Multi Modal Analgesia

Transcription

1 Analgesic Drugs and Pharmacology Richard Craig R.N. B.N. M. Sci. Med (Pain Mgmt) Nurse Consultant Acute Pain Management Service Christchurch Hospital Multi Modal Analgesia Patients benefit from multi modal analgesia following surgery. Combinations of analgesic drugs are used to improve pain relief, reduce the dose of each analgesic drug and reduce intensity of side effects. Types of pain Nociceptor pain - Somatic Structures involved Skin,muscle,bones and tissues. Quality of pain- Easy to localize,stabbing, boring. movement dependant Nociceptor pain. VISCERAL Structures involved-parenchymatous organs,hollow viscera,peritoneum. Quality of pain: Difficult to localize,dull, oppressive,colicky. Neuropathic pain. Structures involved: Nociceptic system(peripheral nerves,spinal cord cerebrum) Quality of pain: Shooting, lancing, electric shock like, burning. Neuropathic pain Structures involved: Nociceptic system(peripheral nerves,spinal cord, cerebrum) Quality of pain: Shooting,lacinating,electric shock-like,burning 1

2 Classes of pain medications Paracetamol Non Steriodal Anti Inflammatories(NSAIDs) Codeine Tramadol Opioids Neuropathic pain options (TCA,Antiepileptics,NMDA receptor antagonists.) Topicals PARACETAMOL Mild to moderate pain Onset 10-30min, peak 1 hr Duration of action 4-6hrs Inexpensive, effective drug High bio availability,well absorbed with low side effect profile. Analgesic, antipyretic, weakly anti inflammatory actions. Adjunct to opioids in severe pain, (opioid sparing). Significant central action??cox 3 inhibitor (animal studies) 4gm/24hr P.O. Adult dose (Regular not PRN). Overdose / hepatic necrosis (alcohol/malnourishment may also be predisposing factors for hepatotoxicity). Dosing Adults:1 gm oral/rectal 4-6 hrly or 1gm IV (Perfalgen) Schoolchildren: 5oomg oral/rectal or 500mg IV Toddlers250mg rectal Infants 125mg rectal (General dose formula for single dose:20mg/kg body weight) Adverse effects In therapeutic doses well tolerated, minimal side effects. Death from overdose rare but does happen. Hepatotoxicity with overdose caused by metabolite N- acetyl-p-benzoquinone imine(napqi). NAPQI normally inactivated by combination with glutathione then excreted via kidneys. Excessive dosing paracetamol may exhaust livers glutathione stores. Antidote Parvalax. NSAIDS (Mechanism of action) Exhibit a spectrum of analgesic anti-inflammatory inflammatory antiplatlet and antipyretic actions. Inhibit the enzyme cyclo-oxygenase oxygenase which metabolizes arachidonic acid to a large number of eicosanoids, including prostaglandins,prostacycline and thromboxane. This mechanism of action explains the wide range of adverse effects of NSAIDS as eicosanoids have protective functions in the intestine mucosa,kidney and are linked to platelet function Anti-inflammatory inflammatory effect is related to reduction of prostaglandins which act as mediators of inflammation. Analgesic effect is result of decreased prostaglandin synthesis in the periphery leading to decreased sensitization of nociceptors. Also cyclo-oxygenase oxygenase inhibition in the CNS reduces prostaglandin formation in spinal cord and brain and thereby central sensitization. 2

3 Non Steroidal Anti Inflammatories (NSAIDS) Mild to moderate pain (unsuitable as the sole agent following major surgery but effective after minor surgery eg day stay/ gynae /dental. Relatively contraindicated post tonsillectomy) Anti inflammatory, anti pyretic,, analgesic. Reduce inflammation by blockade of prostaglandin synthesis. Enhance quality of opioid analgesia, opioid sparing, decrease opioid side effects. Especially good in dynamic movement pain.?? Role in malignancy prevention( eg bowel cancer.) RISKS/ DRAWBACKS Association with G. I. Ulceration and bleeding (cox 1) May cause renal dysfunction (extreme caution with elderly) Asthma in susceptible patients. Ceiling dose. Large and individual variation in minimal effective dose, toxic dose and ceiling dose. Cox 2s all under a cloud ( no platelet inhibition, increased risk of stroke M.I. with chronic use). May cause headache, constipation,cognitive impairment in elderly. Expensive. NSAIDS: Being Sensible Specifically look for contraindications, eg renal status, asthma, hx stomach ulcers Restrict duration of NSAID treatment to 2 to 4 days post op. (STOP DATE) If recommended doses fail to achieve pain relief increasing dose is unlikely to help (ceiling effect) Increasing doses increases risks of adverse effects,(recommended doses are already maximal) If one NSAID fails to achieve pain relief swapping to another is unlikely to help.(unlike opioid rotation). Patients at high risk Aged under 65 yrs and 2 risk factors. Aged over 65 yrs and one risk factor Risk Factors. Hx of peptic ulcer Hx of GI bleeding Concomitant use of meds eg anti coags, steriods. Significant co-morbidities eg CVD, cirrhosis Prolonged and high dose NSAID use. TRAMADOL Analgesic with minimal sedation, G.I. disturbance, resp. depression or abuse potential.(caution still indicated in pts with Hx drug abuse.) Weak Mu opioid agonist.(o-desmethyl Tramadol metabolite) Also has spinal and CNS effects via noradrenergic and serotoninergic pathways. Therefore both opioid and non opioid analgesic. Safer than other opioids in higher doses.(although still possible to cause sedation, resp. depression) Less constipating than other opioids. Tramadol Dosing Can be up to 600mg daily but usually 400mg maintenance dose (50-100mg 4-6hrly) 50mg tramadol approx equal to 60mg codeine for pain relief. Onset 1 hour after oral dose. Peak 2-4 hrs after oral dose. Duration of analgesia 9 hrs (approx) 3

4 DISADVANTAGES High affinity with nausea.( Start low and go slow may avoid this eg 50mg t.d.s.-100mg qid.) Parental tramadol produces less analgesia than equivalent morphine in severe post op pain. Contraindicated for pts taking SSRIs. Expensive. Elderly Patients Over 75 yrs recommended daily max is 300mg/day 50 mg doses may be preferable Some centres do not favour Tramadol in the elderly. Adverse Effects Common- nausea, vomiting, tremor,headache,rash,sweating. More serious reactions- confusion,hallucinations,convulsions,serotonin syndrome,hypertension,hepatic reactions, warfarin interactions. Serotonin Syndrome Tramadol may cause serotonin syndrome. Particularly at high doses or in conjunction with serotonin enhancing agents including anyidepressants,ondansetron,l dopa, lithium, and some illegal drugs such as amphetamines,cocaine,lsd,ecstacy. Diagnosis of Serotonin Syndrome Requires 3 of the following. changes in mental state. agitation. hyperflexia. Sweating. Tremor. diarrohoea. Fever. incoordination. Seizures Tramadol lowers the seizure threshold. Risk increases with excessive dosing. Caution in patients with hx of epilepsy,combination of other drugs which lower the seizure threshold (SSRI,opioids,antihistamines). Other seizure risks eg head injury, alcohol withdrawl,cns infections. 4

5 OPIOIDS TERMINOLOGY: OPIOIDS are drugs which bind to opioid receptors, this includes agonists such as morphine, pethidine and fentanyl as well as antagonists such as naloxone. OPIATES are drugs derived from opium, mostly morphine, codeine and their families. However it is commonly, but incorrectly, used to include other opioid agonists such as pethidine and methadone. NARCOTICS Term was originally used for drugs that produced sleep like state (narcosis), then for drugs (usually from opium) that both produced pain relief and sleep like state, it is no longer a medically useful term because it has been hi jacked into legal circles and is now often used to include many other drugs used illegally such as cannabanoids, amphetamines, etc that have nothing to do with opium. OPIOIDS Cornerstone of post op pain management for moderate to severe nociceptive pain. Effective and inexpensive. Produce sense of wellbeing and promote sleep. Act at supraspinal level (brain stem), spinal cord level(greatest density of opioid receptors around c fibre terminals in lamina 1 and in substansia gelatinosa, (70%Mu, 24% delta, 6% kappa) Peripherally CODEINE Analgesic for mild to moderate pain. Limited use in the management of severe pain. Undergoes less first pass metabolism than oral morphine.(60% effective orally as parentally) Once absorbed 10% of codeine is metabolised by liver to morphine. (CYP-2D6) 10% of adult population lack this ability therefore codeine will be ineffective for them. Probably the most constipating opioid. Abuse potential. Oxycodone OxyNorm=Immediate release tablets. Full dose absorbed in first mins with peak effect in mins. Usually dosed every 4-6 hrs. OxyContin=Controlled release capsule. Initial burst release of 40% of dose in first hour. Remaining 60% of dose releases slowly giving it a 12 hour duration of action. Oxycodone What is the difference between Oxycodone, oxynorm and oxycontin? 5

6 OPIOID RECEPTORS Opioid drugs act as agonists at opioid receptors located in brain spinal cord, urinary and G.I.tracts, lung and peripheral nerve endings. Three principal types of opioid receptor Mu, Kappa,Delta.(op3, op2, op1 new classification) endogenous agonists are B-endorphins, encaphalins and dynorphins respectively. Receptor Actions Mu- analgesia, resp depression,euphoria, bradycardia,pruritis, miosis, n+v, physical dependence,inhibition gut. Delta- analgesia Kappa- analgesia,sedation,dysphoria, diuresis Naloxone Pure opioid antagonist. Rapidly reverses opioid induced analgesia and repiratory depression. Short half life (lasts 1-2 hrs May require further doses (close monitoring) Precipitates withdrawal symptoms in opioid dependant patients. Morphine Gold standard Mu selective agonist Least lipid soluble,metabolised by liver, excreted kidneys. Can be given IM, IV, SC, oral, transmucosal, rectal epidural, intrathecal. Metabolic Toxicity Oral morphine loses 40% of potency to first pass effect. Potency of oral morphine to IV is about 3:1 IV provides rapid titration, shortest duration of action, complete systemic absorption. Morphine is metabolised by the liver to morphine-3-glucuronide (M3G) and morphine- 6-glucuronide (M6G) With impaired renal function M6G may accumulate and contribute to analgesia and prolonged sedation. With high dose morphine administration M3G may antagonise the action of morphine causing myoclonic jerks and hyperalgesia. 6

7 Morphine (cont) Dose required to control pain depends on many factors, and not related to any one parameter. There is no ceiling dose or normal range Right dose is that which controls the pain with fewest side effects. Breakthrough Doses Should be short acting and immediate release. Dose should be appoximately1/6 of daily dose. Eg MorphineSR 30mg bd Breakthrough Morphine IR 10mg IR every hour as needed. The rule of 3! If 3 or more breakthrough doses are needed in 24 hrs for 3 or more days the SR dose should be increased. Pethidine Mu selective agonist, weak affinity for NMDA receptor. Administer IV, IM,oral, rectal, transmucosal, epidural, intrathecal, (Not SC) Myocardial depression with larger doses Metabolised liver, excreted kidneys, contraindicated if taking MOIs. Pethidine Active metabolite norpethidine Accumulation of norpethidine associated with seizures and death. Toxicity will occur in approx 19% of cases where doses exceed 10mg/kg/day OR therapy exceeds 3 days. Impaired renal function increases half life of norpethidine. Naloxone does not reverse (and may aggravate) norpethidine toxicity. Agitation Irritability Nervousness Tremors Twitches Seizures Norpethidine Effects Fentanyl Highly lipid soluble Mu selective agonist Rapid onset, (peak IV 15 mins)short duration of action (IV 30-60mins) Inactive metabolites so good choice in renal impairment. IV, epidural, intrathecal, oral transmucosal ( lollipop ), transdermal (usually not in acute pain and caution in elderly) 7

8 DOSING Dosing schedule for opioids needs to be individualised. (large variation between individuals 5-7 fold.) Response determined in relation to both efficacy AND side effects. Opioid titration (small IV doses) best method for estimating optimal starting dose. In adult patient. In adults AGE rather than weight has been shown to be a better predictor of opioid requirement. Elderly patients require lower doses of opioids to achieve an equivalent analgesic effect and effect is often longer due to age related increase in terminal elimination half life of opioids. Dose Intervals Speed of onset of opioid will be influenced by route and lipid solubility. Time to max blood concentration depends primarily on administration route. Time to maximum effect then depends upon the rate at which the drug crosses to CNS and opioid receptors. 8