PCOL CEE 2

• Pharmacology


  Study of drugs: structure, physical properties, chemical characteristics relevant to its activity as therapeutic agent
• Drug


  Substance that brings about change in biologic function through its chemical actions
• Pharmacokinetics


  Action of the body (Katawan) on the Drug (Absorption, Distribution, Metabolism, Elimination)
• Drugs


  • Enalapril (Ethyl ester of enalaprilat)
  • Olsalazine (Dimer of mesalamine)
  • Chloramphenicol palmitate
• Albumin, Warfarin, Phenylbutazone


  Causes toxicity (bleeding)
• Pharmacodynamics


  Action of the Drug on the Body (Katawan)
• Drug-receptor interaction


  • 1. Affinity: ability of a Ligand to bind to receptors
  • 2. Intrinsic Activity: ability of the ligand to stimulate the receptors
• Agonist


  Binds to regulatory receptors and mimic regulatory effects of the endogenous signaling compounds
• Types of Agonists


  • Full Agonist
  • Partial Agonist
  • Inverse Agonist
• Antagonist


  Drugs that block or reduce the effects of an Agonist
• Types of Antagonism


  • Functional Antagonism (Physiologic Antagonism)
  • Receptor Antagonism (Pharmacologic Antagonism)
  • Chemical Antagonism (Inactivation)
• Types of Antagonism based on interaction

  • Reversible: Temporary (less than 24 hours)
  • Irreversible: Permanent (more than 24 hours)
• Types of Antagonism based on Surmountability


  • Competitive Antagonism: Surmountable
  • Non-competitive Antagonism: Non-surmountable
• Partial Agonist


  Has Affinity but the Intrinsic activity is more than 0 but less than 1
• Types of Receptors


  • Inotropic Receptors (Ligand-gated Ion Channels)
  • Metabotropic Receptors (G-Protein Coupled Receptors)
  • Enzyme-Linked Receptors
  • Gene Transcription-Linked (Nuclear Receptors)
• Graded Dose-Response Relationship Curve


  Relationship of drug concentration and effect
• Quantal Dose-Response Relationship Curve


  Minimum concentration needed to produce a specific response in each member of a population
• Therapeutic Index


  Ratio of the toxic dose to the therapeutic dose
• Therapeutic Window


  Range of doses that are both effective and safe
• Narrow Therapeutic Index Drugs

  • Warfarin
  • Aminoglycosides
  • Lithium
  • Amphotericin B
  • Carbamazepine
  • Phenytoin
  • Phenobarbital
  • Vancomycin
  • Theophylline
  • Digoxin
• Pharmacokinetics


  The fate of the drug during its sojourn through the body
• Types of Drug Interactions

  • Non-competitive
  • Chemical
  • Physiological
  • Pharmacokinetic
• Weak acids


  Reabsorbed into the blood stream when the urine pH is low
• Phase 1 Biotransformation Reactions

  • Methylation
  • Oxidation
  • Deamination
  • Hydrolysis

  
• Auto-induction


  If a drug stimulates its own metabolism
• Glucuronidation


  The addition of glucuronic acid to a drug, usually leads to inactivation of the drug
• Pregnancy Categories

  • A (Safe)
  • B (Prescribed only as needed for maternal health)
  • C (Prescribed only in pregnancy if benefit clearly outweigh the risks)
  • D (Not recommended in pregnancy; prescribed if absolutely necessary)
  • X (Absolute contraindication)
• Clinical Trial Phases


  • Phase 1: Evaluation of pharmacokinetics and safety of drugs
  • Phase 2: Evaluation of efficacy
  • Phase 3: Evaluation of efficacy in larger population
  • Phase 4: Evaluation of adverse events, compliance
• Nervous System Divisions


  • Peripheral Nervous System
  • Central Nervous System
  • Sensory Neurons (Afferent)
  • Motor Neurons (Efferent)
  • Autonomic Nervous System
  • Somatic Nervous System
  • Enteric Nervous System
  • Sympathetic Nervous System
  • Parasympathetic Nervous System
• Autonomic Nervous System


  2 neuron system, origin, neurons/fibers are classified based on the neurotransmitters they use or produce
• Neurotransmitters


  • 4 biosynthetic steps and inhibitors
• Receptors


  • Cholinergic Receptors (Cholinoceptors): Muscarinic & Nicotinic
  • Adrenergic Receptors (Adrenoceptors): Alpha, Beta, Dopamine
• Sympathetic vs Parasympathetic Nervous System Differences


  • Anatomical Difference: Length of Fibers, Location of the Ganglion
  • Neurotransmitter: Preganglion, Postganglion
  • Receptors: Ganglion, Target Organ
• Sympathetic Nervous System Mechanisms

  • Synthesis (-), Storage (-), Release (+/-), Termination
• Adrenergic Effects


  • Alpha 1, Alpha 2, Beta 1, Beta 2, Beta 3
• Association of Adrenergic Effects

  • Alpha 1-Agonists as Vasoconstrictors and Nasal Decongestants
  • Alpha 1-Antagonists for Treatment of Hypertension
  • Alpha 2-Agonists for Treatment of Hypertension
  • Beta 1-Blockers for Treatment of Hypertension, Angina, and Certain Cardiac Arrhythmias
  • Beta 2-Agonists for Treatment of Asthma and Premature Labor
• Selective Alpha-1 Agonists


  • Phenylephrine
  • Phenylpropanolamine
  • Pseudoephedrine
  • Methoxamine
• Blood Pressure


  CO x SVR
• Factors Affecting Blood Pressure


  • Cardiac Output, Heart Rate, Stroke Volume, Cardiac Contractility, Venous Return, Fluid Content, Venous Tone
• Alpha 2 Agonists


  • Clonidine
  • Methyldopa