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A drug that selectively relieves pain by acting in the CNS or on the peripheral pain mechanism ,without significantly altering consciousness
ALGESIA OR PAIN
it is an illdefined , unplesant sensation usually evoked by an external or internal noxious stimulus
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
According to chronicity
Neuropathic Acute
Chronic
Classification
Centrally :
Narcotics Non Narcotics
Peripheral :
Causal Non Causal
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)
Opium:- the dark brown resinous material obtained from poppy plant , papever somniferum & papever & album
opium powder contains Morphine : 10 % Codeine : 0.5% Thebaine : 0.2% Papaverine :1% Noscapine :6%
Chemically
According to source
These opoids peptides acts on the opoids receptor and relieves pain.
All opoids receptor are G protein coupled receptor .stimulation of these receptor inhibit adenyly cyclase resulting in the decrease of intracellular CAMP formation
They 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
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
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.
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.
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 Age Bronchial asthma COPD Head Injury Shock Hypotension Undiagonised acute abdominal pain Renal Failure, Liver diseases and hypothyrodism Unstable personalities
Morphine Vs Pethidine:
1/10th as potent as Morphine, but Efficacy is similar Produces as much sedation, euphoria and respiratory depression in equianalgesic dose and similar abuse potential Less spasmodic action in smooth muscles less miosis, constipation and urinary retention Rapid but short duration of action (2-3 Hrs) Vagolytic effect - Tachycardia Devoid of antitussive action Less histamine release safer in asthmatics
Better oral absorption
it 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.
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 recommended
Dose:- 50-100mg every 4-6 hours.
(400mg/day- maximum)
Opioid Antagonists
1. Pure antagonists: Naloxone, Naltrexone
and Nalmefene
Affinity for all receptors (, and ) Can displace opioids bound to -receptors No action on Normal person but reverses poisoning and withdrawal symptoms in addicts
NALOXONE
Competitive antagonist of all types of opioid receptors But, blocks -receptors at much lower dose Always injected IV (0.4 t0 0.8 mg) - All symptoms of Morphine action are antagonized respiratory stimulation At higher doses 4-10 mg: antagonizes actions of Nalorphine and Pentazocine dysmorphic and psychomimetic effects are not suppressed ( ) Withdrawal symptoms: 0.4 mg doses Morphine and 4-5 mg doses Nalorphine and Pentazocine
Non 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.
NSAIDs
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
Mechanism of action
Arachidonic acid
COX-1
NSAIDs
COX-2
COX-2 inhibitors
Leukotrienes\Prostaglandins
Prostaglandins
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 antiinflamatory 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 Reyes syndrome Salicylism Acute salicylate intoxication
PHARMACOKINETICS
They 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
CONTRAINDICATION
Peptic ulcer patient Bleeding disorder Chronic liver disease Pregnancy
Central analgesic action,it raises pain threshold Weak peripheral anti-inflammotry component Poor ability to inhibit COX in the presence of peroxide Well absorbed orally It is one of most comonnly used over the counter analgesia where anti-inflammatory is not required One of best drug to be used as antipyretic Much safer analgesic DOSE ;500-1000 mg TDS
Better tolerated alternative to aspirin Side affects are milder than aspirin Gastric discomfort , nausea , vomitting are less than aspirin CONTRAINDICATION:: Pregnancy Peptic ulcer
NEMUSLIDES
Slectively 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 NSAIDS
Mild 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 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.