Pain

1. Pain • TWO CLASSES OF DRUGS ARE USED TO REDUCE PAIN OR THE AWARENESS OF PAIN:  ANESTHETICS (MEANING WITHOUT SENSIBILITY), HAVE THIS EFFECT BY REDUCING AWARENESS OR BY BLOCKING CONSCIOUSNESS COMPLETELY.  • THE BARBITURATES AND VOLATILE ANESTHETICS, SUCH AS ETHER, ARE EXAMPLES OF THIS TYPE OF AGENT.  • SECOND CLASS IS THE ANALGESICS (MEANING WITHOUT PAIN).  THEY REDUCE PAIN WITHOUT CAUSING A LOSS OF THE SENSES. 

2. VISCERAL PAIN, SUCH AS INTESTINAL CRAMPS, ARISES FROM NONSKELETAL PORTIONS OF THE BODY.  • OPIATES ARE EFFECTIVE IN REDUCING PAIN OF THIS TYPE.

4. Opium HISTORY ‑DERIVED FROM POPPY PLANT Papavera somniferum. NO TRULY WILD POPULATIONS OF THIS ACTUALLY EXIST. IT WAS SELECTIVELY BRED FROM Papavera setigerum AND EXTENSIVELY CULTIVATED. NO ONE KNOWS WHERE THE PLANT ORIGINATED. THOUSANDS OF KNOWN VARIETIES OF POPPIES, ONLY ONE HAS OPIUM. ‑HISTORY OF MEDICAL USE FOR 6000 YEARS ‑SINCE ALSO PRODUCED EUPHORIA AND RELIEVED ANXIETY, LEAD TO EXTENSIVE RECRE­ATIONAL USE ‑ANNUAL PLANT...3‑4 FT. HIGH WITH LARGE FLOWERS 4‑5 INCHES IN DIAMETER...FLOWERS MAY BE WHITE, PINK, RED, PURPLE, OR VIOLET

5. ‑OPIUM IS PRODUCED AND AVAILABLE FOR COLLECTION FOR ONLY A FEW DAYS, BETWEEN THE TIME THE PETALS DROP AND BEFORE THE SEED POD MATURES COLLECTION IS HIGHLY LABOR INTENSIVE. ‑TO HARVEST, SHALLOW CUTS ARE MADE INTO, BUT NOT THROUGH, THE UNRIPE SEED POD.....AT DUSK ‑DURING NIGHT, WHITE SUBSTANCE OOZES FROM THE CUTS, OXIDIZES TO A RED‑BROWN COLOR, AND BECOMES GUMMY ‑IN MORNING, RESINOUS SUBSTANCE IS SCRAPED AND COLLECTED... WORD OPIUM IS FROM GREEK MEANING "JUICE"

8. POPPY SEEDS FOUND IN NEOLITHIC EUROPEAN SITES FROM 5000 BC. -SUMERIANS (BABYLONIANS) CARVED TABLETS WITH PICTURES OF POPPY 2600 BC. WITH INSCRIPTION HUL "JOY" AND GIL "PLANT".

9. MORPHINE HAS BEEN FOUND IN THEBAN (EGYPTIAN) FUNERAL POTS FROM 1500 BC. ‑IN CLASSICAL LITERATURE OF VIRGIL, SOMNUS, THE ROMAN GOD OF SLEEP, WAS DESCRIBED AS BEING ADORNED WITH OR CARRIED POPPIES AND SOMETIMES AN OPIUM CONTAINER ‑LIKE SANDMAN OF TODAY, SOMNUS WAS PICTURED POURING JUICE FROM THE CONTAINER INTO THE EYES OF THE SLEEPER

10. ‑CHINESE LEGEND HAS THE POPPY PLANT SPRINGING UP FROM THE EARTH WHERE BUDDHA'S EYELIDS FELL WHEN HE CUT THEM OFF TO PREVENT SLEEP FIRST SPECIFIC MEDICAL USE OF OPIUM: EBERS PAPYRUS (1500 B.C.) CALLS IT REMEDY TO PREVENT THE EXCESSIVE CRYING OF CHILDREN.

11. LAUDANUM, DEVELOPED BY DR. THOMAS SYDENHAM ‑CONTAINED "2 OZ STRAINED OPIUM, 1 OZ SAFFRON, AND A DRAM OF CINNAMON AND OF CLOVES DISSOLVED IN A PINT OF CANARY WINE AND TAKEN IN SMALL QUANTITIES" ‑HE HIGHLY ADVOCATED THE USE OF OPIUM 1680: "I CANNOT FORBEAR MENTIONING WITH GRATITUDE THE GOODNESS OF THE SUPREME BEING, WHO HAS SUPPLIED AFFLICTED MANKIND WITH OPIATES FOR THEIR RELIEF..“ ‑19TH CENTURY ‑ OPIUM USE BECAME BIG WITH ENGLISH AND FRENCH WRITERS

12. ‑THOMAS DEQUINCY..PURCHASED LAUDANUM FOR TOOTHACHE..SPENT REST OF LIFE TAKING THE DRUG AND WRITING ABOUT HIS EXPERIENCES WITH IT. "I took it, and in an hour, Oh Heavans ! What a revulsion ! What an upheaving, from its lowest depths, of the inner spirit 1 What an apocalypse of the world within me. What had opened before me -- an abyss of divine enjoyment suddenly revealed. Here was a panacea for all human woes. Here was the secret of happiness, about which philosophers had disputed for so many ages, at once discovered". Thomas de Quincey (1785-1859)

13. ‑ELIZABETH BARRETT BROWNING...ADDICTED TO LAUDANUM ‑SAMUEL TAYLOR COLERIDGE'S "KUBLA KHAN" WAS SAID TO HAVE BEEN CONCEIVED AND COMPOSED IN AN OPIUM REVERIE AND THEN WRITTEN DOWN AS BEST AS HE COULD REMEMBER IT, UNTIL THE DOORBELL RANG AND HE WAS NEVER ABLE TO FINISH HIS WORK. AFTER WWII, PAREGORIC, A COMBINATION OF OPIUM AND CAMPHOR, WAS USED TO TREAT DIARRHEA IN INFANTS!

14. HISTORICAL BIOCHEMISTRY ‑ABOUT 1806, A GERMAN YOUTH, FREDERICH SERTURNER, ISOLATED THE PRIMARY ACTIVE INGREDIENT IN OPIUM. HE TESTED THE NEW DRUG ON HIS FRIENDS AT 10 TIMES THE MODERN RECOMMENDED DOSE! ‑ACTIVE AGENT WAS 10X MORE POTENT THAN OPIUM ‑HE NAMED IT MORPHIUM AFTER MORPHIUS, THE GOD OF DREAMS

15. MORPHIUS

16. ‑LATER WORK FOUND OVER 30 DIFFERENT ALKALOIDS OF OPIUM, WITH THE SECOND MOST IMPORTANT ONE BEING ISOLATED IN 1832 AND NAMED CODEINE, THE GREEK WORD FOR "POPPY HEAD"

17. ‑1874‑ 2 ACETYL GROUPS WERE ATTACHED TO MORPHINE BY CHEMISTS YIELDING HEROIN ‑PLACED ON THE MARKET IN 1898 BY BAYER LABS AS A NONADDICTING SUBSTITUTE FOR CODEINE! ‑CHEMICAL CHANGE WAS IMPORTANT BECAUSE HEROIN IS ABOUT 3X AS POTENT AS MORPHINE ‑2 ACETLY GROUPS INCREASE LIPID SOLUBILITY...ENTERS BRAIN MORE RAPIDLY

18. Aspirin is derived from A = Acetyl and "Spirsäure" = an old (German) name for salicylic acid

19. PHARMACODYNAMICS: ‑MORPHINE IS READILY ABSORBED THROUGH MOST MUCOUS MEMBRANES: NASAL MUCOSA ‑ HEROIN CAN BE SNORTED VIA THE LUNGS - WHEN OPIUM IS SMOKED ‑ADMINISTERED MOST COMMONLY BY SUBCUTANEOUS INJECTION, ALTHOUGH ORAL ADMINISTRATION IS NOT UNCOMMON ‑ONCE ABSORBED, DISTRIBUTION IS FAIRLY UNIFORM IN MOST TISSUES ‑ALTHOUGH IT HAS GREATEST EFFECTS ON CNS, MORPINE DOES NOT CONCENTRATE THERE ‑IN FACT, ONLY SMALL QUANTITY CAN CROSS BBB

20. LATENCY AND DURATION EQUIANALGESIC DOSE LATENCY DURATION (SUBCUTANEOUS) MORPHINE 10MG 30‑60MIN 4‑5HR CODEINE 120MG 30‑60MIN 2‑4HR HEROIN 3‑4MG 15MIN 4‑5HR

21. SMALL TO MODERATE DOSE (5‑10MG) ‑PSYCHOLOGICAL EFFECTS ‑DROWSINESS ‑DECREASED SENSITIVITY TO EXTERNAL AND INTERNAL STIMULI ‑LOSS OF ANXIETY ‑LOSS OF INHIBITION ‑PHYSIOLOGICAL EFFECTS ‑MUSCLE RELAXATION, RELIEF OF PAIN, DEPRESSED RESPIR­ATION, CONSTRICTED PUPILS, NAUSEA (EVEN AT SMALL DOSE), INABILITY TO CONCENTRATE, FOLLOWED BY DREAMY SLEEP HYPOTENSION ‑ MORPHINE RELEASES HISTAMINE IN THE BLOOD. ‑ ALSO DECREASES COUGH REFLEX ‑ CODEINE PRIMARILY USED AS COUGH SUPPRESSANT

22. AT SLIGHTLY HIGHER DOSES ‑ABNORMAL STATE OF ELATION OR EUPHORIA THAT IS DIFFERENT FROM THE USUAL SENSE OF WELL‑BEING...MORE INTENSE ‑IF INJECTED IV, RESULTS IN THE KICK, BANG, OR RUSH...DESCRIBED AS AN ABDOMINAL ORGASM, A SUDDEN FLUSH OF WARMTH LOCALIZED IN THE PIT OF THE STOMACH...NO RUSH IF SMOKED, SNIFFED, SWALLOWED, OR INJECTED SUBCUTANEOUSLY (INITIALLY THOUGHT ADDICTION WAS DUE TO THIS RUSH, BUT CAN BE ADDICTED WITHOUT MAINLINING) ‑UNLIKE OTHER EUPHORIC DRUGS (E.G. MUSHROOMS OR LSD), NO HALLUCINATIONS FOR MORPHINE. IN CONTRAST, UNREFINED AND PURE OPIUM IS HIGHLY HALLUCINOGENIC.

23. ‑AT HIGHEST DOSES, DEPRESSION DEEPENS INTO UNCONSCIOUSNESS ‑PUPILS FURTHER CONSTRICT (PIN‑POINT PUPILS)... MAY BE MISLEADING. OPIATES ACTUALLY PRODUCED WHAT IS CALLED "HIPPUS" OR THE FLUCTUATION OF PUPIL SIZE. PUPILS ARE OCCASSIONALLY PIN-POINT AND OCCASSIONALLY DILATED. ‑ SEVERE RESPIRATORY DEPRESSION (ULTIMATE CAUSE OF DEATH) ‑IMPAIRED HOMEOSTATIC FUNCTIONS...E.G.BODY TEMP FLUCTUATES ‑FLUID RETENTION ‑DECREASED HORMONAL OUTPUT FROM PITUITARY ‑SLURRED SPEECH, PSYCHOMOTOR RETARDATION, MENTAL CLOUDING

24. PURE ANTAGONISTS‑ NALOXONE (NARCAN)... NO MORPHINE‑LIKE EFFECTS...REVERSE EFFECTS OF THE NARCOTIC ALREADY THERE...USED IN EMERGENCY ROOM TO REVERSE EFFECTS OF OVERDOSEOF OPIUM AND THE EFFECTS OF OPIUM POPPIES

25. ENDOGENOUS OPIATES, E.G. ENKEPHALIN, MODULATE THE ACTUAL PAIN INFO CARRIED FROM THE PERIPHERY TO THE HIGHER CENTERS OF BRAIN • THESE ENKEPHALIN CELLS ARE REGULATED BY SEROTONERGIC INNERVATION FROM RAPHE (ROLE OF LSD, NO PAIN)

26. The "Gate Theory of Pain"

29. TOLERANCE: ‑PRODUCES A NEED TO INCREASE THE DOSE OF A DRUG IN ORDER TO ACHIEVE THE SAME MAGNITUDE OF EFFECT...SIGNIFICANT CROSS‑TOLERANCE TO SIMILAR COMPOUNDS ‑TOLERANCE TO OPIATES DEVELOPS VERY RAPIDLY (I.E. A SINGLE DOSE) ALTHOUGH NOT ALL EFFECTS UNDERGO TOLERANCE TO THE SAME EXTENT

30. TOLERANCE: ‑IN GENERAL, THE EUPHORIA AND ANALGESIA SHOW RAPID TOLERANCE, WHILE THE CONSTIPATING EFFECTS AND NAUSEA PERSIST EVEN AFTER PROLONGED OPIATE USE

31. ‑TOLERANCE IS CHARACTERIZED BY A SHORTER DURATION OF ACTION (I.E. A METABOLIC TOLERANCE), A REDUCED INTENSITY OF ANALGESIA AND SEDATIVE EFFECTS, AND A SIGNIFICANT INCREASE IN THE AVERAGE LETHAL DOSE ‑WITH SIGNIFICANT TOLERANCE OFTEN COMES DEPENDENCE AND ADDICTION

32. Tolerance may be at the level of the synapse. • Following the activation of second messengers genes may be affected • The genes trigger production of proteins that wander back to the pre-synaptic neuron and tell it to stop releasing so much dopamine • The end effect is less euphoria

33. ‑DEGREE OF DEPENDENCE CAN ONLY BE MEASURED BY THE SEVERITY OF THE WITHDRAWAL SYMPTOMS WITHDRAWAL ‑SYMPTOMS VARY IN INTENSITY DEPENDING ON HISTORY OF DRUG USE AND THE HEALTH AND PERSONALITY OF THE ADDICT ‑SYMPTOMS ARE NOT CONSIDERED TO BE LIFE THREATENING, ALTHOUGH THEY MAY FEEL LIKE IT ‑FLU‑LIKE BEGIN AT 8-12 HR AND PEAKS AT 48‑72 HOURS AFTER THE LAST DOSE. ESSENTIAL, SYMPTOMS ARE "REBOUND" OF SYSTEMS INITIALLY EFFECTED BY DRUG.

34. ‑SYMPTOMS‑ DILATED PUPILS, LACRIMATION, WEAKNESS AND DEPRESSION, NAUSEA AND VOMITTING, INTESTINAL SPASMS AND DIARRHEA, RUNNY NOSE, HOT AND COLD SWEAT FLASHES, WEIGHT LOSS, MUSCLE SPASMS, AND DEHYDRATION

35. ‑SYMPTOMS WILL USUALLY PERSIST FOR 7 TO 10 DAYS ‑THEY WILL BE SUPPRESSED BY ADMINISTRATION OF THE OPIATE ‑SYMPTOMS WILL APPEAR IF AN ANTAGONIST IS ADMINISTERED...EVEN MORE SEVERE WITHDRAWAL THAN MERE ABSTINENCE WILL CREATE

36. A map of the brain showing the concentration of receptors for the brain's own "feel good" chemicals, called endogenous opioids

37. A three-dimensional view of brain areas where activations of the endogenous opioid receptors during sustained pain were associated with reductions in pain affect, or the emotional quality of the pain experience. the dorsal portion of the anterior cingulate cortex, the thalamus and the nucleus accumbens.

38. Heroin/morphine indirectly causes the increased release of dopamine in the accumbens area

39. Meta-analysis of placebo acupuncture versus no acupuncture “The analgesic effect of acupuncture is smalland cannot be distinguished from bias resulting from incompleteblinding” Madsen, M. V. et al. BMJ 2009;338:a3115

40. IT MAY BE REWARDING TO EAT CERTAIN FOODS BECAUSE THEY THEMSELVES CONTAIN OPIATES E.G. MILK (BETA-CASEOMORPHIN) Dr. Reichelt in Norway, Dr. Cade at the University of Florida, and others found that urine samples from people with autism and schizophrenia contained high amounts of the casomorphin peptide in the urine. … it has opiate properties similar to morphine, and may plug into the same opiate receptor sites in the brain. (from an Autism web site)

41. Additives, Foods, Moods and BehaviourThe dramatic effect that additives and foods can have on the behaviour of our children. “These peptides pass through the gut wall into the blood stream and from where they deliver morphine peptides directly to the brain. Indeed the behaviour of many autistic children is very similar to that of a drug addict a zombie-like, disconnected state when 'high' on their drug alternating with a frenzied, head banging, totally uncontrollable 'cold turkey' state when they are waiting for their next fix.”

42. Structure of 7-8 a.a. that is large, hydrophillic and highly charged, Tyr-Pro-Phe-Pro-Gly-Pro-Ile

43. Myrrh Furanoedesma-1,3-diene (a furosesquiterpene), from the dried resin from the bark of a shrub (found throughout Arabia). It is slightly more potent than morphine and may act via central endogenous opiate receptors to produce analgesia. May also enhance blood clotting.

44. Frankincense Fragrant resin from Boswellia sacra tree. May have anti-inflammatory action similar to aspirin. May 2008 FASEB: may be anxiolytic and anti-depressive as well.

45. Salvia divinorum, whose main active ingredient is the neoclerodane diterpene Salvinorin A, is a hallucinogenic plant in the mint family that has been used in traditional spiritual practices for its psychoactive properties by the Mazatecs of Oaxaca, Mexico. A potent κ opioid agonist with no actions at the 5-HT2A serotonin receptor.

46. Chilli Peppers Capsaicin was initially extracted in 1846. Activates the endogenous vanilloid receptor – a cation channel that is sensitive to noxious chemical and thermal triggers. Activation of this channel leads to the release of the neuropeptide Substance P, a transmitter used by nociceptive sensory afferents to the brain.