Chapter12 Principles of Pharmacodynamics and Medical Chemistry vol.2

Chapter 12 今日のメモ☆

第二回目はMedical Chemistryの項。

Natural Product
 - Alkaloids (N containing compounds)
    ex) morphine(opium poppyケシの果実), atropine(belladonnnaplant), colchicine(autumn crocus)
 - Peptides / polypeptides (Polymers of amino acids)
    ex) somatostatin, glucagon
 - Steroids (derivatives 誘導体 of cyclopentanoperhydrophenanthrene)
    ex) estradiol, testosterone, hydrocortisone
 - Hormones
    ex) insulin, thyroid hormones, conjugated estrogens
 - Glycosides（配糖体）
    ex) digotoxin, streptomycin, doxorubicin
 - Vitamins
    ex) water-soluble vitamines : B₁, B₂, B₃, B₆, B₁₂, C, H     lipid-soluble vitamines : A, D, E, K
 - Polysaccharides
    ex) heparin, tinzaparin, enoxaparin, sucralfate
 - Antibiotics
    ex) penicillin, tetracycline, doxorubicin

Synthetic Product
 - chemical structures closely resembling
    ex) hydroxymorphine, ampicillin
 - similar spacing of functional groups
    ex) losartan (peptidomimeticsペプチド模倣薬)
 - completely new products

Physicochemical Properties（物理化学的特性）
 - Drug Polarity（薬物の極性）　≒　drug's lipid and water solubility
    * Partition Coefficient分配係数 (P) = [Drug]_lipid ／[Drug]_aqueous
    ※log係数で表される

    * water solubility ( or hydrophilicity)
      depends on two factors ; ionic character & hydroge-bounding capabilities(O-, N- )
    * lipid solubility (or lipophilicity)
      nonionizable hydrocarbon chains(-CH₂-CH₂-…) & ring systems (C₆H₆)

 - Ionization of acids & bases
    * ionization constant (Ka)
     ※ acidの場合　1×10[-3] ＞1× 10[-7], 　baseの場合はその逆
    * negative log of ionization constant (pKa)
     ※ acidの場合 pKa = 3 (Ka = 1×10[-3] ) ＞ pKa=5 (Ka = 1×10[-5]), 　baseの場合はその逆

    * Strong acid
      ex) HCl, H₂SO₄, HNO₃, HBr, HlO₃, HClO₄
      ex) -COOH, Ar-OH, -SO₃H, SO₂NH-R, -CO-NH-CO-, -CO-CHR-CO-, CHN₄

    * Strong bases
      ex) NaOH, KOH, Mg(OH)₂, Ca(OH)₂, Ba(OH)₂,
      ex) primary, secondary, or tertiary aliphatic or alicyclic amino group (-NH₂, -NHR, -NR₂)
      ex) aromatic or unsaturated heterocyclic N (weakly basic)
      ex) imine N (-N=C-), hydrazine N (-NH-NH₂), amidine N (-NH-C=N-), guanidine N (CH₄N₃)

    * Weak acids
      ex) CH₃COOHacetic acid(pKa: 4.76)
     in an acid medium : the equilibrium shifts to the left.  ionized < salt
     in an alkaline (basic) medium : ionized > salt

    * Weak bases is opposit to weak acid.
    
    ※percent ionization
      [pH－pKa] = 1 then a 90:10 ratio, [pH－pKa]=2 then a 99:1 ratio

 - Salt (combination of cid and base)
    salts are strong electrolytes（電解質）　（例外； Hg, Cd, lead acetate)

    * Inorganic Salts
      ex) HCl, H₂SO₄, KOH, NaOH
     water solubility : aqueous dissolution↑

    * Organic Salts
     ex) succinic acid（コハク酸）, citric acid（クエン酸） ： hydrophilic
     ex) procaine（プロカイン） ： lipophilic

    * Amphoteric compounds（両性物質）

 - neutralization reaction（中和反応）
    強酸ｖｓ弱塩基、弱酸vs強塩基の組み合わせの際
    non-ionized organic acidとnon-ionized organic baseがprecipitate（沈殿・凝集する）
     ：Drug Incompatibilities（適合性/配合性）に関与
     ex) strong acid : nitrate(NO₃), sulfate(SO₄), hydrochloride(塩酸塩)
     ex) strong base : Na, K, Mg
     ex) "-onium" / "-inium"


Today's question
- Acid & Base(酸と塩基)の問題
Q: Which of the following salts will most likely yield an aqueous solution with a pH<7?
(A) Sodium salicylate
(B) Potassium chlorideMagnesium sulfate
(C) Magnesium sulfate
(D) Potassium penicillin
(E) Atropine sulfate






A: (E) Atropine sulfate
The solution must contain an acidic substance to have a pH <7.  Atropine sulfate is a salt of a weak base and a strong acid; therefore, its aqueous solution is acidic.  Sodium salicylate and potassium penivillin are both salts of strong bases and weak acids; therefore; their aqueous solutions are alkaline.  Magnesium sulfate and potassium chloride are salts of strong bases and strong acids; therefore, their aqueous solutions are neutral.