Identify the role you need: mainly bitterness/spice (aromatic/orange bitters) or mainly bitter-sweet flavor (syrup/soda/coffee).
Start with the listed ratio: use equal drops for bitters-to-bitters swaps; for syrups/sodas/coffee, use less because they change sweetness and body.
Stir, taste, and adjust: if the drink lacks “edge,” add 1–2 more drops; if it tastes too sweet or heavy, reduce the substitute and rebalance with the original mixer.
For citrus-forward drinks, favor aromatic/orange-style substitutes; for darker spirits, a tiny amount of coffee can add “bitters-like” depth.