The actions of drugs in the human body involve many biochemical and physiologic responses affecting multiple body systems. Medications alter physiology in a way that results in a biochemical change. This change becomes the drug response. This section reviews important concepts of pharmacodynamics necessary to understand pharmacotherapeutics as interventions in the toolkit in treating psychiatric illnesses.

33.2.1 Definitions

The intensity of a biologic response produced by a drug is related to the concentration of the drug at the site of action, which is in turn affected by a variety of factors grouped together under the heading pharmacokinetics. There are four pharmacokinetic phases that all affect drug concentration at the site of action.

“Pharmacodynamics” refers to the study of biochemical and physiologic effects of drugs and their mechanisms of action. Foundational to treatment with psychopharmacologic agents is the idea that the symptoms of psychiatric illnesses result from errors of neurotransmission which affect the patient’s ability to accurately perceive incoming information.

Receptors are specific protein-binding sites inside or on the surface of a cell. The receptor is the component of the cell with which the chemical is presumed to interact. When chemicals bind to receptors, various cellular functions are either activated or inhibited.

Drugs generally affect receptors in two ways: they may bind to them, or may change their behavior towards the host cell system. Binding is influenced by the chemical property of affinity. Affinity is a pharmacological concept that describes the degree of attractiveness between a drug and a specific receptor. It is the product of the mutual attractiveness of the molecular structures of the drug and the receptor.

Axons and dendrites have their own receptors. Axon receptors are called presynaptic, while dendrite receptors are called postsynaptic. Both are sensitive to the smallest fluctuation of chemicals and have the ability to self-regulate. Other receptors, autoreceptors, act like light switches, helping individual neurons to down-regulate, up-regulate, or both (see later).

33.2.2 Agonists and Antagonists

• Agonists are drugs or endogenous substances that trigger actions from a cell or another drug. A drug that is an agonist has attraction to bind to a given receptor. It will activate that receptor and subsequently lead to a change in the function of the cell.
  
• Partial agonists are drugs that exert a similar but weaker effect than a full agonist.
  
• Inverse agonists do the opposite of agonists.
  
• Antagonists block the actions of everything in the agonist spectrum. They are chemicals that bind to a receptor and block it, producing no response, and prevent agonists from binding, or attaching, to the receptor.

33.2.3 Efficacy and Potency

The concept of efficacy has to do with how well a treatment, therapy or procedure under ideal conditions produces a desired health outcome (cure, alleviation of pain, return of functional abilities). Maximal efficacy refers to the maximal effect that a drug can produce. In clinical use, the maximal efficacy of a medication may be limited by its undesired side-effects, and true maximal efficacy may not be achievable.

Potency refers to the measure of a drug’s effectiveness as a medication. Potency may be related to the concentration of a drug in plasma, as well as other factors (i.e., transport across cell membranes, competitive antagonists).

33.2.4 Target Symptoms

Symptoms, rather than specific illnesses, are the foci for treatment in psychiatry. Target symptoms are the specific symptoms that a medication aims to alter. Clinicians must identify and understand patients’ target symptoms before starting them on a medication regimen. Patients should also be helped to understand their target symptoms and participate in identifying and monitoring changes in symptoms. Instruments are available to systematically rate symptoms before and after drug administration and to augment clinician impressions (see Chapter 31).

33.2.5 Refractoriness

Refractoriness (also called down-regulation) occurs when agonists continually stimulate cells. As a result, the cells are repeatedly exposed to the same concentration of the drug, which causes the cells to become desensitized and the drug to have diminished effectiveness (efficacy). Understanding the phenomenon of refractoriness is important in caring for psychiatric patients in that they must take the same medication for months to years. Over time, the efficacy of a medication may diminish, causing the symptoms that first required treatment to reappear. This should not be confused with nonadherence or noncompliance with a medication regimen. Early identification of refractoriness and the resulting changes in medication type or dose could prevent a relapse of symptoms.

33.2.6 Steady State and Medication Half-life

Steady state is a condition during which a fairly constant level of medication is affecting neurons continuously and a desirable response is beginning to happen. It may take four or more weeks for neurons to make consistent changes in electrical charge, release of neurotransmitters, and responses from receptors.

The “rule of 5s” refers to a principle of pharmacology which states that it takes a drug five half-lives to build to a steady state in the body. Half-life refers to the time required for half the dose of a drug to be metabolized or eliminated by normal biologic processes. The half-life is dependent upon many factors, including the health of the individual, diet, and individual differences among patients.

33.2.7 Enzymes

Enzymes are a class of proteins that are involved in multiple aspects of chemical neurotransmission. Enzymes increase the rate of chemical reactions without being consumed or permanently altered by the reaction. They also increase reaction rates without altering the chemical equilibrium between products and reactants. Substrates result when an enzyme acts on a molecule. The substrates for each enzyme are unique and selective. Both are involved in the inhibition and binding of drug receptors and determine selectivity of drug action, the relation between the dose of a drug and its effects, and its therapeutic effectiveness. Inhibitors are drugs that block a specific enzyme system, while inducers are drugs that increase the amount of enzyme production.

33.2.8 Metabolism

Drug metabolism occurs via two phases, referred to as I and II. Phase I involves primarily oxidation reactions including dealkylation, hydroxylation, oxidation, deamination, desulfuration, and sulfoxide formation; this is mediated by the cytochrome P450 (CYP450) system. Phase II metabolism involves conjugation or synthetic reactions that render the molecule more water-soluble and hence available for renal excretion.