MED ORG LEC - UNIT 6&7

• Structure Activity Relationship (SAR)

  The relationship between the chemical structure of a drug and its biological activity
• Autonomic Nervous System (ANS)

  Part of the peripheral nervous system that controls involuntary functions like cardiac/smooth muscle, breathing, salivation
• Parts of the Nervous System

  • Central Nervous System (CNS) - brain and spinal cord
  • Peripheral Nervous System (PNS) - neurons and spinal cord
• Divisions of the Peripheral Nervous System

  • Somatic Nervous System (SNS) - voluntary, innervates skeletal muscles
  • Autonomic Nervous System (ANS) - involuntary, innervates organs
• Divisions of the Autonomic Nervous System

  • Sympathetic Nervous System (aka Adrenergic) - thoracolumbar region
  • Parasympathetic Nervous System (aka Cholinergic) - craniosacral region
• Sympathetic Nervous System

  • Short preganglionic neuron, long postganglionic neuron
  • Ganglion site: ACh-Nicotinic
  • Post-ganglion site: Catecholamine-Adrenergic
• Parasympathetic Nervous System

  • Long preganglionic neuron, short postganglionic neuron
  • Ganglion site: ACh-Nicotinic
  • Post-ganglion site: ACh-Muscarinic
• Neurotransmitters

  Acetylcholine (ACh), Norepinephrine (NE), Dopamine (DA), Serotonin, GABA, Endorphins
• Acetylcholine (ACh)

  Found on neuromuscular junction (NMJ) of skeletal muscles and ANS synapses
• Norepinephrine (NE)

  Involved in "fight or flight" response
• Dopamine (DA)

  Involved in Parkinson's disease
• Serotonin

  Involved in sleep, mood, and anxiety
• GABA

  Generally inhibitory in action, involved in treating epilepsy
• Endorphins

  Feel good hormones, released in pleasurable activities
• Synthesis of Acetylcholine (ACh)

  1. Uptake of choline via Choline Transporter

  2. Choline acetyltransferase catalyzes combining of Choline and Acetyl CoA

  3. Cytoplasmic ACh stored in vesicles via VACHT

  4. Ca2+ influx facilitates fusion of vesicle into membrane

  5. Release of ACh into synaptic cleft

  6. ACh binds to receptors and/or inactivated by AChE

  7. Inactivation product Choline recycled
• Cholinergic Receptors

  Nicotinic receptors (nAChRs), Muscarinic receptors (mAChRs)
• Muscarinic receptors (mAChRs)

  • M1, M3, M5 = Gq; M2, M4 = Gi
  • M1 in CNS, M2 in heart, M3 in GI, respiratory, smooth muscle, glands, pupil, lacrimal gland, sweat glands, blood vessels
• Nicotinic receptors (nAChRs)

  • Nm on skeletal muscle, Nn on postganglionic neuronal cell bodies, adrenal medulla
  • Ligand-gated ion channels
• G-protein coupled receptors

  • Also called metabotropic receptors or 7-transmembrane receptor
  • Consist of a single peptide with 7-membrane spanning regions, coupled with a G-protein
• Types of G-proteins

  • Gs - increases adenylyl cyclase activity and Ca2+ currents
  • Gi - decreases adenylyl cyclase activity and K+ currents
  • Go - decreases Ca2+ currents
  • Gq - increases phospholipase C activity
• Cholinergic Agonists

  Drugs that increase levels of ACh available for binding to receptors
• Types of Cholinergic Agonists

  • Acetylcholine analogs
  • Acetylcholinesterase inhibitors
• Anti-Infective Agents

  Agents used to prevent infection
• Types of Anti-Infective Agents

  • Alcohols and Related Compounds
  • Phenols and their Derivatives
  • Oxidizing Agents
  • Halogen-containing Compounds
  • Cationic Surfactants
  • Dyes
  • Heavy Metals
• Muscarinic Agonists (Direct-Choline Esters)

  Bind to muscarinic ACh receptor subtypes M1 to M5 and elicit a response
• Definition of Terms

  • Antisepsis
  • Decontamination
  • Disinfection
  • Sanitization
  • Sterilization
  • Pasteurization
• Muscarinic Agonists (Direct-Choline Esters)

  • Acetylcholine, Methacholine, Carbachol, Bethanechol
• Antisepsis

  Application of an agent to animate tissue for the purpose of preventing infection
• Muscarinic Agonists (Direct-Alkaloids)

  • Pilocarpine, Cevimeline, Arecoline, Muscarine
• Structure-Activity Relationship of Acetylcholine and Cholinergic Agonists

  • Quaternary ammonium group, ethylene bridge, acyloxy group
• Decontamination

  Destruction or marked reduction in the number of activity of microorganisms
• Quaternary Ammonium Group

  • For optimum cholinergic activity, amine group must be quaternary
  • Primary, secondary, tertiary amines less active than quaternary amines
  • Substitution of methyl groups with higher alkyl groups decreases activity
• Disinfection

  Chemical or physical treatment that destroys most vegetative microbes or viruses, but not spores, in or on inanimate surfaces
• Sanitization

  Reduction of microbial load on an inanimate surface to a level considered acceptable for public health purposes
• Quaternary Ammonium Group (Trimethyl ammonium ion/Onium group)

  For optimum cholinergic activity amine group must be quaternary
• Sterilization

  A process intended to kill or remove all types of microorganisms, including spores, and usually including viruses with an acceptably low probability of survival
• Quaternary Ammonium Group

  • Metacholine
  • Betanechol
  • Carbachol
  • Muscarine
• Primary, secondary, and tertiary amines are less active than quaternary amines
• Pasteurization

  A process that kills nonsporulating microorganisms by hot water or steam at 65°C- 100°C
• Substitution of one of the three methyl groups with higher alkyl groups (i.e., ethyl, propyl)

  Makes it less active than ACh