FIBRINOLYTICS (Thrombolytics):

FIBRINOLYTICS (Thrombolytics):  

These are drugs used to lyse thrombi/clot to re-canalize occluded blood vessels (mainly coronary  artery).  

They  are  therapeutic  rather  than  prophylactic  and  work by activating the natural fibrinolytic system. 

The plasminogen-plasmin system 

t-PA-Tissue plasminogen activator;  rt-PA-Recombinant t-PA; PAI-1 Plasminogen activator inhibitor-1 

The clinically important fibrinolytics are:                           

  • Streptokinase  
  • Urokinase                           
  • Alteplase (rt-PA)                          
  • Reteplase                          
  • Tenecteplase 


Obtained  from  hemolytic  Streptococci  group  C,  it  is  the  first fibrinolytic  drug  to  be  used  clinically,  but  is  not  employed  now  except  for considerations of cost. 
Streptokinase is inactive as such; combines with circulating plasminogen  molecules  to  form  an  activator  complex  which  then  causes  limited proteolysis of other plasminogen molecules to generate the active enzyme plasmin. 
It  is  non-fibrin  specific,  i.e.  activates  both  circulating  as  well  as  fibrin  bound plasminogen.  Therefore,  it  depletes  circulating  fibrinogen  and  predisposes  to bleeding.  
Compared  to  newer  more  fibrin-specific  tissue  plasminogen  activators (alteplase,  etc.)  it  is  less  effective  in  opening  occluded  coronary  arteries,  and causes less reduction in MI related mortality.  
There are several other disadvantages as well with streptokinase. 
Antistreptococcal antibodies due to past infections inactivate considerable fraction of the initial dose of Stk.  
A  loading  dose therefore  is  necessary. 
Plasma  t½  is estimated to be 30–80 min.  
Stk  is  antigenic—can  cause  hypersensitivity  reactions;  anaphylaxis  occurs  in 1–2%  patients.  
It  cannot  be  used  second  time  due  to  neutralization  by  antibodies generated  in  response  to  the  earlier  dose.  
Fever,  hypotension  and  arrhythmias  are reported. 
However, being less expensive, it is still used in resource poor areas, but not in Europe or USA. 


It is an enzyme isolated from human urine; but commercially prepared from  cultured  human  kidney  cells.  
It  activates  plasminogen  directly  and  has  a plasma  t½  of  10–15  min.  
It  is  non-antigenic.  
Fever  occurs  during  treatment,  but hypotension and allergic phenomena are rare. 
Urokinase is  indicated  in patients  in whom streptokinase has been given for an earlier episode, but is seldom used now. 

Alteplase  (recombinant  tissue  plasminogen  activator  (rt-PA):  

It  is  produced  by recombinant DNA technology  from  human tissue culture, it is  moderately specific for  fibrin-bound  plasminogen,  so  that  circulating  fibrinogen  is  lowered  only  by  ~ 50%.  
It  is  rapidly  cleared  by  liver  and  inactivated  by  plasminogen  activator inhibitor-1 (PAI-1). 
The plasma t½ is 4–8 min. 
Because of the short t½, it needs to be  given  by  slow  i.v.  infusion  and  often  requires  heparin  co-administration.  
It  is non-antigenic, but nausea, mild hypotension and fever may occur. 
It is expensive. 


It  is a  modified  form  of rt-PA  that  is  longer acting, but somewhat  less specific for fibrin-bound plasminogen. 
The longer duration of action enables bolus dose administration (10 mg over 10 min repeated after 30 min). 


This  genetically  engineered  substitution  mutant  of  native  t-PA  has higher  fibrin  selectivity,  slower  plasma  clearance  (longer  duration  of  action)  and resistance  to  inhibition  by  PAI-1.  
It  is  the  only  fibrinolytic  agent  that  can  be injected  i.v.  as  a  single  bolus  dose  over  10  sec,  while  alteplase  requires  90  min infusion.  
This  feature  makes  it  possible  to  institute  fibrinolytic  therapy immediately on diagnosis of ST segment elevation myocardial infarction (STEMI), even  during  transport  of  the  patient  to  the  hospital.  
Several  randomized multicentric  trials  have  assessed  its  efficacy  in  STEMI  and  found  it  to  be  at  least equally  efficacious  to  alteplase.  
Risk  of  noncerebral  bleeding  may  be  lower  with tenecteplase, but cranial bleeding incidence is similar. 

Uses of fibrinolytics: 

1. Acute myocardial infarction is the chief 
2. Deep vein  
3. Pulmonary  
4. Peripheral arterial occlusion  
5. Stroke 

Leave a Comment