[Particularities of drug dosing at the beginning and end of therapy]

The starting dose of a drug determines both onset of action and tolerability of the compound. In contrast to most drug therapies, which may immediately be started with regular maintenance doses, compounds undergoing substantial autoinduction (e.g. carbamazepine) must be administered at slowly increasing doses to compensate for an initially low clearance and to avoid toxicity. Gradual dose escalation is also necessary whenever a drug induces substantial counter-regulatory reflex activation or adaptation processes. In these cases administration of standard doses may lead to excessive adverse reactions (e.g. cardiac decompensation after initiation of beta-receptor antagonism). Also in these situations cautious dose titration is required. After long-term administration those drugs should be withdrawn only very carefully to avoid potentially life-threatening withdrawal syndromes like hypertensive emergencies after abrupt discontinuation of clonidine or rebound epilepsies after discontinuation of anticonvulsants.