Drugs- Anesthetics (kinder) Flashcards
21 year old male is schedule to undergo a laparoscopic hernia repair on an outpatient basis under general anesthesia. this is the first time he has undergone surgery and he is highly anxious in the preoperative area. which benzodiazepine may be utilized in this situation to reduce his anxiety ?
Benzocaine Fentanyl Midazolam Propofol Thiopental
Benzocaine- local anesthetic Fentanyl- opioid Midazolam- benzodiazepine and the answer Propofol- IV anesthetic Thiopental - barbituate
a 19 yo femal admitted to the ambulatroy surgery center for strabism surgery to correct misalignment of her extraocular muscles. she is other wise healthy and all labs are WNL. which IV induction agent may be used that is rapid in onset and recovery and has antiemetic actions
halothane Nitrous oxide procaine propofol sevoflurane
propofol
has anti-emetic affects too
the chemical with which blood:gas partition coefficient will reach the highest concentration in the brain the fast (assume brain:blood partition coefficients are equal)
- 42
- 47
- 69
- 4
- 8
0.42 - lower the number the faster the anesthesia b/c lower affinity for blood space
- 42- desflurane
- 47- nitrous oxide
- 69- sevoflurane
- 4- isoflurane
- 8 - enflurane
the anesthesiologist prepares to adminster several drugs to a patient as part of a normal perioperative care. which drug lacks the ability to cause generalized CNS depression, lacks the ability to reduce or impair the pt’s level of consciousness, or lacks the ability to prevent or reduce pain
Midazolam
Pancuronium
Propofol
Thiopental
pancuronium - neuromuscular blocking agent
Nitrous oxide is a common component in the technique of balanced anesthesia. it is used in conjunction with a volatile anesthetic. which phrase best summarizes why nitrous oxide cannot be used alone for general anesthesia
Almost total lack of analgesic activity, regardless of concentration
inspired concentrations greater than 10% or so tend to have profound cardiac negative inotropic effects
MAC (minimum alveolar conc) is greater than 100%
such great solubility in blood that its effects take an extraordinary long time to develop
very high frequency of bronchospasm
MAC (minimum alveolar conc) is greater than 100%
even if we gave 100% NO the mac will still be less than 1 MAC
so need to use with another anesthetic
(1) Desflurane
(2) Enflurane
(3) Halothane
(4) Isoflurane
(5) Sevoflurane
volatile inhaled anesthetics
i) Low vapor pressures, high boiling points, liquids at room temperature (20˚C).
nitrous oxide
gaseous inhaled anesthetic
i) High vapor pressure, low boiling point, gas at room temperature.
Name 7 IV anesthetics
i) Propofol (Diprivan)
ii) Fospropofol
iii) Barbiturates
(1) Thiopental and methohexital
iv) Benzodiazepines
(1) Midazolam (Versed), lorazepam (Ativan), diazepam (Valium)
v) Etomidate
vi) Ketamine
vii) Dexmedetomidine (Precedex)
i) Benzocaine
ii) Cocaine
iii) Procaine (Novocain)
iv) Tetracaine
ester
local anesthetics
i) Articaine
ii) Bupivacaine
iii) Lidocaine (Xylocaine)
iv) Mepivacaine (Marcaine)
v) Ropivacaine
amides
local anesthetics
what are 5 primary effects produced by general anesthesia
unconsciousness
amnesia
analgesia
inhibition of autonomic reflexes
skeletal muscle relaxation
b) None of currently available general anesthetics, when used alone, produce all five desired effects.
what are the mechanisms of general anesthesia
Anesthetic drugs may (A) enhance inhibitory synaptic activity or (B) diminish excitatory activity.
blood: gas ratio of nitrous oxide
MAC?
0.47
> 100 = MAC
(ii) Agents with low blood solubility (nitrous oxide, desflurane) reach high arterial pressure rapidly, which in turn results in rapid equilibrium with the brain and fast onset of action.
blood:gas ratio of desflurane
MAC?
0.42
MAC- 6-7
(ii) Agents with low blood solubility (nitrous oxide, desflurane) reach high arterial pressure rapidly, which in turn results in rapid equilibrium with the brain and fast onset of action.
blood:gas ratio of sevoflurane
MAC?
0.69
MAC 2
blood:gas ratio of isoflurane
MAC?
1.4
MAC- <2
blood:gas ratio of enflurane
MAC?
1.8
MAC 8
blood:gas ratio of halothane
MAC
2.3
MAC >40
(iii) Agents with high blood solubility (halothane) reach high arterial pressure slowly, which in turn results in slow equilibration with the brain and a slow onset of action.
what is the driving force for uptake of inhaled anesthetic
alveolar concentration
(2) The two factors that determine how quickly the alveolar concentration changes (can be controlled by anesthesiologist) are what two things?
(1) inspired concentration or partial pressure and (2) alveolar ventilation.
(3) Increases in either the inspired partial pressure or in ventilation will increase the rate of rise in the alveoli and will accelerate induction.
(4) Partial pressure in ¬¬the alveoli is expressed as a ratio of alveolar concentration (FA) over inspired concentration (FI); the faster FA/FI approaches 1 (representing inspired-to-alveolar equilibrium), the faster anesthesia will occur during an inhaled induction.
what is the blood:gas partition coefficient and how is it used clinically
useful index of solubility and defines the relative affinity of an anesthetic for blood compared to inspired gas.
(i) There is an inverse relationship between the blood:gas partition coefficient value and rate of anesthesia onset.
(ii) Agents with low blood solubility (nitrous oxide, desflurane) reach high arterial pressure rapidly, which in turn results in rapid equilibrium with the brain and fast onset of action.
(iii) Agents with high blood solubility (halothane) reach high arterial pressure slowly, which in turn results in slow equilibration with the brain and a slow onset of action.
if an agent is not very soluble, how will this relate to how fast its onset is
if the agent is not very soluble, it will have a faster onset of action
In this schematic diagram, solubility in blood is represented by the relative size of the blood compartment (the more soluble, the larger the compartment). Relative partial pressures of the agents in the compartments are indicated by the degree of filling of each compartment. For a given concentration or partial pressure of the two anesthetic gases in the inspired air, it will take much longer for the blood partial pressure of the more soluble gas (halothane) to rise to the same partial pressure as in the alveoli. Since the concentration of the anesthetic agent in the brain can rise no faster than the concentration in the blood, the onset of anesthesia will be slower with halothane than with nitrous oxide.
what is the effect of increased cardiac output on rate of induction of anesthesia
(a) Increased pulmonary blood flow (increased cardiac output), increases uptake of anesthetic, thereby decreasing rate by which FA/ FI rises, which will decrease the rate of induction of anesthesia.
(b) An increase in cardiac output and pulmonary blood flow will increase uptake of anesthetic into the blood, but the anesthetic taken up will be distributed in all tissues, not just the CNS; increased cardiac output will increase delivery of anesthetic to other tissues and not the brain (cerebral blood flow well regulated).
what are 2 parameters that can be manipulated by anesthesiologists for controlling speed of induction and recovery
1) concentration of anesthetic in inspired air, 2) alveolar ventilation
(a) Concentration in inspired air cannot be < 0, hyperventilation only way to speed recovery.
(1) Recovery from inhaled anesthetics follows some of the same principles in reverse that are important during induction.
(2) Inhaled anesthetics that are relatively insoluble in the blood and brain are eliminated at faster rates than more soluble anesthetics.
(5) Duration of exposure may have a significant impact on recovery.
(a) Accumulation in muscle, skin, and fat increases with prolonged exposure (especially in obese) and blood tension may decline slowly during recovery as anesthetics are slowly eliminated from these tissues.
in decreasing order, what are the inhaled anesthetics that are hepatically metabolized (recovery)
– halothane > enflurane > sevoflurane
what is currently used to describe anesthetic potency
described by minimum alveolar concentration (MAC) required to prevent response to surgical incision.
- 0 MAC is the partial pressure of inhaled anesthetic in alveoli at which 50% of population remained immobile at time of skin incision.
(ii) Patients may need 0.5-2 MAC for successful anesthesia (> 90% of patients will become anesthetized at 1.3 MAC). - MAC is additive: 0.5 MAC of an agent added to 0.5 MAC of another = 1 MAC.
what does a MAC value greater than 100% indicate
(iii) MAC values greater than 100% indicate that even if 100% of the inspired air at barometric pressure is the anesthetic, the MAC value would still be less than 1 and other agents must be supplemented to achieve full surgical anesthesia (e.g., nitrous oxide).
stage 1 - Analgesia
(i) Stage I Analgesia
1. Patient initially experiences analgesia without amnesia; later in Stage I, both analgesia and amnesia produced.
Stage 2 excitement
(ii) Stage II Excitement
1. Patient appears delirious, may vocalize but is completely amnesiac; respirations rapid, heart rate and blood pressure increase.
stage III surgical anesthesia
- Begin with slowing respiratory rate and heart rate; extends to complete cessation of spontaneous respiration (apnea).
- Four planes described based on changes of ocular movements, eye reflexes, and pupil sizes indicating increasing depth of anesthesia
however, a reliable indication that stage III has been achieved is loss of responsiveness to painful stimuli (e.g., trapezius muscle squeeze) and the reestablishment of regular breathing.
stage IV medullary depression
- Severe CNS depression, including vasomotor center in medulla & respiratory center in brainstem. Without circulatory or respiratory support, death would rapidly ensue.
what are the vascular effects of inhaled anesthetics on the brain and in what pt’s is this clinically significant
(c) Inhaled anesthetics decrease the metabolic activity of the brain which generally results in reduction of blood flow; however, volatile anesthetics may also cause cerebral vasodilation (undesirable in patients with increased intracranial pressure).
what are the cardiovascular effects of inhaled anesthetics
all depress normal cardiac contractility (halothane and enflurane more so than others)
(b) Tend to decrease mean arterial pressure in direct proportion to alveolar concentration.
(c) A decrease in arterial blood pressure leads to activation of autonomic nervous system reflexes which may trigger an increase in HR (significant with desflurane and isoflurane, others attenuate baroreceptor response).
what are the effects of volatile anesthetics on the respiratory system and what are some complications of these effects
(a) All volatile anesthetics are respiratory depressants. They cause dose-dependent decrease in tidal volume with increase in respiratory rate which results in rapid, shallow breathing.
(b) Respiratory depressant effects overcome by assisting (controlling) ventilation mechanically.
(c) During prolong exposure, mucus pooling and plugging may result in atelectasis and the development of postoperative respiratory complications (including hypoxemia and respiratory infections).
what are some side effects of volatile anesthetics
specifically–> halothane? sevoflurane?
i) Common side effects include nausea and vomiting.
ii) Halothane may cause hepatitis after a previous first-time exposure (1:20,000-35,000).
iii) Agents metabolized to products including fluoride ions may cause renal toxicity (e.g., sevoflurane).
iv) Inhaled volatile anesthetics may cause malignant hyperthermia, which consists of rapid onset tachycardia and hypercapnia, severe muscle rigidity, hyperthermia, hyperkalemia, and metabolic acidosis (treatment: dantrolene).
treatment of malignant hyperthermia
dantrolene
inhibiting the release of Ca2+ ions by the sarcoplasmic reticulum
what characteristics of IV anesthetics allows them such a rapid onset of action
c) IV agents used for induction of general anesthesia are lipophilic and preferentially partition into highly perfused lipophilic tissues (brain, spinal cord) which accounts for rapid onset of action.
Propofol MOA
i) MOA: presumed potentiation of Cl- current mediated through GABAA receptor complex.
brief context sensitive halftime
what is context sensitive half time
The context-sensitive half-time of common intravenous anesthetics. Even after a prolonged infusion, the half-time of propofol is relatively short, which makes propofol the preferred choice for intravenous anesthesia. Ketamine and etomidate have similar characteristics but their use is limited by other effects.
Effects of Propofol (diprivan) on the CNS
CNS depression
NO Analgesia !!
(c) Decreases cerebral blood flow and the cerebral metabolic rate for oxygen (CMRO2), which decreases intracranial pressure (ICP) and intraocular pressure.
(d) Produces burst suppression in the EEG when administered in large doses, which conveys a neuroprotective effect during neurosurgical procedures (as does decreased CMRO2).
what are the cardiovascular effects of propofol
(a) Compared with other induction agents produces the most pronounced decrease in systemic blood pressure due to profound vasodilation in both arterial and venous circulation leading to reductions in preload and afterload.
(b) Hypotensive effects are augmented by inhibition of the normal baroreflex response.
what is the effect of propofol on the respiratory system
(a) Potent respiratory depressant; generally produces apnea after an induction dose.
(b) Causes a greater reduction in upper airway reflexes than thiopental does, which makes it well suited for instrumentation of the airway, such as placement of a laryngeal mask airway.
what is the therapeutic use of propofol
sedation in the ICU
rapid anesthesia induction
short procedures
fospropofol
similar MOA to propofol (GABA A potentiation)
longer onset and recovery than propofol
ADR= paresthesia (especailly in the perianal region)
used for sedation during monitored anesthesia care
which barbituates are used as IV anesthetics
thiopental and methohexital
MOA of thiopental and methohexital
ii) MOA: act on GABAA receptor to increase duration of channel opening. Presumed to also inhibit excitatory neurotransmission.
Methohexital faster and more complete recovery (shorter elimination t1/2) after bolus injection than thiopental.
used for short procedures and induction of anesthesia
which IV anesthetics do NOT provide analgesia
Propofol
barbituates
etomidate
what are the CNS and respiratory effects of barbituates
CNS depression (sedation to general anesthesia)
NO analgesia
barbiturates decrease electrical activity on EEG and can be used as anticonvulsants.
RESP = (a) Respiratory depressants; induction doses typically produce transient apnea.
which benzodiazepines are used for anesthesia
midazolam, lorazepam, diazepam
MOA of benzodiazepines
ii) MOA: acts on the GABAA receptor to increase receptor sensitivity to GABA (agonist) and enhances inhibitory neurotransmission.
what agent can be used to reverse benzodiazepines
(1) Unique among IV anesthetics as effect can be terminated by administration of selective antagonist, flumazenil (GABA receptor antagonist)
which benzo is the only one that can be used for continuous infusion b/c it has the shortest context half time
(1) Midazolam
CNS effects of benzodiazepines
(a) Potent anticonvulsants used in status epilepticus, alcohol withdrawal, and local-anesthetic induced seizures
Respiratory effects of benzo’s
(a) Severe respiratory depression may occur when administered together with opioids.
what are the therapeutic uses of benzo’s
anti-anxiety
anterograde amnesia
useful as PREMEDICATION
Also used for IV sedation and suppression of seizure activity
MOA of etomidate
IV anesthetic
i) MOA: GABA like effects, acts primarily through potentiation of GABAA mediated Cl- currents.
Therapeutic use of etomidate
rapid induction
short context sensitive half time
alternative to propofol or barbiturates for rapid IV induction of anesthesia, especially in those with compromised cardiac contractility.
NO Analgesia
CNS effects of etomidate ?
CV effects?
Endocrine effects?
(1) CNS effects
(a) Potent cerebral vasoconstrictor; decreases cerebral blood flow and intracranial pressure.
(2) Cardiovascular effects
(a) Minimal hemodynamic effects.
(3) Endocrine effects
(a) Adrenocortical suppression, producing dose dependent inhibition of 11B-hydroxylase, an enzyme necessary for conversion of cholesterol to cortisol.
ADR of etomidate ?
postop nausea and vomiting
Ketamine
MOA
i) MOA: complex; major effect is probably produced through inhibition of NMDA receptor complex (glutamate ionotropic receptor)
rapid onset of action
hepatic metabolism
Ketamine effects on CNS
(a) In contrast to other anesthetics, ketamine considered a cerebral vasodilator and increases cerebral blood flow, as well as cerebral metabolic rate. Not recommended for use in patients with intracranial pathology, especially increased ICP.
(b) Emergence reactions: vivid colorful dreams, hallucinations, out-of-body experiences, and increased and distorted visual, tactile, and auditory sensitivity.
(i) Reactions associated with fear/confusion but euphoric state may also be induced (explains potential for abuse).
(c) “Dissociative anesthesia” wherein patients eyes remain open with slow nystagmic gaze.
CV effects of ketamine
(a) Can increase systemic blood pressure, heart rate, and cardiac output; presumably by centrally mediated sympathetic stimulation.
(b) Ketamine is considered to be a direct myocardial depressant, a property masked by stimulation of the sympathetic nervous system (the depressant actions of ketamine may be more apparent in critically ill patients with limited ability to increase their sympathetic nervous system activity).
what is the therapeutic use of ketamine
IV anesthetic
used for profound analgesia
sympathetic nervous system stimulation, bronchodilation, and minimal respiratory depression make ketamine an important alternative to other anesthetics.
v) Lacrimation and salivation are increased upon administration, and premedication with an anticholinergic may be indicated.
Dexmedetomidine
IV anesthetic
highly selective α2-adrenergic agonist, may be antagonized by α2-antagonists
Significant increase in context-sensitive half-time from 4 minutes after 10 minute infusion to 250 minutes after an 8 hour infusion.
which IV anesthetics DO provide analgesia
ketamine
dexmedetomidine
opioids
CNS effects of dexmedetomidine
(a) Activates CNS α2-receptors, hypnosis presumably from stimulation of α2-receptors in locus caeruleus, and analgesia at level of spinal cord.
(b) Sedative effect resembles physiologic sleep state (activation of endogenous sleep pathways)
CV effects of dexemedetomidine
(a) Moderate decrease in heart rate and systemic vascular resistance, consequently in systemic blood pressure. Bradycardia may require treatment.
what is the therapeutic use of dexemedetomidine
short term sedation of intubated and ventilated pt’s in the ICU
in operating room, may be used as adjunct to general anesthesia or provide sedation;
awakening and the transition to postoperative setting may benefit from dexmedetomidine produced sedative and analgesic effects without respiratory depression.
what is the therapeutic use of opioids
routinely used to achieve postoperative analgesia; used in the intraoperative setting as part of balanced anesthetic regimen.
in terms of naming local anesthetics, how can you tell apart esters versus amides
amides have TWO I’s in their name “articaine” “lidocaine”
esters have one I
-Benzocaine
cocaine
what is the distinguishing charactersitic of local anesthetics
d) Although local anesthetics are often used as analgesics, it is their ability to provide complete loss of sensory modalities that is their distinguishing characteristic.
e) Local anesthesia – drug is delivered directly to target organ and systemic circulation serves only to diminish or terminate its effect.
MOA of local anesthetics
block voltage gated Na channels
these agents are initially uncharged, and diffuse across the axonal membrane to enter the cytoplasm. once inside, they become ionized and block the Na channels from the inside
(1) When progressively increasing concentration of local anesthetics are applied to a nerve fiber, the threshold for excitation increases, impulse conduction slows, the rate of rise of the action potential declines, action potential amplitude decreases, and finally, the ability to generate an action potential is completely abolished.
how does fiber diameter affect anesthetic activity
- Traditional teaching: local anesthetics block smaller diameter fibers first; distance over which such fibers can passively propagate an electrical impulse is shorter.
- However, a variable proportion of large fibers are blocked prior to the disappearance of the small fiber component of the action potential.
- Most notably, myelinated nerves tend to be blocked before unmyelinated nerves of the same diameter. For example, preganglionic B fibers are blocked before smaller unmyelinated C fibers involved in pain transmission.
how does firing frequency of neurons effect anesthetic
- More significant block at higher frequency of depolarization.
- Sensory (pain) fibers have high firing rate & relatively long action potential duration.
- Motor fibers fire at slower rate and shorter action potential duration.
a. As type A delta and C fibers participate in high-frequency pain transmission, this characteristic may favor blockade of these fibers earlier with lower concentration of local anesthetic.
what is the orderly evolution of block in local anesthetics
(1) Orderly evolution of block components beginning with sympathetic transmission and progressing to temperature, pain, light touch, and finally motor block.
what is the effect of added vasoconstrictors to local anesthetics
enhance local action
decrease bleeding and increase anesthesia by decreasing systemic concentration
what are the 2 distinct processes by which anesthetic can cause toxicity
1) systemic effects following inadvertent intravascular injection or absorption of anesthetic from site of administration, and 2) neurotoxicity resulting from local effects produced by direct contact with neural elements
toxicity of local anesthetics in CNS
if a larger dose of anesthetic is required how can you prevent CNS toxicity
– sedation, light headedness, visual and auditory disturbances, and restlessness.
(a) Higher concentration: nystagmus, muscular twitching, followed by tonic-clonic convulsions.
(i) Central stimulation followed by depression; death usually caused by respiratory failure.
(b) When large doses required (for major peripheral nerve block or local infiltration for major plastic surgery) premedication with benzodiazepine will provide some prophylaxis against CNS toxicity.
Toxicity effects on CV system by local anesthetics
arrythmia and cardiac arrest
(a) Local anesthetics block cardiac sodium channels and decrease electrical excitability, conduction rate, force of contraction, and arteriolar dilation, leading to systemic hypotension (NOT the case with cocaine).
(b) Cocaine inhibits norepinephrine reuptake and results in vasoconstriction (which can lead to local ischemia), hypertension, and cardiac arrhythmias.
benzocaine
characteristic ADR?
methemoglobinemia
(2) Used topically for dermatologic conditions, hemorrhoids, and as an anesthetic lubricant (e.g., nasogastric and endoscopic tubes and catheters).
bupivicaine characteristic ADR?
can cause severe cardiovascular toxicity
(1) Agent with long duration of action capable of producing prolonged anesthesia.
(3) Useful in peripheral anesthesia, analgesia for postoperative pain control, anesthetic infiltration for surgical incision pain, epidural infusions, labor analgesia.
therapeutic use of cocaine
(1) The clinically desired properties of cocaine are the blockade of nerve impulses and local vasoconstricting actions secondary to its ability to inhibit local norepinephrine reuptake.
(2) Euphoric properties are primarily due to inhibition of catecholamine reuptake (mainly dopamine in the CNS).
(3) Used primarily as a topical anesthetic of the upper respiratory tract (ear, nose, and throat procedures) where intense vasoconstriction can reduce bleeding
what re some other uses of lidocaine other than a local anesthetic
antiarrhythmic agent
neuralgia pain management as a patch
how does alveolar-venous partial pressure affect time of onset of inhaled anesthetics
Depends on tissue uptake
If venous blood contains significantly less anesthetic than arterial blood
Requires more time to equilibrium
Depends on tissue uptake
If venous blood contains significantly less anesthetic than arterial blood
Requires more time to equilibrium
