12.3 Analgesicshttp://www.nlm.nih.gov/

medlineplus/druginformation.htmlDescribe 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

•     

AspirinAnalgesics: 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

www.wcer.wisc.edu/.../Spr2000/esselman/IBUb.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 1904. • 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,