ANALGESICS

ANALGESIC

A drug that selectively relieves pain by acting on CNS or on peripheral pain mechanisms without significantly altering consciousness

ALGESIA or PAINIt is an illdefined, unpleasent sensation,

usually evoked by an external or internal noxious stimulus

PAIN RECEPTOR Pain receptor in our bodies are nerves that transmit pain.

These are free nerve endings located in various body tissues that respond to thermal, mechanical, & chemical stimuli.

When tissue becomes injured, they release chemicals called prostaglandins and leukotrienes that make the pain receptor more sensitive and these causing pain.

Types of PainPAINAccording to sourceVisceralSomatic

NeuropathicAccording to chronicity

ChronicAcute

Therapeutic management of painClassification: Peripheral (miscellaneous): -Causal -Non causal Central: -Narcotic -Non narcotic

Peripheral AnalgesicCausal: -Treat the cause

eg:- atropine

Non-causal: -Not treat the cause

Examples:1- Local anesthetics (for

superficial tumor)2- Counter-irritant (apply pain

that counteract or mask the original one e.g. acupuncture)

Central AnalgesicOpioids:

Morphine & morphine like drugs

NSAIDs: 1- Aspirin

2- Paracetamol3- Diclofenac4- Piroxicam5- Ibuprofin6- Ketoprofin

OPIOID ANALGESIC“Opium” is a Greek word meaning “juice,” or the

exudates from the poppy.Opium is extracted from poppy seeds (Paper

somniforum)“Opioid” is a natural or synthetic drug that binds

to opioid receptors producing agonist effects.

Fresh capsule of opium poppy Cut capsule showing latex exuding from cut

Classification Chemically

Phenanthrene groupEg: Morphine

Benzolisoquinoline groupEg: Papaverine

MORPHINE• Morphine is the most important alkalloid of opium.

• Many new opioids have been synthesized but none of them are superior to morphine as an analgesic.

• It is the protype of this group.

Mechanism of Action Opioids exert their major effects by interacting with opioid receptors in the CNS Opioids activate 7- transmembrane GPCRs located pre-symaptically and post-symaptically along pain

transmission pathways. High densities of opioid receptors known as mu, delta and kappa are found in the dorsal horn of the spinal

cord and higher CNS centers. Most currently used opioid analgesics act mainly at mu- opioid receptors Morphine acts at kappa receptors in lamina 1 and 11 of the substantia Granulose of the spinal cord and

decreases the release of substance p, which is modulates pain perception in the spinal cord. Opioids have an onset of action that depends on the route of administration . Opioids causes hyper polarization of nerve cells , inhibition of nerve firing and presynaptic inhibition of

transmitter relea Cellular effects of these drugs involve enhancement of neuronal potassium efflux ( hyperpolarizes neurons

and makes them less likely to respond to a pain stimulus ) and inhibition of calcium influx ( decreases neuro- transmitter release from neurons located along the pain transmission pathway )

Opioids relieve pain both by raising the pain threshold at the spinal cord level and more importantly by altering the brains perception of pain

Pharmacological actions Analgesia Respiratory depression Cough suppression Vagal stimulation (bradycardia) Sedation & hypnosis Hypothermia Itching Physical & pshycological dependence Euphoria Histamine release , hypotension….etc

Adverse effects• Morphine can produce a wide range of adverse effects like nausea, vomiting, dizziness,

mental clouding, respiratory depression, constipation, dysphoria, urinary retention, & hypotension, allergic reactions.

• Tolerance- Repeated administration of morphine results in the development of tolerance to some of its effects including respiratory depression, analgesia, sedation, etc .

• Dependence- Opium has been a drug of addiction for many centuries. Its ability to produce euphoria makes it a drug of addiction. Opioids produce both physiological & pshycological dependence. Manifestations are lacrimination, sweating, yawning, anxiety, restlessness..etc.

NSAIDsNon steroidal anti-inflamatory drugs are

aspirine-type or non-opioid analgesics. In addition they have anti-inflamatory,

anti pyretic & uricosuric properties without addiction liability.

The active principle is salicin, that is converted into salicylic acid in body.

Classification

Non selective COX inhibitor

• Salicylic acid derivatives. Eg: aspirine

• Para aminophenol derivatives. Eg: paracetamol

• Pyrazolone derivatives. Eg: Sphenylbutazone

• Indole acetic acid derivatives. Eg: sulindac

• Arylacetic acid derivatives. Eg: diclofenac

• Propionic acid derivatives. Eg: ibuprofen

• Anthralinic acid derivatives. Eg; flufenamic acid

• Oxicams. Eg: piroxicam• Alkanones. Eg: nabumetone

Selective COX-2 inhibitors• Nimesulidde,

celecoxib, rofecoxib…etc

Mechanism of action

Arachidonic acid

COX-1 COX-2

Leukotrienes\Prostaglandin

s

Prostaglandins

Primarily support platelet function

Primarily protect GI-tract mucosa

Primarily mediate inflamation, fever,

pain

NSAIDs COX-2 inhibitors

Pharmacological actions• Analgesia

• Antipyretic actions

• Anti-inflamatory actions

• Respiration stimulation

• Metabolic effects

• Immunological effects

• Uric acid excretion

• Blood- delayed clotting time

Adverse effects Analgesics doses are usually well tolerated but anti-inflamatory doses are

usually associated with adverse effects whed used for a long period.A. G.I tract:- Epigastric distress, nausea, vomiting, erosive gastritis, peptic

ulcer, increase occult blood loss in stools are commonB. Allergic reactions are not common and may be manifested as rashes,

photo sensitivity..etcC. HaemolysisD. NephrotoxicityE. Reye’s syndromeF. Salicylism G. Acute salicylate intoxication

Analgesics used in deintistry

• Non opiod analgesics are mostly used for mild to moderate pain.

• NSAIDsCOX1 & COX2:

Ibuprofen, aspirin, ketrolac, diclofenac COX-2:

celecoxib, rofecoxib, nimesulide.

Acetaminophen• Dose:

-Adult: 0.5 – 1g every 4-6 hrs.-6-12 years: 250-500mg every 4-6hrs.-1-5 years: 150-250mg every 4-6hrs.

• Contraindication: Renal failure, asthma, liver failure.

Nimesulide• Indication:- Acute pain

• Dose:- 100mg twice a day

• Contraindication:- Renal failure, asthma, liver failure

OPIOIDS Although opiod as a class are

effective analgesics, some commonly formulation shows poor analgesic efficacy for dental pain, and is not used for their adverse effects.

Tramadol• Tramadol is a synthetic centraly acting

analgesic indicated to moderate to moderately severe pain.

• Dose:- 50-100mg every 4-6 hours.(400mg/day- maximum)

Combination!!• Analgesic monotherapy has shown

equivocal success in treating dental pain.

• The goal of combining analgesics with different mechanisms of action is to use lower doses of the component drugs.

Acetaminophen combination

• Acetaminophen is an effective analgesic for mild pain, but to manage more severe pain it typically is combined with codeine or one of its derivatives.

• Acetaminophen 1000mg combined with codeine 60mg.• Acetaminophen 1000mg combined with oxycodone 10mg.• Acetaminophen 650mg combined with tramadol 75mg.• Acetaminophen 500mg combined with hydrocodone 7.5mg.

NSAIDs Combination• Ibuprofen 400mg combined

with codeine 60mg.• Ibuprofen 400mg combined

with oxycodone 10mg.• Ibuprofen 400mg combined

with hydrocodone 15mg.• Ibuprofen is also combined

with tramadol.

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