    benzodiazepines at the GABA activated chloride
    channel).

    • The channel molecule acts as both receptor and effector,


    and the result is a change in transmembrane electrical
    potential.
    Receptors Linked to Effectors via G Proteins

    Activation of these receptor by the drug results in activation of separate


    coupling G proteins (located in the intracellular face of the membrane),

    • which either stimulate or inhibit the cyclase. Thus, the receptor and
    effector are linked through the G-coupling protein.

    • The best-defined examples of this group are the sympathomimetic drugs


    • which activate or inhibit adenylyl cyclase (formerly called adenylate
    cyclase) by a multistep process

    • Many types of G proteins have been identified; 3 of the most important


    are :
    • Gs,
    • Gi and
    • Gq
    Gq LINKED Phosholipase C activation
    RECEPTOR REGULATION

    • Receptors are dynamically


    regulated in number, location,
    and interaction with other
    molecules.

    • Tachyphylaxis.
    • Frequent or continuous
    exposure to agonists often
    results in short-term diminution
    of the response, sometimes
    called tachyphylaxis.
    • Example is continuous use of
    nitroglycerin results in loss of
    response
    RECEPTOR REGULATION

    • Down regulation of receptors:


    • Long-term reductions in receptor number may
    occur in response to continuous exposure to
    agonists.

    • Up-regulation of receptors:
    • When receptor activation is blocked for
    prolonged periods (usually several days) by
    pharmacologic antagonists or by denervation.

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