Antiplatelet drugs

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Platelet aggregation inhibitors ( TAH ), also platelet function inhibitors or platelet aggregation inhibitors, are drugs that inhibit the clumping of blood platelets ( thrombocyte aggregation ). They are used in medicine to prevent blood clots ( thrombi ) from forming in blood vessels. For example, they are used in the prevention and treatment of strokes , heart attacks and other circulatory disorders. Colloquially, platelet aggregation inhibitors (like anticoagulants ) are often misleadingly referred to as blood thinners .

Overview

Platelet aggregation inhibitors used in therapy are:

Drug ATC code Application route Assumed
mean daily dose
Picotamide B01AC03
Clopidogrel B01AC04 Orally 75 mg
Ticlopidine B01AC05 Orally 0.5 g
Acetylsalicylic acid  (ASA) B01AC06 Orally 1 tablet
Dipyridamole
(often in combination with acetylsalicylic acid)
B01AC07 Oral
Parenteral
0.4 g
0.2 g
Epoprostenol B01AC09 Parenteral
Iloprost B01AC11 Parenteral
inhalation
0.05 mg
0.15 mg
Abciximab B01AC13 Parenteral 25 mg
Eptifibatide B01AC16 Parenteral 0.2 g
Tirofiban B01AC17 Parenteral 10 mg
Triflusal B01AC18 Orally 0.6 g
Prasugrel B01AC22 Orally 10 mg
Cilostazol B01AC23 Orally 0.2 g
Ticagrelor B01AC24 Orally 0.18 g
Cangrelor B01AC25 Parenteral 50 mg
Vorapaxar B01AC26 Orally 2.08 mg

Classification

Various mechanisms are responsible for the platelet aggregation-inhibiting effect, according to which the following groups are differentiated.

  • Cyclooxygenase inhibitors
Acetylsalicylic acid is an irreversible inhibitor of cyclooxygenase in platelets and thus inhibits the aggregation- enhancing thromboxane pathway of blood platelets.
  • P2Y 12 receptor antagonists
Clopidogrel, ticlopidin, prasugrel, ticagrelor and cangrelor are P2 Y 12 receptor antagonists and inhibit adenosine diphosphate (ADP) -dependent mechanisms of platelet activation. The thienopyridines clopidogrel, ticlopidin and prasugrel are prodrugs from which the platelet aggregation-inhibiting compounds are metabolically formed. They irreversibly inhibit the ADP receptors. Ticagrelor and cangrelor, on the other hand, reversibly block the platelet adenosine receptor P2Y 12 . The platelet aggregation inhibition is comparable to that of prasugrel, but stronger and faster than that of clopidogrel.
  • Phosphodiesterase inhibitors
The PDE-5 inhibitor dipyridamole and the PDE-3 inhibitor cilostazol cause an accumulation of cGMP and cAMP in the platelets by blocking the phosphodiesterases , whereby the calcium release and the platelet activation are inhibited. In addition, dipyridamole, as an adenosine reuptake inhibitor, increases the thrombocyte aggregation-inhibiting effect of the body's own adenosine .
While the mechanisms mentioned so far indirectly inhibit the activation of platelets, a blockade of the glycoprotein GPIIb / IIIa receptors on the platelet surface with the aid of the drugs abciximab , tirofiban or eptifibatide leads to a direct inhibition of the aggregation of the platelets.

Because the effect of these drugs is slightly different for each person, the strength of the inhibition can be determined in the laboratory, for example with the help of platelet aggregometry . In the case of clopidogrel in particular, this is currently the preferred method. Depending on the result, the dose can either be reduced or increased in order to adjust the effect between bleeding tendency (dose too high) and thrombosis tendency (dose too low) as best as possible.

The dual platelet inhibition , also known as "double platelet inhibition", makes use of two active principles for inhibiting platelet aggregation, mostly ASA (irreversible COX inhibitor) and clopidogrel (irreversible ADP receptor antagonist). This combination is mandatory to prevent an occlusion after stent implantation in an arterial vessel .

Vorapaxar is a selective and reversible inhibitor of the PAR-1 receptors and inhibits thrombin- induced platelet aggregation.

Iloprost is a synthetic prostacyclin analogue . Prostacyclin is considered to be the most effective endogenous platelet aggregation inhibitor, which is also used medicinally under the generic name Epoprostenol.

The thromboxane A 2 / prostaglandin H 2 receptor antagonist (TX / PGH 2 receptor antagonist) ifetroban was only used experimentally . By blocking the TX and PGH 2 receptors, it interrupts downstream signaling pathways and prevents platelet activation. In addition to an antithrombotic, the substance is also said to have antihypertensive , antiasthmatic and potentially anti-tumor effects.

Web links

  • Sketch for the "Mechanisms of platelet activation and inhibition" , from: The use of glycoprotein IIb / IIIa receptor antagonists in acute coronary syndromes. Part 1: Treatment of unstable angina (UA) and non-ST elevation myocardial infarction (NSTEMI) . K. Huber et al., Journal für Kardiologie, Volume 12 (2003), pp. 554-560 ( PDF at www.kup.at).

Individual evidence

  1. a b c WHO: ATC / DDD Index 2020 - B01AC Platelet aggregation inhibitors excl. heparin , accessed March 1, 2020.
  2. G. Geisslinger et al .: Mutschler drug effects: Pharmakologie - Klinische Pharmakologie - Toxikologie , 11th edition, 2019. P. 472 ff.
  3. arznei-telegramm 1/2011 , accessed on October 17, 2011.
  4. Holger Jastrow, Artur-Aron Weber: Basics of thrombocyte pharmacology . In: Pharmacy in our time . Vol. 38, No. 4, 2009, pp. 302-304. doi : 10.1002 / pauz.200900318 .
  5. ^ Percutaneous coronary interventions (PCI). Guidelines of the German Society for Cardiology, 2008, accessed on May 30, 2012 .
  6. ^ Medication-releasing coronary stents and balloon catheters coated with medication. Position paper of the DGK. Guidelines of the German Society for Cardiology, 2011, accessed on May 30, 2012 .
  7. Thorsten Schmidt: Infusion, femoral head drilling or infusion after femoral head drilling in the treatment of atraumatic femoral head necrosis (FKN) and bone marrow edema syndrome , dissertation, Chair of Orthopedics at the University of Regensburg (2009). 76 pages. ( PDF , 1.3 MB).
  8. Ifetroban in the " NCI Drug Dictionary", accessed February 29, 2020.
  9. Ifetroban , National Center for Advancing Translational Sciences (NCATS), Inxight: Drugs, accessed February 29, 2020.