• Like
  • Save
VITAMIN K, [MEDICINAL CHEMISTRY] BY P.RAVISANKAR,STRUCTURES OF VITAMIN K1 AND K2, CHEMISTRY, RECOMMENDED DIETARY INTAKE, SOURCES OF VITAMIN K, BLOOD COAGULATION, ROLE OF VITAMIN K, FUNCTIONS, MECHANISM OF ACTION, VITAMIN K DEFICIENCY, DURG INTERACTIONS, S
Upcoming SlideShare
Loading in...5
×

Thanks for flagging this SlideShare!

Oops! An error has occurred.

VITAMIN K, [MEDICINAL CHEMISTRY] BY P.RAVISANKAR,STRUCTURES OF VITAMIN K1 AND K2, CHEMISTRY, RECOMMENDED DIETARY INTAKE, SOURCES OF VITAMIN K, BLOOD COAGULATION, ROLE OF VITAMIN K, FUNCTIONS, MECHANISM OF ACTION, VITAMIN K DEFICIENCY, DURG INTERACTIONS, S

  • 2,133 views
Published

VITAMIN K, [MEDICINAL CHEMISTRY] BY P.RAVISANKAR,STRUCTURES OF VITAMIN K1 AND K2, CHEMISTRY, RECOMMENDED DIETARY INTAKE, SOURCES OF VITAMIN K, BLOOD COAGULATION, ROLE OF VITAMIN K, FUNCTIONS, …

VITAMIN K, [MEDICINAL CHEMISTRY] BY P.RAVISANKAR,STRUCTURES OF VITAMIN K1 AND K2, CHEMISTRY, RECOMMENDED DIETARY INTAKE, SOURCES OF VITAMIN K, BLOOD COAGULATION, ROLE OF VITAMIN K, FUNCTIONS, MECHANISM OF ACTION, VITAMIN K DEFICIENCY, DURG INTERACTIONS, SUMMARY.
BY P. RAVISANKAR, VIGNAN PHARMACY COLLEGE, VADLAMUDI, GUNTUR, A.P, INDIA.

Published in Education , Health & Medicine
  • Full Name Full Name Comment goes here.
    Are you sure you want to
    Your message goes here
    Be the first to comment
No Downloads

Views

Total Views
2,133
On SlideShare
0
From Embeds
0
Number of Embeds
0

Actions

Shares
Downloads
0
Comments
0
Likes
2

Embeds 0

No embeds

Report content

Flagged as inappropriate Flag as inappropriate
Flag as inappropriate

Select your reason for flagging this presentation as inappropriate.

Cancel
    No notes for slide
  • “ K” is derived from the German word “koagulation”

Transcript

  • 1. Prof. RavisankarVignan Pharmacy collegeValdlamudiGuntur Dist.Andhra PradeshIndia.banuman35@gmail.com00919059994000Vitamin K and Blood KoagulationCoagulation
  • 2. Vitamin K is a fat-soluble vitamin that plays an important role in blood clotting.Vitamin K is known as the clotting vitamin .Vitamin K (K from "Koagulations-Vitamin" (clotting of blood)in German.They are 2-methyl-1,4-naphthoquinone derivatives.Vitamin K is Vitamin K" has also been used as a slang term forketamine, an unrelated anaesthetic.Vitamin K is not a single chemical substance but rather a family ofchemically related substances that go by the general name of "vitamin K.".Vitamin K exists in both natural and synthetic forms. The natural forms ofvitamin K include K1(phylloquinone and vitamin K2 (menaquinone from thepurified fish meal, while synthetic froms are vitamin K3(menadione) andK4(menadiol sodium diphosphate)All types of vitamin K fall into a large chemical category of substancescalled naphthoquinones. Within this naphthoquinone category, there aretwo basic types of vitamin K.Vitamin K1 is also called phylloquinones, is made by plants. The secondbasic type, called menaquinones, is made by bacteria in the large intestine.(The only exception to this rule involves a special group of bacteria, calledcyanobacteria, which make phylloquinones instead of menaquinones.
  • 3. WHAT IS IT?RECOMMENDED DAILY INTAKEDIETARY SOURCESVitamin K is also known as anti-hemorrhagicfactor, for its role in the coagulation of bloodVitamin K
  • 4. Fat-soluble vitamin:K1 (Phylloquinone) K2 (Menaquinone)Synthesized by:• Vegetable and plants.Synthesized by:• Bacterial flora of the gut• Minor source
  • 5. 12345678910Basic quinoid nucleusPhytyl3-methyl 2-butenyl (prenyl)(2-methyl-3-phytyl-1,4 naphaquinone)Vitamin K1(2-methyl-1,4 napthaquinone)(3,7,11,15,-tetramethyl-2-hexadecenyl)Quinoid nucleus: 2-methyl-1,4 naphthaquinone.side chain :(prenyl)nclass name :prenyl menaquinone-n, abbrevated as :MK-nclass name=n = 10 vitamin k2 (50 is this is no. of “C” atomsn = 7 vitamin k2 (35)n= 6 (no. of isoprene units)vitamin k2 (30)(4W)
  • 6. Menaquinoe-6- indicates vitamin K2(30)menaquinone-7 indicates vitamink2 (35)6 and 7 implies number of isoprene unitswhile 30 and 35 indicate the number of carbonatoms.trival names of k2prenyl menaquinone-nn=10 vitamin k2 (50)n=7vitamin (35)n=6 vitamin k2 (30)
  • 7. What are current public health recommendations for vitamin K?Adequate Intake (AI) for Vitamin KLife Stage AgeMales(mcg/day)Females(mcg/day)Infants 0-6 months 2.0 2.0Infants 7-12 months 2.5 2.5Children 1-3 years 30 30Children 4-8 years 55 55Children 9-13 years 60 60Adolescents 14-18 years 75 75Adults19 years andolder120 90Pregnancy18 years andyounger- 75Pregnancy19 years andolder- 90Breast-feeding18 years andyounger- 75Breast-feeding19 years andolder- 90http://lpi.oregonstate.edu/infocenter/vitamins/vitaminK/Recommended Daily Intake
  • 8. spinachcabbage,cauliflower,broccoli
  • 9. Cooking does not remove significantamounts of vitamin K from these foods,but freezing does
  • 10. Sources of Vitamin KPeople usually do not suffer from a deficiency ofvitamin K as it is widely found in our daily diet. It isabundantly found in green vegetables like spinach,broccoli,, and cabbage. Cauliflower, yogurt, soyabean, wheat, oat and tomatoes also contain vitaminK.Vitamin K can also be obtained from theconsumption of nuts like cashew nuts, chestnutsand pine nuts.Fruits such as avocado and kiwi fruit are asignificant source of this vitamin.Vitamin K can be found in meat, eggs, cows milkand pigs liver. However, vegetables are a richersource of vitamin K than animals. In addition to allthese natural sources, vitamin K supplements arealso available.
  • 11. FUNCTIONSCOAGULATION CASCADEMECHANISMBlood Coagulation
  • 12. Role of vitamin K:Vitamin K plays a crucial role when it comes to metabolism ofthe bones as well as blood clotting. The low serum concentrationof vitamin K has been affiliated with lower bone mineral density,which essentially leads to an increased risk in hip fractures. Vitamin supplements may also have the ability to improve bone mass inthose women that are postmenopausal. Vitamin K prohibits the calcificationof the arteries, as well as other soft tissue throughout the body – this is anadverse side effect of aging. Vitamin K may also play some kind of role in theregulation of the body’s blood sugar levels as the pancreas (maker of insulin)has the second highest concentration of vitamin K found within the body.Blood clotting – The primary function belonging to vitamin K isto regulate the routine clotting of blood – this is an automaticprocess which begins whenever a blood vessel tears. Vitamin Kplays a role in this by helping the body transport calcium toareas in need.
  • 13. Role of Vitamin KBone healthRole of vitamin K. Bone health – Supplements including vitamin K as aningredient may have the ability to improve bone health aswell as reduce the risk of bone fractures. This isparticularly accurate in women that are postmenopausaland have a risk for osteoporosis. It’s typically seen that ifan individual has higher levels of vitamin K within theirsystem, they’ll have a greater bone density. Alternatively,those that have osteoporosis have low levels of vitamin K.Liver disease – Usage of vitamin K is able to reduce yourchances of bleeding in the liver, which includes a myriadof other conditions like jaundice, malabsorption. Vitamin Khas also been used to help treat those that experienceheavy menstrual bleeding.Vitamin K may also be prescribed to your newborn asthey are at an elevated risk for bleeding in the brain dueto the trauma experienced going through the birth canalduring delivVascular healthVitamin K also decreases calcification in the arteries byabsorbing the hardened calcium to lessen your risk of heartdisease.
  • 14. FunctionsHemostasisDesigned to maintain blood within injured vessels by threesequential events:1. Vasoconstriction2. Platelet plug formation3. CoagulationCoagulationFibrin meshwork forms a blood clot, which providesstructural support to the temporary plug formed by plateletsWithout fibrin, the initial plug would soon fall apartFibrin proteins are the end products of coagulation cascade
  • 15. Coagulation Cascade Clotting factors are generally serineproteases Activated form of one clottingfactor catalyzes the activation of thenext Occurs on the platelet or tissuephospholipids, which only becomesavailable in injuries Activation is amplified at eachstage, resulting in an increasedproduction of fibrin Fibrin clot is formed by theinterplay of the intrinsic, extrinsic,and final common pathwayshttp://www.frca.co.uk/images/clotting_cascade.gif
  • 16. Mechanism – Intrinsic PathwayBegins with activation offactor XII by surfacecontact with a vesselremoved of endotheliumFactor XIII enzymaticallycross-links fibrinFactor XIIIActivatesActivatesActivatesActivatesActivatesFischbach, P. David. Coagulation The Essentials
  • 17. Mechanism – Extrinsic PathwayAlternate method toactivate factor XTriggered by trauma,which activates factor VIITissue phospholipidsprovide surface forclotting factor bindingand activationFactor XIIIActivatesActivatesActivatesFischbach, P. David. Coagulation The Essentials
  • 18. ROLE IN THE MECHANISMEFFECTS OF DEFICIENCY ON THE MECHANISMThe Role of Vitamin K inBlood Coagulation
  • 19. Role in the MechanismIn blood clotting, vitamin K isneeded as a cofactor toactivate clotting factors:•Clotting factor II(prothrombin)•Clotting factor VII(proconvertin)•Clotting factor IX(thromboplastin)•Clotting factor X(Stuart factor)http://www.frca.co.uk/images/clotting_cascade.gif
  • 20. Role in the Mechanism1. Post-translational modification of glutamateresidues in clotting factorsCarboxylation to γ-carboxyglutamate byvitamin K-dependent enzyme systemhttp://www.ch.ic.ac.uk/local/projects/bhonoah/gla.gif
  • 21. Role in the Mechanism2. γ-carboxyglutamate canbetter bind to Ca2+3. Binding of Ca2+allowsanchoring of clottingfactor to phospholipidmembranes of bloodplatelets -> activation4. Activated clotting factorcatalyzes activation of thenext clotting factor in thecoagulation cascadehttp://www.ch.ic.ac.uk/local/projects/bhonoah/binding.gifhttp://www.ncbi.nlm.nih.gov/bookshelf/picrender.fcgi?book=stryer&part=A1378&blobname=ch10f43.jpg
  • 22. Effects of Deficiency on the MechanismVitamin K limits thecarboxylation reactionWithout vitamin K, lackof carboxylation results ininactive clotting factorsHarrison’s Principles of Internal Medicine OnlineTwo enzymes affect ALL vitaminK dependent proteins:1.γ-glutamylcarboxylase (GGCX)2.Vitamin K epoxide reductasecomplex 1 (VKOR-1)
  • 23. SYMPTOMS AND DIAGNOSISCAUSES AND RISK FACTORSMEDICATIONS AND SUPPLEMENTSCASE STUDYVitamin K Deficiencyand Pharmacy
  • 24. The following are some signs(symptoms) of Vitamin-K deficiency:• easy or excessive bleeding• easy or excessive bruising• nosebleeds• bleeding gums• blood in the urine and stool• extremely heavy menstrual bleeding• liver damage or disease• low bone density• arterial calcification• malabsorption in the digestive tract
  • 25. DiagnosisDiagnosis can be confirmed by using blood tests to checkfor increased prothrombin time (PT) or InternationalNormalized Ratio (INR)http://img.medscape.com/fullsize/migrated/423/474/pharm423474.fig1.jpg
  • 26. Causes and Risk FactorsInfants have higher risk of vitamin K deficiency, especially ininfants that don’t use infant formulao Low vitamin K levels in breast milko Poor transport of vitamin K through placentao Low fat stores of vitamin Ko Sterile intestineso Liver immaturityConsequently, all newborns receive a vitamin K injectionright after delivery for prevention
  • 27. Causes and Risk FactorsRisk of dietary vitamin K deficiency is rare in adults unlessother risk factors exist in addition to chronic malnutritionAny disease or surgery that causes malabsorptiono Obstructed biliary tractso Chronic small-intestine diseases like Crohn’s diseaseo Surgery like small intestine resectiono Cystic fibrosiso Persistent diarrhea
  • 28.  DEFICIENCY CAUSED BY In Babies: low levels in human breast milk poor transfer across placenta sterile intestine with no bacteria In Adults: as a consequence of sprue Celiacs Disease destruction of intestinal bacteria by antibiotics lack of bile salts liver conditions, such as viral hepatitis surgical removal of intestines prolonged ingestion of liquid paraffin DEFICIENCY LEADS TO inability of blood to coagulate SYMPTOMS OF TOXICITY none reported
  • 29. Vitamin K shots are routinely administered to newborn babies in U.S.hospitals, birth centers and by some home birth midwives because 1.8out of every 100,000 babies who do not receive vitamin K injectionssuffer permanent injury or death due to uncontrolled bleeding in thebrain (hemorrhagic disease of the newborn) that may be the result ofhaving extremely low levels of vitamin K in their systemsVitamin K is produced by bacteria, including theflora found in our gut. However, a newborn’sgastrointestinal tract is typically sterile for a few daysafter birth. The bodys production of Vitamin K and,therefore, clotting factors, begins by the fourth day oflife, giving babies their ability to clot blood. This iswhy newborns are typically given Vitamin Kinjections shortly after birth in hospitals and somebirth centers
  • 30. Deficiency of vitamin K is quite rare, as it is widelydistributed in many sources of food and also becauseit is produced by the intestinal bacteria. Itsabsorption depends on bile salts and therefore, anydisease of the liver which can impair bile secretion ismore likely to cause a deficiency of this vitamin.Infants, are at a higher risk of suffering from adeficiency of this vitamin, as human milk is not avery rich source of vitamin K. People suffering fromintestinal diseases, like the inflammatory boweldisease, may experience a deficiency of vitamin K, asthe disease can impair intestinal functions. Certainmedications such as antibiotics may also be animportant factor leading to a vitamin K deficiency
  • 31. vitamin K deficiency is rare – almost everyone gets more than enough from their own bacteriaand from their food.Sometime newborn babies don’t have enough vitamin K because they don’t yet have anybacteria to make it in their intestine.To make up for them, most newborns are given an injection of a tiny amount of vitamin K soonafter birth.When adults get vitamin K deficiency, it’s generally because they eat very few green vegetablesor because they have been taking oral antibiotics for a long time.The antibiotics kill off the intestine bacteria that make vitamin K. Sometimes vitamin K deficiencyis caused by liver disease or a problem digesting fat.The major symptom of vitamin K deficiency is that blood clot very slow, so it will bleed for alongtime even from minor injuries.Vitamin K deficiency causes bug black and blue marks from very slight bruises or even for noreason, nosebleeds, blood in your urine and intestinal bleeding.Vitamin K
  • 32. Causes and Risk FactorsThose taking certain medications are also at risk Drugs can reduce Vitamin K levels if they affect liver functionor kill intestinal bacteria that synthesize menaquinones Long-term use of broad-spectrum antibiotics High doses of salicylates like aspirin Anticonvulsants Some sulfa drugs Quinine/quinidine Cholestyramine
  • 33. Medications and SupplementsToxicity:No known excess vitamin K toxicity effects in adultsIn newborns, there is a risk of hemolysis and jaundice
  • 34. Medications and SupplementsDrug Interactions:Orlistat and mineral oil can decrease absorption oforally-administered Vitamin KVitamin K can reduce the effects of oral anticoagulantslike warfarin Vitamin K can thus increase risk of clotting in those patients Avoid taking a lot of vitamin K in supplements or food Use to reverse effects of warfarin before surgery or after overdose
  • 35. FUNCTIONaids in reducing excessive menstrual flowaids the absorption of calcium in boneessential for normal liver functioningessential for synthesis of four proteins that act incoagulationimportant in maintaining vitality and longevitynecessary for formation of prothrombin which isrequired for effective blood clottinginvolved in electron transport mechanism andoxdative phosphorylation
  • 36. INCREASED INTAKES NEEDEDafter prolonged paraffin ingestionfor those with biliary obstructionsfor those with liver diseaseif taking antibiotics for long durationif you have a malabsorption diseasein newborn babiesin overdose of anticoagulant drugs, such as Warfarin,Dicoumarol, which neutralize the effect of Vitamin K
  • 37. Vitamin K used for:-anticoagulant drug overdosereduces excessive menstral flowessential for blood clotting/haemorrhage andbleedinghemorrhagic disease in newborn babiesinhibiting some cancer tumorsovercoming inability to absorb vitaminsovercoming effects of antibiotics on intestinalbacteriaprotection against osteoporosis
  • 38. DESTROYED BYacidsalkaliscommercial processinglight and ultra-violet irradiationoxidizing agentsSYMPTOMS OF DEFICIENCYexcessive bleeding and hemorrhageIn babies:bleeding from the stomach, intestines, umbilical cord siteDEFICIENCY CAUSED BYIn Babies:low levels in human breast milkpoor transfer across placentasterile intestine with no bacteriaIn Adults:as a consequence of sprueCeliacs Diseasedestruction of intestinal bacteria by antibioticslack of bile saltsliver conditions, such as viral hepatitissurgical removal of intestinesprolonged ingestion of liquid paraffinDEFICIENCY LEADS TOinability of blood to coagulateSYMPTOMS OF TOXICITYnone reported
  • 39. Summary Vitamin K is a fat-soluble vitamin that is found in green leafy vegetablesand is involved in blood coagulation Two natural subtypes: K1 (phylloquinone) and K2 (menaquinone) A coagulation cascade produces fibrin to clot blood Vitamin K is involved in the activation of clotting factors Vitamin K is a cofactor in the carboxylation of glutamate residues inclotting factors, leading to Ca2+binding and clotting factor activation Vitamin K deficiency can cause hemorrhage symptoms Vitamin K deficiency is rare in adults, but is a risk in newborns Oral anticoagulants inhibit the effects of vitamin K and vice versa