![Pharmacokinetics :
Not effective due to its poor penetration through GI
mucosa and high first pass effect
parenterally injection → has delayed onset of action ( 5-10
min) and short duration of action ( 25-30 min )
[ causes vasodilation → results in rapid absorption and
biotransformation ]
after absorption → rapidly hydrolysed by plasma
cholinesterase and by esterase in liver → inactive
metabolites PABA and diethylaminoethanol → excreted by
the kidneys into the urine.
Metabolism : Hydrolysis by plasma esterases to PABA
Route of elimination : With normal kidney function, the
drug is excreted rapidly by tubular excretion.
Half life : 7.7 minutes](https://image.slidesharecdn.com/484950localanesthesia-190628071900/85/Local-anesthesia-Mechanism-Of-Action-as-well-as-types-11-320.jpg)
Local anesthesia Mechanism Of Action as well as types
- 1. LOCAL ANESTHESIA By : Suman Bhattarai(ROLL NO :50) Sujan Thapa Magar (ROLL NO :49) Sujan Rai (ROLL NO :48) B.V.Sc & A.H Agriculture and Forestry University
- 2. Local Anesthesia Drugs that are used to produce reversible loss of sensation in a circumscribed area(restricted) of the body Caused by depression of excitation in nerve endings or an inhibition of the conduction process in peripheral nerves and in every type of nerve fibres i.e. Sensory,motor or autonomic No Structural damage to the neurons
- 3. Desirable Properties Of Local Anesthesia Should not be irritating Should not cause any permanent alteration of nerve structure Its systemic toxicity should be low Time of onset of anesthesia should be short Should have high potency so that low concentration should be used Should be free from producing allergic reactions Should be stable in solution and relatively undergo biotransformation in the body
- 4. MECHANISM OF ACTION • Local Anesthetic receptors are located in Na+ channel of axonal membrane • Receptors Consists of 2 gates 1) Activation gate or ‘m’ gate 2) Inactivation gate or ‘h’ gate Note: Action of ‘h’ gate is responsible for blocking of Na+ channels
- 5. MECHANISM OF ACTION Local Anesthesia – Weak bases , Present in Unionized form Enter into cell membrane of Neuron Block Voltage gated Na+ channels by physically plugging the transmembrane pore from inside No entry of Na+ ions into cell No depolarisation
- 6. No depolarisation No generation of action potential No generation of impulse to CNS No conduction of nerve impulse Critical threshold potential required for impulse transmission (-45mA) is not achieved MECHANISM OF ACTION
- 7. No Sensation MECHANISM OF ACTION
- 8. Classification Based on nature of the carbony- containing linkage group in their structure, LA can be classified into 1) ESTER LOCAL ANESTHETICS e.g. Procaine , Benzocaine , Tetracaine 2) AMIDE LOCAL ANESTHETICS e.g. Lidocaine , Prilocaine 3) ETHER OR KETONE LOCAL ANESTHETICS e.g Pramocaine , Dyclonine
- 9. 1) ESTER LOCAL ANESTHETICS Procaine • first synthetic local anesthetic introduced in 1905 • is an ester of diethylaminoethanol and paraamino benzoic acid(PABA) Pharmacological Effects a) Local Action : • Rapidly effective when injected locally • When injected around mixed nerve , causes anesthesia of skin and paralysis of voluntary muscle supplied by the nerve • Reduces the release of acetylcholine from motor nerve endings
- 10. • Local effects : Loss of pain, tempertature and touch, vasodilation, and loss of motor power b) Systemic actions • CNS : Normal dose : rapidly inactivated in the plasma and has little apparent CNS effects High dose : CNS stimulation like restless , tremors and convulsions • Cardiovascular system : Normal doses : No significant effect on heart High doses : Myocardial depressant activity and can decrease automaticity, excitability, contractility, conductivity, and increase refractory period
- 11. Pharmacokinetics : Not effective due to its poor penetration through GI mucosa and high first pass effect parenterally injection → has delayed onset of action ( 5-10 min) and short duration of action ( 25-30 min ) [ causes vasodilation → results in rapid absorption and biotransformation ] after absorption → rapidly hydrolysed by plasma cholinesterase and by esterase in liver → inactive metabolites PABA and diethylaminoethanol → excreted by the kidneys into the urine. Metabolism : Hydrolysis by plasma esterases to PABA Route of elimination : With normal kidney function, the drug is excreted rapidly by tubular excretion. Half life : 7.7 minutes
- 12. Side effects : Low local and systemic toxicity High doses may produce restlessness, tremors, and convulsions followed by CNS depression Cardiovascular toxicity includes hypotension, bradycardia, arrthymias, and possible cardiac arrest Contraindications & Precautions Should not be used in patients suffering from cardiac disease or those hypersensitive to it Vasoconstrictor shouldnot be added to procaine when used for nerve block of extremities ( e.g. tail, toes, ears, penis, e.t.c )
- 13. Drug interaction : Procaine should not be used with sulphonamides as it decreases antimicrobial activity of sulphonamides by enhancing availability of PABA Clinical Uses : Used mainly for nerve block anesthesia Doses : Dogs and cats : 2-5 ml of 2 % solution Large animals : 5-10 ml of 4% solution
- 14. LIDOCAINE : Is an aminoethlyamide and is the prototypical members of amide group of local anesthetics Pharmacological effects : Most properties similar to procaine but produces more prompt, more intense, long lasting, and more extensive anesthesia Rapid onset of action ( blocks conduction within 3 minutes ) Duration of action : 45 min ( without epinephrine ) : 90 min ( with epinephrine ) Pharmacokinetics : Not effective orally as it has high 1st pass effect After absorption, is dealkylated in the liver by mixed function oxidases ( MFOs ) → monoethylglycine and glycine xylidide which retain local anesthetic activity
- 15. These active metabolites biotransformed further before excretion in urine Elimination half life : 90-120 min Side Effects : Same effects as procaine Unlike procaine, early central effects are Drowsiness, dizziness, and tinnitus Overdosage causes muscle twitching, convulsions, cardiac arrthymias, fall in blood pressure, coma & respiratory depression and arrest Contraindications and precautions : Contraindicated in patients with known hypersensitivity to amide type local anesthetic
- 16. Most widely used local anesthetic for infiltration, regional, nerve block, epidural and also topical anesthesia Clinical Uses Use of epinephrine is contraindicated with lidocaine, if it is used in treatment of ventricular arrthymias For epidural injection (2 % soln) : Dogs and Cats : 0.2 ml/kg Sheep : 3-4 ml Cattle : 5-6 ml Doses
- 17. Pramocaine : Ether or ketone local anesthetic Used primarily on skin or mucous membrane as a topical anesthetic HCL salt form of pramocaine is water soluble and hence more easily absorbed into skin Used to relieve pain or itching caused by conditions such as sunburn or minor burns, insect bites, poison, minor cuts and scratches.
- 18. Thank you