Pharmacology: Generalized Anesthetics – Flashcards
Unlock all answers in this set
Unlock answersquestion
What are the two kinds of inhaled general anesthetics?
answer
• Nitrous oxide (N2O): gas at ambient temperature. • Halogenated hydrocarbons: vaporized volatile liquids
question
Name the halogenated hydrocarbon anesthetics.
answer
Examples of halogenated hydrocarbons are halothane, enflurane, isoflurane, desflurane, sevoflurane and methoxyflurane.
question
Name the intravenous anesthetics.
answer
They include barbiturates, propofol, ketamine and etomidate.
question
What is induction for general anesthesia?
answer
It's *the time from administration of an anesthetic to the development of surgical anesthesia*. During induction it is essential to avoid the dangerous excitatory phase (stage II, delirium). *General anesthesia is normally induced with an IV anesthetic such as thiopental*. At that time, additional inhalation, or IV drugs comprising the selected anesthetic combination may be given to produce the desired depth of surgical (Stage III) anesthesia. This often includes co-administration of an IV skeletal muscle relaxant to facilitate intubation and relaxation.
question
What is the maintenance period of general anesthesia?
answer
It is the period during which the *patient is surgically anesthetized and then monitored*. Anesthesia is usually maintained by the administration of inhaled anesthetics in conjunction with opioids (fentanyl) because inhalation agents are not good analgesics.
question
What is the recovery period of general anesthesia?
answer
It's *the time between discontinuation of anesthesia administration and regaining of consciousness.* The anesthetic mixture is withdrawn and a return to consciousness is monitored.
question
What is Stage I of general anesthesia?
answer
Stage I is analgesia and amnesia.
question
What is Stage II of general anesthesia?
answer
Stage II is characterized by excitement, delirium, vomiting, and irregular respiration. In order to avoid this stage, thiopental is given intravenously beforehand.
question
What is Stage III of general anesthesia?
answer
Stage III is marked by surgical anesthesia and unconsciousness.
question
What is Stage IV of general anesthesia?
answer
Stage IV is characterized by medullary depression, absent eye movement, and respiratory and cardiovascular failure.
question
How do you know when Stage III of general anesthesia has been reached?
answer
The most reliable indications that Stage III has been achieved are *loss of the eyelash reflex and establishment of a respiratory pattern that is regular in rate and depth*.
question
When are inhaled gases used in general anesthesia?
answer
Inhaled gases are primarily used for the *maintenance of anesthesia after administration of an IV agent*. The depth of anesthesia can be rapidly altered by rapidly changing concentration of inhaled anesthetic.
question
What are the common features of inhaled general anesthetics?
answer
• Decreased cerebrovascular resistance with increased perfusion • Bronchodilation with decreased minute ventilation. • Potency correlates with liposolubility • Rate of onset is inversely correlated to blood solubility • Recovery is due to redistribution from the brain
question
What is the mechanism of action for inhaled anesthetics?
answer
Inhaled anesthetics *facilitate GABA-mediated inhibition at GABA-A receptors*. Most inhaled anesthetics also inhibit nicotinic receptors. The glycine receptor is another ligand-gated ion channel that may function as a target for inhaled anesthetics.
question
What is the minimum alveolar concentration of an inhaled anesthetic?
answer
The MAC of an anesthetic is defined as the *concentration that results in immobility in 50% of patients when exposed to a noxious stimulus* such as surgical incision. It's expressed as % of gas in a mixture required to achieve the effect and *represents the ED50* on a quantal dose-response curve.
question
How does MAC correlate with potency?
answer
Numerically, *MAC is low for potent anesthetics* such as halothane (MAC = 0.75), and *large for less potent agents* such as nitrous oxide (105.0). Therefore, 1/MAC is an index of potency of the anesthetic.
question
Describe the slope of the dose-response curve for inhaled anesthetics.
answer
The slopes of the dose-response curves for inhalational anesthetics are steep. Thus, although only 50% of individuals may fail to respond to stimulation at 1.0 MAC, 95% of patients may fail to respond to stimulation at 1.1 MAC.
question
Is MAC higher in infants or the elderly?
answer
MAC is higher in infants and lower in the elderly.
question
Do sex, height, and weight affect the MAC?
answer
No. Sex, height and weight don't significantly affect MAC.
question
How do adjuvant drugs for anesthesia affect the MAC?
answer
Some adjuvant drugs can change anesthetic requirements greatly. For example, when drugs such as the opioid analgesics or sedative-hypnotics are present, MAC is decreased, which means that the inspired concentration of anesthetic should be decreased accordingly.
question
How do hypothermia, hypothyroidism and pregnancy affect the MAC?
answer
Hypothermia, hypothyroidism and pregnancy decrease MAC.
question
How do anxiety and thyrotoxicosis affect the MAC?
answer
Anxiety and thyrotoxicosis increase MAC.
question
What is meant by saying that MAC is additive?
answer
Nitrous oxide can be used as a "carrier" gas, decreasing the anesthetic requirement of other anesthetics. For example, 0.7 MAC of isoflurane and 0.3 MAC of nitrous oxide yield 1 MAC.
question
What is the Meyer-Overton Correlation?
answer
The potency of an anesthetic can be predicted from its liposolubility. A useful measure of liposolubility is the oil:gas partition coefficient, [λ(oil:gas)]. *The potency of an anesthetic increases as its liposolubility increases. In other words, as λ(oil:gas) increases, the MAC decreases.*
question
What determines the speed of anesthetic induction?
answer
The rate depends on the solubility properties of the anesthetic, its concentration in the inspired air, pulmonary ventilation rate, pulmonary blood flow, and the concentration (partial pressure) gradient of the anesthetic between arterial and mixed venous blood.
question
How is anesthetic solubility measured?
answer
The *blood:gas partition coefficient* [λ(blood:gas)] is a useful measure of solubility and defines the relative solubility of an anesthetic for the blood compared to air. The blood:gas partition coefficients for desflurane, nitrous oxide and sevoflurane, which are not very soluble in blood, are low. At the other extreme, the value is greater than 10 for agents such as methoxyflurane.
question
How does the blood solubility of an anesthetic correlate with the rise in its arterial tension?
answer
There is an inverse relationship between blood solubility of an anesthetic and the rate of rise of its tension in arterial blood. Consequently, a low blood:gas partition coefficient determines a faster onset of anesthesia.
question
How does λ(oil:gas) relate to λ(blood:gas) for an anesthetic?
answer
Anesthetics with larger λ(oil:gas) tend to have larger λ(blood:gas). This means that more potent inhaled anesthetics tend to have slower onsets.
question
How does anesthetic gas tension relate to ventilation?
answer
The rate of rise of anesthetic gas tension in arterial blood is directly dependent on both the rate and depth of ventilation; the magnitude of the effect varies with the blood:gas partition coefficient. *An increase in pulmonary ventilation will cause only a slight increase in arterial tension if the anesthetic has low blood solubility, but can significantly increase tension of anesthetics with moderate or high blood solubility.* For example, a fourfold increase in ventilation rate almost doubles the arterial tension of halothane during the first 10 minutes of anesthesia but increases the arterial tension of nitrous oxide by only 15%.
question
How does pulmonary blood flow affect the tension of inhaled anesthetics?
answer
*Increased pulmonary blood flow (increased CO) slows the rate of rise in arterial tension, particularly for those anesthetics with moderate to high blood solubility.* This is because increased pulmonary blood flow exposes a larger volume of blood to the anesthetic; thus, blood "capacity" increases and tension rise slowly. A decrease in pulmonary blood flow has the opposite effect and increases the rate of rise of arterial tension of inhaled anesthetics.
question
How does the arteriovenous gradient reflect solubility of an inhaled anesthetic?
answer
An anesthetic which is highly soluble in tissues will have a high arteriovenous gradient and thus a slow onset of action.
question
How does solubility affect the elimination of inhaled anesthetics?
answer
For agents with low blood/tissue solubility, recovery from anesthesia should mirror anesthetic induction, regardless of the duration of anesthetic administration. For agents with high blood/tissue solubility, recovery will be a function of the duration of anesthetic administration, because the accumulated anesthetic in the fat acts as a reservoir. *The rate of recovery from anesthesia is faster for agents with low blood:gas partition coefficients.* Nitrous oxide, desflurane and sevoflurane display recovery times that are significantly shorter than halothane or isoflurane.
question
How are most inhaled anesthetics metabolized?
answer
Most are cleared by the lungs into the expired air. However, metabolism by enzymes of the liver and other tissues may also contribute to the elimination of anesthetics.
question
Describe the metabolism of halothane.
answer
Oxidative metabolism forms trifluoroacetic acid and release of bromide and chloride ions. Under conditions of low oxygen tension, halothane is metabolized to the chlorotrifluoroethyl free radical, which is capable of reacting with hepatic membrane components.
question
Which inhaled fluorinated anesthetics undergo the least amount of metabolization?
answer
*Isoflurane and desflurane* are the least metabolized of the fluorinated anesthetics, with only traces of trifluoroacetic acid appearing in the urine.
question
How are enflurane and sevoflurane metabolized?
answer
Their *metabolism forms fluoride*, which doesn't reach toxic levels under normal circumstances. In addition, *sevoflurane is degraded by contact with the carbon dioxide adsorbent in anesthesia machines, yielding a vinyl ether called "compound A" that can cause renal damage* if high concentrations are absorbed.
question
How is methoxyflurane metabolized?
answer
Over 70% of absorbed methoxyflurane is metabolized by the liver with the release of fluoride at concentrations that can be nephrotoxic.
question
Rank the inhaled anesthetics in terms of the extent of metabolism.
answer
In terms of the extent of metabolism of inhaled anesthetics the rank order is: Methoxyflurane > halothane > enflurane > sevoflurane > isoflurane > desflurane > nitrous oxide.
question
How do halothane and enflurane affect the cardiovascular system?
answer
Halothane and enflurane *reduce arterial pressure mainly by myocardial depression (reduced cardiac output), with little effect on vascular resistance*. Halothane sensitizes the myocardium to circulating catecholamines, which may lead to ventricular arrhythmias. This effect is less marked for isoflurane, sevoflurane and desflurane.
question
How do isoflurane, desflurane and sevoflurane affect the cardiovascular system?
answer
Isoflurane, desflurane and sevoflurane produce greater vasodilation than halothane or enflurane, and they have minimal effect on cardiac output.
question
Which inhaled anesthetics are better for patients with impaired myocardial function?
answer
*Isoflurane, desflurane and sevoflurane* may be better choices for patients with impaired myocardial function.
question
Which inhaled anesthetic is less likely to lower blood pressure than others?
answer
Nitrous oxide is less likely to lower blood pressure than are other inhaled anesthetics.
question
How do inhaled anesthetics affect the respiratory system?
answer
All volatile anesthetics have *bronchodilating properties and act as respiratory depressants*; *isoflurane and enflurane are the most depressant, and nitrous oxide is the least depressant*. Halothane, sevoflurane, and nitrous oxide are also non-pungent; *isoflurane and desflurane are pungent*, making them less suitable for induction of anesthesia in patients with bronchospasm.
question
How do inhaled anesthetics affect the kidneys?
answer
All inhaled anesthetics decrease the GFR and RBF.
question
How do inhaled anesthetics affect the CNS?
answer
They *increase cerebral blood flow by reducing vascular resistance*; this can cause *increased intracranial pressure*. This increase in blood flow is often clinically undesirable in patients who have increased intracranial pressure because of a brain tumor or head injury.
question
Which inhaled anesthetic has the least effect of cerebral blood flow?
answer
Nitrous oxide increases blood flow the least. Nitrous oxide has low anesthetic potency, but exerts marked analgesic and amnesic actions.
question
How do high doses of enflurane affect the CNS?
answer
At higher doses, enflurane may lead to development of a spike-and-wave pattern and mild generalized muscle twitching. However, this seizure-like activity does not have adverse clinical consequences.
question
How do inhaled anesthetics affect the liver?
answer
All inhaled anesthetics decrease hepatic blood flow.
question
How do inhaled anesthetics affect uterine smooth muscle?
answer
Halogenated hydrocarbon anesthetics are potent uterine relaxants. This effect can be used when profound uterine relaxation is required for intrauterine fetal manipulation or manual extraction of a retained placenta during delivery. Nitrous oxide has little effect on uterine musculature.
question
When should N2O be avoided?
answer
N2O exchanges with nitrogen in air-containing cavities in the body. N2O enters the cavity faster than nitrogen escapes; therefore, it increases the volume and/or pressure of the cavity. As a consequence, N2O should be avoided in the following clinical settings: *pneumothorax, obstructed middle ear, air embolus, obstructed loop of bowel, intraocular air bubble, pulmonary bulla, and intracranial air.*
question
Which inhaled anesthetic is associated with hepatotoxicity?
answer
*Halothane exposure may cause a potentially severe and life-threatening hepatitis*. It's a very rare occurrence (1/35,000). There is no specific treatment for halothane hepatitis, and liver transplantation may ultimately be required.
question
Which inhaled anesthetic is associated with nephrotoxicity?
answer
The *nephrotoxic potential of methoxyflurane has limited its clinical use in anesthesia*. Renal dysfunction following methoxyflurane is caused by inorganic fluoride released during the extensive metabolism of the anesthetic by hepatic and renal enzymes.
question
How can susceptibility to malignant hyperthermia be assessed?
answer
Establish susceptibility via an *in vitro caffeine-halothane muscle contracture test*. A small piece of muscle is obtained under regional or general anesthesia and attached to a device which measures the force of contraction. The muscle strip is then exposed to either halothane or caffeine and the response measured. A response to halothane or a response to low concentrations of caffeine are diagnostic for malignant hyperthermia-susceptible muscle.
question
Which inhaled anesthetic is associated with hematotoxicity?
answer
Prolonged exposure to *nitrous oxide* decreases methionine synthase activity and causes megaloblastic anemia. This is a potential occupational hazard for staff working in poorly ventilated dental operating suites.
question
Which barbiturates are used as IV anesthetics?
answer
*Thiopental and methohexital!* Thiopental is the barbiturate most commonly used for induction of anesthesia, often in combination with inhaled anesthetics. These agents have high liposolubility, which promotes rapid entry into the brain and results in surgical anesthesia in one circulation time (less than one minute).
question
What are ultra-rapid barbiturate anesthetics used for?
answer
These agents are used for induction of anesthesia and for short surgical procedures. Their anesthetic effects are terminated by redistribution from the brain to other tissues, but hepatic metabolism is required for their elimination from the body.
question
Why is thiopental better for use in patients with cerebral swelling than inhaled anesthetics?
answer
Thiopental decreases intracranial pressure.
question
Why are barbiturates a concern as anesthesia for asthma patients?
answer
All barbiturates can cause apnea, coughing, chest wall spasm, laryngospasm and bronchospasm.
question
Are barbiturates analgesics?
answer
No. Barbiturates do not produce analgesia; some evidence suggests that they may cause hyperalgesia.
question
How does IV barbiturate anesthesia affect the heart and lungs?
answer
They are respiratory and circulatory depressants.
question
What is propofol?
answer
*Propofol is the most popular IV anesthetic*, widely used for outpatient surgical procedures, in intensive care settings, and in balanced anesthesia. It produces anesthesia at a rate similar to that of the barbiturates, and recovery is faster. It's used for both induction and maintenance of anesthesia.
question
Does propofol cause vomiting?
answer
No, postoperative vomiting is uncommon; propofol has antiemetic actions.
question
True or False: Propofol is not an analgesic.
answer
True. Propofol does not produce analgesia.
question
How is propofol metabolized?
answer
It's rapidly metabolized in the liver at a rate ten times faster than thiopental.
question
What is fospropofol?
answer
Fospropofol is a prodrug that is converted to propofol in vivo.
question
What are the side effects of propofol?
answer
• Potent respiratory depressant • *Reduces intracranial pressure* • Hypotension (decreased peripheral vessel resistance)
question
What is etomidate?
answer
It's an *IV anesthetic primarily used for anesthetic induction of patients at risk for hypotension.* It causes minimal cardiovascular and respiratory depression and lacks analgesic effects. It reduces intracranial pressure and has been associated with nausea and vomiting. It may cause adrenocortical suppression via inhibitory effects on steroidogenesis, with decreased plasma levels of hydrocortisone.
question
What does ketamine do, and what is the mechanism of action?
answer
It produces dissociative anesthesia, characterized by catatonia, amnesia and analgesia, with or without loss of consciousness via blockade of NMDA receptors. It is very useful for poor-risk geriatric patients and high-risk patients in cardiogenic or septic shock because of its cardiostimulatory properties.
question
What is the only IV general anesthetic that causes both analgesia and cardiovascular stimulation?
answer
*Ketamine!* Heart rate, arterial blood pressure and cardiac output increase. Cardiovascular stimulation is due to stimulation of the central sympathetic nervous system and to inhibition of the reuptake of norepinephrine at sympathetic nerve terminals.
question
How does ketamine affect intracranial pressure?
answer
Ketamine increases intracranial pressure. In this regard ketamine resembles inhaled anesthetics as a potentially dangerous drug when intracranial pressure is elevated.
question
What are the adverse effects of ketamine?
answer
Use of ketamine has been associated with postoperative disorientation, sensory and perceptual illusions, and vivid dreams ('emergence phenomena'). *Diazepam, midazolam, or propofol, given before the administration of ketamine reduce the incidence of these adverse effects.*
question
How can neuroleptic analgesia be converted into neuroleptic anesthesia?
answer
Neurolept analgesia can be converted to neurolept anesthesia by the concurrent administration of 65% nitrous oxide in oxygen. The combination of fentanyl and droperidol is available as a fixed ratio preparation called Innovar.
question
How do neuroleptic compounds mix with opioids to produce neuroleptic analgesia?
answer
Neuroleptic compounds (droperidol) produce a state of quiescence with reduced motor activity, reduced anxiety, and indifference to the surroundings. Unconsciousness is not necessarily induced, and patients are responsive to commands. When a potent opioid analgesic, such as fentanyl, is combined with droperidol, a state of neuroleptic analgesia is established, during which a variety of diagnostic or minor surgical procedures can be accomplished; these include endoscopy, radiological studies, burn dressings, and the like.
question
Which drugs are often given as adjuvants to general anesthesia?
answer
• Diazepam, lorazepam, and midazolam • Morphine and fentanyl • Pancuronium or succinylcholine • Antiemetics, such as ondansetron • Antimuscarinics like scopolamine
