Physiology

Subdecks (10)

Cards (1105)

  • There are two types of cardiac cells
    1. Working cardiomyocytes with long APs
    2. AP cells with short APs
  • All electrical phenomena in the heart rely on movement of ions across membranes
  • Disturbances in normal periodic electrical activity in the heart result in cardiac arrhythmia
  • Gap junctions allow large areas of the heart to contract almost simultaneously
  • There are two main type of cardiac action potentials
    • Fast (non-pacemaker cells; most cardiomyocytes)
    • Slow (pacemaker cells; the SA node)
  • The fast action potential of the heart has a rapid depolarization but a very long duration (long refractory period) to prevent tetanic contraction and allow the ventricles to empty their contents and refill before the next contraction
  • Fast action potential phases
    1. Resting potential (K+ going out)
    2. Depolarization (Na+ coming in a lot)
    3. Initial repolarization (all channels blocked)
    4. Plateau (Ca2+ coming in)
    5. Repolarization (all channels blocked)
    6. Return to resting potential (K+ going out)
  • The SA node is a grouping of cells in the right atrium near the vena cavae that can spontaneously produce action potentials without neural input
  • The SA node acts as the pacemaker for the entire heart, so the rate at which it fires determines the heart rate
  • Cells of the SA node don’t have a steady resting potential, instead they have a slowly depolarizing state called the pacemaker potential
  • SA node cells can trigger action potentials at a negative membrane potential, therefore action potentials can be triggered easily
  • Sequence of contraction of the heart
    1. Blood flows into both atria
    2. The atria contract to send blood to the ventricles
    3. Both ventricles contract simultaneously to send blood out of the heart
  • Cardiac conducting system
    A network of specialized cardiac cells that can quickly propagate electrical signals from the SA node through the heart to the ventricles
  • The cardiac conducting system
    1. SA node sends APs throughout atria (Rapid conduction velocity)
    2. AP is sent to ventricles through the atrioventricular node (conduction velocity slows permitting atrial relaxation prior to ventricular contraction)
    3. AP is sent through the Bundle of His to the left and right bundle branches (Conduction velocity is very fast so both entire ventricles are activated simultaneously)
    4. AP is sent through the Purkinje fibers around the heart (conduction velocity continues to be very fast)
  • ECGs use 12 recording electrodes on the skin that are placed such that current is measured along the longitudinal axis of the heart, which allows the atrial and ventricular currents to be measured seperately
  • Components of an ECG recording
    1. P wave (Atrial depolarization, hidden by the ventricular depolarization)
    2. QRS complex (Ventricular depolarization)
    3. T wave (ventricular repolarization)
    4. PR interval (the time of passage through the AV conduction system)
    5. QT interval (The time it takes ventricles to depolarize and repolarize)
  • Solid dosage forms are most widely used for administration of medicines
  • Boiling point is really only important for volatile compounds as administration of a drug becomes much more difficult
  • Boiling and melting points typically increase as the molecular weight of a molecule increases
  • Crystallization is typically controlled by efficiency of packing molecules
    • more planar compounds crystalize better
    • fewer alkyl chains (less flexibility = higher MP = increased crystallization)
    • more ring systems (increased rigidity = better stacking = more order in the system)
    • intermolecular attractive forces (polarization and pi stacking = more order in the system)
  • The more ordered molecules are (i.e. less flexible), the more crystalline they are (higher MP)
  • There are three methods of manipulating melting points
    1. Salt formation: common for amines and acids (treat an amine with an acid or acid with a base)
    2. Introduction of symmetry: allows molecules to pack together tightly (think aromatic rings being Para)
    3. Making derivatives with something that tends to crystallize (basically attaching compound to a crystallizing compound)
  • For some drug molecules, different crystal forms (habits) are possible. When the molecules pack differently within said crystals it is referred to as polymorphic
  • Differences in crystal form may affect solubility, rate of absorption, and bioavailability of drugs
  • Habits (crystal forms) can by modified by crystallization conditions and additives
  • Theory of solvation
    1. Drug molecule ”removed” from crystal
    2. Cavity created in solvent
    3. Drug molecule inserted into solvent cavity
  • Lipinski’s Rule of 5
    1. Molecular weight of < 500
    2. Partition coefficient (logP < 5)
    3. No more than 5 H-bond donors
    4. No more than 10 H-bond acceptors
    5. H-bond donors and acceptors counted by ATOMS not LONE PAIRS
  • The rule of 3 is essentially the same as the rule of 5 just smaller for smaller molecules
  • In recent years, drug molecules have gotten progressively larger than the 500 molecular weight presented by Lipinski
  • The Veber Rule
    1. No more than 10 rotatable bonds
    2. Polar surface area <140 A
  • Cell permeability is controlled in part by polar surface area. A more rigid molecule will have lower polar surface area and will not be as susceptible to promiscuous binding to metabolic enzymes or transporters
  • Polar surface area (PSA) is the surface sum over all polar atoms in a molecule.

    PSA calculations were extremely slow
  • Topological polar surface area was developed as a more rapid calculation of polar surface area using structural features
  • Thomas Lemke developed a system for predicting solubility based on the functional groups present using a table wherein you count the associated carbons with the functional groups, then compare the sum of the carbons with the number of carbons in the molecule itself