I. Drugs of General Anesthesia

university of babylon 4th years
college of nursing anesthesia lec.6
_dr. naji yassesr al-mayyahi ____________________________________________________________

i. drugs of general anesthesia
the drug that can bring about a reversible loss of consciousness. anaesthetists, physician assistants or nurse anaesthetists administer these drugs to induce or maintain general anaesthesia to facilitate surgery. some of these drugs are also used in lower dosages for pain management. the biological mechanisms of the action of general anaesthetics are not well understood.
the mechanism by which drugs can cause a reversible loss of consciousness is still the subject of intense debate. an enduring finding has been that lipid solubility correlates with anaesthetic potency, indicating a lipophilic site of action. suitable sites are the cell membrane bilayer and the proteins imbedded in it. all anaesthetics can affect voltage-gated ion channels, but in general these effects occur at greater concentrations than those necessary to produce anaesthesia. neurotransmitter receptors, particularly the ligand-gated ion channels, are particularly sensitive to anaesthetic agents. attention is drawn to the receptors activated by the excitatory amino acids as ketamine blocks the channel of the n-methyl-d-aspartate (nmda) receptor. however, many anaesthetics enhance inhibitory transmission via the ?-aminobutyric acid a (gabaa) receptor, although the binding site that mediates this effect varies for individual agents. recent evidence suggests that some separation between the wanted and unwanted effects of anaesthetics may be possible.


injection: intravenous agents (non-opioid):
while there are many drugs that can be used intravenously to produce anesthesia or sedation, the most common are:
injectable anaesthetics are used for the induction and maintenance of a state of unconsciousness. anaesthetists prefer to use intravenous injections, as they are faster, generally less painful and more reliable than intramuscular or subcutaneous injections. among the most widely used drugs are:
• propofol
• barbiturates such as thiopentone/thiopental
• ketamine:
• propofol, marketed as diprivan among others, is a short-acting medication that results in a decreased level of consciousness and lack of memory for events.[2] its uses include the starting and maintenance of general anesthesia, sedation for mechanically ventilated adults, and procedural sedation. it is also used for status epilepticus if other medications have not worked. it is given intravenously. maximum effect takes about two minutes to occur and it typically lasts five to ten minutes.

• common side effects include :
• irregular heart rate,
• low blood pressure,
• burning sensation at the site of injection,
• stopping of breathing. other serious side effects may include seizures, infections with improper use, addiction, and propofol infusion syndrome with long-term use. it appears to be safe for using during pregnancybut has not been well studied in this group. however, it is not recommended during cesarean section.[2] propofol is not a pain medication, so opioids such as morphinemay also be used.
sodium thiopental
sodium thiopental is an ultra-short-acting barbiturate and has been used commonly in the induction phase of general anesthesia. its use has been largely replaced with that of propofol. following intravenous injection, the drug rapidly reaches the brain and causes unconsciousness within 30–45 seconds. at one minute, the drug attains a peak concentration of about 60% of the total dose in the brain. thereafter, the drug distributes to the rest of the body, and in about 5–10 minutes the concentration is low enough in the brain that consciousness returns.
a normal dose of sodium thiopental (usually 4–6 mg/kg) given to a pregnant woman for operative delivery (caesarian section) rapidly makes her unconscious, but the baby in her uterus remains conscious. however, larger or repeated doses can depress the baby
sodium thiopental is not used to maintain anesthesia in surgical procedures because, in infusion, it displays zero-order elimination kinetics, leading to a long period before consciousness is regained. instead, anesthesia is usually maintained with an inhaled anesthetic (gas) agent. inhaled anesthetics are eliminated relatively quickly, so that stopping the inhaled anesthetic will allow rapid return of consciousness. sodium thiopental would have to be given in large amounts to maintain an anesthetic plane, and because of its 11.5- to 26-hour half-life, consciousness would take a long time to return.[6]
sodium thiopental is always administered intravenously, as it can be fairly irritating severe tissue necrosis and sloughing can occur if it is injected incorrectly into the tissue around a vein.

ketalar is used for:
inducing anesthesia (lack of sensation or feeling) before surgery or certain procedures that do not require skeletal muscle relaxation. it may also be used for other conditions as determined by your doctor.
ketalar is an anesthetic. it works in the brain to inhibit painful sensations.
do not use ketalar if:
• you are allergic to any ingredient in ketalar
• you have a condition in which a large increase in blood pressure would be harmful
• you are taking droxidopa
contact your doctor or health care provider right away if any of these apply to you
before using ketalar:
some medical conditions may interact with ketalar. tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:
• if you are pregnant, planning to become pregnant, or are breast-feeding
• if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement
• if you have allergies to medicines, foods, or other substances
• if you have a history of head trauma or injury, bleeding in the brain, a stroke, increased spinal fluid pressure, increased pressure in the eye, bladder or urinary problems, heart problems (eg, congestive heart failure), high blood pressure, mental or mood problems, or thyroid problems
• if you have a history of alcoholism or you are intoxicated by alcohol
dosage:
as with other general anesthetic agents, the individual response to ketalar is somewhat varied depending on the dose, route of administration, and age of patient, so that dosage recommendation cannot be absolutely fixed. the drug should be titrated against the patient s requirements.
induction:
intravenous route:
the initial dose of ketalar administered intravenously may range from 1 mg/kg to 4.5 mg/kg (0.5 to 2 mg/lb). the average amount required to produce five to ten minutes of surgical anesthesia has been 2 mg/kg (1 mg/lb).
alternatively, in adult patients an induction dose of 1 mg to 2 mg/kg intravenous ketamine at a rate of 0.5 mg/kg/min may be used for induction of anesthesia. in addition, diazepam in 2 mg to 5 mg doses, administered in a separate syringe over 60 seconds, may be used. in most cases, 15 mg of intravenous diazepam or less will suffice. the incidence of psychological manifestations during emergence, particularly dream-like observations and emergence delirium, may be reduced by this induction dosage program.



inhalation:
inhalational anaesthetic substances are either volatile liquids or gases, and are usually delivered using an anaesthesia machine. an anaesthesia machine allows composing a mixture of oxygen, anaesthetics and ambient air, delivering it to the patient and monitoring patient and machine parameters. liquid anaesthetics are vapourised in the machine. all of these agents share the property of being quite hydropinghobic (i.e., as liquids, they are not freely miscible—or mixable—in water, and as gases they dissolve in oils better than in water).
many compounds have been used for inhalation anaesthesia, but only a few are still in widespread use. such as isoflurane , sevoflurane and halothane,


inhaled anesthetic agents include nitrous oxide (the oldest of all anesthetics) are indicated for the induction and maintenance of general anesthesia .however, inhalation anesthetic agents are rarely used alone and various halogenated agents: desflurane (halogenated solely with fluorine—halogenation increases potency and is essential to ensure nonflammability), halothane (halogenated with fluorine, chlorine, and bromine), isoflurane (halogenated with fluorine and chlorine), and sevoflurane (halogenated solely with fluorine). halothane was the first fluorinated inhaled anesthetic that was wildly successful, rapidly displacing all other potent inhaled anesthetics. efforts to develop other halogenated anesthetics with more of the characteristics of the ideal inhaled anesthetic agent than halothane led to the introduction of isoflurane, desflurane, and sevoflurane.
characteristics of the ideal inhaled anesthetic agent include ample potency, low solubility in blood and tissues, resistance to physical and metabolic degradation, and a protective effect in and lack of injury to vital tissues. physical and metabolic degradation can yield compounds that cause injury. other ideal characteristics include the lack of a propensity to cause seizures, respiratory irritation, and circulatory stimulation little or no effect on the ozone layer and a low acquisition cost.
solubility of inhalation drugs in blood can effect rate of drug diffusion / uptake, because blood acts like a sponge which soaks up and holds drug away from brain initially.
inhalation anesthetic agents are halogenated hydrocarbons or ethers. most are liquids @ room temperature in closed containers, but easily volatilize when open to the atmosphere. exceptions are nitrous oxide is a gas, and desflurane (lowest volatility). all are non-explosive, do not support combustion (except nitrous oxide) and are non-irritating when inhaled (except desflurane).
muscle relaxe drugs:
neuromuscular-blocking drugs block neuromuscular transmission at the neuromuscular junction,[1] causing paralysis of the affected skeletal muscles. this is accomplished either by acting presynaptically via the inhibition of acetylcholine (ach) synthesis or release or by acting postsynaptically at the acetylcholine receptors of the motor nerve end-plate

. in clinical use, neuromuscular block is used adjunctively to anesthesia:
1-to produce paralysis, firstly to paralyze the vocal cords,
2- permit intubation of the trachea,
3- and to optimize the surgical field by inhibiting spontaneous ventilation,
4- causing relaxation of skeletal muscles. because the appropriate dose of neuromuscular-blocking drug may paralyze muscles required for breathing (i.e., the diaphragm), mechanical ventilation should be available to maintain adequate respiration.
patients are still aware of pain even after full conduction block has occurred hence, general anesthetics and/or analgesics must also be given to prevent anesthesia awareness.

1-neuromuscular-blocking drugs (short acting)
succinylcholine
succinylcholine is used for:
relaxing muscles during surgery or when using a breathing machine (ventilator). it is also used to induce anesthesia or when a tube must be inserted in the windpipe. it may also be used for other conditions.
succinylcholine is a depolarizing muscle relaxant. it works by keeping muscles from contracting, which causes paralysis of the muscles in the face and those used to breathe and move.
do not use succinylcholine if:
• allergic to any ingredient in succinylcholine
• recently had a severe burn, trauma, nerve damage, or an upper body movement injury
• you have a personal or family history of muscle disease or malignant hyperthermia (a life-threatening state that includes high body temperatures)
before using succinylcholine:
some medical conditions may interact with succinylcholine. tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply :
• pregnant, planning to become pregnant, or are breast-feeding
• taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement
• if you have allergies to medicines, foods, or other substances
• if you have had a severe allergic reaction (eg, severe rash, hives, difficulty breathing, dizziness) to another neuromuscular blocking agent (eg, pancuronium)
• glaucoma, blood electrolyte problems (eg, high or low potassium levels, low calcium levels), liver or kidney problems, a tumor that has spread, an infection, anemia, a certain thyroid problem (myxedema), stomach or intestinal ulcers, decompensated heart problems, decreased activity or deficiency of plasma cholinesterase, a bone fracture, or muscle spasms
• dehydrated or have recently had eye surgery or an eye injury
• history of stomach infections or bleeding in the brain


















2-neuromuscular-blocking drugs (long acting)
agent time to onset
(seconds) duration
(minutes) side effects
atracurium
(tracrium) 90 30 min or less[9]
• hypotension, transiently,[9] by release of histamine
• toxic metabolite called laudanosine, greater accumulation in individuals with renal failure
vecuronium
(norcuron) 60 30–40[9]
few,[9] may cause prolonged paralysis[9] and promote muscarinic block
rocuronium
(zemuron) 75 45–70[citation needed]
may promote muscarinic block
pancuronium
(pavulon) 90 180 or more[citation needed]
• tachycardia (slight)[9]
(no hypotension)[9]

tubocurarine
(jexin) 300 or more[9]
60–120[9]
• hypotension (by ganglion-block and histamine release)[9]
• bronchoconstriction (by histamine release)[9]

gallamine
(flaxedil) 300 or more[9]
60–120[9]
• tachycardia







elimination
muscle relaxants can have very different metabolic pathways and it is important that the drug does not accumulate if certain elimination pathways are not active, for example in kidney failure
since these drugs may cause paralysis of the diaphragm, mechanical ventilation should be at hand to provide respiration.
in addition, these drugs may exhibit cardiovascular effects, since they are not fully selective for the nicotinic receptor and hence may have effects on muscarinic receptors.[8] if nicotinic receptors of the autonomic ganglia or adrenal medulla are blocked, these drugs may cause autonomic symptoms. also, neuromuscular blockers may facilitate histamine release, which causes hypotension, flushing, and tachycardia.
in depolarizing the musculature, suxamethonium may trigger a transient release of large amounts of potassium from muscle fibers. this puts the patient at risk for life-threatening complications, such as hyperkalemiaand cardiac arrhythmias.
certain drugs such as aminoglycoside antibiotics and polymyxin and some fluoroquinolones also have neuromuscular blocking action as their side-effect.