451 PHL 3 rd lecture Analgesics Awatif B. Al-Backer

Drugs that selectively inhibit the perception (sensation) of the pain Analgesics Definition Drugs that selectively inhibit the perception (sensation) of the pain Classification 1- Peripheral (miscellaneous): - Causal - Non-causal 2- Central: - Narcotic - Non-narcotic Awatif B. Al-Backer

- Stimulation of skin & mucous membranes - Fast response Deep: Types of Pain Superficial: - Stimulation of skin & mucous membranes - Fast response Deep: - Arises from muscles, joints, tendons, heart ..etc. - Slow response causing sweating, nausea, & vomiting Awatif B. Al-Backer

Peripheral Analgesics Causal -Treat the cause Example: 1. Atropine relief colic (antispasmodic) 2. Ergotamine treat migraine 3. Colchicines treat gout Non-causal - Does not treat the cause Examples: 1- Local anaesthetics (for superficial tumor) 2- Counter-irritant (apply pain that counteract or mask the original one e.g. acupuncture) Awatif B. Al-Backer

Narcotics Non-narcotic Central Analgesics - NSAID 1- Aspirin The class - Opioids (morphine & morphine like drugs) Examples 1- Natural (as codeine) 2- Semi synthetic e.g. dihydromorphine& diacetylmorphine (heroin) 3- Synthetic e.g. pethidine 4- Endogenous opiates as endorphins & encephalins Non-narcotic - NSAID 1- Aspirin 2- Paracetamol 3- Diclofenac 4- Piroxicam 5- Ibuprofin 6- Ketoprofen Awatif B. Al-Backer

Central Analgesics Awatif B. Al-Backer Non-narcotic Subcortical “thalamus” No antagonist Dull pain e.g. headache, toothache & backache Low No addiction. ↑in bleeding tendency & ulcer Inhibits prostaglandin synthesis by inhibition of cycloxygenase enzyme Narcotics Site of Cortex & thalamus action Antagonist Naloxone, nalorphine & levallorphan Uses Sever & deep pain e.g. cancer, MI, & anginal pain Potency High Side effect Addiction MOA ‡ of opiatereceptors (m, k ,s, d) and relief the pain through the release of endorphine & encephalins Awatif B. Al-Backer

Screening Methods For Analgesics Principle:- Pain is induced to a suitable animal and the response of the animal to the painful stimuli is recorded before and after administration Awatif B. Al-Backer

2- Chemical ( Writhing method) Screening methods Narcotics: 1- Thermal method a- Hot plate b- Tail flick 2- Mechanical method Non-narcotic: 1- Electrical method 2- Chemical ( Writhing method) Awatif B. Al-Backer

Instrument: Hot plate analgesiometer Painful stimulus: Heat (55°C) Material Animal: Mouse Instrument: Hot plate analgesiometer Painful stimulus: Heat (55°C) Drug used: Morphine (0.5 % - 25 mg/kg) Onset of action: licking of the feet, or jump out of the beaker ( normally occur within 20 sec.) Awatif B. Al-Backer

Instrument: Tail-flick analgesiometer Material:- Animal: Mouse Instrument: Tail-flick analgesiometer Painful stimulus: Heat (by apply a beam of light 130°C) Drug used: Morphine Onset of action: flicking of the tail (Cut off- point_ should be less than or equal to 6 sec.) Awatif B. Al-Backer

Writhing Method Principle: The painful stimulus is induced by IP injection of an irritant substance (e.g. acetic acid) Writhing: Stretching of the body, withdrawing of the limb, retraction of the abdomen & the stomach touches the ground Awatif B. Al-Backer

Painful stimulus: Chemicals e.g. acetic acid Continue Material Animal: Mouse Painful stimulus: Chemicals e.g. acetic acid Drug used: NSAID e.g. Na salicylate Drug Onset of writhing No. of writhing Acetic acid (control) Na salicylate (100mg/kg) Na salicylate (200mg/kg) Awatif B. Al-Backer

The no. of writhing measured within 10 min. after the onset time. Continue N.B:- After treatment with Na. Salicylate, the onset of writhing will be delayed & the no. of writhing will decrease which explain the analgesic property of NSAIDs. The no. of writhing measured within 10 min. after the onset time. Awatif B. Al-Backer

Awatif B. Al-Backer