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Pharmacology of Analgesics

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Chronic Pain Management in General and Hospital Practice

Abstract

Basic aspect: Each analgesic drug acts under its pharmacokinetics and pharmacodynamics. Pharmacokinetics is defined how each drug is affected by the body, whereas pharmacodynamics is defined how each drug affects the body.

Pharmacokinetics: A number of different models have been developed in order to simplify many processes that take place in the interaction between the body and the drugs. Although the multi-compartment model gives the best approximation to real processes of drugs inside the body, the monocompartmental models and especially two compartmental models are the most frequently used, as many factors are involved in using the multi-compartment model.

The various compartments are commonly referred to as the LADME scheme, liberation, absorption, distribution, metabolization, excretion. Based on this conception, various compartment models are proposed.

Pharmacodynamics: The study of the biochemical and physiological effects of drugs on the body metabolism. The majority of drugs either activates or inhibits normal physiological and/or biochemical processes in the body or inhibits vital processes of endo- or ectoparasites and microbial organisms. There are seven main actions: stimulating action, derepressing action, blocking/antagonizing action, exchanging/replacing substances, direct beneficial chemical reaction (radical scavenging), direct harmful chemical reaction (cytotoxicity).

Clinical Aspect: Nonsteroidal anti-inflammatory drugs (NSAIDs) should be considered as the first choice of treatment for superficial somatic pain. Adjuvant drugs may enhance the efficacy of analgesics or have analgesic activity of their own. NSAIDs inhibit the activity of cyclooxygenase isoenzymes COX-1 and COX-2 and, consequently, the synthesis of prostaglandins. Prostaglandins affect vascular tone and permeability, modulates inflammation, and influences pain perception. Acetylsalicylic acid (aspirin) is effective in the treatment of most types of mild-to-moderate pain. Ketorolac is available in both oral and parenteral formulations. Intolerance to NSAIDs is most likely to occur in individuals with a history of asthma, nasal polyps, and chronic urticarial states. Therapeutic doses of NSAIDs may cause nausea and vomiting and have been associated with abdominal pain, diarrhea, and dyspepsia. NSAIDs may also have side effects such as antithrombotic effect, hepatotoxicity, renal toxicity, cardiovascular toxicity, CNS side effects (tinnitus, dizziness, anxiety, drowsiness, confusion, disorientation, depression, and severe headaches), miscarriage in pregnancy, overdosage in children, drug–drug interactions.

There are three types of opioid receptors: mu (μ), delta (δ), and kappa (K). Opioid-receptor agonists produce analgesia by acting primarily at μ-receptors found in the brain, brainstem, spinal cord, and primary afferent sensory neurons. Morphine is the naturally found archetypic opioid analgesic. It is a naturally existing strong, full μ-receptor agonist. Oxycodone is a semi-synthetic strong full μ-receptor agonist. Codeine is a naturally occurring weak, full μ-receptor agonist. Tramadol is a weak, centrally acting μ-receptor agonist with norepinephrine and serotonin reuptake inhibiting activity. Tapentadol is a weak, centrally acting μ-receptor agonist/norepinephrine reuptake inhibitor.

Side effects and precautions of opioid-receptor agonists include intolerance, gastropathy, respiratory depression, CNS side effects (dizziness, drowsiness, sedation, and cognitive changes), tolerance, dependence, discourage (in pregnancy). Basic principle in prescription of analgesic drugs is reviewed in mild, moderate, or severe pain.

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Authors and Affiliations

  1. Niigata University Graduate School of Medicine, Niigata, Japan

    Koki Shimoji

  2. Pain Control Institute, Tokyo, Japan

    Koki Shimoji

  3. Department of Anesthesiology, Red Cross Hospital, Tokyo, Japan

    Hitoshi Fujioka

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  1. Koki Shimoji
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  2. Hitoshi Fujioka
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Correspondence to Koki Shimoji .

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  1. Pain Control Institute, Shinjyuku, Tokyo, Japan

    Koki Shimoji

  2. Feinberg School of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA

    Antoun Nader

  3. Guy’s and St Thomas’ Hospital, Pain Management Centre, London, UK

    Wolfgang Hamann

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Shimoji, K., Fujioka, H. (2021). Pharmacology of Analgesics. In: Shimoji, K., Nader, A., Hamann, W. (eds) Chronic Pain Management in General and Hospital Practice. Springer, Singapore. https://doi.org/10.1007/978-981-15-2933-7_5

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  • DOI: https://doi.org/10.1007/978-981-15-2933-7_5

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