Drugs and Hemostasis

7/23/2019 Drugs and Hemostasis

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THE HEMOSTATIC SYSTEM IS VERY COMPLEX

IT CONSISTS OF THE FOLLOWING

FORMATION OF FIBRIN (COAGULATION)DEGRADATION OF FIBRIN

(FIBRINOLYSIS)

PLATELETS

BLOOD VESSELS

COMING TO COAGULATION WE HAVE

EXTRINSIC SYSYTEMINTRINSIC SYSTEM


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EXTRINSIC SYSTEM INTRINSIC SYSTEM

DAMAGED TISSUE VESSEL WALL

DAMAGE ( XII, XI)

TISSUE FACTOR

(VII) FINAL COMMON PATHWAY

X, V, calciu, !"#$!"#li!i%

PROTHROMBIN THROMBIN

FIBRINOGEN FIBRIN


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COAGULANTS

VITAMIN & ' & PHYTONADIONE & MENA*UINONE

&+ SYNTHETICMENADIONE

MISCELLANEOUS' FIBRINOGEN ANTIHEMOPHILIC

FACTOR

ADRENOCHROME ETHAMSYLATE


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Vitamin K is a fat sol!l" #itamin "ss"ntial fo$

s%nt&"sis of 'lottin( fa'to$s II) VII) IX an* X +

Vitamin K is o!tain"* in ,a$t f$om foo* an* in,a$t f$om !a't"$ial flo$a in t&" !o-"l -&i'&

s%nt&"si."s t&" #itamin+

/am in 0121 ,$o*'"* a !l""*in( *iso$*"$ in'&i'3"n !% f""*in( a *"fi'i"nt *i"t+ It -as '$"*

!% a sol!l" f$a'tion of &o( li#"$

DIETARY4 G$""n L"af% V"("ta!l"s) li#"$

RDA 5 6750778(9 *a%


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ACTION 5 A'ts As A Co Fa'to$) Cas"s

'a$!o:%lation of (ltamat" $"si*"s of t&"

.%mo("n ,$ot"insEXCRETION4 ;% (l'$oni*" 'on


8/53

USES

0+H"mo$$&a(" o$ t&$"at"n"* !l""*in( *" to'oma$in o$ inan*ion" anti 'oa(lants

2+H%,o,$ot&$om!in"mia of t&" ,$"mat$" infant

a*minist$ation of ,&%tom"na*ion" to mot&"$ 056

m() > to 2> &$s !"fo$" *"li#"$% o$ 7+? m(93( im tot&" !a!%

? H%,o,$ot&om!in"mia *" to int"stinal

mala!so$,tion

> As,i$in o#"$*osa("


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TOXICITY

Ra,i* i# in


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FI;RINOGEN

T&is is (i#"n in &"mo,&ilia ) ato afi!$ino("n"mi' stat"s

7+6 ( is infs"* i#

ANTI HEMOPHILIC FACTOR

Con'"nt$at"* anti &"mo,&ili' (lo!lin is s"* fo$

&"mo,&ilia

It is s&o$t a'tin( + A'tion lasts fo$ 052 *a%s 6507 IU 93(i# $","at"* @502 &o$l%

A/RENOCHROME MONO SEMICAR;AONE

R"*'"s Ca,illa$% F$a(ilit%

Cont$ols Oo.in( F$om Ra- S$fa'"s

P$"#"nts mi'$o#"ss"l !l""*in(


11/53

Us"* in ",ista:is

&"mat$ia

mi'$o $"tinal &"mo$$&a("

s"'on*a$% &"mo$$&a(" f$om -on*s

ETHAMSYLATE

R"*'"s 'a,illa$% !l""*in( -&"n ,lat"l"ts a$" a*"Bat"+

Us"* in ,$"#"ntion an* t$"atm"nt of !l""*in( in m"no$$&a(ia)aft"$ a!o$tion) ",ista:is) mal"na) &"mat$ia)

SI/E EFFECTS

Nas"a) Ras& )Fall In ;,)

H"a*a'&"


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LOCAL HEMOSTATICS OR STYPTICS

T&"s" a$" s!stan'"s s"* to sto, !l""*in( f$om a

lo'al a,,$oa'&a!l" sit" "( toot& so'3"ts o,"n

-on* T&"% s&ol* n"#"$ !" in


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> RUSSELS VIPER VENOM

A'ts as a t&$om!o,lastin+ Us"* to sto, ":t"$nal !l""*in(

in &"mo,&ili's+ E( !ot$o,as" 'on#"$ts fi!$ino("n to fi!$in6 VASOCONSTRICTORS "( A*$"nalin"

@ ASTRINGENT "( Tanni' a'i* D27 in Gl%'"$in"

Cas"s lo'al ,$ot"in 'oa(lation+ /"nat$"s t&" s$fa'"

,$ot"in a$$"sts mi'$oo.in(

'ommonl% s"* in *"ntist$%


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ANTICOAGULANTS

USED IN VITRO

A HEPARIN

B CALCIUM COMPLEXING

AGENTS

S#%iu ci-.a-/,

S#%iu #0ala-/,

S#%iu /%/-a-/


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+ USED IN VIVO

A+HEPARIN 1 HEPARINOIDS

B ORAL ANTICOAGULANTS

COUMARIN' WARFARIN,DICUMAROL

INANDIONE'PHENINDIONE (2#-

u$/%


16/53

H",a$in -as *is'o#"$"* !% a m"*i'al st*"nt= M'l"an -o$3in( at t&" =o&n Ho,3ins

m"*i'al s'&ool in 010@+ &" fon* t&at t&"":t$a'ts of #a$ios tiss"s D!$ain li#"$ &"a$ta''"l"$at"* 'lottin(+ ;t ":t$a't of li#"$ notonl% fail"* to a''"l"$at" !t a'tall%

$"ta$*"* 'lottin(+

ACTIONS

0+ ANTICOAGULATION

2+ ANTIPLATELET

?+ LIPEMIA CLEARING


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ANTICOAGULATION

A'ts instantl%) s"* in #i#o an* in #it$o+A'ts

in*i$"'tl% !% a'ti#atin( ,lasma anti t&$om!inIII

T&" 'om,l": t&"n !in*s to t&" 'lottin( fa'to$s

of t&" int$insi' an* 'ommon ,at&-a%s an*

ina'ti#at"s t&"m+ In&i!ition of fa'to$ Xaas

-"ll as t&" t&$om!in m"*iat"* 'on#"$sion of

fi!$ino("n to fi!$in+

Lo- 'on'"nt$ations ,$olon( aPTT !t t&" &i(&

'on'"nt$ations ,$olon( !ot& aPTT an* PT


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ANTIPLATELET ACTION

Hi(& *os" in&i!its ,lat"l"t a(($"(ation an* ,$olon(s

!l""*in( tim"LIPEMIA CLEARANCE

In


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ADVERSE DRUG EFFECT

0+ ;l""*in(

2+ T&$om!o'%to,"nia

?+ Ost"o,o$osis>+ S3in n"'$osis

6+ T$ansi"nt alo,"'ia

@+ H%,"$s"nsiti#it%


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HEPARIN IS ANTAGONISE/ ;YPROTAMINE SULPHATE

NEUTRALISES HEPARIN WEIGHT ;Y

WEIGHT+ 0MG IS NEE/E/ FOR EVERY077IU OF HEPARIN+ MAXIMUM /OSE

USE/ IS 67MG+ GIVEN ;Y SLOW IV

INFUSION+


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CONTRAIN/ICATIONS

0+ ;LEE/ING /ISOR/ERS

2+ SEVERE HYPERTENSION

?+ SU; ACUTE ;ACTERIAL EM;OLISM

>+ OCULAR AN/ NEURO SURGERY

6+ CHRONIC ALCOHOLICS

@+ CIRRHOSIS

+ RENAL FAILURE

+ CONCURRENT A/MINISTRATION OF ASPIRIN

AN/ OTHER ANTIPLATELET /RUGS


22/53

LOW MOLCULAR WEIGHT HEPARIN

S"l"'ti#"l% in&i!its t&" fa'to$ Xa +

A'ts !% in*'in( a 'onfo$mational '&an(" in

ATIII

Has a !"tt"$ 'tan"os !ioa#aila!ilit%+ O/

aPTT an* 'lottin( tim"s a$" not ,$olon("*+

La! monito$in( is not n""*"* *$in(a*minist$ation

/os" is 'al'lat"* on t&" !o*% -"I(&t !asis


23/53

USES

0+ P$o,&%la:is Of /VT An* Plmona$%

Em!olism

2+ Maintains t&" Pat"n'% Of Cannla" an*S&nts In /ial%sis Pati"nts


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ORAL ANTICOAGULANTS

HISTORY

In 012> a &"mo$$&a(i' *is"as" -as

*"s'$i!"* in t&" 'attl"+ T&" 'attl" -"$"f""*"* on s,oil"* s-""t 'lo#"$ &a%+ T&is

'ontain"* a '&"mi'al !is&%*$o:%'oma$in

It -as initiall% s"* as $at ,oison


25/53

MODE OF ACTION

Us"* onl% in #i#o

;"&a#" as 'om,"titi#" anta(onists of

#itamin 3

Int"$f"$" -it& t&" #itamin 3 *","n*"nt

'lottin( fa'to$s in t&" li#"$


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/"s'a$!o:%,$ot&$om!in P$ot&$om!in

Vitamin K D&%*$oBinon" #itamin K D",o:i*"

NA/ NA/H

BLOC&ED BY ORAL ANTI COAGULANTS


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T&" 'a$!o:%lation is "ss"ntial fo$ t&"

a!ilit% of t&" 'lottin( fa'to$s to !in*'al'im an* to ("t !on* to

,&os,&oli,i* s$fa'"s

E:am,l"s J

/i'ma$ol4 ,$olon("* &alf lif"+ F$"B"nt

GIT *ist$!an'"

Ra'"mi' Wa$fa$in So*im5most ,o,la$


28/53

A/VERSE /RUG EFFECT

0+ ECCHYMOSIS2+ EPISTAXIS

?+ HEMATURIA

>+ ;LEE/ING IN GIT

6+ INTRACRANIAL OR INTERNAL

HEMORRHAGE


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TREATMENT OF OVERDOSAGE

WITHHOL/ THE ANTI COAGULANT

GIVE FRESH ;LOO/ TRANSFUSION

ALTERNATIVELY FRESH FROEN PLASMA

CAN ALSO ;E GIVEN

SPECIFIC ANTI/OTE VITAMIN K IS GIVEN


30/53

FACTORS ENHANCING THE EFFECT OF

ORAL ANTI COAGULANTS

0+ /E;ILITY

2+ MALNUTRITION) MALA;SORPTION

D SUPPLY OF VITAMIN K TO LIVER ISRE/UCE/

?+ LIVER /ISEASE) CHRONIC ALCOHOLISM

>+ HYPERTHYROI/ISMD CLOTTINGFACTORS ARE /EGRA/E/ FASTER

6+ NEW ;ORNS


31/53

FACTORS /ECREASING THE EFFECT

OF ORAL ANTICOAGULANTS

0+ PREGNANCY

2+ NEPHROTIC SYN/ROME

?+ GENETIC WARFARIN RESISTANCE


32/53

USES OF ORAL ANTICOAGULANTS

0+ /VT ) PULMONARY EM;OLISM

2+ MYOCAR/IAL INFARCTION

?+ RHEUMATIC HEART /ISEASE

>+ CERE;ROVASCULAR /ISEASE

6+ VASCULAR SURGERY

@+ PROSTHETIC VALVES

+ /ISSEMINATE/ INTRAVASCULAR

COAGULATION


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COMPARISON

HEPARIN WARFARIN

M'o,ol%sa''&a$i*" Coma$in

I#) s' o$al

Imm"*iat" a'tion *"la%"* a'tion

/$ation is >5@ &$s ?5@ *a%s

In#it$o an* In#i#o In#i#o

P$otamin" sl,&at" Vitamin 3

;lo'3s X) t&$om!in s%nt&"sis of 'lottin(

fa'to$s in&i!it"*


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FI;RINOLYTICS D THROM;OLYTICS

T&"s" a$" *$(s s"* to l%s" t&$om!i o$ 'lot to $"'anal%s"

o''l*"* !loo* #"ss"ls+

PLASMINOGEN

ACTIVATORS INHI;ITORS

PLASMIN

FI;RIN FI;RIN

/EGRA/ATION

PRO/UCTS


35/53

Som" ? -""3s aft"$ a 'lot is fo$m"*) t&"

fi$m fi!$in t&$"a*s a$" !$o3"n *o-n !% a

,o-"$fl "n.%m") 'all"* Plasmin+

Aft"$ t&" !$"a3in( *o-n) !$o3"n *o-n

f$a(m"nts of fi!$in) 'all"*) fi!$in

*"($a*ation ,$o*'ts) a$" *issol#"* in

t&" ,lasma an* t&" 'lot *isa,,"a$s+ T&isis fi!$inol%ti' m"'&anism


36/53

ACTIVATORS

TISSUE PLASMINOGEN ACTIVATOR

UROKINASE STREPTOKINASE

INHI;ITORS EPSILON AMINO CAPROIC ACI/

TRANEXAMIC ACI/

APROTININ


37/53

STREPTOKINASE

F$om t&" &"mol%ti' st$",to'o''s ($o, C

Anti("ni') 'an 'as" ana,&%la:is o$&%,"$s"nsiti#it%

UROKINASE

Nonanti("ni'ALTEPLASE

Nonanti("ni'

V"$% ":,"nsi#"RETEPLASE


38/53

USES

0+ ACUTE MYOCAR/IAL INFARCTION

2+ /EEP VEIN THROM;OSIS?+ PULMONARY EM;OLISM

>+ PERIPHERAL ARTERIAL OCCLUSION


39/53

ANTIFIBRINOLYTICS

In&i!it ,lasmino("n a'ti#ato$ an* *issoltion of 'lotE,silon amino 'a,$oi' a'i*is t&" s,"'ifi' anti*ot"

of fi!$inol%ti' a("nts

T$an":ami' a'i*o'',i"s t&" sit" on t&" fi!$in at-&i'& ,lasmino("n is !on*

USESJ

O#"$*osa(" of fi!$inol%ti's aft"$ tonsill"'tom% o$

,$ost$at" s$("$%

Toot& ":t$a'tion in &"mo,&ilia's


40/53

P$osta'%'lin in&i!it ,lat"l"t a(($"(ationT&$om!o:an" ,$omot"s ,lat"l"t a(($"(ation

/RUGS0+ ASPIRIN

2+ /IPYRI/AMOLE

?+ SULFINPYRAOLE

>+ TICLOPI/INE

ANTIPLATELET DRUGS


41/53

0+ ASPIRIN

In&i!its '%'loo:%("nas" an* t&$om!o:an"

s%nt&"sisIn&i!its $"l"as" of A/P f$om ,lat"l"ts

2+/IPYRI/AMOLER"#"$si!l% in&i!its ,lat"l"t ,&os,&o*i"st"$as"

C%'li' AMP a'ti#it% in'$"as"*) ,lat"l"t a'ti#it%

*"'$"as"*


42/53

?+SULFINPYRAONE

U$i'os$i' *$(+ C%'loo:%("nas" in&i!ito$+

/"'$"as"s t&$om!o:an" an* ,$osta'%'lin

s%nt&"sis

>+ TICLOPI/INE

Int"$a'ts -it& t&" ,lat"l"t m"m!$an"

It is $"lati#"l% n"- *$(


43/53

RECENT ADVANCES

;io'&"mi'al mani,lation of st$",to3inas" an*

,lasmino("n mi:t$"s &a#" $"slt"* in

t&"$a,"ti' a("nts

E( a'"t%lation of a'ti#" sit" s"$in" of st$",to3inas"5

,lasmin 'om,l": fo$ms 'om,on* ;RL2@120

It !in*s fi!$in in ina'ti#" fo$m an* onl% !"'om"s

a'ti#at"* slo-l% *" to slo- *"a'%lation of t&"a'ti#" sit"


44/53

Isolation an* s!s"B"nt 'lonin( of tiss",lasmino("n a'ti#ato$ ,$o*'"s $"'om!inant

,lasmino("n a'ti#ato$ $PA

T&is 'om,on* &as a ($"at"$ s,"'ifi'it% fo$ fi!$in

allo-in( fi!$inol%sis to ta3" ,la'" -it&ot*"#"lo,m"nt of a s%st"mi' &"mo$$&a(i' stat"


45/53

MANAGEMENT OF HEMORRHAGE

T&"$" a$" 6 st",s in t&is

PLANNING OF INCISION'a#oi* la$(" !loo*

#"ss"ls

SECURING OF BLEEDING VESSELS -it&HEMOSTATS

?+ H"mostasis t&$o(& t&" APPLICATION OF

PRESSURE 3i-" $3a4$>+ Us" of HEMOSTATIC AGENTS


46/53

WHITEHEA/S VARNISH

Consists of t&" follo-in(

;"n.oin 07 ,a$ts

Sto$a: +6 ,a$ts

;alsam of tol 6 ,a$ts

Io*ofo$m 07 ,a$ts

Sol#"nt "t&"$ , to 077 ,a$ts

Half in'& $i!!on (a." is soa3"* in -&it"&"a*s

#a$nis&+ It is $"mo#" in > &o$s o$ it ma% (i#" to*$% so'3"t


47/53

SURGICEL4 O:i*is"* $"("n"$at"* '"lllos"

!ioa!so$!a!l"

It *issol#"s to fo$m a'i*i' ,$o*'ts -&i'&

'oa(lat" ,lasma ,$ot"ins -it& &"mo(lo!in

,$o*'in( a !la'3 sti'3% 'lot

;ONE WAX4;EES WAXD %"llo- 4 ,a$ts !% -t

OLIVE OIL 5 2 ,a$ts !% -t

PHENOL 5 0 ,a$t !% -t


48/53

/RUG INTERACTIONS

T&$om!ol%ti' a("nts nsai*s) slfin,%$a.on")anti'oa(lants) ,lat"l"t in&i!ito$s in'$"as"s&"mo$$&a("

Anti'oa(lants ACE in&i!ito$sQ &%,"$3al"mia

NSAI/S) "t&a'$%ni' a'i* '",&alos,o$ins #al,$oi' a'i*,$o,%lt&i$a'il anti'oa(lant *$(s $"slts in!l""*in(

Nit$o(l%'"$in" anta(onis"s t&" anti'oa(lant "ff"'t of&",a$in


49/53

C&lo$t&ali*on") C&lo$*ia.",o:i*")Halo,"$i*ol)

s,i$inola'ton") Rifam,i'in *"'$"as" anti'oa(lant

a'ti#it%

Amio*a$on") /islfi$am) Halot&an" in'$"as" -a$fa$in

a'ti#it%

Va$ios anti!ioti's aff"'t t&" anti'oa(lation of-a$fa$in !% alt"$in( !a't"$ial s%nt&"sis of #itamin 3 in

t&" GI t$a't "( '",&alos,oins) C&lo$am,&"ni'ol

)M"t$oni*a.ol") T"t$a'%'lin"s

Vitamin E in &i(& *os"s in&i!its #itamin K

Ga$li' ,$o*'"s anti,lat"l"t "ff"'t


50/53

INTERNATIONAL NORMALISED RATIO

Usall% ,$ot&$om!in tim"s a$" ass"ss"* *$in( t&"

t$"atm"nt+

It is &"l,fl if t&" la!s ,"$fo$min( t&" t"sts to

'ont$ol o$al anti'oa(lants &a#" a stan*a$*is"*a,,$oa'& so t&at $"slts a$" 'om,a$a!l" !"t-""n

*iff"$"nt '"nt$"s

INR 5 PROTHROMBIN TIME OF PATIENT

PROTHROMBIN TIME OF LAB


51/53

NORMAL VALUE IS '6

IT IS AN ADVANTAGE IF RESULTS ARE

REPORTED AS A RATIO RATHER THAN

A PERCENTAGE OR INDEX


52/53

REFERENCES Clini'al P&a$ma'olo(% !% /R La$"n'") P N

;"nn"t) t&"*ition

Ess"ntials of m"*i'al ,&a$ma'olo(%

K / T$i,at&i 6t&"*ition

/" G$'&%s Clini'al &"matolo(% in m"*i'al

,$a'ti'" 6t&"*ition

Kill"% an* Ka% An otlin" of o$al s$("$% ,a$t 2

Clini'ians manal of o$al an* ma:illofa'ial s$("$%?$*"*ition


53/53

THANK YOU

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Drugs and Hemostasis