Pharmacology Book

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Vitamin K

Aka: Vitamin K, Vitamin K1, Phylloquinone, Phytomenadione, Phytonadione, Vitamin K2, Menaquinone, Vitamin K3, Menadione
  1. Background
    1. Vitamin K is a fat soluble Vitamin synthesized in plants (esp. green leafy vegetables)
    2. Three forms of Vitamin K
      1. Vitamin K1 (Phytomenadione, from plant sources)
        1. Primary source of ingested Vitamin K in humans
      2. Vitamin K2 (Menaquinone, from Bacteria)
      3. Vitamin K3 (Menadione, synthetic Vitamin K)
    3. Sources
      1. Green leafy vegetables
      2. Liver
      3. Cheese
      4. Butter
      5. Egg yolk
  2. Physiology
    1. Vitamin K is required for Coagulation Factors 2,7, 9, 10 and Protein C and Protein S
    2. Vitamin K Deficiency may result in Bleeding Disorders
      1. Hemorrhagic Disease of the Newborn
    3. Vitamin K Toxicity or Overdose may result in Hemolytic Anemia or Kernicterus
    4. Warfarin (Coumadin) is a Vitamin K mimic that functions as a competitive antagonist to Vitamin K epoxide reductase
      1. Results in Vitamin K Deficiency
  3. Indication
    1. Reversal of excessive Anticoagulation with Coumadin
  4. Dosing (See Coumadin Protocol)
    1. Routes: IV, IM, SQ, PO
      1. Oral route is preferred in most cases (consistently absorbed with excellent efficacy)
      2. IV route is indicated in life threatening bleeding or intolerance to oral administration
        1. IV route risks anaphylactic reaction (esp. rapid infusion)
      3. Intramuscular Injection (of any medication) is not recommended with supratherapeutic INR
        1. Risk of Muscle and extremity injury due to localized bleeding
      4. Subcutaneous administration is not recommended due to unpredictable absorption
    2. INR 4 to 10
      1. Give Vitamin K 1-2 mg orally
      2. Dilute parenteral Vitamin K 1-2 mg in flavored drink
      3. Administer Vitamin K 0.5-1 mg IV if not able orally
    3. INR over 10 without bleeding complications
      1. Vitamin K 3 mg SC or slow IV infusion (over 15-30 min)
      2. Check INR at 6 hours
      3. Consider repeating Vitamin K at 6 hours if unchanged
    4. Serious bleeding complication at any elevated INR
      1. Replace Clotting Factors
        1. Vitamin K 10 mg SC or slow IV infusion
        2. Fresh Frozen Plasma (FFP) 15 ml/kg
        3. Prothrombin Complex Concentrate (PCC) 50 U/kg
      2. Check INR at 6 hours
  5. Precautions
    1. Anticoagulant-laced Synthetic Cannabinoids
      1. Drugs contaminated with Brodifacoum rat poison
      2. May require Vitamin K doses as high as 50 mg orally tid for months
      3. Extortionary Vitamin K prices of $50 per 5 mg Vitamin K tab, may cost $45,000 per month
      4. (2018) Presc Lett 25(6):35 [PubMed]
  6. Research: Guideline Studies (See Coumadin Protocol)
    1. Consensus Conference (Dalen) advocates giving
      1. Vitamin K SC/IV for INR > 6
      2. Dalen (1995) Chest 108 (sppl):225S-522S (Consensus) [PubMed]
    2. Retrospective study of 51 Arizona Patients with INR >6
      1. No Vitamin K given in 48 patients, Coumadin stopped
      2. No adverse outcomes or major bleeding
      3. Glover (1995) Chest 108:987-90 [PubMed]
    3. Oral Vitamin K 1 mg acts faster than subcutaneous
      1. Crowther (2002) Ann Intern Med 137:251-4 [PubMed]

Vitamin K 3 (C0025270)

Definition (CSP) synthetic vitamin K; 2-methyl-1,4-naphthoquinone.
Definition (MSH) A synthetic naphthoquinone without the isoprenoid side chain and biological activity, but can be converted to active vitamin K2, menaquinone, after alkylation in vivo.
Concepts Pharmacologic Substance (T121) , Organic Chemical (T109) , Vitamin (T127)
MSH D024483
SnomedCT 69169004, 69576000, 412244007
LNC LP15951-4, MTHU014694
English Menadione, Vitamin K3, Vitamin K3 preparation, Vitamin K3 (substance), Vitamin K<sub>3</sub> (substance), Vitamin K<sub>3</sub> preparation, Vitamin K<sub>3</sub>, vitamin K3, VITAMIN K A 03, vitamins menadione (discontinued), menadione (discontinued) (medication), menadione (discontinued), Vitamin K 3 [Chemical/Ingredient], vitamin k3, 2-Methyl-1,4-naphthalenedione, 2-Methyl-1,4-naphthoquinone, 2-Methylnaphthoquinone, Vitamin K 3, MENADIONE, menadione, Menadione preparation, Menaphthone preparation, Vitamin K>3< preparation, Vitamin K>3<, Menadione preparation (product), Vitamin K>3< (substance), Menadione preparation (substance), Menadione (substance)
German 2-Methyl-1,4-Naphthoquinon, 2-Methyl-1,4-Naphthalenedion, 2-Methyl-1,4-Naphthochinon, VITAMIN K A 03, Menadion, Vitamin K3
Swedish Vitamin K3
Spanish menaftona, vitamina K<sub>3</sub>, vitamina K3 (sustancia), vitamina K3, vitamina K<sub>3</sub> (sustancia), preparado con menaftona, preparado con menadiona (producto), menadiona (producto), preparado con vitamina K>3<, preparado con vitamina K3, preparado con vitamina K<sub>3</sub>, preparado con menadiona, preparado de menadiona (sustancia), vitamina K>3< (sustancia), vitamina K>3<, menadiona, menadiona (sustancia), Menadiona, Vitamina K 3
Czech vitamin K 3, menadion
Finnish K3-vitamiini
Russian MENADION, VITAMIN K 3, ВИТАМИН K 3, МЕНАДИОН
Japanese メナジオン, ビタミンK3
Polish Witamina K3
French Vitamine K3, Ménadione
Italian Vitamina K3
Portuguese Menadiona, Vitamina K 3
Sources
Derived from the NIH UMLS (Unified Medical Language System)


Vitamin K 1 (C0031862)

Definition (NCI_CRCH) Form of Vitamin K containing a double-bond in its single isoprenoid side chain.
Definition (NCI) An analogue of the naphthoquinone vitamin K found in plants. The vitamins K are essential for blood coagulation as it is necessary for the hepatic synthesis of the coagulation factors II, VII, IX, and X; deficiency results in a bleeding diathesis. These vitamins are lipo-soluble; absorption via intestinal lymphatics requires the presence of bile salts. (NCI04)
Definition (MSH) A family of phylloquinones that contains a ring of 2-methyl-1,4-naphthoquinone and an isoprenoid side chain. Members of this group of vitamin K 1 have only one double bond on the proximal isoprene unit. Rich sources of vitamin K 1 include green plants, algae, and photosynthetic bacteria. Vitamin K1 has antihemorrhagic and prothrombogenic activity.
Concepts Pharmacologic Substance (T121) , Vitamin (T127) , Organic Chemical (T109)
MSH D010837
SnomedCT 66656000, 63136007
LNC LP17945-4, MTHU024798
English Phylloquinone, Phytomenadione, Phytonadione, Vitamin K1, 1,4-Naphthalenedione, 2-methyl-3-(3,7,11,15-tetramethyl-2-hexadecenyl)-, (R-(R*,R*-(E)))-, Vitamin K1 preparation, Vitamin K1 (substance), Vitamin K<sub>1</sub> (substance), Vitamin K<sub>1</sub> preparation, Vitamin K<sub>1</sub>, phytonadione, vitamin K1, phylloquinone, VITAMIN K A 01, phytonadione (medication), vitamin K1 (medication), vitamins phytonadione, Vitamin K 1 [Chemical/Ingredient], vitamin k 1, vitamin k1, PHYTONADIONE, phytomenadione, Vitamin K 1, Phylloquinone preparation, Phytomenadione preparation, Phytonadione preparation, Vitamin K>1< preparation, Vitamin K>1<, Phytonadione preparation (product), Vitamin K>1< (substance), Phytonadione preparation (substance)
Swedish Vitamin K1
Czech vitamin K 1, fytonadion, fyllochinon
Finnish K1-vitamiini
Russian FITONADION, FILLOKHINON, VITAMIN K1, VITAMIN K 1, FITOMENADION, ВИТАМИН K 1, ВИТАМИН K1, ФИЛЛОХИНОН, ФИТОМЕНАДИОН, ФИТОНАДИОН
Spanish preparado con vitamina K1, preparado con vitamina K<sub>1</sub>, vitamina K<sub>1</sub>, vitamina K1, vitamina K<sub>1</sub> (sustancia), vitamina K1 (sustancia), fitonadiona, preparado con fitonadiona (producto), fitonadiona (producto), preparado con fitonadiona, preparado con filoquinona, preparado con fitomenadiona, preparado con vitamina K>1<, preparado de fitonadiona (sustancia), vitamina K>1< (sustancia), vitamina K>1<, Filoquinona, Fitomenadiona, Fitonadiona, Vitamina K 1
Japanese ビタミンK1, フィトナジオン, フィトメナジオン, フィロキノン
Italian Fitomenadione, Fitonadione, Vitamina K1, Fillochinone
German VITAMIN K A 01, Phyllochinon, Phytomenadion, Phytonadion, Vitamin K1
Polish Fitomenadion, Witamina K1
French Phytoménadione, Vitamine K1, Phylloquinone, Phytonadione
Portuguese Vitamina K1, Filoquinona, Fitomenadiona, Fitonadiona, Vitamina K 1
Sources
Derived from the NIH UMLS (Unified Medical Language System)


Vitamin K (C0042878)

Definition (MSH) A lipid cofactor that is required for normal blood clotting. Several forms of vitamin K have been identified: VITAMIN K 1 (phytomenadione) derived from plants, VITAMIN K 2 (menaquinone) from bacteria, and synthetic naphthoquinone provitamins, VITAMIN K 3 (menadione). Vitamin K 3 provitamins, after being alkylated in vivo, exhibit the antifibrinolytic activity of vitamin K. Green leafy vegetables, liver, cheese, butter, and egg yolk are good sources of vitamin K.
Definition (MEDLINEPLUS)

Vitamin K helps your body by making proteins for healthy bones and tissues. It also makes proteins for blood clotting. If you don't have enough vitamin K, you may bleed too much.

Newborns have very little vitamin K. They usually get a shot of vitamin K soon after they are born.

If you take blood thinners, you need to be careful about how much vitamin K you get. You also need to be careful about taking vitamin E supplements. Vitamin E can interfere with how vitamin K works in your body. Ask your health care provider for recommendations about these vitamins.

Most people get their vitamin K from plants such as green vegetables, and dark berries. Bacteria in your intestines also produce small amounts of vitamin K.

Definition (NCI_NCI-GLOSS) A nutrient that the body needs in small amounts to function and stay healthy. Vitamin K helps to form blood clots (a mass that forms when blood platelets, proteins, and cells stick together) and maintain strong bones. It is fat-soluble (can dissolve in fats and oils) and is found in green leafy vegetables, broccoli, liver, and vegetable oils. Vitamin K is also made by bacteria that live in the large intestine. Not enough vitamin K can lead to bleeding and bruising.
Definition (NCI) The term "vitamin K" refers to a group of chemically similar fat-soluble compounds called naphthoquinones: vitamin K1 (phytonadione) is found in plants and is the primary source of vitamin K for humans through dietary consumption, vitamin K2 compounds (menaquinones) are made by bacteria in the human gut, and vitamin K3 (menadione) is a water-soluble preparation available for adults only. Vitamin K is necessary for the liver to produce the coagulation factors II, VII, IX, and X, as well as the clotting factors protein C, protein S, and protein Z; vitamin K deficiency can result in deficiencies of these coagulation factors and excess bleeding. An injection of vitamin K is routinely given to newborn infants to prevent vitamin K deficiency bleeding, also known as hemorrhagic disease of the newborn. Vitamin K deficiency is rare in adults but may result from chronic malnutrition or an inability to absorb dietary vitamins.
Definition (NCI_CRCH) Fat soluble vitamin that is a coenzyme during the synthesis of the biologically active form of a number of proteins involved in blood coagulation and bone metabolism. Vitamin K's structure typically consists of a methylated naphthoquinone ring from which one or more unsaturated aliphatic side chains are attached at the 3-position of the ring.
Definition (CSP) group of lipoid thrombogenic agents based on the bicyclic naphthoquinone ring system; act by inducing prothrombin transcription in liver.
Concepts Lipid (T119) , Vitamin (T127)
MSH D014812
SnomedCT 65183007, 74226000
English Vitamin K, Vitamin K (Obsolete), vitamin K (medication), vitamin K, Vitamin K [Chemical/Ingredient], K vitamin, vitamin k preparation, k vitamins, 2-methyl-3-(3,7,11,15-tetramethylhexadec-2-enyl)naphthalene-1,4-dione, Vitamin K preparation, Vitamin K product, Vitamin K (substance), Vitamin K preparation (product), Vitamin K preparation, NOS, Vitamin K, NOS, Vitamin K preparation (substance), VITAMIN K
Swedish Vitamin K
Czech vitamin K
Finnish K-vitamiini
Russian VITAMIN K, VIKASOL, ВИКАСОЛ, ВИТАМИН K
Spanish preparado con vitamina K (producto), vitamina K (producto), preparado con vitamina K, preparado de vitamina K (sustancia), vitamina K (sustancia), vitamina K, Vitamina K
Polish Menandion, Witamina K
French Vitamine K
German Vitamin K
Italian Vitamina K
Portuguese Vitamina K
Sources
Derived from the NIH UMLS (Unified Medical Language System)


Vitamin K 2 (C0086605)

Definition (NCI_CRCH) Form of Vitamin K containing a double-bond in all of its multiple isoprenoid side chains, usually numbering between 2 -13.
Definition (MSH) A group of substances similar to VITAMIN K 1 which contains a ring of 2-methyl-1,4-naphthoquinione and an isoprenoid side chain of varying number of isoprene units. In vitamin K 2, each isoprene unit contains a double bond. They are produced by bacteria including the normal intestinal flora.
Concepts Organic Chemical (T109) , Pharmacologic Substance (T121) , Vitamin (T127)
MSH D024482
SnomedCT 22606007
English Menaquinone, Vitamin K Quinone, Vitamin K2, Vitamin K2 (substance), Vitamin K<sub>2</sub> (substance), Vitamin K<sub>2</sub>, VITAMIN K A 02, Vitamin K 2 [Chemical/Ingredient], vitamin k2, menaquinone, menaquinones, Menaquinones, Vitamin K 2, Vitamin K>2<, Vitamin K>2< (substance)
German Vitamin K (Chinon), Menachinone, VITAMIN K A 02, Menachinon, Vitamin K2
Swedish Vitamin K2
Czech menachinon, vitamin K 2
Finnish K2-vitamiini
Russian VITAMIN K 2, MENAKHINON, ВИТАМИН K 2, МЕНАХИНОН
Spanish vitamina K<sub>2</sub> (sustancia), vitamina K<sub>2</sub>, vitamina K2, vitamina K2 (sustancia), menaquinona, vitamina K>2< (sustancia), vitamina K>2<, Menaquinona, Vitamina K 2
Japanese ビタミンK2, メナキノン, ビタミンKキノン, メナキノン類
Italian Menachinone, Menachinoni, Vitamina K chinone, Vitamina K2
Polish Witamina K2
French Ménaquinones, Vitamine K2
Portuguese Menaquinona, Vitamina K 2
Sources
Derived from the NIH UMLS (Unified Medical Language System)


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