When norepinephrine is depleted, tyramine is no longer effective Tolerance Decreased responsiveness to repeated doses of same or related drug.
Time scale is days - weeks.
Heart rate increases in face of vasodilator. Organophosphates inactivate acetylcholinesterase permanently. New enzyme must be synthesized to repaire drug action. Alkylating anticancer drugs, e.g., cyclophosphamide. Breaks DNA chain and or causes cross-linking of the DNA strands.