PCOL notes

• PHARMACOLOGY


  Study of drugs
• Drugs


  • Effects that the drug can elicit in the body: MOA of Drug
  • ADME → Fate of the drug in the body
  • Clinical uses of the drug
• Pharmacodynamics


  What the drug does to the body?
• Pharmacokinetics


  What the body does to the drug?
• Pharmacotherapeutics


  Study of rational drug use in the management of certain diseases
• Drug


  Any article/agent used in the mitigation, diagnosis, prevention, treatment, and cure of diseases in man and in animals
• Main divisions of pharmacology

  • Pharmacodynamics
  • Pharmacokinetics
  • Pharmacotherapeutics
• General mechanisms by which drugs determine their effects

  • Interaction with RECEPTORS
  • Alteration of the activity of ENZYMES
  • ANTIMETABOLITE action
  • NON-SPECIFIC Chemical or Physical Interactions

  
• Receptors


  Naturally occurring target macromolecules which mediate actions of endogenous physiologic substances

  
• Ligands

  • Natural compounds: Neurotransmitters, Hormones, Autocoids
  • Exogenous compounds: Drugs → introduced in the body
• Signal Transduction Mechanisms

  • Ligand-gated ion channels (Ionic receptors)
  • G protein-coupled receptors (Metabotropic)
  • Tyronise Kinase-linked receptors
  • Nuclear receptors

  
• Ligand-gated ion channels


  Fastest: Timescale of milliseconds, Membranous (Cell membrane located), Hyperpolarization, Depolarization
• G protein-coupled receptors


  Dominant: Most abundant type of receptors, majority of receptors in the body are g-protein mediated, Receptors has a linked g-protein, Delayed: Timescale of seconds, Membranous (Cell membrane located), Adenylate Cyclase System, IP3/DAG System

  
• Tyronise Kinase-linked receptors

  Involves tyrosine residues that undergo phosphorylation → causing multiple responses, Timescale of minutes, Membranous (Cell membrane located)
• Nuclear receptors

  Nuclear located, Most delayed: Timescale of hours, A.k.a: Intracellular receptor, RNA synthesis
• Enzyme

  Responsible for the conversion of substrates to certain products, With the aid of enzyme, metabolic reaction is possible
• Antimetabolite action

  Acting as a nonfunctional analog of a naturally occurring metabolite; interferes with normal metabolism, Exhibit counterfeit mechanism → tells if analogue compound is fake → inhibition of pathway, Analogues of purine and pyrimidine bases
• Non-specific chemical or physical interactions


  Drug promotes effect even without protein target, Chemical Interaction: Drug promotes neutralization an acid-base reaction, Chelation: Chelating agents, used during heavy metal poisoning, Physical Interaction: Mannitol → drug that exhibits (induce) osmosis → solvent (the one that moves)
• Ligand terminologies

  • Affinity – ability of a ligand to bind to the receptors
  • Intrinsic Activity – ability of a ligand once bound to activate the receptor

  
• Ligand classes

  • Agonists
  • Antagonists
• Agonists

  Capable of binding to, and activating, a receptor, Full Agonists, Partial Agonists, Inverse Agonists

  
• Antagonists

  Bind to the receptor but do not initiate a response; block the action of an agonist or endogenous substance that works through the receptor, Competitive Antagonists, Non-competitive Antagonists

  
• Graded-dose response curve


  Expresses an individual's response to increasing doses of a drug

  
• Magnitude of response


  Depicted as a function of the logarithm of the dose administered; proportional to the number of receptors with which a drug effectively interacts

  
• Efficacy

  Measure of the ability of a drug to elicit the MAXIMUM pharmacologic response
• Potency


  Relative measure of the ability of a drug to produce half of the maximum response, Defined as the dose needed to achieve 50% of maximum response (efficacy)
• Ceiling dose


  The smallest dose which produces the maximum response, Plateau → no matter how much you increase the dose you produce the same effect
• Slope

  Indicates changes in response; Steep curve implies a small change in dose produces a large change in response
• Efficacy VS. Potency

  Dose: Potency, Y-axis: Efficacy, Left or right plotted value: Potency, High or low plotted value: Efficacy

  
• Competitive Antagonism

  Graph: Shift to the right, Efficacy: Same height
• Non-competitive Antagonism

  Graph: Shift to the right, Efficacy/Response: Lower height (bumababa)
• Quantal-dose response curve


  Relates the dosage of a drug to the frequency with which a designated response will occur within a population, Y-axis: Percentage of people affected, Beneficial effect to some: Observed at lower doses of drug, Toxic effect for some: Observed at high doses of drug

  
• Median Effective dose (ED50)

  Defines as the effective dose in 50% of the given population
• Toxic Dose (TD50)

  Defines as the toxic dose in 50% of the given population
• Therapeutic Index


  Defined as the measurement of the relative safety, Formula: TD50/ED50, Results: ↑ TI value = Safer drug
• Autonomic Drugs topic flow

  • A. Anatomy and Physiology of the ANS
  • B. Sympathetic Drugs
  • C. Parasympathetic Drugs
• Autonomic Nervous System (ANS)

  Subdivision of the peripheral efferent nervous system; controls involuntary activity, Peripheral efferent neurons: Motor neurons → carries responses coming from the brain to effector organs, Responses: Involuntary, Effector organs: Smooth muscles, Exocrine glands, Heart

  
• Motor neurons of ANS

  • Preganglion → Closer to the brain
  • Postganglion → Closer to the effector organ
• Subdivisions of ANS

  • Parasympathetic Nervous System
  • Sympathetic Nervous System
  • Enteric Nervous System

  
• Synaptic transmission

  Describes the mechanism of impulse across the synapse, Synapse: Actual gap observed in the neurons, Pre-synapse: Sending neurons, Synthesis of neurotransmitters, storage in form of vesicle, release via exocytosis of neurotransmitters, Enzymes are present too that causes metabolism that can potentially destroy these neurotransmitters, Synaptic cleft: Metabolizing enzymes, Post-synapse: Receiving cell, Majority of receptors are present, Metabolizing enzymes