Module 2: Basic Pharmacology of Controlled Drugs and Substances

Lesson 1

Psychostimulants/amphetamines – Pharmacodynamics/mechanism of action

The mechanisms of action of these stimulants are similar. Methylphenidate selectively inhibits presynaptic transporters (i.e., reuptake) for dopamine and norepinephrine and is dependent on normal neuronal activity. It also increases levels of synaptic dopamine and norepinephrine. Dextroamphetamine and amphetamine salts cause the release of dopamine, norepinephrine, and serotonin (5-HT) into the synapse, and this occurs independently of normal neuronal activity. It also inhibits the MAO enzyme which is responsible for the breakdown of the affected neurotransmitters (Edmunds & Mayhew, 2014).

Effects include increased alertness and energy, a feeling of well-being, decreased appetite, rapid heartbeat and breathing, increased blood pressure, sweating, dilated pupils, and dry mouth. A person may become talkative, restless, excited, feel powerful, superior, aggressive, and hostile, or behave in a bizarre, repetitive fashion. Very large doses produce flushing, pallor, very rapid or irregular heartbeat, tremors, severe paranoia, and frightening hallucinations. Death can result from use as a consequence of burst blood vessels in the brain, heart failure, or very high fever. Violence, accidental or otherwise, is the leading cause of amphetamine-related death (Canadian Pharmacists Association, 2014).

Chronic heavy users may develop malnutrition and amphetamine psychosis, a mental illness similar to paranoid schizophrenia. They may also be prone to violence. Impurities injected with the drug can block or weaken small blood vessels. Kidney damage, lung problems, stroke, or other tissue injury can also result (Canadian Pharmacists Association, 2014).

Although chronic use results in tolerance to the mood-elevating effects of amphetamines, tolerance does not appear to develop to the beneficial effects in the treatment of attention-deficit hyperactivity disorder or narcolepsy. Like cocaine, amphetamines can produce very powerful psychological dependence leading to compulsive patterns of use. Although major physical signs of withdrawal do not occur after chronic high-dose users abruptly discontinue amphetamine use, they may experience extreme fatigue and prolonged but disturbed sleep, and, subsequently, irritability, tiredness, and depression (Canadian Pharmacists Association, 2014).

Amphetamines include dexamphetamine, methamphetamine, and methylphenidate. Amphetamine was first used to treat depression, obesity, narcolepsy, and respiratory depression, and as an energizer in World War II (Poole Arcangelo & Peterson, 2013).


  • Canadian Pharmacists Association. (2014). E-Therapeutics. Ottawa: Author.
  • Edmunds, M.W. & Mayhew, M.S. (2014). Pharmacology for the Primary Care Provider (4th ed.). St. Louis, MO: Mosby
  • Poole Arcangelo, V., Petersen, A.M. & Wilbur (2016). Pharmacotherapeutics for advanced Practice: A practical approach. Wolters Kluwer: Philadelphia.