Narcotics & non-narcotics analgesics

Narcotics & non-narcotics analgesics, mechanism of action, pharmaceutical chemistry

1. NARCOTICS & NON-NARCOTICS ANALGESICS K. N eha

2. I ntroductions Analgesic = relieves pain. Narcotic analgesics used to provide relief from moderate-to-severe acute or chronic pain. Also called as opiates , opioid analgesics, or narcotics. Examples: Morphine, codeine Narcotic analgesics work by binding to opioid receptors, part of the opioid system that controls pain, pleasurable and addictive behaviors. Opioid receptors are more abundant in the brain and spinal cord but are also located elsewhere in the body such as the stomach and the lungs. The main opioid receptor that narcotic analgesics bind to is the mu ( μ ) receptor . Non-Narcotic analgesics (Non-Opioids) are   medications used to control mild to moderate persistent pain and inflammation. Examples: Aspirin and paracetamol . Some types of these medications can be given during surgery to reduce post-surgical pain and lessen the need for narcotics. They also may be used in combination with other medications or therapies to treat moderate to severe pain.

3. Mechanism of action

4. Morphine and related drugs Structure Activity Relationship (SAR) of morphine Narcotic analgesics

5. Morphine sulphate Brand name: Roxanol It is found in the opium poppy, Papaver sominferum (family: Papaveraceae ). Morphine is also an  endogenous opioid ( synthesized by white blood cells ) & can cause tolerance, psychological and physical dependence. It acts directly on the central nervous system (CNS) to increase feelings of pleasure and warm relaxation. Codeine ( 3-methylmorphine ) Brand name: Tylenol Opiate a lkaloid   Codeine  is an prodrug  of  morphine. It is metabolized in the liver by the cytochrome P450 enzyme to produce morphine, which is ten times more potent against the mu receptor . It acts on the central nervous system to have an analgesic effect. 2 H₂SO₄.5H₂O

6. Meperidine hydrochloride B rand name:   Demerol Also known as Pethidine Meperidine  mimics the actions of endogenous neuropeptides via opioid receptors such as the mu-opioid receptor, thereby producing characteristic morphine-like effects including analgesia, euphoria, sedation, respiratory depression, miosis , bradycardia and physical dependence . Anilderine hydrochloride Brand name: Leritine an opioid receptor agonist belonging to the  piperidine  class with analgesic activity. anileridine  mimics the endogenous opioids resulting in a decrease of nociceptve neurotransmitters and eventually an analgesic effect.

7. Diphenoxylate hydrochloride Brand name: Lomotil A  piperidine  derivate, chemically related to narcotic  meperidine , with antidiarrheal activity and devoid of central nervous system (CNS) activity.  Diphenoxylate  acts on opioid receptors in the gastrointestinal tract, thereby decreasing gastrointestinal motility and causing constipation or preventing diarrhoea. Loperamide hydrochloride Brand name: Lopravik P iperidine  derivative and opioid agonist with antidiarrheal activity.  Loperamide  acts on the mu-receptors in the intestinal mucosa. This leads to a decrease in gastrointestinal motility by decreasing the circular and longitudinal smooth muscle activity of the intestinal wall.   Loperamide  is not significantly absorbed from the gut and does not cross the blood-brain barrier. Therefore it has no central nervous system effects.

8. Fentanyl citrate Brand name: Actiq synthetic opioid related to the phenylpiperidines with analgesic and anesthetic properties . Fentanyl  exerts its analgesic effect by selectively binding to the mu-opioid receptor in the central nervous system (CNS), thereby mimicking the effects of endogenous opiates. Synthesis:

9. Methadone hydrochloride Brand name: Dolophine M ethadone  mimics the actions of endogenous peptides at CNS opioid receptors, primarily the mu-receptor, resulting in characteristic morphine-like effects including analgesia, euphoria, sedation, respiratory depression, miosis , bradycardia and physical dependence. Synthesis:

10. Propoxyphene hydrochloride Brand name: Darvon This agent mimics the effects of the endogenous opiate  dextropropoxyphene , by binding to mu receptors located throughout the central nervous system. Pentazocine Brand name: Talwin Activates κ-opioid receptors and blocking μ-opioid receptors.  It fairly frequently causes hallucinations, nightmares and delusions. Levarphanol tartarate Brand name: Levo-Dromoran S ynthetic   phenanthrene  with potent opioid analgesic activity. Levorphanol tartrate mimics the actions of endogenous peptides at CNS opioid receptors, thereby producing the characteristic morphine-like effects.

11. Side effects Drowsiness Sleepiness Dizziness Constipation Breathing difficulty Itching or a skin rash Loss of appetite Low blood pressure Miosis (constriction of the pupil of the eye) Nausea and vomiting Problems with urination Shakiness or a tremor Slow heartbeat

12. Narcotic antagonists An  antagonist used to counteract the effects of narcotics, used   for the complete or partial reversal of opioid overdose, including respiratory depression.  Narcotic antagonists blocks the euphoric (and all other) effects of opiates. Nalorphine hydrochloride ( N- allylnormorphine ) Brand name: Nalline M orphinane alkaloid . I t produces a broad spectrum of unpleasant effects. Nalorphine is a mixed opioid agonist–antagonist. It is an   antagonist at mu opioid receptors and an agonist at kappa opioid receptors. Nalorphine inhibits the   cholinesterases  of mouse brain, bovine erythrocytes and horse serum. .

13. Levallorphan tartarate B rand name: Lorfan Levorphanol  is an opioid pain reliever. It acts on certain centers in the  brain to give you pain relief . It is an opioid modulator of the morphinan family used as an opioid analgesic and opioid antagonist/antidote . Naloxone hydrochloride B rand name:   Prenoxad It is commonly used to counter decreased breathing in opioid overdose. Naloxone may also be combined with an opioid, to decrease the risk of opioid misuse . Naloxone  blocks or reverses the effects of opioid medication, including extreme drowsiness, slowed breathing, or loss of consciousness.

14. Anti-inflammatory agents Sodium salicylate Brand name:   Acnevir Sodium salicylate irreversibly acetylates cyclooxygenases I and II, thereby inhibiting prostaglandin synthesis and associated inflammation and pain.  Aspirin Brand name: Fiorinal A lso known as  acetylsalicylic acid  (ASA ). Oldest analgesic on the market . For pain or fever, effects begin within 30 minutes. Aspirin is generally ineffective for those pains caused by muscle  cramps , bloating, gastric distension, or acute skin irritation. Non-Narcotic analgesics

15. Mefenamic acid Brand name: Mefic A nthranilic acid derivative U sed to treat acute pain including  muscle and  back pain, toothache and menstrual pain . Synthesis: Meclofenamate sodium B rand   name: Meclomen U sed for joint, muscular pain, arthritis and dysmenorrhea . Also used in menstrual pain, as well as to decrease bleeding in women who have abnormally heavy menstrual blood loss.

16. Indomethacin Brand name: Artisid U sed to treat moderate to severe osteoarthritis , rheumatoid arthritis, gouty arthritis, or  ankylosing spondylitis.  It works by inhibiting the production of prostaglandins, endogenous signaling molecules known to cause these symptoms . Sulindac Brand name : Clinoril Arylalkanoic acid derivatives Used to treat pain or inflammation caused by arthritis, ankylosing spondylitis, tendinitis, bursitis, or gout . Tolmetin Brand name: Tolectin It is used primarily to reduce hormones that cause pain, swelling, tenderness, and stiffness in conditions such as osteoarthritis and rheumatoid arthritis, including juvenile rheumatoid arthritis. 

17. Zompriac Brand name: Zomax It is a pyrrole-acetic acid. prostaglandin synthetase   inhibitor. It was more effective than aspirin or codeine  alone. Diclofenac Brand name: Voltaren N onsteroidal anti-inflammatory drug used to treat pain and inflammatory diseases such as gout . A lso indicated for the treatment of ankylosing spondylitis.  Ketorolac B rand name: Toradol   C ompetitive blocker of the  cyclooxygenase  (COX ) enzyme. Ketorolac is effective when administered with paracetamol to control pain in newborns because it does not depress  respiration as do opioids.

18. Ibuprofen Brand Name:  Advil Ibuprofen is used to reduce fever and treat pain or inflammation caused by many conditions such as headache, toothache, back pain, arthritis, menstrual cramps, or minor injury . Synthesis: Naproxen Brand Name:  Aleve M ember of the 2-arylpropionic acid Nonselective  COX inhibitor. Onset of effects is within an hour and last for up to twelve hours.

19. Piroxicam Brand name: Feldene Oxicam  class  N on-selective  COX  inhibitor. G iven by parenteral routes. Phenacetin Brand name: Saridon  I t acts on sensory tracts of the spinal cord.  O ne of the first non-opioid  analgesics. Chronic use of phenacetin is known to lead to analgesic nephropathy . Acetaminophen (paracetamol) Brand name: Tylenol drug of choice for reducing  fever . First-line treatment for migraine . I neffective for acute low back pain.

20. Antipyrine ( phenazon ) Brand name:   Auralgan G iven by mouth and as ear drops O ften used to test effects of other drugs on liver enzymes. Symptomatic treatment of acute otitis media. A ct primarily in the CNS, increasing the pain threshold by inhibiting cyclooxygenase. Phenylbutazone Brand name: Winopyrine Pyrazolone   derivative Inhibits cyclooxygenase Initially used for the treatment of rheumatoid arthritis and   gout. In the United States and United Kingdom it is no longer approved for human use Severe adverse effects such as suppression of white blood cell production and aplastic anemia.