This presentation will cover several areas starting theoretically and moving through to practical application



Download 494.35 Kb.
Page4/6
Date conversion02.12.2016
Size494.35 Kb.
1   2   3   4   5   6

Prostaglandins have many physiological functions including gastric mucosal protection, renal tubular function and intrarenal vasodilation, bronchodilatation, production of endothelial prostacyclin that leads to vasodilation and prevents platelet adhesion, and platelet thromboxane that results in platelet aggregation and vessel spasm. Such physiological roles are mainly regulated by COX-1 and are the basis for many of the adverse effects associated with ns NSAID use. Tissue damage induces COX-2 production leading to synthesis of prostaglandins that result in pain and inflammation, and COX-2 induction within the spinal cord may play a role in central sensitisation. COX-2 may also be ‘constitutive’ in some tissues,

including the kidney, cardiovascular system and brain (Kam & So, 2009). NsNSAIDs are ‘nonselective’ cyclo-oxygenase inhibitors that inhibit both COX-1 and COX-2. Aspirin acetylates and inhibits cyclo-oxygenase irreversibly but nsNSAIDs are reversible inhibitors of the enzymes. The coxibs have been developed to inhibit selectively the inducible form (Simmons et al, 2004; Gajraj & Joshi, 2005; Botting, 2006).



NSAIDs

Mechanism of Action:Inhibition of Cyclo-oxygenase enzymes (type 1 & 2);Reduce concentrations of PGE2 :

Sensitise peripheral nociceptors to histamine and bradykinin;Centally Increase Substance P and Glutamate Increase sensitivity of second order neurons Decrease NTs from descending pathway



Benefits:Opioid Sparing; Reduced incidence of opioid side effects: Anti-inflammatory effects

Adverse Effects: Platelet Dysfunction; Gastrointestinal Ulceration; Nephrotoxicity; Impaired bone healing; Hypersensitivity

 Non Steroidal anti-inflammatory drugs.(NSAID’s)



  • All have three properties in common

  • analgesic

  • anti-pyretic

  • anti inflammatory

  • Primary action is the inhibition of the production of cyclo-oxygenase (COX) and thus the inhibition of the production of prostaglandins, prostacyclin and thromboxane




  • Prostaglandin function

  • released in response to cell damage

  • sensitise and activate nociceptors to bradykinin

  • some are hyperalgesic PGI2 and PGE2

  • PGE2 inhibits acid secretion and increases mucous secretion in the stomach.

  • Exert a pyretic effect through the hypothalamus

  • vasodilatation and diuresis within the kidney

  • responsible for many endocrine functions

Generic name NNT Elimination 1/2 life Hrs



  • Ibuprofen (400mg) 2.7 2

  • Diclofenac (50mg) 2.3 1




  • Naproxen 15

  • Indomethacin 6

  • Ketoralac 10mg 6

  • Piroxicam (Feldene) 53

Non Steroidal Anti -Inflammatory Drugs



  • Used with caution in the elderly.

  • The route of administration does not influence the potential for serious side effects.

  • Safer to use the NSAIDs with lowest observed risk e.g Ibuprofen, Diclofenac.

Contraindications must be respected.



  • Prior gastric ulceration

  • Concurrent use of oral anticoagulants.

  • Interaction with Ace inhibitors and B blockers.

  • Concurrent use of gentamicin.

NSAID’s


  • Effective for mild to moderate pain

  • Reduces opioid requirement

  • Drug of choice after day case surgery.

  • Selective COX 2 inhibitors e.g meloxicam

(elim. 1/2 life 20 hrs), IV paracoxib (single dose given in theatre) replaces celebrax, (elim. ½ life 10 – 20 min – is a prodrug (no effects on body needs to be metabolized to have effect) – converted to valdecoxib (1/2 life 6 – 8hrs).

Cox 2 inhibitors have less GIT side effects, does not affect platelet aggregation and thromboxane production.


Non Steroidal anti-inflammatory drugs( NSAID’s)

  • Most exhibit a spectrum of action including:

  • analgesic

  • anti-pyretic

  • anti-inflammatory

  • anti-platelet

  • Primary action is the inhibition of the production of cyclo-oxygenase (COX) and thus the inhibition of the production of prostaglandins, prostacyclin and thromboxane

  • Alone are effective for mild to moderate pain and are seen as a component of multimodal therapy for severe pain.

  • May reduce opioid requirements by up to 30%

  • ? Drug of choice after day case surgery.

  • The route of administration does not influence the potential for serious side effects

  • Selective COX 2 inhibitors e.g celecoxib

    • has little or no effect on COX 1 at therapeutic doses.


Potential side effects

    • renal dysfunction

    • gastric irritation

    • reversible platelet dysfunction.

    • trigger asthma

  • Safer to use the NSAID’s with shorter half life e.g. Diclofenac, Ibuprofen, or COX 2.

  • IV - Parecoxib sodium (dynastat) Cox 2 (only given in theatre)

  • Contraindications must be respected.

Paracetamol &NSAIDs Key messages

1. Paracetamol is an effective analgesic for acute pain; the incidence of adverse effects comparable to placebo (S) (Level I [Cochrane Review]).

2. Non-selective NSAIDs are effective in the treatment of acute postoperative and low back pain, renal colic and primary dysmenorrhoea (N) (Level I [Cochrane Review]).

3. Coxibs are effective in the treatment of acute postoperative pain (N) (Level I [Cochrane Review]).

4. With careful patient selection and monitoring, the incidence of nsNSAID-induced

perioperative renal impairment is low (U) (Level I [Cochrane Review]).

5 Non-selective NSAIDs do not increase the risk of reoperation for bleeding after

tonsillectomy in paediatric patients (Q) (Level I [Cochrane Review]).

6. Coxibs do not appear to produce bronchospasm in individuals known to have aspirinexacerbated respiratory disease (U) (Level I).

7. In general, aspirin increases bleeding after tonsillectomy (N) (Level I).

8. Non-selective NSAIDs given in addition to paracetamol improve analgesia compared with paracetamol alone (U) (Level I).

9. Paracetamol given in addition to PCA opioids reduces opioid consumption but does not result in a decrease in opioid-related side effects (N) (Level I).

10. Non-selective NSAIDs given in addition to PCA opioids reduce opioid consumption and the incidence of nausea, vomiting and sedation (N) (Level I).

11. Non-selective NSAIDs and coxibs are effective analgesics of similar efficacy for acute pain (U) (Level I).PTER 4

12. Preoperative coxibs reduce postoperative pain and opioid consumption, and increase patient satisfaction (N) (Level I).

13. Coxibs given in addition to PCA opioids reduce opioid consumption but do not result in a decrease in opioid-related side effects (N) (Level I).

14. Coxibs and non-selective NSAIDs have similar adverse effects on renal function (U) (Level I).

15. Non-selective NSAIDs do not significantly increase blood loss after tonsillectomy but do increase the need for reoperation due to bleeding (N) (Level I).

16. Parecoxib and/or valdecoxib compared with placebo do not increase the risk of

cardiovascular adverse events after non-cardiac surgery (N) (Level I).

17. Coxibs and non-selective NSAIDs are associated with similar rates of adverse

cardiovascular effects, in particular myocardial infarction; naproxen may be associated with a lower risk than other non-selective NSAIDs and celecoxib may be associated with a lower risk than other coxibs and non-selective NSAIDs overall (N) (Level I).

18. Perioperative non-selective NSAIDs increase the risk of severe bleeding after a variety of other operations compared with placebo (N) (Level II).

19. Coxibs do not impair platelet function; this leads to reduced perioperative blood loss in comparison with non-selective NSAIDs (S) (Level II).

20. Short-term use of coxibs results in gastric ulceration rates similar to placebo (U) (Level II).

21. Use of parecoxib followed by valdecoxib after coronary artery bypass surgery increases the incidence of cardiovascular events and is therefore contraindicated (S) (Level II). The following tick boxes þ represent conclusions based on clinical experience and expert opinion.

;; Adverse effects of NSAIDs are significant and may limit their use (U).

;; The risk of adverse renal effects of non-selective NSAIDs and coxibs is increased in the presence of factors such as pre-existing renal impairment, hypovolaemia, hypotension, use of other nephrotoxic agents and ACE inhibitors (U).


Inhalational agents Key messages

1. Nitrous oxide has some analgesic efficacy and is safe during labour (U) (Level I).

2. Nitrous oxide is an effective analgesic agent in a variety of other acute pain situations (U) (Level II).

3. Methoxyflurane, in low concentrations, may be an effective analgesia in the hospital and prehospital setting (N) (Level IV).APTER 4

The following tick boxes þ represent conclusions based on clinical experience and expert opinion.

;; Neuropathy and bone marrow suppression are rare but potentially serious complications of nitrous oxide use, particularly in at-risk patients (U).

;; The information about the complications of nitrous oxide is from case reports only. There are no controlled studies that evaluate the safety of repeated intermittent exposure to nitrous oxide in humans and no data to guide the appropriate maximum duration or number of times a patient can safely be exposed to nitrous oxide. The suggestions for the use of nitrous oxide are extrapolations only from the information above. Consideration should be given to duration of exposure and supplementation with vitamin B12, methionine, and folic or folinic acid (U).

;; If nitrous oxide is used with other sedative or analgesic agents, appropriate clinical

monitoring should be used (U).

 

 



NMDA-receptor antagonists

NMDA receptor/ion channel complexes are sited peripherally and centrally within the nervous system (De Kock & Lavand’homme, 2007). Activation of NMDA receptors via glutamate release from excitatory synapses augments the propagation of nociceptive information and is linked to learning and memory, neural development and neuroplasticity, as well as acute and chronic pain states and opioid-induced tolerance. At the spinal level, NMDA receptor activation results in the development of central sensitisation manifested clinically as hyperalgesia and allodynia

(De Kock & Lavand’homme, 2007; Hocking et al, 2007). The NMDA-receptor antagonists ketamine, dextromethorphan, amantadine, memantine and

magnesium have been investigated for the management of acute pain.


NMDA antagonist Ketamine

  • Used as an analgesic in sub-anaesthetic doses

  • Ketamine bolus loading in PAR

  • May be administered as intravenous infusion - refer to protocol in Pain service folder

  • NMDA receptor antagonist

  • Useful in neuropathic and inflammatory induced pain, patient’s with opioid tolerance.

  • Opioid sparing


Ketalar/Ketamine

Generic Ingredients: ketamine hydrochloride


Company Hospira Australia Pty Ltd
Pregnancy Category  B3*   Drugs which have been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human fetus having been observed. Studies in animals have shown evidence of an increased occurrence of fetal damage, the significance of which is considered uncertain in humans. 

Permitted in sport

Use: Nonbarbiturate IV and IM anaesthetic esp for short procedures; induction prior to other general anaesthetics; supplement to low potency agents

Contra: Hazardous raised BP conditions eg severe CV disease, heart failure, severe or poorly controlled hypertension, recent MI, stroke history, cerebral trauma, intracerebral mass/ haemorrhage

Prec: Acute, chronic alcoholism; incr CSF pressure, IOP; psychiatric illness, neurosis; acute intermittent porphyria; seizures; intracranial mass, lesions, head/ globe injury, hydrocephalus; pulmonary, URTI; hyperthyroidism; hypovolaemia; dehydration; mild-mod hypertension; tachyarrhythmias; abuse potential; sole use in pharynx, larynx, bronchial tree, visceral pain pathway procedures; renal, hepatic impairment; cirrhosis; rapid IV admin (< 60 sec); cardiac disease (monitor); pregnancy; lactation (should not use); others, see full PI

Adverse: Arrhythmia; incr/ decr BP, pulse; respiratory depression, apnoea, laryngospasm; diplopia; nystagmus; emergence reaction (hallucination, illusion, delirium, confusion, excitement, irrational behaviour); anaphylaxis; incr muscle tone; GI effects incl hypersalivation; inj site reaction

Interact: Halogenated hydrocarbon anaesthetics, barbiturates, narcotics; benzodiazepines; ergometrine; theophylline; atracurium; tubocurarine; CNS depressants incl skeletal muscle relaxants; thiopental; thyroid hormones; antihypertensives

Ketalar Solution for injection (S8) Ketamine (HCl); benzethonium Cl; single use vial


Dose Individualise dose; for IMI or slow (60 sec) IVI. Induction. IVI: range 1-4.5 mg/kg; 2 mg/kg usually produces anaesthesia within 30 sec, lasting 5-10 min. IMI: range 6.5-13 mg/kg; 10 mg/kg usually produces anaesthesia within 3-4 min, lasting 12-25 min; see full PI. Maintenance. May admin additional incremental IV, IM doses (1/2 to full induction dose). Hepatic impairment, cirrhosis: consider dose reduction
Pack 200 mg/2 mL [5]

Reference MIM’s online 2011



NMDA Antagonists

Ketamine:NMDA receptor antagonism theoretically reduces central sensitisation, hyperalgesia and opioid tolreance

Currently role in postoperative pain relief is complex; Insignificant difference in pain ; Clinically insignificant opioid sparing

Psychomimetic side effects – hallucination, nighmares
NMDA antagonist


  • Ketamine

  • Mechanism of action

  • selective blocking agent of the excitatory receptor NMDA.

  • ? other mechanisms of action

  • Used in neuropathic pain states at low doses.

Ketamine is a water- and lipid-soluble drug that rapidly penetrates into the CNS. Like the barbiturates, ketamine accumulates rapidly and then undergoes redistribution with subsequent degradation in the liver

ketamine acts by interrupting association pathways between the thalamocortical and the limbic systems



NMDA receptor antagonists:Ketamine doses (0.15–1 mg/kg),

exerts a specific NMDA blockade & hence, modulates central sensitization .(2)


Acute neuropathic pain after surgery Parenteral ketamine (NMDA receptor antagonist, 5mg/hr) & Lignocaine (neuronal membrane stabilisation, 5mg/kg over 30–40min followed by 0.5–1.5mg/kg/hr) can be given in the acute phase to alter both peripheral and central neuronal plasticity. Treatment may take up to a week or more. This should be supervised by a suitably qualified pain specialist

NMDA-receptor antagonists ANZCA’s Key messages

1. Perioperative low-dose ketamine used in conjunction with patient-controlled analgesia morphine is opioid-sparing and reduces the incidence of nausea and vomiting (N) (Level I

[Cochrane Review]).

2. In general, a perioperative low-dose ketamine infusion is opioid-sparing, but does not produce a clinically significant reduction in pain scores or opioid-related adverse effects (S) (Level I).

3. Ketamine is a safe and effective analgesic for painful procedures in children (N) (Level I).

4. Ketamine and dextromethorphan have preventive (U) but not pre-emptive analgesic effects (N) (Level I).

5. Magnesium does not reduce postoperative pain scores or opioid consumption and has no preventive analgesic effect (N) (Level I).

6. Ketamine may improve analgesia in patients with severe acute pain that is poorly

responsive to opioids, although evidence is conflicting (W) (Level II).

7. Ketamine reduces postoperative pain in opioid-tolerant patients (N) (Level II).

The following tick box þ represents conclusions based on clinical experience and expert opinion.

;; The primary role of low dose ketamine is as an ‘antihyperalgesic’, ‘antiallodynic’,

‘tolerance-protective’ and preventive analgesic, rather than as an analgesic per se (N).

 

Antidepressant Tricyclic anti-depressants

Drug Name: Amitryptiline

Mechanism of action:

Increase available serotonin and noradrenaline by blocking reuptake.


  • Increase endorphin levels

  • The analgesic effect appears quicker that their antidepressant effect. (3-4 days versus 3 weeks).

  • The dose required for an analgesic effect is lower that that required for their antidepressant effect.

  • They have a muscle relaxant effect in diffuse musculoskeletal pain.

  • They may enhance the analgesia produced by opioids.

  • They are often used for neuropathic burning pain.

  • Side effects

  • sedation and anticholinergic effects including dry mouth, constipation and urinary retention.

  • Cardiac arrhythmias, glaucoma, weight gain and loss of libido

  • start at a low dose so that patients can become accustomed to using them

  • sometimes their side effects are beneficial e.g improvement in sleep due to sedation.


Antidepressant drugs ANZC’s Key messages

1. In neuropathic pain, tricyclic antidepressants are more effective than selective

serotonergic re-uptake inhibitors (S) (Level I [Cochrane Review]).

2. Duloxetine is effective in painful diabetic neuropathy and fibromyalgia (N) (Level I

[Cochrane Review]).

3. There is no good evidence that antidepressants are effective in the treatment of chronic low back pain (R) (Level I [Cochrane Review]).

4. Tricyclic antidepressants are effective in the treatment of chronic headaches (U) and fibromyalgia (N) (Level I).

5. Antidepressants reduce the incidence of chronic neuropathic pain after herpes zoster (U) (Level II).



Note: withdrawal of previous key message:

Antidepressants reduce the incidence of chronic neuropathic pain after breast surgery This has been deleted as the information and evidence supporting it has been withdrawn.HAPTER 4

The following tick boxes represent conclusions based on clinical experience and expert opinion.

;; Based on the experience in chronic neuropathic pain states, it would seem reasonable to use tricyclic antidepressants and selective serotonin re-uptake inhibitors in the management of acute neuropathic pain (S).

;; To minimise adverse effects, particularly in elderly people, it is advisable to initiate

treatment with low doses (U).

 

Anticonvulsant drugs

Anti-convulsants


  • Drug Names:Carbamazepine /Sodium Valproate Gabapentin

  • Mechanism of action

  • stabilise nerve cell membranes by blockade of voltage sensitive sodium channels

  • Increase brain serotonin, and GABA

  • reduce evoked and spontaneous activity of spinal neurons with and without peripheral nerve injury

  • ? modulates voltage dependant calcium channels.

  • Used in neuropathic pain to combat pain described as shooting / knife like.

  • Side effects

  • dizziness, sedation, gait disturbance, GIT upset, liver dysfunction, thrombocytopenia and bone marrow depression.

Gabapentin does not have the above severe adverse side effects 

Anti-convulsants

  • Carbamazepine /Sodium Valproate

  • Gabapentin




  • Mechanism of action

  • stabilise nerve cell membranes by blockade of voltage sensitive sodium channels

  • Increase brain serotonin, and GABA

  • reduce evoked and spontaneous activity of spinal neurons with and without peripheral nerve injury

  • ? modulates voltage dependant calcium channels.

  • Used in neuropathic pain to combat pain described as shooting / knife like.

  • Side effects

  • dizziness, sedation, gait disturbance, GIT upset, liver dysfunction, thrombocytopenia and bone marrow depression.

  • Gabapentin does not have the above severe adverse side effects.


Anticonvulsant drugs Key messages

1. Gabapentin is effective in the treatment of chronic neuropathic pain (Q); lamotrigine is most likely ineffective (N) (Level I [Cochrane Review]).

2. Carbamazepine is effective in the treatment of trigeminal neuralgia (N) (Level I [Cochrane Review]).

3. Pregabalin is effective in the treatment of chronic neuropathic pain related to diabetic neuropathy (N) (Level I).

4. Perioperative gabapentinoids (gabapentin/ pregabalin) reduce postoperative pain and opioid requirements (U) and reduce the incidence of vomiting, pruritus and urinary retention, but increase the risk of sedation (N) (Level I).

The following tick box þ represents conclusions based on clinical experience and expert opinion.

;; Based on the experience in chronic neuropathic pain states, it would seem reasonable to use anticonvulsants in the management of acute neuropathic pain (U).

Anti-arrhythmic agents; Membrane stabilisers


  • Intravenous lignocaine (Beirs Block)

  • Oral mexiletine (not used in Theatre)

  • Sodium channel blockers which act to suppress abnormal activity in damaged neurones, without blocking normal nerve conduction.


Membrane stabilisers ANZCA’s Key messages

1. Both lignocaine (lidocaine) and mexiletine are effective in the treatment of chronic neuropathic pain (S); there is no difference in efficacy or adverse effects compared with carbamazepine, amantadine, or morphine (N) (Level I [Cochrane Review]).

2. Perioperative intravenous lignocaine reduces pain and opioid requirements following abdominal surgery (S) as well as nausea, vomiting, duration of ileus and length of hospital stay (N) (Level I). The following tick boxes represent conclusions based on clinical experience and expert opinion.

;; Based on the experience in chronic neuropathic pain states, it would seem reasonable to use membrane stabilisers in the management of acute neuropathic pain (U).

;; Lignocaine (intravenous or subcutaneous) may be a useful agent to treat acute

neuropathic pain (U).


1   2   3   4   5   6


The database is protected by copyright ©dentisty.org 2016
send message

    Main page