/**
 * Drug Interaction and Safety Checking System
 *
 * Provides comprehensive drug safety checks:
 * - Drug-drug interactions
 * - Contraindication checking
 * - Dosing validation
 * - Allergy cross-reactivity
 * - Organ function-based adjustments
 * - Pregnancy/lactation safety
 * - QT prolongation risk assessment
 * - CYP450 interaction analysis
 *
 * Data sources would include:
 * - FDA drug labels
 * - DrugBank
 * - PharmGKB
 * - Clinical Pharmacology databases
 */
import { EventEmitter } from 'events';
export interface Drug {
    name: string;
    genericName: string;
    brandNames?: string[];
    drugClass: string;
    rxNormId?: string;
    ndc?: string;
    atcCode?: string;
    mechanism?: string;
    metabolism?: {
        cyp450?: CYP450Profile;
        renalExcretion?: number;
        hepaticMetabolism?: number;
    };
}
export interface CYP450Profile {
    substrates?: string[];
    inhibitors?: string[];
    inducers?: string[];
}
export interface DrugInteraction {
    drug1: string;
    drug2: string;
    severity: 'contraindicated' | 'major' | 'moderate' | 'minor';
    type: 'pharmacokinetic' | 'pharmacodynamic' | 'additive' | 'synergistic' | 'antagonistic';
    mechanism: string;
    clinicalEffect: string;
    management: string;
    documentation: 'established' | 'theoretical' | 'case-report';
    references?: string[];
}
export interface Contraindication {
    drug: string;
    condition: string;
    severity: 'absolute' | 'relative';
    reason: string;
    alternatives?: string[];
}
export interface DosingGuideline {
    drug: string;
    indication: string;
    standardDose: string;
    renalAdjustment?: {
        gfrThreshold: number;
        adjustment: string;
    }[];
    hepaticAdjustment?: {
        childPughClass: 'A' | 'B' | 'C';
        adjustment: string;
    }[];
    ageAdjustment?: {
        ageThreshold: number;
        adjustment: string;
    }[];
    weightBasedDosing?: {
        formula: string;
        maxDose?: string;
    };
}
export interface AllergyCheck {
    reportedAllergy: string;
    drugToCheck: string;
    crossReactivity: boolean;
    riskLevel: 'high' | 'moderate' | 'low' | 'none';
    relatedAllergens: string[];
    recommendation: string;
}
export interface SafetyAlert {
    id: string;
    type: 'interaction' | 'contraindication' | 'allergy' | 'dosing' | 'organ-function' | 'pregnancy' | 'qt-prolongation' | 'black-box';
    severity: 'critical' | 'high' | 'moderate' | 'low';
    title: string;
    description: string;
    affectedDrugs: string[];
    recommendation: string;
    overridable: boolean;
    requiresDocumentation: boolean;
    references?: string[];
}
export interface PatientSafetyProfile {
    patientId: string;
    allergies: {
        allergen: string;
        reactionType: 'anaphylaxis' | 'rash' | 'angioedema' | 'gi' | 'other';
        severity: 'severe' | 'moderate' | 'mild';
    }[];
    renalFunction: {
        gfr: number;
        creatinine: number;
        dialysis: boolean;
    };
    hepaticFunction: {
        childPughClass?: 'A' | 'B' | 'C';
        bilirubin?: number;
        albumin?: number;
        inr?: number;
        ascites?: 'none' | 'mild' | 'moderate-severe';
        encephalopathy?: 'none' | 'grade-1-2' | 'grade-3-4';
    };
    cardiacStatus: {
        qtcInterval?: number;
        lvef?: number;
        arrhythmiaHistory?: boolean;
        pacemakerIcd?: boolean;
    };
    currentMedications: {
        drug: string;
        dose: string;
        frequency: string;
        startDate?: Date;
    }[];
    demographics: {
        age: number;
        weight: number;
        gender: 'male' | 'female';
        pregnant?: boolean;
        breastfeeding?: boolean;
    };
    geneticFactors?: {
        cyp2d6?: 'poor' | 'intermediate' | 'normal' | 'rapid' | 'ultra-rapid';
        cyp2c19?: 'poor' | 'intermediate' | 'normal' | 'rapid' | 'ultra-rapid';
        dpyd?: 'deficient' | 'intermediate' | 'normal';
        ugt1a1?: '*28/*28' | '*28/*1' | '*1/*1';
        tpmt?: 'poor' | 'intermediate' | 'normal';
    };
}
export declare class DrugSafetyService extends EventEmitter {
    private interactionDatabase;
    private contraindicationDatabase;
    private dosingGuidelines;
    private allergenCrossReactivity;
    private qtProlongingDrugs;
    private blackBoxWarnings;
    constructor();
    /**
     * Perform comprehensive safety check
     */
    performSafetyCheck(patient: PatientSafetyProfile, proposedDrugs: {
        drug: string;
        dose: string;
        route: string;
    }[]): Promise<{
        safe: boolean;
        alerts: SafetyAlert[];
        summary: {
            criticalAlerts: number;
            highAlerts: number;
            moderateAlerts: number;
            lowAlerts: number;
            overallRisk: 'critical' | 'high' | 'moderate' | 'low' | 'minimal';
        };
        recommendations: string[];
    }>;
    /**
     * Check drug-drug interactions
     */
    checkDrugInteractions(drugs: string[]): Promise<SafetyAlert[]>;
    /**
     * Check contraindications
     */
    checkContraindications(drugs: string[], patient: PatientSafetyProfile): Promise<SafetyAlert[]>;
    /**
     * Check allergy cross-reactivity
     */
    checkAllergies(drugs: string[], allergies: PatientSafetyProfile['allergies']): Promise<SafetyAlert[]>;
    /**
     * Check dosing based on organ function
     */
    checkDosing(drugs: {
        drug: string;
        dose: string;
        route: string;
    }[], patient: PatientSafetyProfile): Promise<SafetyAlert[]>;
    /**
     * Check QT prolongation risk
     */
    checkQTProlongation(drugs: string[], patient: PatientSafetyProfile): Promise<SafetyAlert[]>;
    /**
     * Check pregnancy and lactation safety
     */
    checkPregnancySafety(drugs: string[], patient: PatientSafetyProfile): Promise<SafetyAlert[]>;
    /**
     * Check black box warnings
     */
    checkBlackBoxWarnings(drugs: string[]): Promise<SafetyAlert[]>;
    /**
     * Check pharmacogenomic considerations
     */
    checkPharmacogenomics(drugs: string[], genetics: NonNullable<PatientSafetyProfile['geneticFactors']>): Promise<SafetyAlert[]>;
    /**
     * Get recommended alternatives for a contraindicated drug
     */
    getAlternatives(drug: string, reason: string, patientProfile: PatientSafetyProfile): string[];
    private initializeDatabases;
    private addInteraction;
    private findInteraction;
    private mapInteractionSeverity;
    private checkCrossReactivity;
    /**
     * Generate a medication reconciliation report
     */
    generateMedicationReconciliation(patient: PatientSafetyProfile): Promise<{
        currentMedications: string[];
        interactions: DrugInteraction[];
        recommendations: string[];
        summary: string;
    }>;
}
export default DrugSafetyService;
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