antikoagulan, tblytik.pptx

7/27/2019 antikoagulan, tblytik.pptx

http://slidepdf.com/reader/full/antikoagulan-tblytikpptx 1/49

Anti anaemia

Dr. Rika Yuliwulandari, PhD



Anti anemia

Fe ---

Hb production

Anemia hipochromic microciticsd

Vit B12 (Cyanocobalamine), Folic acid

DNA synthesis

Ery production and maturation

Anemia megaloblastic

Def B12: + Neurologic disorders



Fe

In the body

3.5 g ( complex structure with protein)

70% is essential/funcsional (66% in Hb, 3% inmyoglobin, 0.5 % in citocrom oxidase, succinildehydrogenase, xanthine oxidase, 0.1% in transferin

30% is non essential (25% in feritin and

hemosiderin, 5% in parenchime) Fe Depot

Women: 200-400 mg

Man: 1 g



Pharmacokinetic

Absorption: duodenum

In mucosa: Ferro ----- into ferri (for erythropoiesis ordepot as ferritin)

Severe anemia, hypoxia: erythropoiesis increase 5x

Absorption of fe increase in Fe deficiency

Decrease of Fe depot

Increase erythropoiesis

Fe from food: 5-10%, esp from meat, egg and theirproducts.

Abs of Fe ↑: Cobal, Inosin, Etimin, Vit C, Hcl, Suksinat

Abs of Fe ↓: Phosphat, Anticid (Ca Co3, MgCl2, Al(OH)3



Fe depot:

Iv: bind to Apo ferritin, depot in liver

Po: depot in lien and bone marrow From erythrocyte ---- depot in lien and bone marrow

Excretion:

0.5-1 mg/day Through: skin epithelial cell, GI epithel, sweat, urine,

feces, nail, cut hair

Menstruation: 0.5-1 mg/day

Intake Fe depends on

Age, sex, Hb, Depot Fe

Man 10 mg/day, women 12 mg/day (+5 mg in

pregnancy and lactation)



Natural Fe resource:

5 mg/100 mg: Liver, Heart, Yeast, Nuts, dry fruits, 1-5 mg/100 mg: meat, fish, birds, green vegetables,

beans

1 mg/100 mg: milk and its products, other

vegetables

Se:

Po: intolerance

Stomach ache (7-20%), constipation (15%), diarrhea (5%),colic

↓ dose, take Fe after meal

Feces black



Se

Im: local reaction (pain in inj site, brown colouring, localirritation)

Sistemic reaction in 0.5-0.8 % cases, 10-20 min post inj.

Headeache, Myalgia, Hemolysis, Tachikardia, Flushing, Sweating,Nausea, vomitus, Bronchospasm, Hypotension, Collapse circular

30 min-24hrs post inj

Syncope, chills, fever, rash, urticaria, chest pain, myalgia,encephalopathy, shock, heart block

Acute intoxication (30 min – several hrs)

Often in children: irritation, corrosion until necrosis of GI tr.

Nausea, vomitus, diarrhea, hematemesis, black feces, shock,CVS collapse, pylorus stenosis, dead

Tx: Vomitus, lavage if < 1hr, Milk, egg to bind Fe, Tx shock

dehydration, acidosis, Chellating agent: deferoxamin



Chronic intoxication:

Hemosiderosis

Indication:

Anemia def . Fe:

Blood lost

Multipara

Growth period

Posology:

Oral: Fero salt (sulfat, fumarat, glukonat, suksinat,

glutamat, laktat)---- absorbsi similar, PK different Fe salt in sitrat, tartrat, carbonat, pirofosfat, feri is difficult

to absorb

FeSo4.7H2O: 20% Fe, 3 dd I tab, 6 months

Fe fumarat: 600-800 mg/day, divided dose



Parenteral: deep im, iv

Indication: if tolerant to oral, if not responsive to oral

Iron dextran (imferon): 50 mg/5 ml, total dose 250 mg

Fe/1 g Hb def. Im: start with 50 mg ---- 100-250 mg/day

Iv: max 25 mg/day ---- increase every 2-3 days untul 100mg/day, slow injection within 20-50 mg/min



Anti Anemia Megaloblastic

Vit B12 and Folic Acid ----- for erythropoiesis

Due to:

Low intake, malabsorbtion, increase uptake, increaseblood destruction, increase excretion

B12 deficiency:

Hematopoiesis disturb, neurologic disorder, GIepithelial cell, general dibilitas

Anemia perniciosa addison, parasite investation----esp. in adult



B12 in adult:

1 ug/day

Excretion: 3-7 ug/day to gal bladder ---- reabsorb ingut

Source of B12

Animal: liver, ren, heart, scallop, egg yolk, milk, seafood

Internal: B12 is produced in colon, bind to prot-----but absorption in ileum --- not effective

Pharmacokinetic

Abs: good and fast for iv and im

T max: 1 hr post im, -12 hrs po

Abs decrease: chellatin a ent, sorbitol hi h dose



Transport of B12

Bind to protein

Beta glikoprotein Alfa glikoprotein (transkobalamin I)

Inter alfa glikoprotein (transkobalamin II)

B12 level

Blood N: 200-9 – pg/ml

Depot: 1-10 mg (in liver)

Indication: Anemia pernicious

Dose:

Severe anemia pernicious + neurologic disorder,liver: 100 ug B12, 1-5 mg Folic acid, im ---- 100 ug

B12 im, 1-2 mg Folic acid po



Dose maintenance

100 ug pe 5-10 days ----- 100-200 ug/month untilery count 4.5 million/m3

Posology of B12

B12 sol: 10-1000 ug/ul

Liver extract sol in water

Depo B12 inj

Not recommended: Inj hidroxocobalamin ---- form Anti body to transcobalamin II

SE: allergy to B12, usually inj of liver extractf



Folic Acid

Source:

Liver, Yeast, Fresh Green vegetable

Easily damage during cooking

Function:

Synthesis purin and pirimidin

Interconversion amino acid (serin-glisin, histidin-glutamic acid, homosistein-methionin)

Daily need: 50 ug/day (increase in infection,anemia hemolytic, cancer)



Folat deficiency:

Disease complication

Ileum disease

Alcoholism ---- food intake low

Liver toxic due to alcohol

Anemia hemolytic

Drugs Methotrexate

Trimetoprim

Symptom: hematopoisis megaloblastic, glositis,

diarrhea, low body weight

Pharmacokinetic

Abs good in 1/3 prox of Gitr

Excretion: ren in metabolic



Posology

Inj: 5 mg/ml solution

In multivitamin tab and anti anemia ta

Indication:

Prev and tx folat deficiency

Dose:

0.5-1 mg/day, po , 10 days ----- 0.1-0.5 mg/day



Anticoagulant, Fibrinolytic and

Antiplatelet



Usage

Tx thromboembolism Heart failure

Diabetes Mellitus

Vein varicosis Arterial damage

---- Trauma, smoking, op, immobilization, pregnancy,

drug with estrogen---- Anti coagulant, Anti thrombosis, Thrombolytic

Tx of bleeding

---- Hemostatic



Homeostasis

Primary Hemostasis

Within seconds

1. Vasospasm: contract to stop bleeding

Vasoconstriction of the blood vessel by Prostacyclin (PI2),Thromboxane A2 (TXA2) and serotonin (5-HT). Slows down thebleeding.

2. Platelet Plug: Platelet adhesion

Role of thrombin, adenosine diphosphate (ADP), PI2, TXA2, 5-HT andprostaglandins.

Secondary Hemostasis

Takes several minutes. Stabilizes the soft clot andmaintains vasoconstriction.

3. Fibrin Clot: Conversion of prothrombin to thrombin.

Thrombin stimulates the conversion of fibrinogen (Blood protein) topolymerized fibrin (mesh).

4. Dissolution of the clot by fibrinolysis: degradation of clot after tissue repair

The hemostatic process is a protective mechanism to prevent blood loss from the circulatory system.



Blood Coagulation:

Intrinsic Pathway Blood comes in contact with the subendothelial

surface or negatively charged surface resultingfrom an injury to the blood vessel.

The Hageman factor (factor XII) binds to thesubendothelial surface. It is then cleaved to XIIa.XIIa activates XI to form XIa. XIa activates IX toform IXa which then activates factor X to Xa.

Extrinsic Pathway Tissue factor (factor III) is located on the

membrane of most cells. Once activated, itconverts VII to its active form, VIIa. A complex of VIIa+III+calcium+a phospholipid converts factor Xto its active form, Xa.

Common Pathway Factor Xa is the convergence point for both the

intrinsic and extrinsic pathways.

Factor Xa converts prothrombin to active thrombin.

Thrombin is required for the conversion of solublefibrinogen to insoluble fibrin protein. The fibrinmeshwork is then stabilized by active factor XIIIa.



EMBOLISM THR

THROMBOSIS

A thrombus is a blood clot in an intactblood vessel. It forms under normalphysiological and pathologicalconditions. When a thrombus dislodges,it becomes an embolus.



ANTI COAGULANT



Purpose

To prevent blood coagulation

Thrombus

Emboli

In vitro blood coagulation

3 groups:

Parenteral anticoagulant (Heparin)

Oral anticoagulant

Chelating anti coagulant



Anticoagulants Parental(Heparin)

Heparin endogen

Produced by mast cell

May have a role in immunologic reaction

D

D



Heparin Sodium, Heparin Calcium



Anticoagulants (Parental) cont.

Enoxaparin: Heparin

Analog; Fractionated,Low molecular weight

heparin (LMWH; 2000-

9000 g/mol)

Factor IIa is thrombin

aPTT is not used



Heparin Sodium, Heparin Calcium: 5000-30,000 g/mol.

Clinical Use: Prevention and treatment of embolism (i.e., post-op or following

myocardial infarction), deep vein thrombosis, pulmonaryembolism.

Initial management of unstable angina or acute myocardialinfarction.

Pregnancy, in case anticoagulant is needed

MOA:

Increases the activity of antithrombin III Inactivates thrombin and F Xa High doses will inhibit platelet aggregation.

Pharmacokinetics: Administration: oral is not absorbed i.v. and s.c.. Immediate onset (30-60 mins); Hepatic elimination and excretion, some excreted unchanged in urine. Dosage is determined by the activated partial thromboplastin

time (aPPT; 1.5-2 times is normal). IM tidak dianjurkan

Not found in placenta and breast milk



Side effects: Hemorrhage.

Gi bleeding Hematuria

Allergic reaction Chill, febrile, urticaria, anaphylactic syock

Long term Myalgia, osteoporosis Alopecia Trombositopenia in 25% of px Necrosis in injection site

Contraindications:

existing bleeding condition or bleeding tendency. Hemophilia, increase capillary permeability, abortus imminens,

endocarditis, intra cranial bleeding etc

During and post op Px with high dose of ethanol, alcoholic, hypersensitive to

heparing

Drug Interactions: Risk of bleeding is increased by salicylates

In case of overdose: protamine sulfate (positive charge binds heparin). 1 mg protamine --- 80-100 usp heparin



Monitoring:

Right dose

Accurate laboratory test

Whole blood clotting time

PTT: partial tromboplastin time aPTT: activated partial thromboplastine time

Normal: 40 sec

aPTT 60-80 sec

Posology: Pe: sol 1000-40.000 u/ml

Depo: 20.000 – 40.000 u/ml



Dose:

Iv: 5000 unit ----- 5000-10.000 u/4-6j depend onBW and response

Infus: Heparin 20.000-40.000 u in 1l D5%/NaCl0.9% for 24 hrs

Deep sc

For prophylaxis of thromboemboli 5000 u 2hrs pre op ---- 5000 u /12hrs



Anticoagulants (Oral)

Coumarins: dicumarol and warfarin; warfarin is structurally related to vitamin K.

Clinical Use: Treatment of embolism, deep vein thrombosis or atrialfibrillation, patients with prosthetic valves (at risk for thrombosis).

MOA: Inhibits the synthesis of factors II, VII, IX and X by inhibiting theproduction of active vitamin K.

Active

form



Coumarins: dicumarol and warfarin; warfarin isstructurally related to vitamin K.

Pharmacokinetics: Route of administration: p.o.; 100% absorbed; 99%bound to plasma proteins; slow onset of activity; Hepatic elimination and

excreted in the urine. Dicumarol is incompletely absorbed from the gut.- Wardaron* po, im, iv

Side effects: Hemorrhage in 2-4%.

Contraindications: Patients with Hemophilia.

Drug Interactions: Drugs that inhibit CytoP450 Enzymes will increase levels, ie cimetidine,

Macrolide antibiotics, antifungal agents. Drugs that induce CytoP450 enzymes will decrease levels, ie rifampin

and Barbiturates.

In case of overdose: Vitamin K (phytonadione)

Sensitive to oral anticoagulant:- Cachexia, new born baby, liver failure

Decrease response to oral anticoagulant:

- renal insufficiency, febrile, scorbut



Calcium binder anticoagulant

Natrium sitrat

Na sitrat + Calcium:

Often for transfusion

Oxalat acid

For anticoagulant in vitro

Toxic

Natrium edetat

Bind calcium – komplek calcium natrium edetat



THROMBOLYTIC



Dissolve thrombus

Indication

Acute Myocard infark Vein thrombosis

Pulmonal emboli

Arterial thrombo emboli Iv cathether

Valve replacement

Streptokinase, urokinase, aktiator plasminogen,rt-PA (recombinant hujan tissue-typeplasminogen activator)

Very expensive, tight monitoring



These agents are enzymes or large proteins that dissolve clots,

ie., an existing thrombus in pts with myocardial infarction,thrombotic stroke or pulmonary embolism.



Fibrinolytic Drugs:(Thrombolytics)

Urokinase; enzyme obtained from urine MOA: Directly activates plasminogen; isolated from human

kidney, therefore less chance of evoking an allergic reaction.

Dose: loading 1000-4500 iu/kg iv --- infus 4400 iu/kg/hr

Streptokinase: protein obtained from streptocci;anistreplase (a preformed complex of streptokinase andplasminogen)

MOA: Combines with plasminogen to form an active complexthat converts plasminogen to plasmin to dissolve the fibrin.

Dose: iv for IMA 1.5 million unit, infus for 1 hr

Acut vein thrombosis, lung emboli, acut arterial thrombosis:loading dose 250.000 iu inful 30 min ---- 100.000 iu/hr (24 hrsfor lung emboli, 24-72 hrs for arterial thrombosis, 72 hrs for

deep vein thrombosis)



Thrombolytics

Pharmacokinetics: Parental administration, i,.v.

Side effects: hemorrhage, hypersensitivity reactions andreperfusion arrythmias.

Contraindications: Bleeding disorders; recent surgery;severe hypertension.

Drug Interactions: Increases risk of bleeding with

dicumarol, warfarn, heparin, aspirin, ticlopidine,abciximab.

In case of overdose: Aminocaproic acid inhibitsfibrinolysis by competitively blocking plasminogen

activation.



ANTITHROMBOTIC



Antiplatelet drugs:

Aspirin, sulfinpirazon, dipiridamol, dextran

Epoprostenol (prostasiklin, PGI2I), ticlopidin



Antiplatelet Agents

GP: glycoprotein

vWF: von Willebrand’s factor



Antiplatelet Agents

Aspirin Clinical Use: Prevention of atherosclerosis, thrombosis,

transient ischemic attacks; unstable angina.

MOA: Irreversible cyclooxygenase inhibitor and inhibits theformation of thromboxane A2.

Pharmacokinetics: Oral administration

Side effects: Bleeding; gastrointestinal irritation,hypersensitivity reactions and thrombocypenia.

Contraindications: Bleeding disorders, hypersensitivity and

Reye’s syndrome.

Drug Interactions: Increased hypoglycemic effects of sulfonylureas, inhibits uricosuric effect of probenecid.

In case of overdose: Forced Alkaline Diuresis Recommended dose: 325 mg/day



Antiplatelet Agents

Dipyridamole Clinical Use: Prosthetic valves; may be used as an adjunct

with aspirin therapy.

MOA: Lowers platelet calcium and increases the formation of cAMP (weak antiplatelet drug) , coronary vasodilator.

Pharmacokinetics: Oral administration

Side effects: GI distress, headache, dizziad4eness and rash.

Contraindications: Hypersensitivity to this drug

Drug Interactions: Increases risk of bradycardia with Betaadrenergic receptor antagonists.



Antiplatelet Agents

Clopidogrel (Plavix®) Clinical Use: Prevention of atherosclerosis, thrombosis,

transient ischemic attacks; unstable angina.

MOA: Inhibits the binding of ADP to its receptor whichis involved in the activation of platelet glycoproteinreceptors binding to fibrinogen.

Pharmacokinetics: Oral administration; eliminated in

urine and feces.

Side effects: Bleeding, neutropenia andthrombocytopenia.



Antiplatelet Agents Ticlopidine (Ticlid ®)

Clinical Use: Patients intolerant to aspirin; preventsthrombotic stroke.

MOA: Inhibits ADP-induced expression of platelet glycoproteinreceptors and reduces fibrinogen binding and plateletaggregation. Effects on platelet function are irreversible.

Pharmacokinetics: Oral administration; eliminated in the urineand feces

Side effects: Bleeding; mild to moderate neutropenia,increased cholesterol and triglyeride levels.

Contraindications: Bleeding disorders, severe liver disease

Drug Interactions: Inhibits cytoP450 drug metabolizingenzymes.



Antiplatelet Agents

Abciximab Clinical Use: Percutaneous transluminal coronary

angioplasty as adjunct with aspirin and heparin.

MOA: Binds to platelet glycoprotein IIb/IIIa receptors

and prevents binding to fibrinogen.

Pharmacokinetics: Parental administration, i.v.

Side effects: Bleeding, thrombocytopenia, hypotension

and bradycardia.

Contraindications: Aneurysm, bleeding, recent surgery,stroke

Drug Interactions: Unknown



HEMOSTATIC AGENTS



To stop bleeding

Local hemostatic Absorbable hemostatic: spons gelatin, oksisel, human

fibrin foam

Astringent: ferry cloride, argenti nitrate, tanic acid

Coagulant: Russels viper venom Vasoconstrictor: epinephrin, norepinephrin

Sistemic hemostatic

Antihemolytic factor (F VIII)

Cryoprecipitated antihemophylic factor

Desmopressin, tranexamid acid, Aminocaproic acid,Complex factor IX

For Hemophili, von Willebrand disease



Aminocaprioic acid, Tranexamic acid,Antihemophilic factor, Antiinhibitorcoagulants, Factor IX complex and

Desmopressin

Clinical Use: Decrease bleeding which may be due tohereditary deficiencies, surgery, or thrombolytic

overdose.

antikoagulan, tblytik.pptx

Documents