1 / 19

NON-OPIOID DRUG SIDE EFFECTS: COGNITIVE EFFECTS OF CENTRALLY ACTING DRUGS WHEN  FOR PAIN

NON-OPIOID DRUG SIDE EFFECTS: COGNITIVE EFFECTS OF CENTRALLY ACTING DRUGS WHEN  FOR PAIN. High level literature evidence almost non-existent Cochrane Data base of systematic reviews etc. Other sources Literature search Road accident research Units Sleep Disorder Units - sleep hygiene, OSA.

violet-pope
Télécharger la présentation

NON-OPIOID DRUG SIDE EFFECTS: COGNITIVE EFFECTS OF CENTRALLY ACTING DRUGS WHEN  FOR PAIN

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. NON-OPIOID DRUG SIDE EFFECTS:COGNITIVE EFFECTS OF CENTRALLY ACTING DRUGS WHEN  FOR PAIN • High level literature evidence almost non-existent • Cochrane Data base of systematic reviews etc. • Other sources • Literature search • Road accident research Units • Sleep Disorder Units - sleep hygiene, OSA

  2. NON-OPIOID DRUG SIDE EFFECTS • Drugs • Antidepressants, anticonvulsants, benzodiazepines,b-blockers, antihistamines • Cognitive effects data • Usually available for primary indication • Similar data for pain patients is sparse • Medline search (1985 - present) • Few meta-analyses for above drug classes • Issue of combination therapy • Poly  treatments - possible drug interactions • ? Observed cognitive effects are due to which drug • Data more likely to be available for add on therapy

  3. METHODOLOGICAL ISSUES (1) • Consider the cognitive effects of untreated or poorly treated 1o indication • Depression, epilepsy, pain • Superimposed impact of drug needs to be evaluated against this background • Volunteer studies - many problems • No underlying pathology • Short  period (max 7 days) & low drug doses • Composition of neuropsychological test battery (also an issue for patient studies) • Timing of tests

  4. METHODOLOGICAL ISSUES (2) • Ideally need randomised, double blind, placebo controlled monotherapy in optimised doses resulting in a functional pain free individual • Realistically, cognitive effects assessed at steady state after months of therapy • Time dependent changes in cognitive effects, worse after initiating therapy • Studies of newer agents often controlled by patent holder

  5. THE BOTTOM LINE !! • Impact of  drugs on return to work • Particularly high risk occupations • Some investigations re a battery of tests to administer in work place to predict risk • Driving Motor Vehicles • Volunteer studies and examination of accidents • Lack of congruence between volunteer (ie laboratory studies) and road accident data • Lab studies deficient in both directions • Cognitive function • Circadian changes throughout the day • Sleep hygiene has an influence on the above • Cognitive function  with  age (test dependent)

  6. DRIVING MOTOR VEHICLES • Volunteer Studies • Simulated driving • reaction time & attention span assessments • Neuropsychological quentionnaires • Effects related to equivalent BAC (extensive data) • Accident data - qualitative assessments of alcohol, licit and illicit drugs in: • Accidents involving death • Accidents involving injury • Random road-side sampling • Frequently blood concentrations are measured

  7. 2nd. GENERATION DRUGS • Usually show efficacy in 1o indication equivalent to first generation drugs (rarely are they more effective) • Maybe more potent (? advantages) • Pharmacokinetic advantages (leads to better compliance) • Usually superior adverse event profile • Preferred because of the balance between efficacy and side effects

  8. ANTIDEPRESSANTS (TCA V’s SSRI’s) • TCA’s - meta-analyses demonstrate significant analgesic effect (NNT = 3) • Mechanism of action • Inhibit reuptake of noradrenalin and 5HT • Cholinergic receptor inhibition  dry mouth, constipation, urinary retention, blurred vision and cognitive dysfunction • H1 receptor inhibition  sedation, impaired motor function • a1 adrenergic receptor inhibition  imbalance, impaired co-ordination, orthostatic hypotension, tachycardia

  9. ANTIDEPRESSANTS - SSRI’s • Do they work (? analgesic effect), meta-analyses not as favourable (small patient numbers  less adequate data base) • Selectively block 5HT reuptake (presynaptic neurones) • Adverse events • nausea, headache, anxiety, nervousness, insomnia, drowsiness, fatigue, sexual function • Patient studies (depression) - side effects • Sertraline, amitriptyline versus placebo • Short term (2 - 3 weeks) - sertraline = amitriptyline • Long term - sertraline , amitriptyline 

  10. TCA’s VERSUS SSRI’s - COGNITIVE EFFECTS • Volunteer studies • TCA’s - 10 - 20 % acute impairment • Paroxetine - no impairment compared to placebo • Patient studies (cf aged matched controls) • TCA’s - lower cognitive function • SSRI’s - improved cognitive function (shows impact of disease on cognitive function) • Brake reaction time (BRT) • assesses inter alia, sedation • SSRI’s - do not effect BRT • TCA’s - result in extra stopping distance equivalent to a BAC of 0.08%

  11. ANTICONVULSANTS - ESTABLISHED DRUGS • Minor cognitive changes in short term (4 months) • Relative to pre state (cognitive deficits) • Cognitive function  on drug withdrawal (carbamazepine, valproate) • Carbamazepine results in less cognitive deficits than phenytoin

  12. ANTICONVULSANTS -GABAPENTIN & LAMOTRIGINE • Add on therapy V’s placebo (epilepsy) • No effects on tests of concentration, memory or psychomotor performance • Drowsiness with gabapentin (> 2.4 gm / day) • Effective doses (seizure frequency  ) • Volunteer studies ( V’s carbamazepine, phenytoin) • Good design (r, db, crossover) • Comprehensive battery of tests • New drugs better - gabapentin (25% variables), lamotrigine (50% variables)

  13. BENZODIAZEPINES • Profound effects on cognitive function & ability to drive • Cognitive function  on drug withdrawal • Still significant deficits at 6 months (cf age and IQ [not anxiety] matched controls) • Attention,visual-spatial ability compromised the greatest • Patients lack insight to these effects • Role in pain patients highly questionable • Implications for driving, rehabilitation

  14. DRUG IMPACT ON SLEEP • Consider influence of pain (fatigue, cognition) • Drugs: • TCA’a - sleeptime (TST), effects  over time & are more profound in elderly • SSRI’s -  w,  TST, performance  or mild  • Antipsychotics -  sedation • Benzodiazepines -  sedation,  performance,  TST (but with rebound insomnia on cessation) • b-blockers - w,  insomnia & nightmares (more common with lipophilic drugs & in elderly), few consistent neuropsychological effects • Older anticonvul - TST, mild, mod  performance • Newer anticonvul - little polysomnographic lab data avail and only as add on therapy

  15. ALCOHOL & CANNABINOIDS - BEHAVIOURAL EFFECTS • Low blood concs effect psychomotor test performance (range of tests) • Higher concs  negative effects • Same blood concs. - more profound effects in absorption cf elimination phase • 50 % total negative effects • BAC = 0.073% THC = 11 ng / ml • Different ranking between drugs • Alcohol - driving test most sensitive (THC = 6th.) • THC - tracking test most sensitive (Alcohol = 5th.)

  16. DRUGS & MOTOR ACCIDENTS • No uniform effects across drug classes (volunteer studies) • Alcohol & illicit drug extensively studied • Some motor accident data for  & illicit drugs • Attempt to relate this data to a qualitative expert opinion re impact of drugs in causing accident or death (again, alcohol & illicit drugs data more available) • Measured drug conc - assay methodology issues • Therefore, conservative estimates

  17. PRESCRIBED DRUGS - ROAD ACCIDENTS • Subdivided into fatal & injured drivers • Fatal accidents • Alc (32%), drugs (illicit + , 16.3%), benzo (8.5%), barbit (1.2%), methadone (0.4%), opiates (2.8%) • Similar percentages for injuries • Suspected driving under the influence • 42%, 82%, 38%, 4%, 12%, 3.6% & TCA’s (4.1%) • Estimated 3.5 - 7% of accidents caused by psychoactive medicines • Diazepam - RR = 3.1 injurious accident

  18. DRIVING & WORKPLACE SAFETY - TEST BATTERY • 10 Computerised tests evaluated • 40 Volunteers with BAC ranging from 0.01 - 0.12% • Performance decrements statistically correlated to BAC • 97% Specificity (assessed being fit / total fit) • > 80% Sensitivity (identified unfit / total unfit) at high BAC • 60% Sensitivity at low BAC • Clearly a good concept, but there is a long way to go

  19. CONCLUSIONS • Inadequate data re cognitive effects of non-opioid drugs  for pain • Need to consider cognitive effects of pain • Issue of poly drug treatment of pain • 2nd. Generation drugs are better, BUT do they have equivalent analgesic effects • Benzodiazepines have profound effects and have no place in treating pain • Hope of test battery to predict workplace safety & driving still requires significant development

More Related