3. Pain, analgesia and anaesthesia

Section 3. Pain, analgesia and anaesthesia




3.2 Opioid analgesia 91


3.3 Nonsteroidal anti-inflammatory drugs and paracetamol 102


3.4 Anaesthesia 109



3.1. Pain, analgesia and anaesthesia – overview



Drugs that provide pain relief are called analgesics. Ideally analgesics should relieve pain without affecting other sensations or consciousness. Following the administration of any analgesic it is important to reassess the pain felt by the patient and evaluate the effect of the drug.

Anaesthesia is a loss of feeling in a part or all of the body. In pharmacology it is the reduction of pain that allows otherwise painful procedures to be carried out. General anaesthesia renders the patient unconscious whereas local anaesthesia blocks sensory nerve transmission in one area.


Pain


Pain is an unpleasant sensory and emotional experience that is also a protective mechanism and as such gives warning of the presence of injury or disease.


▪ Pain alerts us to damaging forces in and around our bodies.


▪ The sensation of pain is evoked by the excitation of nerve cells in the brain but pain intensity is difficult to measure objectively.


▪ It is associated with emotion such as anxiety, fear and alarm more than many other sensations.


▪ Acute pain is a common symptom that frequently aids diagnosis, as in acute appendicitis or myocardial infarction. Usually it may be effectively dealt with by analgesia and the cause can be found and treated.


▪ Chronic pain causes much suffering and often appears to serve little purpose. It may be debilitating for the patient and is often the most difficult type of pain to treat, often not responding to standard analgesic drugs.


▪ Chronic pain syndrome is a term used to describe the situation when disease appears to have disappeared but pain persists.


▪ Pain is an unpleasant sensory experience that relies on the nervous system to conduct impulses to the brain where sensation is interpreted. Should anything interfere with this pathway, such as damage to the spinal cord, pain will not be felt no matter how much damage is occurring to the body.


▪ Neuropathic pain can occur as a result of injury or disease to the nerve tissue itself. This can disrupt the ability of the sensory nerves to transmit correct information to the brain which may then interpret painful stimuli as present even though there is no obvious or known physiological cause for the pain. Neuropathic pain is very difficult to treat and does not respond well to opioids or nonsteroidal anti-inflammatory drugs (NSAIDs).



▪ Pain can sometimes appear to come from where an amputated limb used to be. This is known as phantom limb pain and may be excruciating and difficult to treat.


▪ Pain felt is not just determined by the intensity of the painful stimulus but is also a subjective experience with strong central and emotional components. This means that intense pain may sometimes be felt when the brain’s interpretation of a harmless stimulus is deranged. An example of this is seen in trigeminal neuralgia when a minimal mechanical stimulus to the face triggers brief but excruciating pain in one of the branches of the trigeminal nerve in the face.


▪ Emotions such as fear, anxiety and depression are inseparable from pain and can alter the intensity and response to pain.


Pain relief


Drugs that relieve pain are chosen according to the cause and severity of the pain. They fall into the following categories:


▪ Narcotic or opioid analgesics such as morphine. These act on the central nervous system (CNS) reducing the appreciation of pain but sometimes causing drowsiness.


▪ Paracetamol and NSAIDs such as aspirin which act peripherally to reduce pain and inflammation, especially of musculoskeletal origin. Do have some central action too.


▪ Local anaesthetics such as lidocaine that suppress conduction along sensory nerve fibres from the painful area.


▪ Adjuvant drugs that are used alongside analgesics in pain management. These include various centrally-acting nonopioid drugs such as amitriptyline, an antidepressant, and gabapentin, an antiepilepsy drug .


▪ Drugs for specific conditions – carbamazepine for trigeminal neuralgia, ergotamine for migraine.

The World Health Organisation (WHO) has produced an analgesic ladder as a guide to prescribing pain relief. The ladder forms the basis of many approaches to the use of analgesic drugs and essentially has three steps. If the patient does not experience pain relief on one step of the ladder, they should move onto the next.

Step 1: nonopioids – paracetamol and NSAIDs.

Step 2: mild opioids – codeine, dihydrocodeine – may be combined with paracetamol or a NSAID.

Step 3: strong opioids – e.g. morphine – larger doses give more pain relief – no ceiling effect.

Drugs used in analgesia and anaesthesia are described in the chapters within this section.


3.2. Opioid analgesia



It has been known since 1975 that opioid peptides are actually produced by our own bodies. These include endorphins, enkephalins and dynorphins that are sometimes called ‘the brain’s own morphine’. These endogenous opioids are neurotransmitters in the pain inhibitory pathway and attach to opioid receptors in the CNS. Their presence explains why the brain actually has opioid receptors.


Opioid receptors


All opioids, whether produced by our own bodies, naturally occurring in the opium poppy or chemically synthesised, interact with specific opioid receptors and thus produce their effects.


▪ There are three major subtypes of opioid receptor named mu (μ), kappa(κ) and delta (δ). Morphine is an agonist at all three types of receptor.


▪ μ Receptors are responsible for most of the analgesic effects of opioids and some of the major unwanted effects e.g. respiratory depression, euphoria, dependence.


▪ κ Receptors do contribute to analgesia at the spinal level but produce less side effects and do not cause dependence.


▪ δ Receptors are more important in the peripheries but do contribute to analgesia.


▪ Drugs may be agonists, antagonists, partial agonists or mixed agonists–antagonists at opioid receptors.


▪ Some drugs are pure agonists. They may be typical morphine-like drugs such as fentanyl that have a high affinity for the μ receptor but also include weak agonists such as codeine.


▪ A weak analgesic like codeine will compete for receptors with a strong drug like morphine and so reduce the efficacy of the latter.


▪ Some opioid drugs may be an agonist at one type of receptor and an antagonist at another.


▪ The effects of opioids are blocked by antagonists such as naloxone, an antidote to opioids.





B978044310217200003X/fx1.jpg is missingAn opioid is any substance that produces morphine-like effects that are antagonised by naloxone.


Morphine


Morphine will be described in full and other opioids briefly discussed.



Clinical effects





▪ Morphine is still the most valuable opioid for severe pain and is the standard to which all other opioids are compared. It is not just an analgesic but also relieves anxiety and produces mental detachment and euphoria.



Box 3.1
CNS depressant and stimulant effects of morphine






















CNS depressant effects CNS stimulant effects
Analgesia CTZ – vomiting
Respiratory depression Constriction of the pupil
Suppression of cough reflex Increased spinal reflexes
Drowsiness and sleep Stimulates the vagus nerve

Occasionally convulsions


▪ Its effects on the peripheral nervous system include constipation, histamine release, urinary retention and increased smooth muscle tone.


Central effects



Analgesia




▪ Morphine both eliminates pain and allows tolerance to pain.


▪ If the pain is still present, it is no longer unpleasant.


▪ It is effective in most kinds of acute and chronic pain.


▪ It remains the drug of choice in terminal cancer care.


Euphoria




▪ Induces a state of relaxation, tranquillity, detachment and well-being that we call euphoria. This is an important component of its analgesic effect.


▪ Occasionally it can cause dysphoria (a feeling of unpleasantness).


▪ Different opioids produce different amounts of euphoria. This is mediated by the μ receptor and does not occur with codeine.


▪ Euphoria depends on the circumstances. In distressed patients it is marked but in those accustomed to chronic pain it is not present although the pain is relieved.


▪ It also causes sleepiness, lethargy and inability to concentrate but this may be destroyed by nausea and vomiting.



Depression of the cough reflex




▪ This does not correlate closely with the analgesic action and respiratory depressant action – may be a different receptor.


▪ Codeine suppresses the cough in subanalgesic doses.


Pupillary constriction




▪ Due to a stimulatory effect on the nucleus of the third cranial nerve.


▪ Important diagnostically in overdosage.


Nausea and vomiting




▪ Chemoreceptor trigger zone (CTZ) of the vomiting centre is stimulated and nausea occurs in approximately 40% of those receiving morphine, vomiting in approximately 15%.


▪ Worse if ambulant.


▪ Does not appear separable from the analgesic action.


▪ Tolerance to this effect occurs with prolonged use.


▪ May be reduced by the administration on an antiemetic such as cyclizine.


Stimulation of the vagus nerve




▪ This may cause bradycardia and lowering of blood pressure. May be important when used as an analgesic in acute myocardial infarction.


▪ Reduced output from the hypothalamus to the sympathetic nervous system contributes to vasodilation and hypotension.



Tolerance to morphine





▪ Tolerance is present when an increase in dose is needed to produce the same effect.


▪ Tolerance develops rapidly and may be detected within 12–24 hours of commencement of administration.


▪ The duration of tolerance after the cessation of drug taking varies from a few days to weeks.


Dependence





▪ Both physical and psychological in nature.


▪ Some physical dependence may be detected within 24 hours of regular administration.


▪ Dependence appears to be less when the drug is given for analgesia rather than taken for pleasure.


▪ If physical dependence occurs there are definite withdrawal symptoms when the drug is stopped.


Indications


Moderate to severe pain, especially of visceral origin:


▪ acute pain


▪ following injury


▪ perioperative analgesia


▪ postoperative pain


▪ myocardial infarction


▪ acute left ventricular failure with pulmonary oedema


▪ on a regular basis for terminal cancer-related pain.


Routes of administration



Oral





▪ Oral absorption is incomplete and 70% of the dose is removed by first-pass metabolism, necessitating a larger dose by this route.


▪ Immediate-release tablets may be given every 4 hours.


▪ Modified-release preparations are taken twice daily for long-term pain control.


▪ Oral morphine solutions are also available.


Rectal





▪ Suppositories of morphine 10 mg.


Injection





▪ May be given by subcutaneous or intramuscular route for acute pain, 10–15 mg every 4 hours if necessary.


▪ Analgesia starts within 20 minutes of subcutaneous injection and within 10 minutes of intravenous. The effect peaks after about 1 hour and lasts up to 4 hours.


▪ By slow intravenous injection a quarter to half the intramuscular dose may be given.


▪ Produces analgesia rapidly by this route and the effect peaks in about an hour.


▪ May also be administered as patient-controlled analgesia (PCA) according to hospital protocols.


Contraindications





▪ Acute respiratory depression.


▪ Phaeochromocytoma.


▪ Asthma attack.



▪ Paralytic ileus.



Box 3.2
Head injuries



Morphine is not given to patients with a head injury


• It interferes with pupillary responses


• Carbon dioxide retention caused by respiratory depression results in cerebral vasodilation – in patients with raised intracranial pressure this can lead to alterations in brain function


Cautions





▪ Hypotension.


▪ Asthma (avoid during attack).


▪ Enlarged prostate.


▪ Pregnancy and breast feeding. Opioids cross the placental barrier and so can produce respiratory depression in the newborn.


▪ Care in liver failure but sometimes tolerated well.


▪ Reduce dose in renal impairment or avoid as accumulation occurs causing prolonged action. Morphine is excreted as a metabolite in the urine.

In palliative care these cautions will not always be a deterrent.


Adverse effects


Many of these have been described earlier under clinical effects. They often limit the size of the dose that can be given. The most serious side effect is respiratory depression.


▪ Nausea and vomiting.


▪ Constipation.


▪ Drowsiness.


▪ Tolerance and dependence.

Larger doses produce:


▪ respiratory depression, hypotension, muscle rigidity.

Other side effects include:


▪ difficulty passing urine


▪ dry mouth, sweating, headache, facial flushing, vertigo


▪ bradycardia, tachycardia, postural hypotension, palpitations


▪ hallucinations, mood changes


▪ decreased libido


▪ rashes.





B978044310217200003X/fx2.jpg is missingDependence on morphine is uncommon when the drug is used to treat pain.



Effects of overdosage





▪ Respiratory depression is the main danger.


▪ The patient may be drowsy or unconscious and the pupils are pinpoint.


▪ Cyanosis may be present.


▪ The antidote is naloxone, the opioid antagonist, which may be given intravenously.


Acute withdrawal in opioid dependency


Fear does play a part. After missing only one injection an opioid addict senses mild withdrawal distress.


▪ First 8–16 hours – increasingly nervous, restless and anxious.


▪ Within 14 hours frequent yawns, sweating profusely, running eyes and nose.


▪ All increase in intensity then ‘goose flesh’ occurs and the pupils dilate.


▪ Severe twitching of the muscles occurs within 36 hours and painful cramps in both the legs and the abdomen.


▪ All body fluids are released copiously and vomiting and diarrhoea are acute.


▪ There is very little appetite for food.


▪ Insomnia is present.


▪ The respiratory rate increases.


▪ Blood pressure increases moderately.


▪ Temperature increases by about 0.5 degrees on average and subsides after the third day.


▪ Basal metabolic rate rises steeply in the first 48 hours.


▪ Peaks within 48–72 hours after the last injection of the drug and subsides over the next 5–10 days.

If an addict chooses acute withdrawal, this is known as ‘cold turkey’ and is possible but is unnecessarily cruel.


▪ Methadone is a great help in these situations ( page 100). It is given orally and has a long half-life of 48 hours.


▪ Chlorpromazine and benzodiazepines may be given as well to help.


Opioid antagonists





▪ Produce little effect on their own but block the effects of opioids.


▪ Naloxone is a full antagonist of morphine. It reverses the action of opioids at all three subtypes of receptor. It has greatest affinity for the μ receptor.


▪ The sedative effects, respiratory depression and adverse cardiovascular effects are blocked within 1–2 minutes.


▪ The duration of the antagonist effect is dose dependent but is shorter than morphine so that one dose may be insufficient and an infusion is sometimes required.


▪ If it is administered to opioid addicts, an acute withdrawal occurs.


▪ It may cause hypertension, pulmonary oedema and cardiac arrhythmias.


Diamorphine (heroin)




Mechanism of action





▪ As for morphine and is metabolised to morphine.


▪ Highly lipid soluble and enters the brain more rapidly than morphine so its action starts a little sooner.


▪ Twice as potent as morphine, but rapidly metabolised to morphine.


▪ Greater solubility than morphine so requires a smaller volume for injection. This is important in palliative care when the patient may be emaciated.


Clinical effects





▪ Causes more euphoria but relatively less nausea, constipation and hypotension than morphine.


▪ Is the opioid most frequently used by drug addicts.





B978044310217200003X/fx3.jpg is missingAn addict may take 300 mg of heroin several times a day and some may take as much as 600 mg in one dose. A non-addicted person would die of respiratory depression after such a dose. Addicts who return to the habit after a longish break may inadvertently overdose themselves by using the old dose when tolerance has gone.


Indications





▪ Acute pain, especially myocardial infarction.


▪ Acute pulmonary oedema.


▪ Chronic pain in palliative care.

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Jun 15, 2016 | Posted by in NURSING | Comments Off on 3. Pain, analgesia and anaesthesia

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