This document discusses various antiplatelet and fibrinolytic drugs used to inhibit platelet activation and aggregation in acute coronary syndrome (ACS). It describes the classes and mechanisms of action of antiplatelet drugs including cyclooxygenase inhibitors like aspirin, phosphodiesterase inhibitors like dipyridamole, ADP receptor antagonists like clopidogrel and ticagrelor, and GPIIb/IIIa receptor inhibitors like abciximab. It provides details on dosing, indications, adverse effects and drug interactions for individual drugs.
Oral hypoglycemic drugs are used only in the treatment of type 2 diabetes which is a disorder involving resistance to secreted insulin. Type 1 diabetes involves a lack of insulin and requires insulin for treatment. There are now four classes of hypoglycemic drugs:
Oral hypoglycemic drugs are used only in the treatment of type 2 diabetes which is a disorder involving resistance to secreted insulin. Type 1 diabetes involves a lack of insulin and requires insulin for treatment. There are now four classes of hypoglycemic drugs:
A condition in which the heart is unable to pump sufficient blood
to meet the metabolic demand of the body and also unable to receive it back because every time after a systole.
Sulfonyl ureas pharmacology Presented by arjumandPARUL UNIVERSITY
Sulfonylureas are most commonly used Oral Hypoglycemic drugs helpful in treating Diabetes Mellitus .
They show their effects on beta cells of the pancreas to release insulin which maintains the blood sugar level.
They are also called as ATP sensitive Potassium[K] channel blockers
Medicinal chemistry 5 semester all synthesis Anjali Bhardwaj
Learn All
Medicinal Chemistry synthesis of
B.Pharmacy 5th Semester
As per PCI Syllabus
List Of Drug synthesis as per PCI Syllabus for B.Pharmacy 5th Semester
-Diphenhydramine hydrochloride -Furosemide
-Triprolidine hydrochloride -Methyldopate hydrochloride
-Promethazine hydrochloride -Disopyramide phosphate
-Cimetidine -Warfarin
-Meclorethamine -Tolbutamide
-Mercaptopurine -Benzocaine
-Methotrexate -Procaine
-Nitroglycerin -Dibucaine
-Isosorbide dinitrite
-Acetazolamide
-Chlorthiazide
A condition in which the heart is unable to pump sufficient blood
to meet the metabolic demand of the body and also unable to receive it back because every time after a systole.
Sulfonyl ureas pharmacology Presented by arjumandPARUL UNIVERSITY
Sulfonylureas are most commonly used Oral Hypoglycemic drugs helpful in treating Diabetes Mellitus .
They show their effects on beta cells of the pancreas to release insulin which maintains the blood sugar level.
They are also called as ATP sensitive Potassium[K] channel blockers
Medicinal chemistry 5 semester all synthesis Anjali Bhardwaj
Learn All
Medicinal Chemistry synthesis of
B.Pharmacy 5th Semester
As per PCI Syllabus
List Of Drug synthesis as per PCI Syllabus for B.Pharmacy 5th Semester
-Diphenhydramine hydrochloride -Furosemide
-Triprolidine hydrochloride -Methyldopate hydrochloride
-Promethazine hydrochloride -Disopyramide phosphate
-Cimetidine -Warfarin
-Meclorethamine -Tolbutamide
-Mercaptopurine -Benzocaine
-Methotrexate -Procaine
-Nitroglycerin -Dibucaine
-Isosorbide dinitrite
-Acetazolamide
-Chlorthiazide
This a is a slide set (42 slides) covering clinically used drugs for lipid lowering. This is an updated version of the lecture series for the 2021-2022 academic year. Suitable for intermediate level learners
Information about the importance of the platelet and functions.
Classification of drugs used for antiplatelet properties. And a brief discussion about the drugs.
June 3, 2024 Anti-Semitism Letter Sent to MIT President Kornbluth and MIT Cor...Levi Shapiro
Letter from the Congress of the United States regarding Anti-Semitism sent June 3rd to MIT President Sally Kornbluth, MIT Corp Chair, Mark Gorenberg
Dear Dr. Kornbluth and Mr. Gorenberg,
The US House of Representatives is deeply concerned by ongoing and pervasive acts of antisemitic
harassment and intimidation at the Massachusetts Institute of Technology (MIT). Failing to act decisively to ensure a safe learning environment for all students would be a grave dereliction of your responsibilities as President of MIT and Chair of the MIT Corporation.
This Congress will not stand idly by and allow an environment hostile to Jewish students to persist. The House believes that your institution is in violation of Title VI of the Civil Rights Act, and the inability or
unwillingness to rectify this violation through action requires accountability.
Postsecondary education is a unique opportunity for students to learn and have their ideas and beliefs challenged. However, universities receiving hundreds of millions of federal funds annually have denied
students that opportunity and have been hijacked to become venues for the promotion of terrorism, antisemitic harassment and intimidation, unlawful encampments, and in some cases, assaults and riots.
The House of Representatives will not countenance the use of federal funds to indoctrinate students into hateful, antisemitic, anti-American supporters of terrorism. Investigations into campus antisemitism by the Committee on Education and the Workforce and the Committee on Ways and Means have been expanded into a Congress-wide probe across all relevant jurisdictions to address this national crisis. The undersigned Committees will conduct oversight into the use of federal funds at MIT and its learning environment under authorities granted to each Committee.
• The Committee on Education and the Workforce has been investigating your institution since December 7, 2023. The Committee has broad jurisdiction over postsecondary education, including its compliance with Title VI of the Civil Rights Act, campus safety concerns over disruptions to the learning environment, and the awarding of federal student aid under the Higher Education Act.
• The Committee on Oversight and Accountability is investigating the sources of funding and other support flowing to groups espousing pro-Hamas propaganda and engaged in antisemitic harassment and intimidation of students. The Committee on Oversight and Accountability is the principal oversight committee of the US House of Representatives and has broad authority to investigate “any matter” at “any time” under House Rule X.
• The Committee on Ways and Means has been investigating several universities since November 15, 2023, when the Committee held a hearing entitled From Ivory Towers to Dark Corners: Investigating the Nexus Between Antisemitism, Tax-Exempt Universities, and Terror Financing. The Committee followed the hearing with letters to those institutions on January 10, 202
Normal Labour/ Stages of Labour/ Mechanism of LabourWasim Ak
Normal labor is also termed spontaneous labor, defined as the natural physiological process through which the fetus, placenta, and membranes are expelled from the uterus through the birth canal at term (37 to 42 weeks
Operation “Blue Star” is the only event in the history of Independent India where the state went into war with its own people. Even after about 40 years it is not clear if it was culmination of states anger over people of the region, a political game of power or start of dictatorial chapter in the democratic setup.
The people of Punjab felt alienated from main stream due to denial of their just demands during a long democratic struggle since independence. As it happen all over the word, it led to militant struggle with great loss of lives of military, police and civilian personnel. Killing of Indira Gandhi and massacre of innocent Sikhs in Delhi and other India cities was also associated with this movement.
Francesca Gottschalk - How can education support child empowerment.pptxEduSkills OECD
Francesca Gottschalk from the OECD’s Centre for Educational Research and Innovation presents at the Ask an Expert Webinar: How can education support child empowerment?
Safalta Digital marketing institute in Noida, provide complete applications that encompass a huge range of virtual advertising and marketing additives, which includes search engine optimization, virtual communication advertising, pay-per-click on marketing, content material advertising, internet analytics, and greater. These university courses are designed for students who possess a comprehensive understanding of virtual marketing strategies and attributes.Safalta Digital Marketing Institute in Noida is a first choice for young individuals or students who are looking to start their careers in the field of digital advertising. The institute gives specialized courses designed and certification.
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2024.06.01 Introducing a competency framework for languag learning materials ...Sandy Millin
http://sandymillin.wordpress.com/iateflwebinar2024
Published classroom materials form the basis of syllabuses, drive teacher professional development, and have a potentially huge influence on learners, teachers and education systems. All teachers also create their own materials, whether a few sentences on a blackboard, a highly-structured fully-realised online course, or anything in between. Despite this, the knowledge and skills needed to create effective language learning materials are rarely part of teacher training, and are mostly learnt by trial and error.
Knowledge and skills frameworks, generally called competency frameworks, for ELT teachers, trainers and managers have existed for a few years now. However, until I created one for my MA dissertation, there wasn’t one drawing together what we need to know and do to be able to effectively produce language learning materials.
This webinar will introduce you to my framework, highlighting the key competencies I identified from my research. It will also show how anybody involved in language teaching (any language, not just English!), teacher training, managing schools or developing language learning materials can benefit from using the framework.
Honest Reviews of Tim Han LMA Course Program.pptxtimhan337
Personal development courses are widely available today, with each one promising life-changing outcomes. Tim Han’s Life Mastery Achievers (LMA) Course has drawn a lot of interest. In addition to offering my frank assessment of Success Insider’s LMA Course, this piece examines the course’s effects via a variety of Tim Han LMA course reviews and Success Insider comments.
Unit 8 - Information and Communication Technology (Paper I).pdfThiyagu K
This slides describes the basic concepts of ICT, basics of Email, Emerging Technology and Digital Initiatives in Education. This presentations aligns with the UGC Paper I syllabus.
Read| The latest issue of The Challenger is here! We are thrilled to announce that our school paper has qualified for the NATIONAL SCHOOLS PRESS CONFERENCE (NSPC) 2024. Thank you for your unwavering support and trust. Dive into the stories that made us stand out!
Acetabularia Information For Class 9 .docxvaibhavrinwa19
Acetabularia acetabulum is a single-celled green alga that in its vegetative state is morphologically differentiated into a basal rhizoid and an axially elongated stalk, which bears whorls of branching hairs. The single diploid nucleus resides in the rhizoid.
Model Attribute Check Company Auto PropertyCeline George
In Odoo, the multi-company feature allows you to manage multiple companies within a single Odoo database instance. Each company can have its own configurations while still sharing common resources such as products, customers, and suppliers.
2. Introduction
• Antiplatelet agents are used both prophylactically
and acutely in the setting of ACS to inhibit platelet
activation and/or aggregation
• 4 main classes of antiplatelet drugs:
– Cyclooxygenase (COX-1) Inhibitors
• ASA is prototype and only one used
– Phosphodiesterase (PDE) inhibitors
• dipyridamole is prototype
– ADP receptor antagonists
• clopidogrel, prasugrel, ticagrelor
– GPIIb/IIIa receptor inhibitors
• Abciximab, eptifibatide, tirofiban
3.
4. Wh ite HD. Am J C ar diol. 1 99 7; 80 (4 A): 2B- 10 B.
Mechanism of action for platelet activation
7. Aspirin
• Mechanism of Action:
– Irreversibly blocks cyclooxygenase (COX-1)
activity by acetylating the enzyme
– Prevents the conversion of arachidonic acid to
TXA2 in platelets
• TXA2 promotes platelet aggregation and
vasoconstriction
– Platelet-induced TXA2 synthesis is blocked
for the life of the platelet (7-10 days)
8. Aspirin
• Mechanism of Action:
– COX-1 inhibition also prevents the
formation of PGI2 in vascular endothelium
• PGI2 promotes vasodilation and inhibits platelet
aggregation
• endothelium can regenerate COX-1 restoring
PGI2 production within hours
– net result is that aspirin preferentially
inhibits TXA2 rather than PGI2, favoring
vasodilation and inhibition of platelet
aggregation
– Aspirin does not inhibit platelet adherence
9. Aspirin
• Indications:
– UA/NQWMI
– Prevention of MI
– H/O thrombotic stroke or transient ischemic
attacks (TIAs)
– Alternative to warfarin to prevent thrombosis in
certain populations of patients with atrial fibrillation
– Intermittent claudication
– Antipyretic, analgesic and anti-inflammatory
– Chemoprevention of colon cancer
– Kawasaki’s Disease
10. Aspirin
• Dosing of aspirin:
– Recommended dose varies depending on
indication
– Antiplatelet doses range from 81-325
mg/day
• usual dose for ACS, acute MI, etc is 325 mg
given immediately upon symptoms
• prophylactic dose ranges from 81 - 325 mg
daily
• higher doses may decrease effectiveness due
to decreased ability to regenerate PGI2
11. Aspirin
• Dosing of aspirin:
– 325 mg daily for chemoprevention
– Higher doses used for anti-inflammatory,
analgesic and antipyretic indications
12. Aspirin
• Adverse effects of ASA occur in
response to PG and TX inhibition and
are dose-dependent:
– GI effects (due to PGE2 inhibition)
• abdominal pain
• heartburn
• nausea
• GI ulceration and bleeding
– enteric coated products and buffered
products may decrease GI symptoms
13. Aspirin
• Adverse effects of ASA occur in
response to PG and TX inhibition and
are dose-dependent:
– Bleeding (due to inhibition of TXA2)
• d/c 7 days prior to elective surgery
– Renal dysfunction (due to inhibition of renal
PGs)
• progressive dysfunction with chronic use
– Exacerbation of asthma (due to shifting of
AA metabolism to lipoxygenase pathway)
• increases LT formation which are known
inflammatory mediators in asthma
14. Aspirin
• Other adverse effects:
– tinnitus, headache, dizziness, confusion,
hearing loss and metabolic acidosis due to
salicylate toxicity
– hypersensitivity reactions ranging from
rash to angioedema to anaphylaxis
– Reye syndrome
• do not administer to children under the age of
16
– Avoid during pregnancy (esp. during 3rd
trimester)
• prolonged labor, increased risk for antepartum
and postpartum hemorrhage
15. Aspirin
• Drug interactions:
– NSAIDs: increased risk for bleeding
– warfarin: increased risk for bleeding
– other antiplatelets: increased risk for
bleeding
– plasma protein binding displacement
interactions:
• variable depending on specific medications
taken concurrently
– valproic acid
– tolazamide
– tolbutamide
16. Dipyridamole (Persantine)
• Mechanism of Action:
– inhibits cyclic nucleotide phosphodiesterase
(PDE) which causes cAMP breakdown
• results in increased cAMP and inhibition of
platelet aggregation
• increased cAMP also results in vasodilation
– blocks adenosine uptake into cells
• A2 receptors stimulate platelet adenylate cyclase
and inhibit platelet activation
17. Dipyridamole (Persantine)
• Clinical use:
– adjunct to coumarin anticoagulants
(warfarin) in patients with prosthetic heart
valves who cannot take aspirin
– cardiac stress testing
• use for this indication declining as adenosine is
being used
18. Dipyridamole (Persantine)
• Usual dose:
– 75-100 mg four times daily (PO)
• Adverse effects:
– exacerbation of angina following IV
administration during stress testing
– hypotension (IV)
– GI upset (PO)
– dizziness (PO)
19. Dipyridamole (Persantine)
• Drug interactions:
– increased risk for bleeding when given in
combination with ASA and other antiplatelets
or anticoagulants
– theophylline
• patients on theophylline may require higher
doses of dipyridamole during stress testing (hold
theo for 36 hours prior to test)
20. Dipyridamole/ASA combination
(Aggrenox)
• Aggrenox is combination of 25 mg aspirin and
200 mg dipyridamole in a sustained release
formulation to be taken twice daily
• Approved for use to reduce the risk of stroke in
patients with TIAs or with history of thrombotic
stroke
• Adverse effects and drug interactions are a
combination of those seen with ASA and
dipyridamole individually
21. Cilostazol (Pletal)
• A quinolinone derivative
• MOA:
– inhibits cellular phosphodiesterase, particularly
phosphodiesterase III (PDE III) leading to
increased levels of cAMP
• cAMP causes vasodilation and inhibition of platelet
aggregation
• Clinical use:
– Indicated to reduce symptoms of intermittent
claudication (increases walking distance)
22. Cilostazol (Pletal)
• Contraindications:
– CHF of any severity (other oral
phosphodiesterase inhibitors have
been shown to increase mortality in
patients with CHF
– hypersensitivity to any components
of the product
23. Cilostazol (Pletal)
• Drug Interactions:
– Cilostazol could have pharmacokinetic
interactions because of effects of other
drugs on its metabolism by CYP3A4 (eg,
erythromycin, ketoconazole) or CYP2C19
(eg, omeprazole)
– Platelet function inhibitors: Cilostazol
could have pharmacodynamic
interactions with other platelet function
inhibitors including aspirin, ticlodipine or
clopidrogel
24. Cilostazol (Pletal)
• Usual dose:
– 100mg PO BID 1/2 hour before, or
two hours after meals
– decrease to 50mg PO BID if given
concurrently with CYP inhibitors
25. Cilostazol (Pletal)
• Adverse Effects:
– headache
– diarrhea
– palpitations
– CHF has been reported with other
PDE III inhibitors; contraindicated
for use in patients with CHF
26. ADP Antagonists
(Thienopyridines)
• Clopidogrel, Prasugrel, Ticagrelor
• MOA:
- inhibit platelet aggregation by inhibiting ADP-
induced platelet fibrinogen binding (this links
platelets together to form aggregates or
“plugs”)
- Clopidogrel and Prasugrel are irreversible
inhibitors
- Ticagrelor is reversible
- Antiplatelet effect takes 24-48 hours to
develop ; Loading dose employed
27. ADP Antagonists
(Thienopyridines)
• Dosing of Plavix:
– Loading Doses are used to decrease the time to maximal
platelet inhibition
• 75 mg po QD takes 7 days for maximal effect
• 300mg po X1 before PCI takes 6-10 hours for maximal effect
• 600mg po x1 before PCI takes 2 hours for maximal
– Maintenance Dose
• 75 mg po qd
– requires transformation by the liver
– following oral administration, the time to peak concentration is
about 2 hours
– the effect of clopidogrel continues for several days after
discontinuing the drug
28. ADP Antagonists
(Thienopyridines)
• Adverse effects:
– both can cause GI upset, diarrhea and rash
• Drug Interactions:
– CYP 2C19 inhibitors may decrease
effectiveness because decreased conversion
to active metabolite
30. ADP Antagonists
(Thienopyridines)
• Prasugrel (Effient™)
– NewerADP antagonist
– FDA indications
• Reduces rate of thrombotic cardiovascular events
(eg, stent thrombosis) in patients with unstable
angina, non-ST-segment elevation MI, or ST-
elevation MI (STEMI) managed with percutaneous
coronary intervention (PCI)
31. ADP Antagonists
(Thienopyridines)
• Prasugrel (Effient™)
– Dosing
• Loading Dose 60mg
• Maintenance Dose 10mg (in combination with
Aspirin 81-325mg/day)
– Adverse effects similar to other
Thienopyridines
• Bleeding risks may be higher for certain patient
populations (see warnings)
32. ADP Antagonists
(Thienopyridines)
• Prasugrel (Effient™)
– Contraindications
• Peptic Ulcer disease
• Intracranial hemmorrahge
• TIA/Stroke
– Warnings
• Bleeding risk increased in patients ≥75, <60kg,
recent CABG or other surgical procedure,
concomitant use of Warfarin, NSAIDS
• D/c ≥7 days before CABG and avoid in patients
with probable need for CABG
33. ADP Antagonists
(Thienopyridines)
• Ticagrelor (Brilinta™)
– Newest ADP antagonist
– FDA indications
• ACS (with aspirin)-Reduces risk of cv death, MI,
stroke and stent thrombosis
– Dosing
• Loading Dose 180mg
• Maintenance Dose 90mg BID (in combination with
Aspirin 81mg/day)
– Do not use a higher dose of aspirin as it reduces
effectiveness
34. ADP Antagonists
(Thienopyridines)
• Ticagrelor (Brilinta™)
– Drug Interactions
• Avoid with strong CYP 3A4 inhibitors
– Adverse effects
• Bleeding
• Bradycardia, dyspnea, gynecomastia in men
35. ADP Antagonists
(Thienopyridines)
• Ticagrelor (Brilinta™)
– Contraindications
• Peptic Ulcer disease
• Intracranial hemmorrahge
• Severe hepatic impairment
– Warnings
• ↑Risk of bleeding in patients with advanced age,
invasive procedures, and use of medications that
increase bleeding risk and moderate hepatic
impairment.
• stopped five days before surgery if possible. B
36. GPIIb/IIIa Inhibitors
• Includes the agents tirofiban (Aggrastat) and
eptifibatide (Integrilin)
• both are antagonists of the platelet glycoprotein (GP)
IIb/IIIa receptor - the major platelet surface receptor
involved in platelet aggregation
• both inhibit ex vivo platelet aggregation in a dose-
and concentration-dependent manner
• to be effective, > 90% of these receptors have to be blocked
• Potent antithrombotic effects and has been shown to
decrease mortality and reinfarction
37. GPIIb/IIIa Inhibitors
• Clinical Use:
– Indicated for use in acute coronary syndrome,
including patients who are to be managed
medically and those undergoing percutaneous
coronary intervention (PCI)
• PCI (balloon angioplasty or stent placement) is
associated with acute and late (3-6 month) occlusion
• acute occlusion is reduced by antiplatelet agents started
before the procedure and heparin during and after the
procedure
• late stenosis does not improve with antiplatelet agents
(may improve with new drug eluting stents)
38. GPIIb/IIIa Inhibitors
• Clinical Use:
– Used as adjunct to PCI for the prevention
of acute cardiac ischemic complication in
patients that are high risk for abrupt
closure of the treated coronary artery
– Patients with UA/MSTEMI not responding
to medical therapy when PCI is planned
within 24 hours
39. GPIIb/IIIa Inhibitors
• Clinical Use:
– Integrilin has broadest indications for use:
• Elective, urgent or emergency PCI
• Patients with UA/NQMI who are medically
managed and those undergoing PCI
– Aggrastat is not used in elective, urgent or
emergency PCI
• Higher doses are being studied to see if this
improves efficacy
40. GPIIb/IIIa Inhibitors
• Dosing of Aggrastat:
– Loading infusion rate (0.4 mg/kg/min for 30
min.) followed by maintenance infusion
rate (0.1 mg/kg/min)
– Larger margin of safety than Reopro
• Reversible platelet aggregation due to short
half-life (2 hours)
• Platelet function is restored toward baseline
(<50% inhibition) within 4 hours after infusion.
– Used in combination with aspirin and
heparin
41. GPIIb/IIIa Inhibitors
• Dosing of Integrilin
– Bolus and constant infusion rate based on
indication and patient characteristics
• weight, serum creatinine
• see protocol
– Reversible following cessation of infusion
(half-life 2.5 hour)
– originally intended for use with ASA &
heparin
• Reevaluation of the PURSUIT Trial (March 2001)
suggests that monotherapy with eptifibatide is
reasonable (although most everyone continues to
receive combination therapy)
43. Abciximab (Reopro)
• MOA:
– Fab fragment of a human-murine
monoclonal antibody that binds to the
platelet glycoprotein (GP) IIb/IIIa receptor
leading to inhibition of platelet aggregation
44. Abciximab (Reopro)
• Clinical Use:
– Used as an adjunct to percutaneous transluminal
angioplasty (PCTA) for the prevention of acute
cardiac ischemic complications in patients at high
risk for abrupt closure of the treated coronary
vessel
– Patients with UA/NQMI not responding to medical
therapy when PCI is planned within 24 hours
– Abciximab use in patients with UA or NQWMI not
undergoing PCI shows no significant benefit
(GUSTO trial)
45. Abciximab (Reopro)
• Dosing:
– Low margin of safety
• long half-life affects platelet function for 12-24
hours after infusion
• no antidote for over-dose
– abciximab is used with aspirin and heparin
– usual dose is 0.25 mg/kg via I.V. bolus
given 10-60 minutes before the start of
PCI, followed by continuous infusion (10
mcg/min) for 12 hours
46. Abciximab (Reopro)
• Adverse Reactions:
– Bleeding
– Formation of antibodies occurs in up to
6.5% of patients; percentage increases
with repeated use
– Anaphylaxis has NOT been reported
– Severe thrombocytopenia occurs with
repeat exposure
48. Introduction
• Physiological fibrinolysis/thrombolysis:
– Fibrin clots are dissolved endogenously by
the action of plasmin, a proteolytic enzyme
formed by the cleavage of the plasma protein
plasminogen
– Plasminogen is activated endogenously by
tissue plasminogen activator (tPA) which is
released from endothelial cells
– tPA binds preferentially to the plasminogen
bound to fibrin and activates it with less effect
on circulating plasminogen
49. Introduction
• Fibrinolytic drugs, sometimes called “clot
busters” are used to dissolve fibrin clots
whenever the presence of a clot causes
imminent danger to the patient
– Acute treatment of myocardial infarction is the
primary indication for these agents
– Also used in the setting of thrombotic stroke,
PE and for catheter patency
• The earlier the drug is given to dissolve
the blockage in the vessel, the better the
patient prognosis
50. Introduction
• Best outcome occurs with drug
administration within one hour of onset
• Protocols allow administration of the
fibrinolytic agent up to six hours from the
onset of MI
• Risk of hemorrhage with these drugs is
great, even more than with antiplatelet and
anticoagulant agents
52. Streptokinase
• (Kabikinase, Streptase):
– enzyme derived from beta hemolytic streptococcus
– forms a complex with plasminogen via 1:1 stable,
noncovalent binding to induce a conformational
change that exposes the active site of plasminogen
leading to its activation
– administered by IV infusion, intracoronary infusion
and into occluded cannulae
– available as powder for injection; dosed in
international units
53. Streptokinase
• Indications:
– acute evolving transmural MI, DVT, arterial
embolism and occluded AV cannulae
• Adverse effects:
– Allergic reactions including bronchospasm,
breathing difficulty, itching, rash, flushing
– Hemorrhage
• Least expensive of the treatment
alternatives
54. Anistreplase
• A complex of streptokinase and
plasminogen with the catalytic center of
the complex blocked by an anisoyl group
• deacylation of the complex occurs in vivo ;
half-life of fibrinolytic activity is
approximately 94 minutes compared to 23
minutes for streptokinase alone
• administered by IV injection over 2-5
minutes in a dose of 30 units
56. Urokinase
• Acts directly on plasminogen to
enzymatically activate it to plasmin
• administered similarly to streptokinase
• protein is of human origin from urine or
kidney cell cultures
• not as antigenic as streptokinase
• considerably more expensive than
streptokinase
58. Tissue plasminogen activator
• genetically engineered version of human
tPA
• 100-fold more potent at activating
plasminogen bound to fibrin than
circulating plasminogen
• should limit the risk of widespread
fibrinolysis and hemorrhage
• cleared by hepatic metabolism with a half-
life of 5-10 minutes
59. Tissue plasminogen activator
• Indications:
– indicated for acute MI
– more recently approved for treatment of acute
ischemic stroke within 3 hours of onset of
symptoms
• Adverse effects:
– hemorrhage
60. tPA-absolute contraindications
• > 3 hours onset of sxs
(stroke indication)
• Sustained BO
>185/100
• Hx of intracranial
neoplasm, AVM,
Aneurysm, or
intracranial
hemorrhage
• Active internal
bleeding
• Gl bleeding with/in 21
days
• Recent MI
• Major surgery w/in 14
days
62. Reteplase
• recombinant fibrinolytic agent
• advantage over tPA is the dosing regimen
• two injections of 10 units injected over a
two minute period with the second
injection 30 minutes after the first are
given rather than continuous IV infusion
with tPA
• cost is similar between the two
63. Tenecteplase (TNKase)
• Fibrinolytic agent indicated for acute MI
• Dosing
– Advatange over tPa
– Single bolus over 5 seconds
– Dose dependent upon weight
• Max 50mg
• <60kg give 30mg
• Add 5mg for every 10kg (max 50mg)
• Contraindications, ADRs, costs the same as
other agents
64. Aminocaproic acid (Amicar)
• fibrinolytic antagonist
• inhibits plasminogen activator substances
• used to treat excessive bleeding due to
hyperfibrinolysis
• can be given orally or IV
• dosing regimen is 5 grams to start and 1-
1.25 grams hourly; continue for up to 8
hours or until bleeding is controlled