Anaesthetic and muscle relaxant agents

Dr David N.Musyoka

Local Anaesthetics
reversibly block sodium nerve .

Clinical use
1. To block pain sensation. 2. Block sympathetic vasoconstrictor impulse to specific areas.

Clinical use
newer agents : 1. irritation, 2. toxicity, 3. faster,

Chemistry, cocaine&lidocaine

chemistry
cationic form is most active uncharged penetration
LA receptor hard accessibe from ext side.

EXAMPLES
ESTERS cocaine Procaine(novocain) Tetracaine(pontocaine) AMIDES Lidocaine(xylocaine) Mepivacaine (carbocaine,isocaine) bupivacaine(marcaine) Etidocaine(duranest) Prilocaine(citanest) Ropivacaine(naropin) 4 2 16 16 3 16 medium medium long long medium long POTENCY 2 1 16 DURATION OF ACTION medium short long

pharmacokinetics
injection. Vasoconstrictors reduce. Lipid sol bupivacaine less affected by vasoconstrictors, Cocaine has sympathomimetic

cont
widely distributed, Metab&Excretion. LA liver prilocaine>etidocaine>lodocaine>mepivacaine>ro pivacaine>bupivacaine>levobupivacaine(slowest urine. )

pharmacodynamics
The MOA of LA is blockade of voltage-gated sodium channels. voltage & time dependent high conc LA ca+ spinal toxicity.

pharmacodynamics
The smaller and more lipophilic + water solubility =faster

pharmacodynamics
tetracaine,etidocaine and bupivacaine more potent and longer blocked first r smaller B&C fibers small type A delta fibers, pain is first finally motor. Vasoconstrictor retards removal CVS&CNS toxicity

Clinical pharmacology of local anesthetics

Provides analgesia Administration. 1. Topical , 2. nasal mucosa, 3. wound margins 4. Infiltration 5. Epidural/subarachnoid 6. neuropathic pain syndromes eg IV LIDOCAINE,

TOXICITY
1.CNSlow doses; sleepiness,visual& auditory disturbances, early symptom tongue numbness and a metallic taste. At higher doses; ,tonic-clonic, nystugmus ,death, CNS depression Cocaine cardiac toxicity,htn&arrhythmias

TOXICITY
2.NEUROTOXICITY; All LA Lidocaine & chloroprocaine most

TOXICITY
3 CARDIOVASCULAR LA vasodilation Exception Cocaine block reuptake norepinephrine . Bupivacaine most cardiotoxic

TOXICITY
4.HEMATOLOGIC EFFECTS Prilocaine-= o-toluidine = methb high =cyanotic treat ascorbic acid.

TOXICITY
5. ALLERGIC REACTIONS Ester=p-aminobenzoic . Rare in amides.

END
QUESTIONS

GENERAL ANESTHETICS
includes; 1. Analgesia 2. Amnesia 3. Loss of consciousness 4. Inhibition of sensory and autonomic reflexes 5. Skeletal muscle relaxation

GA
ideal drug. 1. smoothly and rapidly. 2. Prompt recovery, 3. No SE, 4. Wide margin of safety

TYPES OF GENERAL ANESTHETICS

Inhaled Anesthetics: 1. Nitrous oxide;gas at ambient temp and pressure 2. Halothane, 3. Enflurane, 4. Isoflurane, 5. Desflurane, 6. Sevoflurane & 7. Methoxyflurane are volatile liquids.

TYPES OF GENERAL ANESTHETICS

Intravenous anesthetics: 1. Barbiturates(thiopental,methohexital) 2. Benzodiazepines(midazolam,diezepam) 3. Opiodanalgesics. (morphine,fentanyl,sufentanil,alfentanil,remifen tanyl 4. Propofol 5. Ketamine Misc,droperidol,etomidate,dexmedetomidine

SIGN (Guedels & STAGES OF ANESTHESIA

diethyl ether, slow onset of action

SIGN & STAGES OF ANESTHESIA

1. analgesia without amnesia, 2. Excitement & amnestic, resp is irregular .; 3. surgical anesthesia , regular resp to ceasation ocular movements,eye reflexes and pupil size. 4. Stage of Mdullary Depression; -support.

INHALED ANESTHETICS
Induction and maintainance. Common NO ,desflurane,isoflurane,sevoflurane Uptake and distribution depends on. 1 solubility in blood. 2 Anesthetic conc in inspired air. 3 Pulm ventillation 4 Pulm blood flow 5 Arteriovenous conc gradient

INHALED ANESTHETICS
ELIMINATION- by lungs &liver Metabolism methoxyflurane>halothane>enflurane>sevofl urane>isoflurane>desflurane>nitrous oxide, Desflurane has high incidence of coughing.

pharmacodynamics
MOA 1. inhibitory GABA A-receptor chloride channel, synaptic. 2. Memb hyperpolarization actvation of ligandgated potassium channels. 3. Inhibition of nicotinic acetylcholine receptor isoforms Ketamine functions by antagonism of excitatory neurotransmitter glutamic acid on NMDA receptor

MAC
Minimum alveolar anesthetic concentration median conc(partial pressure of anesthetic as a percentage of 760mmHg) immobility in 50% esposed noxious stimuli.

EFFECTS ON SYSTEMS
CVS Halothane,desflurane,enflurane,sevoflurane and isoflurane all decrease MAP. Halothane&enflurane-reduce cardiac output. Isoflurane,desflurane and sevo have a depressant effect on arterial pressure-decrease systemic vascular resistance. Halothane-bradycardia via vagal stimulation. Des &iso incr HR Desflurane increases both HR&BP All increase rt atrial pressure ie depression of myocardium,halothane&enflurane more than isoflurane Arrhythmias-sensitize myocardium to catecholamines-pheo/anxiety

EFFECTS ON SYSTEMS
RS except nitrous oxide All decrease tidal vol& increase RR, Isoflurane &enflurane most depressant. PaCO2 depress mucocilliary clearance Halothane&sevoflurane have bronchodilator cough desflurane.

BRAIN Decr metab rate Incr cerebral blood flow by red vascular resistance Enflurane avoid in pts with seizures,

EFFECTS ON SYSTEMS
KIDNEY All decr GFR All incr renal vasc resistance LIVER All decr hepatic blood flow
UTERINE SMOOTH MUSCLE NO has little effect here Halogenate == muscle relaxants

SIDE EFFECTS
HEPATOTOXICITY; Halothane,hypovolemia,obese immune mediated. NEPHROTOXICITY. enflurane metab in the kidney.

SIDE EFFECTS
MALIGNANT HYPERTHERMIA succunylcholine-tachycardia and HTN,severe muscle rigidity,hyperthermia,hyperkalemia&acidosis.

Clinical uses

INTRAVENOUS ANESTHETICS
DRUGS: Thiopental Etomidate Ketamine Propofol(diprivan) Have rapid anesthetic action tha the fastest inhaled agents like desflurane &sevoflurane. Useful for induction.

BARBITURATES
Thiopental-short acting,rapid onset of action, rapidly crosses bbb then redistributes, Reduces cerebral blood flow.cardiovacular depression, hepatic and renal decr in blood flow. Exacerbate pophyrias, synthesis of hepatic ALA.

BENZODIAZEPINES
Diezepam,lorazepam,midazolam Sedatives and amnestic Flumazenil is antidote.

OPIOD ANALGESICS
Morphine 1-3mg/kg Fentanyl-slow onset of action Alfentanil-rapid onset of action Remifentanyl -,,,,, In high doses can be used for GA in pts with limited cardiovascular reserve Antidote -naloxone

PROPOFOL
Popular Fast onset and fast recovery Pt also feel better Post op, nausea & vomitting less Used for both induction &maintainance of anesthesia Metab rapidly in the liver Causes low BP-low peri resistance,also negative inotropic Apnea and pain at the site of injection Muscle movts,hypotonia tremors may occur

etomidate
Rapid onset moderately fast recovery, Cardiovascular stability,decreased steroidegenesis,involuntary muscle movts

KETAMINE
Produces dissociative anesthesiacatatonia,amnesia&analgesia without LOC. Moa-blockade of the memb effects of the excitatory neurotransmitter glutamic acid at the NMDA(N-methyl-D-aspartate receptor subtype) Lipophilic,hepatic metab with urinary and biliary excretion It causes analgesis with CVS stimulation-reduced reuptake of norepinephrine.

KETAMINE
Increases cerebral blood flow,02 consumption,&ICP. Associated with post op disorientation,perceptual illusions,vivid dreams-so called emergence phenomena Good for geriatric and unstable pts