Phar 722 Pharmacy Practice III

1
Phar 722Pharmacy Practice III

• Vitamins-
• Pyridoxine (B6)
• Spring 2006

2
Pyridoxine Study Guide

• The applicable study guide items in the Vitamin
  Introduction
• History
• Nomenclature
• Structures of the vitamins and conversion to the
  cofactor forms
• Functions of the cofactor forms including the
  specific types of reactions
• Deficiency conditions
• Drug-vitamin interactions
• Dietary and commercial forms of the vitamin

3
History

• First isolated in 1934 as a factor responsible
  for curing a type of rat dermatitis.
• Much recent research has been conducted at Oregon
  State University.
• There is no historical disease associated with
  this vitamin.
• The importance of this vitamin was discovered
  when an infant milk formulation was sold without
  pyridoxine.
• The infants developed convulsions and there were
  deaths.
• Initially, there was confusion as to whether
  there was a contaminant in the milk.

4
Chemistry

• There are three forms of the vitamin.
• Pyridoxine is found in plants.
• Common commercial form.
• Pyridoxal found in animals.
• Never commercial.
• Pyridoxamine found in animals.
• Not found in common vitamin preparations.
• The forms found in animals came from eating
  vegetable sources or other animals.

5
Pyridoxine Uptake and Metabolism

• All three forms are absorbed from the intestine
  and transported to the liver where they are
  phosphorylated.
• All three are interchangeable as their respective
  phosphate esters.
• Transport throughout the body seems to be on
  serum albumin.
• Pyridoxal phosphate is considered the cofactor
  form of the vitamin.

6
(No Transcript)
7
Biochemical Functions

• Transamination
• Nearly every amino acid requires pyridoxal
  phosphate (PLP) for its metabolism.
• Decarboxylation of amino acids
• DOPA to dopamine
• Histidine to histamine
• 5-OH-Tryptophan to serotonin
• Production of glucose-1-P from glycogen.
• Conversion of homocysteine to cysteine and
  glycogenic end products.
• Other reactions where an amine moiety is part of
  the reaction scheme.

8
(No Transcript)
9
Pyridoxine deficiency-1

• Deficiencies are seen with this vitamin.
• In infants there is a characteristic type of
  convulsions which is reversible when pyridoxine
  supplements are given.
• Deficient infants also show a characteristic
  electrical encephalogram. (This was "discovered"
  when infants were fed an infant formula lacking
  pyridoxine.)
• Pyridoxine has shown no beneficial results for
  adults with convulsive disorders.
• The neuropathies seen in pyridoxine deficiencies
  probably relate to its requirement for the
  biosynthesis of three neurotransmitters
  serotonin from tryptophan and norepinephrine and
  epinephrine from L-DOPA (Dihdroxyphenylalanine).
  L-DOPA is formed from tyrosine by DOPA
  decarboxylase, a pyridoxal P containing enzyme.

10
(No Transcript)
11
Pyridoxine deficiency-2

• Considering the central role that this vitamin
  plays in amino acid metabolism, it is a wonder
  that there aren't more visible signs of this
  deficiency.
• A change in the glucose tolerance curve has been
  reported in pyridoxine deficient subjects.
• Elevated homocysteine may indicate a pyridoxine
  deficiency, but it also can indicate problems
  with folic acid and cobalamin status.
• There have been reports that pyridoxine
  supplements might be beneficial for neuropathies,
  particularly those that are drug-induced, and
  carpal tunnel syndrome.
• Proof of its role in treating depression and
  carpal tunnel syndrome is equivocal.
• Because it is required in the conversion of
  tryptophan to niacin, pyridoxine may have a
  niacin-sparing effect.

12
Drug Vitamin Interactions-1

• Isoniazid (INH)
• The widely used antitubercular drug isoniazid,
  INH, can induce a pyridoxine deficiency.
• A peripheral neuritis develops.
• This interaction has no relationship to INH's
  antitubercular activity.
• Therefore, pyridoxine supplements do not require
  altering INH dosing schedules.
• Penicillamine
• This drug is a copper chelator used in Wilsons
  Disease (copper storage disease) and has two
  amine groups.
• There may have been an interaction of some type
  with the earlier high dosage oral contraceptives.
• This was based on a tryptophan load test.

13
(No Transcript)
14
Drug Vitamin Interactions-2

• L-DOPA
• Parkinsonian patients taking L-DOPA must restrict
  their use of pyridoxine containing vitamin
  supplements to formulations containing only the
  adult RDA.
• Excessive amounts of pyridoxine will cause
  peripheral decarboxylation of L-DOPA (from DOPA
  decarboxylase in the mucosa) producing dopamine.
  
• This reduces the amount of L-DOPA that will cross
  the blood brain barrier.

15
Hypervitaminosis Pyridoxine

• A certain mystique has built up around this
  vitamin resulting in individuals overdosing
  themselves.
• Most of this mystique focuses on the role of
  pyridoxal P in the conversion of glycogen to
  glucose-1-P.
• Example Marathon runners take pyridoxine for
  the
• final boost to finish the race.
• Serious neurological problems have been seen in
  doses of 1 - 6 gm/day for 2 - 40 months.
• Megadosing below 2 gm/day seem safe, but all of
  this information is based mostly on anecdotal
  reports.
• There is an UL for this vitamin, considerably
  below the 2 gm/day.

16
Dosage Forms

• Commercial Form
• Synthetic pyridoxine

17
DRIs-1

• AI
• Infants (0 - 12 months) 0.1 - 0.3 mg/day (0.014
  mg/kg to 0.033 mg/kg)
• EAR
• Children (1 - 13 years) 0.4 - 0.8 mg/day
• Males (14 - 19 years) 1.1 mg/day
• Females (14 - 19 years) 1.0 mg/day
• Men (19 - 50 years) 1.1 mg/day
• Men (51 years) 1.4 mg/day
• Women (19 - 50 years) 1.1 mg/day
• Women (51 years) 1.3 mg/day
• Pregnancy 1.6 mg/day
• Lactation 1.7 mg/day

18
DRIs-2

• RDA
• Children (1 - 13 years) 0.5 - 1.0 mg/day
• Males (14 - 19 years) 1.3 mg/day
• Females (14 - 19 years) 1.2 mg/day
• Men (19 - 50 years) 1.3 mg/day
• Men (51 years) 1.7 mg/day
• Women (19 - 50 years) 1.3 mg/day
• Women (51 years) 1.5 mg/day
• Pregnancy 1.9 mg/day
• Lactation 2.0 mg/day
• UL
• Children (1 - 18 years) 30 - 80 mg/day
• Adults (19 an older) 100 mg/day

19
Food Sources

• Wheat germ
• Milk
• Legumes
• Meat
• Vegetables
• Dietary forms will be the various cofactor
  structures.