Table 1.

Network configurations of the selected hypertensive drug–drug pairs

Drug A	Drug B	Network separation (sAB)	Network pattern	Description
Drug combinations
Hydrochlorothiazide	Nifedipine	0.14	P2	Synergistic reduction of blood pressure in spontaneously hypertensive rats.
Hydrochlorothiazide	Nebivolol	0.29	P2	Hydrochlorothiazide and Nebivolol reduce both diastolic blood pressure and systolic blood pressure vs. baseline in patients.
Captopril	Oxprenolol	0.33	P2	Effectively control blood pressure without any negative metabolic effects.
Hydrochlorothiazide	Telmisartan	0.36	P2	Co-treat hypertension.
Hydrochlorothiazide	Amiloride	0.42	P2	Prevent glucose intolerance and improve blood pressure control compared with monotherapy.
Captopril	Isradipine	0.49	P2	Co-treatment is more effective than captopril given with a low dose of hydrochlorothiazide.
Hydrochlorothiazide	Spironolactone	0.59	P2	Co-treat hypertension and water retention in patients with congestive heart failure or nephrotic syndrome.
Adverse drug interactions
Nadroparin	Spironolactone	−0.11	P1	Increased hyperkalemic activities by co-treatment.
Hydrochlorothiazide	Diazoxide	−0.90	P1	Increased blood sugar more than expected.

Network proximity and drug–drug–disease network pattern analyses for 9 selected drug pairs involving anti-hypertensive drugs on the hypertension disease module. Two network patterns, Overlapping Exposure (P1) and Complementary Exposure (P2), are illustrated in Fig. 2a, b