12.3 Analgesics 12.3 Analgesics us/druginformation.html Describe and Explain the different ways in which analgesics prevent pain

Pain Receptor Nerves that transmit the pain Free nerve endings that transmit the pain based on thermal/ mechanical/ chemical stimuli Pain receptor generate an impulse Pain results from interaction between various impulses arriving at the spinal cord and the brain

Prostaglandins Injures tissues release prostaglandin and leukotriene Make the pain receptors more sensitive

Prostoglandin Prostaglandins have an extraordinarily wide range of biological effects controlling blood pressure and controlling inflammation. blood clotting, kidney function and the reproductive system and are the subject of a great deal of research to produce new drugs.

Analgesics Understanding how neurons work comes from study of membrane potential (i.e. the difference in electrical charge between inside and outside of the neuron); To record a membrane potential two electrodes are needed: intracellular and extracellular

Aspirin Analgesics: relives pain Mild : aspirin, acetaminophen( metabolic byproduct of phenacetin) -same as Tylenol, Paracetamol, ibuprofen ( sold as Actiprofen, Advil, MortrinIB, Medipren) NSAIDS ( non-steroidal anti-inflammatory drugs) Mild analgesics : non addictive

Mild Analgesics Block the enzyme –cyclooxygenase / controlled synthesis of prostaglandins responsible for constricting of blood vessels increase the body temperature Direct effect on hypothalamus / body’s heat regulating center / produces fever Cause swelling and pain / increase the permeability of capillaries, allowing water to pass out into nearby tissues

Mild Analgesics Lower the concentration of prostaglandins Reduce fever And inflammation

Endorphins and enkephalin

Enkaphalin

Endorphin Endorphin comes from the words endogenous morphine. Endogenous means developing from within. Endorphins are similar to the narcotic morphine in their functions,. They occur naturally in the brain and bloodstream.

Endorphin a group of peptide hormones that bind to opiate receptors and are found mainly in the brain. Endorphins reduce the sensation of pain and affect emotions.

Endorphin Russian scientists claim a beating on the buttocks with a strong cane is the perfect way to cure everything from depression to alcoholism by releasing the body's natural "happy chemicals" known as endorphins.

B3.2 Salicylic acid Describe the uses of derivatives of salicylic acid as mild analgesics and compare the advantages and disadvantages of using aspirin and paracetamol acetaminophen)

Salicylic acid /Acetyl salicylic acid

Salicylic Acid Antipyretic / fever reducer Mild analgesic / pain killer Strong/ damages the membrane lining the mouth, esophagus and stomach Chemically modified to sodium salt of acid Less unpleasant, but turn to acid in the stomach acetyl salicylic acid / reduce acidity/ non irritating /taken orally

Synthesis

Hydrolysis + H2O CH3COOH

ASA Prodrug :less active form of drug that is converted to the active form of drug after administration Sometimes sold as sodium salt of ASA / Alka Seltzer. / ionic bonding / dissolves in water

ASA The presence of OH and COOH group on benzene ring makes salicylic acid as strong acid Other derivatives are insoluble due the presence of aromatic ring

Uses of the Derivatives of salicylic acid ( Miracle drug) Antipyretic: reduces fever Anti-inflammatory Anti-platelet agent / prevent abnormal blood clotting, anti clotting agent (inhibits the production of prostaglandins) Mild analgesic – minor aches/pains, headaches, sunburn, arthritis

Disadvantages of ASA Stomach upset due to acidity in aq. Solution Gastrointestinal bleeding following use of alcohol 0.5% who take ASA (and 3-5% asthmatic) are allergic to ASA leading to skin rashes, respiratory difficulty Accidental poisoning in infants Development of Reye’s syndrome/ liver and brain disorder can result in coma, brain damage and death ( children who took ASA for chicken pox symptoms)

Base hydrolysis

Pain reliever

Aspirin Substitute Paracetomol Active ingredient in many OTC USES: Anti –pyretic / reduces fever Analgesics reduce pain Does not upset stomach

Acetaminophen NOT an anti-inflammatory Can cause blood disorder and kidney damage Over dose can cause liver damage, brain damage, coma and even death

Acetaminophen

Phenacetin

Ibuprofen (2-[4-(2-Methylpropyl)phenyl]propanoic Acid, Isobutylphenylpropionic Acid) Same as ASA but fewer stomach problems Anti-inflammatory Wide margin of safety, Lower effective dose Large doses /kidney problems b.html b.html

2-(4-Isobutyl-phenyl)-propionic acid ibuprofen

Opium

Strong Analgesics Relief of very severe pain, include narcotics : heroin, codeine, morphine Addictive Controlled substances

Heroin

Strong Analgesics

Local anesthetics Pain killers in localizes areas Lidocaine and procaine (Novocaine) Used in dentistry

Novocaine t is the first injectable local anesthetic to be synthesized, commonly known as Novocain. The German Chemist, Alfred Einhorn, developed it in Procaine is the precursor to cocaine. Procaine works to anesthetize a patient for about 15 minutes. To prolong anesthesia epinephrine is added as a vasoconstrictor.

Procaine/Cocaine Cocaine blocks Na+ passage through the axon cell membrane and inhibits the reuptake of Dopamine and Serotonin resulting in psycho-stimulation.

Procaine Procaine blocks nerve conductance via inhibiting Na+ at the membrane, thus no psycho-stimulation. Both reactions are brief. Drug Interactions? Procaine is thought to reduce the effects of sulfonamide antibiotics. How is this medication administered? Oral injection.

Lidocaine

General Anesthetics B9-447

SEROTONIN, happy neurotransmitter. 5-hydoxytryptamine, is naturally produced in the pineal gland, which lies at the centre of our brain. “It is essential to numerous body function including appetite control, sleep, memory and learning, temperature regulation, mood, behavior, cardiovascular function, muscle contraction, endocrine regulation and depression.

DOPAMINE, 4-(2-aminoethyl)benzene-1,2-idol, is produced in several areas of the brain including the substantia nigra. It is central to movement coordination, cognitive functions (by mediating signal transduction in the frontal lobe thus affecting memory, attention, and problem- solving in particular), latent inhibition and creative drive.

Dopamine Its release is stimulated by naturally rewarding experiences such as happy foods (bananas!), drugs,