Analgesics PDF

ANALGESICS DR JCM SILVA MBBS NICM What is inflammation..  Redness  Pain  Heat  Swelling of tissue Goals in treatment  Primary goal is to relieve the pain  Types of analgesics we use 1. Opioids 2. NSAIDS 3. Steroidal analgesics NSAIDS( Non steroidal Anti Inflammatory...

ANALGESICS DR JCM SILVA MBBS NICM What is inflammation..  Redness  Pain  Heat  Swelling of tissue Goals in treatment  Primary goal is to relieve the pain  Types of analgesics we use 1. Opioids 2. NSAIDS 3. Steroidal analgesics NSAIDS( Non steroidal Anti Inflammatory Drugs)  Principle of action Analgesic Anti inflammatory Anti pyretic Properties  Less potent analgesics  Non addicting  Anti-inflammatory, Anti pyretic ,Anti Analgesic action, Anti pateletic action  Somatic pain  Higher TI  So safe Adverse effects  GIT-Gastric ulceration Dyspepsia Nausea Vomiting Erosions  Hypersensitivity  Liver damage  AKI  Thrombocytopenia  HTN  CCF  Headache  Hallucination  Depression  Tremors  Confusion Aspirin( Acetylsalicylic acid)  Natural and synthetic source  Weak organic action  Irreversible Cox inhibitor Pharmacological action  Anti-inflammatory action  Analgesic  Anti pyretic  Anti plateletic  Also Stimulate the respiratory centre Gastric irritation Hepatic damage Hyperuricaemia Increase steroidal secretion Anti-inflammatory action  Inhibition of PG synthesis by blocking cox 2 enzyme  Interfere with the peripheral chemical mediators of inflammation. Inhibit granulocyte adherence to the vascular system, stabilises the lysomes and inhibit migration of leucocytes and macrophages to the site of inflammation Analgesic action  Central- Inhibit the pain stimuli at a subcortical line  Peripheral- chemical mediators inhibition Anti platelet function inhibit cyclooxygenase thereby decrease thromboxane A2 and inhibit platelet aggregation Antipyretic action  Inhibit PG2 synthesis which set the temperature point in the hypothalamus  Block the response to IL -1 produced by the macrophages Indications  Mild to moderate pin  Acute Rh arthritis  RHF  Arterial thrombi embolism  MI  Migraine  Sperm motility  Acute pericarditis A/E  Gastric ulcers  Impaired clotting  Hepatic and renal damage  Tinnitus, Deafness  Ryes syndrome  Allergy Contradictions  Gastric ulcer  Coagulation disorders  Hepatic and renal failure  Pregnancy  Gout  Allergy  Gout How it cause gastric ulcers  Inhibit COX and thereby inhibit mucus formation and causes erosions  Why contraindicated in 3rd trimester  Inhibition PG synthesis will lead to delay labour  Closure of premature ductus arteriosus  Newborn coagulation diseases Drug interaction  Increase aspirin elimination with corticosteroid  With warfarin it acts synergistically  Increase metabolism of aspirin when given with barbiturates  Antagonises and delay action in Antacids  With HCO3 weaken the effect-of aspirin  Prolong the penicillin's  Causes hypercalciuria by inhibit probenecid action Paracetamol  Inhibit PG synthesis by reversible inhibition of cox  Pharmacological action Weak analgesic Antipyretic Little or less anti inflammatory Pharmacokinetics  Rapidly absorbed by GIT  Excreted by kidney  Metabolised by liver  Daily dose 1-2tabs 4-6 hly  Maximum 4 g daily dose  Lethal dose 150 g/kg  Fatal 200mg / kg A/E  Hepatoxicity  Renal damage in long term use  Allergy PCM overdose NSAIDS Ibuprofen  Potent analgesic  Anti-inflammatory action  Anti plateletic function  Indications are Rh arthritis Osteoarthritis Indomethacin  Strong anti-inflammatory than aspirin  Antipyretic  Analgesic  Rapid absorption from GIT  Safe in gout and when on anticoagulants  Antagonises the anti-hypertensives( Beta blockers and , ACE inhibitors)  Indications RH arthritis Ankylosing spondylitis Osteoarthritis Gout PDA Pericarditis Pleurisy  A/E Nausea, vomiting, ulcerations Frontal headache Dizziness, vertigo Confusion Allergy Neutropenia Thrombocytopenia,  Contranducations Pre existing gastric ulcer Pregnancy, lactation Children Renal disorders Psychiatric disease Epilepsy Parkinson's Diclofenac Na  Potent anti-inflammatory, anti-pyretic and analgesic  Inhibit COX enzyme  Indications Rh arthritis Osteoarthritis Musculoskeletal pains Tendinitis Postop Dysmenorrhea Priloxicam  Antipyretic  Anti analgesic  Tolerated well than indomethacin and aspirin  Pharmacological- anti inflammatory Antipyretic Analgesic Alter function of platelets  A/E Gastric erosions Prolong bleeding Bronchoconstriction's Cox 2 inhibitors  1st gen- meloxicam,Nimwsulide  2nd gen-celecoxib, Valdecoxib,Roecoxib  Indications 1. OA 2. RHA 3. Primary dysmenorrhea 4. Musculoskeletal pain 5. Acute gout What is this GOUT  Metabolic disease characterized by intermittent attack of acute arthritis due to deposition of crystals monosodium urate in synovial joints  Management 1. Relieve inflammation ( NSAIDS, COLCHICINE,CORTICOSTEROIDS) 2. Prevent uric acid synthesis- allopurinol 3. Eliminate the urates-urosuric agents- Probenecid colchicine  Alkaloid  Plasma life is 1h  Absorbed from gout  Metabolized in liver  Pharmacological actions area 1. Anti inflammatory 2. Anti analgesic 3. No effect on urate metabolism 4. Specific to gout  Disadvantages 1. Slow 2. Bloody diarrhea 3. Renal damages  Indications 1. Gout 2. Sarcoid arthritis 3. Hepatic cirrhosis Why are we not using Aspirin in Gout  Inhibit uric acid excretion can cause hyperuricemia Opioid analgesics  Acts on dorsal horn of the spinal cord and higher centres  Produce analgesia through modulation by binding effects to the receptors in spinal cord and higher centre  Fast 1st past metabolism  Cross the placenta  Dependency-excessive craving due to repeated administration  Tolerance-reduce pharmacological effect due to repeated administration  Oral- codein,dynydrocodein,  IM/ IV- morphine, pethidine  S/C – morhine  Intra dermal- fentanyl  Buccal- fentanyl  Rectal- pethidine, pentazocin  Trans nasal- morphine, diamorhine, fentanyl  Epidural- fentanyl,diamorhine Mechanism of action Action  CNS Analgesia brain- act on the pain modulating descending pathway and inhibit the neurones Spinal cord-inhibit neurotransmitter to spinal cord, inhibit dorsal neurones, thalamic inhibition Sedation Euphoria Respi depression ( reduce response to co2 challenge)  Cough suppression Meiosis Truncal rigidity Nausea and vomiting CVS Bradycardia Increased ICP Increased cerebral blood flow Cerebral vasodilation  GIT Costipation Biliary colics Gu tract Reduced real plasma flow Bladder and ureteral tone increased Prolongation of labor  Endocrine Increases somatotropin,LH,Prolaction, ADH release Other Flushing Sweating ,dizziness , nausea, vomiting Hallucination Toxicity  Dysphoria  Respiratory depression  Nausea and vomiting  Increased ICP  Hypotension  Constipation  Urinary retention  Urticaria,  Itching Clinical uses  Analgesics  Labour  Acute pulmonary oedema  Cough  Diarrhoea  Anaesthesia Contraindications  Head injury  Pregnancy  Opioid agonist  Impaired lung function  Impaired hepatic function  Endocrine diseases( Addison’s aND myxoedema) S/S of withdrawal  Rhinorrhoea  Lacrimation  Hyperventilation  Muscular aches  Vomiting  Anxiety  Diarrhoea  Piloerection  Yawning Morphine  Mechanism of action Presynaptic release of neurotransmitters( reduce ca influx) Hyperpolarization and inhibiting the-post synaptic neurones(reduce k efflux) Inhibition of cell firing Properties  Routes- IV, IM, S/C, oral  Distribution- 1/3 is protein bounded and can cross the placenta  2 h is the plasma ½ life  Duration 4-6 h  Metabolises in the liver  Excreted through renal Indications  Analgesic  MI  Travellers diarrheas  Cough  Anaesthetic premedication  Restlessness Effect of eye  Constriction of pupil by oculomotor nucleus excitation  Increase accommodation  Reduce IOP in both norma and glaucomatous eye A/E  Respiratory depression  Nausea  Vomiting  Constipation  Urinary retention  Bronchospasm  Hypotension  Tolerance Contraindications  Head injury  Acute abdomen  Respiratory diseases  Bradycardia  Hypotension  Liver diseases S/S of toxicity  Miosis  Coma  Respiratory depression  Cold clammy skin  Hypothermia  Absent reflexes  Cyanosis  Loss of skeletal muscle tone  Death Management in poisoning  Basic management with ABCD  NALAXONE immediately as antidote Pethidine  Synthetic morphine  Less potent  Short duration of action  Large doses can cause mydriasis, antispasmodic effect, atropine like effect  Antihistaminic actions Fentanyl  Synthetic opioid  Lipid soluble  IV; intradermal; Buccal administration  Duration 1-2h  Hepatic metabolism  Narcotic potency is high  Less sedation  Marked truncal rigidity  Can cross BBB  Decrease cerebral metabolism and blood volume  Indications Chronic pain Anaesthesia Tramadol  Centrally acting  Inhibit androgenic uptake by CNS  Contradicted in seizures Nalaxone  Opioid antagonist  Reverse opioid activity in 1-3 minutes  Duration of action1-4h  Indications opioid overdoes Drug Addicts Reduce alcoholism Thank You!!!!!!!