Analgesic

Presented by :- 3rd year BDS

A drug that selectively relieves pain by acting in the CNS or on the peripheral pain mechanism ,without significantly altering consciousness

ALGESIA OR PAINit is an illdefined , unplesant sensation

usually evoked by an external or internal noxious stimulus

ANALGESICS

Free nerve endings are the receptor for pain

These are mainly of two types and are connected to the AD and C fibres

These AD and C fibres carry the pain sensation to the CNS

PAIN RECEPTOR

PAINAccording to source

Visceral

Somatic

Neuropathic

According to chronicityChronic

Acute

TYPES OF PAIN

Classification

Centrally : Narcotics

Non Narcotics

Peripheral : Causal

Non Causal

THERAPEUTIC MANAGEMENT OF PAIN

Causal: -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)

PERIPHERAL ANALGESIC

OPIOIDS/NARCOTICS

Morphine like analgesics

NON OPIOIDS/

NON NARCOTICS

Aspirin like analgesics

Aspirin Paracetamol Diclofenac Piroxicam Ibuprofin Ketoprofin

CENTRAL ANALGESICS

opium powder contains -Morphine : 10 %

Codeine : 0.5%

Thebaine : 0.2%

Papaverine :1%

Noscapine :6%

OPIOIDS Opium:- the dark brown resinous material

obtained from poppy plant , papever somniferum & papever & album

CLASSIFICATION

Chemically

Phenanthrene groupEg: Morphine

Benzolisoquinoline groupEg: Papaverine

Morphine is the prototype of the group.

Opoids agonists produces analgesia by binding to the specific G protein coupled receptor that are located in the CNS involved in tranmission and modulation of pain

RECEPTOR TYPE :

the opoids mu , kappa and delta is identified in various nervous system sites and in other tissues

Endogenous opoids peptides released in the body in response to the pain are :-

These opoids peptides acts on the opoids receptor and relieves pain.

MORPHINE

Endophorin mu [µ]

Dynophorin kappa [ķ]

Enkephalin delta [δ]

Nociceptin N/OFQ (orphanin FQ receptor)

All opoids receptor are G protein coupled receptor .stimulation of these receptor inhibit adenyly cyclase resulting in the decrease of intracellular CAMP formationThey also facilate the opening of K+ channel leading to hyperpolarisation and inhibit the entry of ca++ into thr cell. In addition to this they inhibit the opening of ca++ channel

All these result in decrease in intracellular ca++ which of in turn , decrease the release of neurotransmitter which are involved in transmission of pain

Opoids also directly inhibit the transmission of pain in the dorsal horn ascending pathway

CELLULAR ACTIONS::

CNS :

Analgesia : morphine produces spinal and supraspinal analgesia by acting on the mu , kappa and delta receptor

Respiratory depression

Cough depression

Sedation

Euphoria

Miosis

Nausea and vomitting

PERIHERAL ACTIONS :Release of histamine

Constipation

Increase in intrabilliary pressure

Bronchoconstriction

PHARMACOLOGICAL ACTIONS

Most opoids are well absorbed when given by subcutaneous,intramuscular and oral routes

Given orally ,absorption of morphine is slow and incomplete .morhine undergoes extensive first pass metabolism.

PHARMACOKINETICS

ADVERSE EFFECTS

Morphine can produce a wide range of adverse affects like

Nausea,Vomiting,Dizziness,Mental clouding, Respiratory depression,Urinary retention Hypotension

Allergic reaction including skin rashes,pruritus and wheal at the site of injection of morphine may be seen

TOLERANCE:repeated admistration of morphine result in the development of tolerance to some of its affects including respiratory depression,analgesia,sedation and euphoriant effects

DEPENDENCE :opium has been a drug of addiction for many centuries.its ability to produce euphoria make it a drug of addiction,they produces both psychological and physical dependence

sudden cessation of opoids or admistration of opoid antagonists produces significant withdrawl symptoms in such dependent individual.

WITHDRAWAL SYMPTOMS

Drug seeking behavior

Lacrimation

Yawning

Sweating

Restlessness

Mydriasis

Tremors

Nausea

Tachycardia

MANAGEMENT OF ADDICTION

MORPHINE is slowly withdrawn over several days and substituted by oral METHADONE

it is orally effective it has longer duration of action withdrawl symptoms are mild

1mg methadone will substitute 4 mg morphine.later methadone is gradually reduced and completely stopped within 10 days

Morphine – Contraindications

Two Extremes of AgeBronchial asthma COPDHead InjuryShock – HypotensionUndiagonised acute abdominal painRenal Failure, Liver diseases and hypothyrodismUnstable personalities

Other opoids

Morphine Vs Pethidine:1/10th as potent as Morphine, but Efficacy is similarProduces as much sedation, euphoria and respiratory depression in equianalgesic dose and similar abuse potentialLess spasmodic action in smooth muscles – less miosis, constipation and urinary retentionRapid but short duration of action (2-3 Hrs)Vagolytic effect - TachycardiaDevoid of antitussive actionLess histamine release – safer in asthmaticsBetter oral absorption

PETHIDINE

FENTANYLit is 100 times more potent than morphine as an analgesic.It is highly lipid soluble and fast acting.

It has mild side effects on the cvs it slightly reduces heart rate and blood pressure

unklike morphine it does increases the intracranial pressure.

It is not a histamine liberator.

It is combined with droperidol ,a neuroleptic agent to produce neuroleptanalgesia.

Because of this fentanyl is a commonly used opoid analgesic.

Tramadol is a synthetic centraly acting analgesic indicated to moderate to moderately severe pain.

It is used in the treatment of labour pain and even cancer pain.

It inhibit reuptake of serotonin and norepinephrine,hence admisistration with MAO-I is not recommendedDose:- 50-100mg every 4-6 hours.

(400mg/day- maximum)

Tramadol

Opioid Antagonists1. Pure antagonists: Naloxone, Naltrexone

and Nalmefene• Affinity for all receptors (μ, δ and κ)• Can displace opioids bound to α-receptors• No action on Normal person but reverses poisoning

and withdrawal symptoms in addicts

2. Mixed Agonist-antagonists: Nalorphine, Pentazocine, Butorphanol and Nalbuphine

3. Partial/weak μ agonist and κ antagonist: Buprenorphine

NALOXONECompetitive antagonist of all types of opioid receptorsBut, blocks μ-receptors at much lower doseAlways injected IV (0.4 t0 0.8 mg) - All symptoms of Morphine action are antagonized – respiratory stimulationAt higher doses 4-10 mg: antagonizes actions of Nalorphine and Pentazocine – dysmorphic and psychomimetic effects are not suppressed (δ)Withdrawal symptoms: 0.4 mg doses – Morphine and 4-5 mg doses – Nalorphine and Pentazocine

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: phenylbutazone

• Indole acetic acid derivatives. Eg:

indomethacin• 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.

G.I tract:- Epigastric distress, nausea, vomiting, erosive gastritis, peptic ulcer, increase occult blood loss in stools are common

Allergic reactions are not common and may be manifested as rashes, photo sensitivity..etc

Haemolysis

Nephrotoxicity

Reye’s syndrome

Salicylism

Acute salicylate intoxication

PHARMACOKINETICSThey are rapidly absorbed from the upper GIT tract.

They are hiighly bound to plasma protein

Salicyclates are well distributed throughout the tissue and body fluids;metabolised in the liver by glycine and glucoronide conjugation.

In low doses , elimination follows zero order kinetics and with high doses as the metabolizing enzyme get saturated,it switches over to zero order kinetics

DOSE Analgesic dose:600 mg three times a day

Anti-inflammatory dose:3-6g/day

CONTRAINDICATION

Peptic ulcer patient

Bleeding disorder

Chronic liver disease

Pregnancy

ANALGESICS USED IN DENTISTRY

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

• NSAIDsCOX1 & COX2:

aspirin,ibuprofen,ketrolac, diclofenac

COX-2:celecoxib, rofecoxib,

nimesulide.

Central analgesic action,it raises pain thresholdWeak peripheral anti-inflammotry componentPoor ability to inhibit COX in the presence of peroxideWell absorbed orallyIt is one of most comonnly used over the counter analgesia where anti-inflammatory is not requiredOne of best drug to be used as antipyreticMuch safer analgesicDOSE ;500-1000 mg TDS

PARACETAMOL

Better tolerated alternative to aspirin

Side affects are milder than aspirin

Gastric discomfort , nausea , vomitting are less than aspirin

CONTRAINDICATION::

Pregnancy

Peptic ulcer

DOSE 400-800 mg TDS

IBUPROFEN

NEMUSLIDESSlectively COX -2 inhibitor

Weak inhibitory action on PG synthesis

Used primarily for short lasting painful inflammatory like sports injury,sinusitis,dental surgery and post operative pain

Because of the risk of hepatotoxicity it is banned now

DOSE 100 mg daily

CHOICES OF NSAIDSMild to moderate pain with little inflammation-Paracetamol or low dose Ibuprofen

Acute muscoskeletal/injury associated inflammation-Diclofenac,Ibuprofen

Exacerbation of acute pain-high dose Aspirin,indomethacin

Severe pain-Aspirin or combination with narcotic drug

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 CombinationIbuprofen 400mg combined

with codeine 60mg.Ibuprofen 400mg combined

with oxycodone 10mg.Ibuprofen 400mg combined

with hydrocodone 15mg.Ibuprofen is also combined

with tramadol.

CLOVES AS AN ANALGESICS

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