1. Pediatric hematologist oncologist
Dr Babak Abdolkarimi
Pediatric hematologist oncologist
2و3 اسفند96-هرمزگان-قشم

2. Introduction:
What drugs are needed, to treat the vast majority of SCD patients can be taken orally?
The development of Hydroxyurea has been a major advance in the treatment of sickle cell disease, but is only partially effective in preventing vaso-occlusive crises.

3. Approach ameliorate the sequelae of HbS polymerization:
1. genetic approaches
2.non-genetic approaches

5. Etiology of VOC:
1.adhesion(phosphatidylserine exposure, Oxidative damage dyselasticity, Abnormal intracellular signaling)
2.inflammation(hypoxia/reperfusion,Platelet activation)
3. coagulation(Platelet activation, phosphatidylserine exposure
4.HbS polymerization(dehydration)
5. NO scavenging(HbS polymerization)

6. approaches to inhibiting HbS polymerization
1. Block intermolecular contacts in the sickle fiber 2. Induce HbF synthesis
3. Increase oxygen affinity
4. Reduce concentration of 2,3-DPG
5. Reduce intracellular Hb concentration.

7. Drug clasifications: 1. Anti-polymerization drugs(Niprisan,
SCD-101, GBT440, Aes-103)
2. adhesion cell blocker:
a.Heparines(Sevuparin,LMWH,Dalteparin,UFH)
b. P,E -selectin blocker(Rivipansel,selG1
c. signaling adhesion blocker(propranolol)
d. Nonspecific inhibitors of adhesion(Poloxamer 188/surfactant,IVIg ,Simvastatin)

8. 3. Anti-inflammatory drugs(Regadenoson, NKTT120,Montelukast,Ziluton)
4. HbF Inducer(Hydroxyurea, Tetrahydrouridine, Decitabine, HQK-1001, Pomalidomide) 5. Hemoglobin-modifying and anti-sickling agents( SCD-101, Sanguinate, Senicapoc, Aes-103, SCD-101, MP4CO)
6. Anticoagulants and antiplatelet agents(Abciximab, Dipyridamole/Magnesium, Eptifibatide, Prasugrel, Ticagrelor,ASA,Warfarin,Rivaroxaban,Apixaban)

9. Endari The mechanism of action of the amino acid
L-glutamine in treating sickle cell disease (SCD) is not fully understood but it seems inhibit Oxidative stress(chronic hemolysis & vaso-occlusive events).
Pyridine nucleotides and NADH, preventing oxidative damage in RBCs by reducing glutathione.

10. Take home message: Available & safe drugs in IRAN: 1.Montelukast
2.Propranolol
3.ASA
4.IVIg
5.Simvastatin 6. Dipyridamole/Magnesium 7. Aspirin
8.Rivaroxaban