Kinin and Kallikrein Inhibitors
Kinin and Kallikrein Inhibitors
These inhibitors are crucial therapeutic agents targeting the kallikrein-kinin system (KKS), playing vital roles in inflammation, coagulation, and vascular function.
Key Points:
- Essential regulators of inflammatory processes
- Critical in hereditary angioedema management
- Important role in coagulation cascade
- Therapeutic targets in multiple disorders
- Emerging pediatric applications
Mechanism and Types
Kallikrein Inhibitors:
- Plasma Kallikrein Inhibitors:
- Ecallantide (Kalbitor®)
- Lanadelumab (Takhzyro®)
- BCX7353
- C1 esterase inhibitor
- Tissue Kallikrein Inhibitors:
- Aprotinin
- Trasylol
- Synthetic inhibitors
Kinin Inhibitors:
- Bradykinin Receptor Antagonists:
- Icatibant
- HOE 140
- NPC 17731
- ACE Inhibitors (indirect effect)
- Specific B1/B2 receptor antagonists
Mechanism of Action:
- Direct enzyme inhibition
- Receptor antagonism
- Pathway modulation
- Feedback regulation
Clinical Applications
Primary Indications:
- Hereditary Angioedema (HAE):
- Acute attack treatment
- Prophylactic therapy
- Breakthrough episode management
- Surgical Applications:
- Cardiopulmonary bypass
- Major trauma surgery
- Organ transplantation
- Other Conditions:
- Severe sepsis
- DIC management
- Inflammatory conditions
- Post-surgical bleeding
Administration Routes:
- Subcutaneous injection
- Intravenous administration
- Oral formulations (emerging)
- Topical applications
Pediatric Usage
Age-Specific Considerations:
- Dosing Adjustments:
- Weight-based dosing
- Age-specific protocols
- Safety considerations
- Special Populations:
- Neonates
- Infants
- Adolescents
Pediatric Indications:
- Pediatric HAE management
- Congenital heart surgery
- Major pediatric surgery
- Trauma management
- Inflammatory conditions
Therapeutic Considerations
Drug Selection Factors:
- Patient age and weight
- Condition severity
- Route of administration
- Cost considerations
- Available formulations
Monitoring Parameters:
- Clinical response
- Safety parameters
- Drug levels
- Coagulation profile
- Adverse effects
Side Effects:
- Common effects:
- Injection site reactions
- Hypersensitivity
- Gastrointestinal symptoms
- Serious concerns:
- Anaphylaxis
- Bleeding risk
- Thrombotic events
Research Updates
Current Developments:
- Novel Agents:
- Oral kallikrein inhibitors
- Long-acting formulations
- Combination therapies
- Clinical Trials:
- Pediatric studies
- New indications
- Safety evaluations
Future Directions:
- Novel delivery systems
- Targeted therapies
- Biomarker development
- Personalized medicine approaches
