Medication MOA / Clinical Effects Adverse Effects/ Precautions/ PK/PD Notes/ Precaution

Contraindications/ Monitoring
Warfarin Vitamin K antagonists ADE: Weak acid = high protein binding • ANTIDOTE: vitamin K and PCC, or fresh
• Inhibit vit K 2,3- • Bleeding • 4-OH = acidic – allow formation of frozen plasma
epoxide reductase • Skin necrosis = due to reduced soluble Na-salts • Mutation of enzyme VKOR = Warfarin
(VKOR) and vitamin activity of protein C • Lipophilic substituent @ 3-position resistance
K quinone reductase • Sold as racemic mixture: S(-) isomer is 4x
• Inhibit clotting Contraindication: Onset: 2-3 days – inhibit vitamin K/ indirect potent than R(+) isomer
factors II, VII, IX, and • Pregnancy = ability to cross placenta inhibit clotting factors ***CYP2C9 => S isomer = CYP2C9 inhibition lead
protein C = bleeding in fetus + abnormal bone to significant INCREASE in therapeutic effect
formation (carboxyglutamate Absorption: rapidly F=1
Indirect anticoagulation depleted)
Monitoring Distribution: 95-99% plasma protein bound
• Prothrombin time (PT) - range 10-13s => 1-5% active free drug
normal
• INR = range 2-3 is normal Metabolism:
• Major: 6 and 7 hydroxylation; ketone
reduction
• Minor: 4-hydroxylation, aliphatic
hydroxylation

Elimination: highly lipid soluble = slow

elimination
• Hepatic clearance => inactive
• Almost no unchanged drug in urine

Medication MOA / Clinical Effects Adverse Effects/ Precautions/ PK/PD Notes/ Precautions/
Contraindications/ Monitoring Contraindications
Heparin UFH
Heparin Indirect inhibit factors IIa ADE: Polysaccharide polymer of alternating sugar units (N- • ANTIDOTE: Protamine sulfate –
and Xa • Bleeding 2-4% (GI, urinary tract or soft acetyl-D-glucosamine and uronic acid linked by α 1-4 from salmon sperm – highly basic
• Anion groups (sulfate tissues bonds) helps neutralizes heparin
and carboxylate) = • Osteoporosis – large doses and long- • @Physiological pH = polysulfate anions = • HIT ** When platelet count drop
ionic bind to (+) active term uses (>1 month) acidic = administered as salt up to 50% or < 100,000/mL
site (distinct Penta • HIT – heparin Induced • Large MW 5-30kDa  Significant sign when drop
Starting bolus dose saccharide) of Absorption: only 30% after SC
Thrombocytopenia = cause by body up to 30% = need
80U/kg then follow aPTT antithrombin III develop immunity to heparin intervention = STOP heparin
Distribution: high protein bound => decrease BA,
 Conformation and START lepirudin OR
Contraindication: increase variability (cause side effects if bind to argatroban
change
• HIT osteoblast i.e.)
 • ONLY catalytic Monitoring Metabolism:
• aPTT (activated partial thromboplastin • Partially metabolized in liver
time) = monitor factors II and X • Rapid depolymerization => inactive
 range 70-140 sec metabolites (sugar molecules)
 monitor q6h till therapeutic then • Desulfation
QD
• Level of UFH = titration by protamine
• Platelet count – HIT Elimination: inactive metabolites excreted thru
kidney

Medication MOA / Clinical Effects Adverse Effects/ Precautions/ PK/PD Notes/ Precautions/
Contraindications/ Monitoring Contraindications
Low Molecular Weight Heparin LMWH
Enoxaparin (Lovenox) Indirect inhibit factors Xa > ADE: Oligosaccharides (less than 18 sugar molecules) • ANTIDOTE: Protamine sulfate –
Dalteparin (Fragnin) IIa • Bleeding – less than UFH • MW 4-6 kDa only partially reverse
Tinzaparin (Innohep) • Exact same specific • Injection site reactions (minor • Isolated from heparin using gel filtration • HIT ** When platelet count drop
Penta saccharide bleeding/bruising, pain/stinging) chromatography up to 50% or < 100,000/mL
• Shorter = insufficient • < 2% HIT – 100% cross reactivity in Absorption: 90% after SC
inhibit Xa and patients with HIT history Significant sign when drop up to 30% =
Thrombin at the same Distribution: low protein bound => higher BA, less need intervention =
time Contraindication: variability (less cause side effects if bind to osteoblast
• HIT i.e.)
Monitoring
• signs of HIT Metabolism:
• Partially metabolized in liver
• Rapid depolymerization => inactive
metabolites (sugar molecules)
• Desulfation

Elimination: kidney, follow 1st order

• Longer half-life – less frequent administration
• PK more predictable
Pentasaccharide
Fondaparinux Specific indirect inhibit Xa ADE: Specific pentasaccharide sequence in heparin = high • ANTIDOTE: no antidote
• Bleeding – less than UFH affinity for antithrombin III • Weight-based dose = predictable
• Injection site reactions (minor • 3 D-glucosamine + 2 uronic acid residues PK and plasma levels with normal
bleeding/bruising, pain/stinging) • 3 D-glucosamine central contains a unique 3- kidney function
O-sulfate • Kidney function every 5-7 days
Contraindication: • Synthetic = less variation
• Patient with kidney impairment (CrCl < • Highly sulfonated
30mL/min) Absorption: F=1 after SC
Monitoring
• Kidney function Distribution: No protein binding = no risk of HIT

Metabolism: Not metabolized

Elimination: excreted unchanged in urine

Medication MOA / Clinical Effects Adverse Effects/ Precautions/ PK/PD Notes/ Precautions/
Contraindications/ Monitoring Contraindications
Hirudin (Hirudinum) – IV – Direct inhibit factors IIa ADE: Hirudin (Hirudinum) – 65 aa protein from leech salivary gland – highly • ANTIDOTE:
irreversible ONLY • Bleeding – less likely anionic C-terminus = irreversible idarucizumab
• Binds and inactivate (Praxbind) – for
Lepirudin (Refludan) – IV both free thrombin and Contraindication: Lepirudin (Refludan) – recombinant Hirudin 65 aa protein dabigatran
– irreversible / kidney clot-bound thrombin = •  FDA approved for HIT reversal
elimination inhibit downstream Monitoring
• Liver and kidney function, Bivalirudin (Angiomax) – 20 aa protein analogue
effects
Bivalirudin (Angiomax) -IV depend on drug choices  Rapid onset, short DOA
• Do not require
– reversible / kidney and  Less risk of bleeding
activated antithrombin
liver elimination  FDA approved for PCI angioplasty
III  Can be used in HIT
Argatroban (Novastan) –
IV – reversible / liver Argatroban (Novastan) – peptidomimetic binds selectively and reversibly
elimination to active site of thrombin
 Rapid onset, short DOA
Dabigatran (Pradaxa) –  54% protein bound
Oral – reversible - kidney  CYP3A4/5 = main metabolism
and liver elimination  Excreted by biliary secretion = safe in renal impairment
 FDA approved for HIT

Dabigatran (Pradaxa) – as effective and safe as LMWH for VTE

prevention, and as warfarin for atrial fibrillation
 Prodrug
 80% excreted in urine
 NO MONITORING required = predictable PK, lack CYP rxn, rapid
onset and offset
Medication MOA / Clinical Effects Adverse Effects/ Precautions/ PK/PD Notes/ Precautions/ Contraindications
Contraindications/ Monitoring
Rivaroxaban (Xarelto) Direct inhibit factors Xa – highly ADE: Oxazolidineone derivative – similar to linezolid • ANTIDOTE: Andexanet alfa and PCC
selective antibiotics  Andexanet alfa = recombinant
• FDA approved for stroke Contraindication: version of human factor Xa
prophylaxis in [Link] patients • PK predictable, no need for monitoring  PCC = increase plasma levels of vit
Monitoring • Oral bioavailability K dependent factors II, VII, IX, ad X
• Renal function if possible = • Rapid onset + protein C and S
Apixaban (Eliquis) renal dose adjustment • Renal elimination  PCC dose based on factor IX
Baxtrixaban (Bevyxxa) • Liver function = dose
content of vials
Edoxaban (Savaysa) adjustment CYP metabolism and P-gp – rivaroxaban and
apixaban
• concomitant with ketoconazole,
ritonavir, clarithromycin,
erythromycin, fluconazole, rifampin,
etc.
Older age and body weight may also increase
BA

Medication MOA / Clinical Effects Adverse Effects/ Precautions/ PK/PD Notes/ Precautions/
Contraindications/ Monitoring Contraindications
COX Inhibitors
Aspirin Irreversibly inactivate COX ADE: Absorption: rapidly in stomach • For prophylaxis, dose much
• Covalent acetylation of Ser closes • GI upset lower than analgesic dose
the COX active site • Hypersensitivity to NSAID Distribution: N/A • In the treatment of acute
• Result = Inhibit TXA2 biosynthesis in ischemic stroke, avoid aspirin
platelets Contraindication: Metabolism: plasma esterase = hydrolyzed for 24 hours following
**TXA2 causes platelets to change shape, • Hypersensitivity to NSAID to salicylic acid (active) , t1/2 = 15-20 mins
administration of a
release granules and aggregate**
Monitoring thrombolytic; administration
**Platelets do not contain DNA or RNA = Elimination: Urine
• N/A within 24 hours increases the
can not regenerate new COX enzyme **
risk of hemorrhagic
• Stroke, MI, and ischemic attack transformation
prophylaxis
**81-160 mg/day**
Medication MOA / Clinical Effects Adverse Effects/ Precautions/ PK/PD Notes/ Precautions/
Contraindications/ Monitoring Contraindications
Phosphodiesterase-3 (PDE3) Inhibitors
Dipyridamole Inhibit PDE3 Glucuronidation and biliary excretion
 Increase cAMP
 Increase vasodilation
 Inhibit platelet aggregation
For stroke patient
 Used with aspirin

ADP-receptor, aka. P2Y12, binding Inhibitors

Clopidogrel (Plavix) *Thienopyridines – Prodrug ADE: Absorption: • Due to irreversible bind to
Prasugrel Irreversible antagonists = bind at active site • Bleeding, diarrhea, skin rash Distribution: P2Y12 receptors,
Ticlopidine ▪ For MI and stroke reduction • Neutropenia [ticlopidine] thienopyridines possibly cause
Ticagrelor (Brilinta) ▪ For ACS, with aspirin combination Metabolism: toxicity
Cangrelor - IV (DAPT) Contraindication: *Thienopyridines: prodrug – metabolized • Why P2Y12 receptor? – binding
to active species in liver via CYP3A4 and of ADP to P2Y12 induces
*Nucleoside analogues – cyclopentane ring, Monitoring: CYP2C19 changes in platelet shape +
*Thienopyridines similar to ribose + purine - active drug • sign of bleeding **active metabolite = thiophene oxidation initiates platelets aggregation
*Nucleoside analogues Reversible antagonists = allosteric = bind at open ring**
other sites **Thiol forms disulfide bridge with cysteine
*** Fast on and offset *** residues of P2Y12 receptor**

Elimination:
Glycoprotein GPIIb/IIIa receptor Antagonists
Abciximab (ReoPro) Block the binding site, GPIIb/IIIa, of ADE: Abciximab: offset 2 days = platelet function • Abciximab = antigen binding
Eptifibatide (Integrelin) fibrinogen @ the platelet surface • Bleeding (lesser risk in E and T returns portion of chimeric human-
Tirofiban (Aggrastat)  Prevent cross-link of fibrinogen because of their short DOA) mouse antibody for GPIIb/IIIa
 Prevent aggregation Eptifibatide: cyclic heptapeptide receptor = large MW
Contraindication: • Compose of lysine-glycine-
▪ For unstable angina, MI, PCI aspartate
procedures Monitoring: • Highly specific but low binding
• Platelet count affinity = Reversible
• sign of bleeding • Eliminate via kidney as
unchanged and deaminated
metabolite
• Short DOA

Tirofiban: peptidomimetic
• Reversible
• Eliminate in urine and fecal as
unchanged
• Short DOA
Medication MOA / Clinical Effects Adverse Effects/ Precautions/ PK/PD Notes/ Precautions/
Contraindications/ Monitoring Contraindications
Fibrinolytics
Streptokinase (Streptase) Streptokinase: protein produced by β- ADE: Streptokinase PK: • ANTIDOTE: aminocaproic acid,
Alteplase (Activase) haemolytics streptococci • Hypersensitivity - • Short half-life < 30 mins => frequent tranexamic acid
Reteplase (Retavase) MOA: Must bind with plasminogen to form [streptokinase] too short to lyse clots • Alteplase at high dose can
1:1 complex = Activator • Hemorrhage activate free plasminogen =>
 No intrinsic activity by itself Alteplase: hemorrhage
 Plasminogen complex also Contraindication: • Short half-life < 5 mins
• Dose of tPA is 0.9 mg/kg
catalyzes breakdown of • Hypersensitivity to NSAID • Require IV bolus followed by IV
fibrinogen and factors V, VII (maximum dose for any patient
infusion
 Fibrin-nonspecific Monitoring = 90 mg)
• N/A Reteplase: 10% of total dose = IV bolus over 1
Alteplase: unmodified human tPA • Longer half-life 14-18 min minutes
produced using recombinant DNA • Reduce hepatic elimination 90% remaining = IV infused over 60
MOA: high affinity for plasminogen bound
minutes
to fibrin in a thrombus
 Fibrin-specific
 Low affinity for free plasminogen

Reteplase: recombinant deletion mutant of

human tPA missing the 1st 172 aa
MOA: similar to alteplase
 With modified, reduces binding
and selectivity to fibrin
 Still fibrin-specific
 ANTIDOTE
Medication MOA / Clinical Effects Adverse Effects/ Precautions/ PK/PD Notes/ Precautions/ Contraindications
Contraindications/ Monitoring
Vitamin K
Vitamin K1 – phytonadione Used in Bleeding disorder caused ADE: depends on route of Absorption: • Preferred vit K1 than K3 and K4
Vitamin K3 – menadione by overdose Warfarin admin • Vit K1 absorption  Safe in infants – K3 and K4
Vitamin K4 • Vit K1 most often for • IM = significant risk of required bile acids produce hyperbilirubinemia and
everyone, except those hematoma formation • Vit K3 and K4 absorb kernicterus in neonates)
has problem related to • IV = severe allergic passively in the intestine  Safe in patients with G6DP
bile acids reaction (death) with Distribution: N/A deficiency - vit K3 and K4 cause
• Vit K3 and K4 use only in rapid infusion
hemolysis
cholestasis and pancreatic Contraindication: Metabolism: short half-life 3-5hr
 More lipid soluble = rapid onset +
dysfunction Monitoring po, effects not seen until 24hr+
smaller dose required
• N/A
Elimination: N/A • If given IV, infuse slowly to avoid
allergic reaction
• Not good option for immediately treat
massive acute hemorrhage => use PCC
• Can use in minor acute hemorrhage
 Use IV plasma initially then vit K1
therapy
Protamine
Protamine sulfate Used in Bleeding disorder caused ADE: • Only PARTIAL reverse LMWH
1mg IV/ 100U heparin by overdose Heparin • Anaphylaxis reaction • Not antidote for pentasaccharide
• Arginine rich = highly • Hypotension • Dose protamine also depends on time
basic • In the absence of elapsed = heparin eliminated rapidly +
• High affinity to highly heparin, protamine avoid bleeding
acidic heparin than interacts with fibrinogen 30 mins => dose 0.5 mg/100U heparin
antithrombin III and platelets => >2hr => dose 0.25 – 0.375mg/100U heparin
anticoagulation
Anti-fibrinolytics
Aminocaproic acid (Amicar) Used in Bleeding disorder caused ADE: Lysine analogues
Tranexamic acid (Cyclokapron) by tPA agents • Hypotension
• Competitively inhibit • Thrombus formation
plasminogen activator
• High affinity for the 5
lysine binding sites for
plasminogen