GENERAL ANESTHESIA
The physiologic state of general anesthesia includes: analgesia, amnesia, loss of consciousness, inhibition of sensory and autonomic reflexes and skeletal muscle relaxation. A combination of inhaled and intravenous drugs is used to decrease the adverse effect.
Stages of general anesthesia:
4 stages according to the depth of CNS depression
1- Stage of analgesia: initially analgesia and late associated with amnesia.
2- Stage of delirium: the patient appears to be delirious and axcited with irregular respiratory rate and volume.
3- Stage of surgical anesthesia: recurrence of regular respirationextend to complete cessation of spontaneous respiration, with changes in ocular movement, eye reflex and pupil size.
4- Stage of medullary depression:(over dose): sever depression of vasomotor center and respiratory center in medulla.
Mechanism of action
General anesthesia act as agonist at GABA (γ-aminobutyric acid) and gkycol receptors, opening chloride channel so the influx of chloride ions into the neuron results in hyperpolarization. This prevent propagation of nerve impulse and render the patient unconscious.
Inhaled anesthesia:
Includes: ntrous oxide(N2O) as gas, halothane, enflurane, isoflurane, desflurane, desflurane, sevoflurane, methoxyflurane which are volatile liquid.
Pharmacokinetics:
depth of anesthesia is dependent on the concentration of anesthetic in the CNS, this required transfer of that anestheticfrom the alveolar air to blood and then to brain. This transfer depends mainly on the solubility properties of the anesthetic, increase blood solubility (high blood / gas partition coefficient) lead to slow induction of anesthesia because blood acts as reservoir for the drug so that does not enter the brain and vise versa, other factors include concentration in the inspired air (+ relation), pulmonary ventilation rate (+ relation) and pulmonaru blood flow (- relation).
The lung is the major route of elimination, however metabolism by enzymes of the liver and other tissues may also contribute to the elimination of volatile anesthetics.
Anesthetics that are insoluble in the blood and brain are eliminated faster, the sequence of solubility include: halothane ˃ enflurane ˃ isoflurane ˃ sevoflurane ˃ desflurane.
Adverse effects:
1- CVS: decrease arterial blood pressure due to decrease cardiac output and peripheral vascular resistance and change in heart rate.
2- Respiratory system: respiratory depression, decrease respiratory volume, and increase respiratory rate (except N2O).
3- Brain: increase cerebral blood flow because they decrease cerebral vascular resistance and increase intracranial pressure and decrease metabolic rate.
4- Decrease hepatic blood flow and decrease glomerular filtration rate..
5- N2O can cause nausea, vomiting, interference with the synthesis of methionin and DNA.
Intravenous anesthetics
Pharmocokinetics: I.V anesthetics allow rapid induction because blood concentration can be raised rapidly, also recovery occurs rapidly as the drug is redistributed around the body depending on the lipid solubility and arterial conc. of ubound nonionized fraction of the drug so the plasma concentration reduces. Anesthesia is usually induced using I.V anesthetics and then maintained with volatile anesthetics.
1- Short acting barbiturates: e.g thiopental and methohexital, which rapidly cross BBB (high lipid solubility) causing hypnosis (loss of consciousness) in sufficient doses.thiopental diffuses rapidly out of the brain so has short duration of action.
Thiopental causes:
respiratory depression. Dose dependent decrease in arterial blood pressure, stroke volume and cardiac output. Decrease cerebral blood flow so it is desirable in patients with head trauma and brain tumors, it decreases cerebral metabolic rate. Decrease hepatic blood flow and GFR without affecting their functions.
respiratory depression. Dose dependent decrease in arterial blood pressure, stroke volume and cardiac output. Decrease cerebral blood flow so it is desirable in patients with head trauma and brain tumors, it decreases cerebral metabolic rate. Decrease hepatic blood flow and GFR without affecting their functions.
2- Benzodiazepines:
diazepam, lorazepam and midazolam are used for premedication because of their sedative and amnestic properties. Bdiazepam and lorazepam are not water soluble so require non aqueous vehicle (cause local irritation). Midazolam is water soluble but become lipid soluble at physiologic PH and cross BBB. Large dose benzodiazepines can prolong the post anesthetic recovery period. Benzodiazepines antagonist (flumazenil) can be used to accelerate recovery from excessive sedative action but not from respiratory depression.
3- Opioid analgesics:
morphine, fentanyl, sufentanil, alfentanil and remifentanil large doses are required to achieve general anesthesia, but this can cause chest wall rigidity and impairing ventilation so post operative respiratory depression required prolonged assisted ventilation and administration of opioid antagonist (naloxone). Opioid analgesics can also be used at low doses by spinal cord route to produce excellent postoperative analgesia.
morphine, fentanyl, sufentanil, alfentanil and remifentanil large doses are required to achieve general anesthesia, but this can cause chest wall rigidity and impairing ventilation so post operative respiratory depression required prolonged assisted ventilation and administration of opioid antagonist (naloxone). Opioid analgesics can also be used at low doses by spinal cord route to produce excellent postoperative analgesia.
4- Propofol:
the onset of action is similar to that of barbiturate with rapid recovery. The drug is metabolized in the liver and excreted in urine. Adverse effect:
respiratory depression. Decrease blood pressure due to decrease peripheral resistance, with greater negative inotropic effect on the heart. Postoperative nausea and vomiting is less common because propofol has antiemetic action.
5- Etomidate:
has rapid loss of consciousness with no analgesic effects, the drug has short duration of action its metabolized in the liver with only 2% excreted unchanged in urine. Etomidate causes: minimal cardiovascular depression, hypotension and minimal respiratory depression. nausea and vomiting. adecortical suppression with inhibition of steroidogenesis.
6- ketamine:
produces catatonia, amnmesia and analgesia. Acts by blocking the membrane effects of the excitatory neurotransmitter glutamic acid at NMDA receptor ( N-methyl-D-aspartate). It is lipophilic drug metabolized in the liver and undergo urinary and biliary excretion.
Ketamine causes:
increase heart rate, blood pressure and cardiac output by excitation of the central sympathetic NS and inhibition of reuptake of epineohrine and norepinephrine. Ketamine markedly increase cerebral blood flow, oxygen consumption and increase intracranial pressure in addition to decrease respiratory rate.
increase heart rate, blood pressure and cardiac output by excitation of the central sympathetic NS and inhibition of reuptake of epineohrine and norepinephrine. Ketamine markedly increase cerebral blood flow, oxygen consumption and increase intracranial pressure in addition to decrease respiratory rate.
Local anesthetics:
Associated with loss of sensation without loss of consciousness. Mechanism of action: local anesthetics prevent the initiation and propagation of the nerve impulse (action poitential), by reducing the passage of sodium through valtage-gated sodium ion channels, they raise the threshold of excitability.
Types of local anesthetics
1- amides: include
1- lignocaine (lidocaine) 4M.
2- prilocaine 3M.
3- bupivacaine 16L.
4- levobupivacaine 16L
5- Ropivacaine 16L
Indication:
1- topical.
2- Cardiac arrhythmias.
3- Peripheral nerve block.
4- Spinal anesthesia.
2- Ester: include
1-Cocaine 2M.
2- procaine 1S.
3- tetracaine 16L.
4- benzocaine (surface use only).
Cocaine can caiuse:
1- euphoria and feeling of well being.
2- Arrhythmias and hypertension because it prevents the uptake of catecholamines into sympathetic nerve endings so increase their concentration at receptor sites.
Useful local anesthetics must be:
1- water soluble.
2- Rapid onset.
3- Good duration .
4- Safe, nontoxic and not leave any local after effect.
Absorption of local anesthetics depends on:
1- dose.
2- Site of injection (the high vascular tissue the high absorption into circulation so the lesser duration of action.
3- Drug-tissue binding.
4- The presence of vasoconstrictors (e.g. epinephrine) delay absorption into circulation and prolong the local action.
5- Physicochemical properties of the drug.
Indication of local anesthesia:
1- simple operation that not need for general anesthesia.
2- Major operation with sedation.
3- Adjunct with general anesthesia.
4- Topical for sever pain and itching.
5- Infiltration local anesthesia e.g. dentist operation.
6- Subarachnoid and intrathecal (this may diffuse to the CSF and cause convulsions and neurotoxicity.
7- Regional nerve block.
Adverse effects:
1- CNS:
1- visual and auditory disturbances.
2- parasthesia, tremor.
3- anxiety, rigidity,convulsion and then depression.
2- CVS:
1- arrhythmias.
2- Hypotension.
3- Collapse.
3- respiratory depression.
4- Skin allergy.
Contraindication:
1- complete heart block
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