Pain Pharmacology Introduction (PDF)

12.3.5 Introduction to the Pharmacology of Analgesia and Pain Relief Pharmacology division  PHARMACOLOGY OF ANALGESIA AND PAIN RELIEF Learning objectives At the end of this session, you will be able to describe: The main types of pain experienced by patients. The gener...

12.3.5 Introduction to the Pharmacology of Analgesia and Pain Relief Pharmacology division  PHARMACOLOGY OF ANALGESIA AND PAIN RELIEF Learning objectives At the end of this session, you will be able to describe: The main types of pain experienced by patients. The general treatments for nociceptive pain. The general treatments for neuropathic pain. Local anaesthesia as used in dental procedures. 2 PHARMACOLOGY OF ANALGESIA AND PAIN RELIEF Pain is defined by the International Association for the Study of Pain (IASP) as an unpleasant sensory and emotional experience associated with actual or potential tissue damage. Cerebral cortex Following stimulation of the sensory nerves, the signal is transmitted via the spinal cord to the cerebrum and then to cerebral cortex where it is perceived as a cerebrum sensation. Sensory nerves Spinal cord Pain is subjective and dependent on individual differences. 3  PHARMACOLOGY OF ANALGESIA AND PAIN RELIEF TYPES OF PAIN Nociceptive pain Neuropathic pain ✓ Pain generated via nociceptors ✓ Pain arising from damage to which respond to thermal, /disease of the nervous systems mechanical, chemical insult. (peripheral and/or central). ✓ May be superficial or more deep- set. ✓ May be as a consequence of; e.g.: stroke or cancer. ✓ May be caused by; e.g.: soft tissue damage, infection, or inflammation. 4 PHARMACOLOGY OF ANALGESIA AND PAIN RELIEF TYPES OF PAIN Nociceptive pain Neuropathic pain Thermal, Mechanical, Stroke or cancer Chemical insult Damage to or disease Soft tissue damage, of the nervous infection or systems inflammation. Peripheral and/or Pain generated via nociceptors central Pain Pain 5 Treatment of pain types  A- Treatment of nociceptive pain 1. NSAIDs (non-steroidal anti-inflammatory drugs) INJURY Arachidonic acid Leukotrienes (Asthma mediators) COX-1 COX-2 NSAIDs Protective Inflammatory Prostaglandins Prostaglandins Pain Inflammation Protect gastric mucosa Pyresis 7 1. Treatment of nociceptive pain by NSAIDs Prostaglandins are released during/after injury and infection, which leads to inflammation and pain. Prostaglandins are produced from arachidonic acid by the action of the enzyme cyclo-oxygenase (COX). Inhibiting the action of COX will reduce the production of prostaglandins and reduce inflammation and pain. Therefore, they can treat the underlying cause (inflammation). 8 1. Treatment of nociceptive pain - NSAIDs Non-steroidal anti-inflammatory drugs (NSAIDs): They’re COX inhibitors so will be anti-inflammatory and analgesic. Examples: aspirin, ibuprofen, piroxicam, mefenamic acid, diclofenac, ketoprofen, indomethacin, naproxen Suitable for general aches and pains, dental pain (e.g.: after tooth extraction), period pain (dysmenorrhea), headache, hangovers, arthritis, musculo-skeletal pain. NSAIDs are also anti-pyretic (against fever) 9 1. Treatment of nociceptive pain – NSAIDs NSAIDs Side-effects (due to the COX inhibition): a- Prostaglandins have a protective effect on gastric mucosa; NSAID cause stomach irritation and ulceration in extreme cases. Ibuprofen lowest risk, naproxen highest risk. b- NSAIDs can precipitate an asthma attack in sensitive individuals,(due to increase in leukotrienes) [Use with care in asthmatic patients!] c- Patients who are allergic to aspirin must avoid ALL NSAIDs d- Aspirin should not be used in children under 16 (risk for Reye’s syndrome)]. 10  Treatment of nociceptive pain 2. - Paracetamol / Acetaminophen Paracetamol = UK and Acetaminophen = US. Analgesic and anti-pyretic activity similar to aspirin and ibuprofen, but very little anti-inflammatory activity. Side-effects may be less than other NSAIDs. Can be fatal in overdose (effect on liver). Use with caution in liver impairment (poor metabolism). 11  Treatment of nociceptive pain 3. Opioids Opioids are also known as "narcotics" An "opioid" is a general term to describe any drug or compound which resembles morphine in its biological action. They are isolated from opium poppy. Opioids may have a variety of chemical structures. Natural ligands are endorphins and enkephalins (natural pain killers) endorphins and enkephalins release can be stimulated by exercise and excess chilli/curry eating. 12  Treatment of nociceptive pain 3. Opioids Opioids act as agonists on the opioid receptors. Opioid receptors are located in the brain, spinal cord, and GI tract. Opioid receptors are sub-divided into mu (μ), delta (δ), and kappa (κ) receptors. 13  Treatment of nociceptive pain 3- Opioids Analgesic effect is mainly due to action on  receptors. Side-effects are due to their action on , δ and κ receptors: Receptor Associated side effect (s)  Euphoria (overwhelming feeling of happiness) δ Convulsions κ Dysphoria (dissatisfaction with life) &δ Respiratory depression – Physical dependence – Nausea & vomiting &κ Pupil constriction – Sedation (pinpoint pupil) 14  Treatment of nociceptive pain 3-Opioids General rules for opioid treatment ✓ Try non-opioid first (single or combination). ✓ Start with the lowest strength opioid, e.g. codeine, either alone or in combination with an NSAID. ✓ Monitor the relationship between efficacy and side-effects. Morphine use ✓ Commonly used post-operatively (relatively short-term) or for the treatment of pain associated with cancer (long-term). ✓ Typical starting dose 20 to 30 mg per day orally. ✓ Increase as necessary 15  Treatment of nociceptive pain 3 - Opioids Chemistry & pharmacology of codeine, morphine, diamorphine: Codeine and diamorphine: are pro-drugs (converted in the body to morphine) Therefore, Intact codeine and diamorphine bind less well to the  receptor than morphine. A- Codeine: It is de-methylated by the enzyme CYP 2D6 in the liver to produce morphine (Analgesic effect of codeine is related to the extent of the conversion to morphine (normally about 10 %). ✓ Some patients lack CYP 2D6, so have no clinical response to codeine analgesia. 16  Treatment of nociceptive pain 3 - Opioids Chemistry & pharmacology of codeine, morphine, diamorphine: B- Diamorphine It is more lipophilic than morphine so crosses the blood brain barrier into the CNS more easily. Diamorphine is hydrolysed by esterases to produce 6-acetyl morphine after one hydrolysis reaction then morphine after two hydrolysis reactions. 6-acetyl morphine is more potent at the  receptor than morphine. Overall diamorphine is a more effective drug than morphine. 17  B. Treatment of neuropathic pain More difficult to treat than nociceptive pain, as the underneath causes and biological processes are more diffuse and less well understood. Initial treatment is as for nociceptive pain - "trial and error“. Some centrally (on brain) acting drugs developed for other uses have some effect on neuropathic pain: ✓ Gabapentin and pregabalin (anti-convulsants) ✓ Amitriptyline (anti-depressant) ✓ Some severe side effects, eg sedation, confusion 18  PHARMACOLOGY OF ANALGESIA AND PAIN RELIEF WHO Pain ladder Originally developed for the treatment of pain associated with cancer. Now used for all types of pain. An adjuvant is (something to help with the pain control / manage side effects) 19  WHO Pain ladder Opioid for moderate/severe pain ± non-opioid ± adjuvant Opioid for mild/ moderate pain ± non-opioid ± adjuvant non-opioid ± adjuvant 20  II- Anaesthesia Anaesthesia is defined as: A loss of sensation or an inability to feel pain. It is used to remove the sensation of pain from patients undergoing surgery. Types: 1- General anaesthesia: relates to complete loss of sensation i.e.: unconsciousness for major operations. 2- Local anaesthesia: relates to loss of sensation in a specific part of the body to allow minor operations (e.g.: dental extractions). 21  Dental local anaesthetics Most commonly used drug is lidocaine. The tertiary nitrogen (N) will partially ionise in aqueous media, such as the injection solution. The un-ionised form of the drug will cross the membrane into the nerve cell. In the cell it will be partially ionise again. 22  Dental local anaesthetics In the cell it will be partially ionise again. The ionised form blocks the Na+ channels inside the nerve cell, so there is no Na+ influx and no action potential, hence no pain sensation. Duration of action is a few hours. Its Action is terminated by hydrolysis of the amide group. 23  Dental local anaesthetics Duration of action is potentiated by epinephrine (adrenaline) Epinephrine (adrenaline) prolongs the effect of local anaesthetics: It acts as a vasoconstrictor that reduces blood flow from the injection site. Reduces the removal of the drug from the injection site. 24  PHARMACOLOGY OF ANALGESIA AND PAIN RELIEF Conclusion Pain relief and anaesthesia have complicated pharmacology. The general rule for treatment is to try to understand the biological basis of the pain and treat that. Start with NSAIDs and work up to opioids if necessary. Watch out for side effects. Local anaesthetics causes loss of sensation in a specific part of the body The use of epinephrine prolongs the effect of local anaesthetics. 25