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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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