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90 Cards in this Set
- Front
- Back
responsible for termination of effect of many anesthetic drugs
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As plasma concentration falls, some drug leaves the highly perfused organs to maintain equilibrium. This redistribution from the vessel-rich group is responsible for termination of effect of many anesthetic drugs.
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______________ freely cross from plasma into the glomerular filtrate.
absorbtion happens how? |
Non–protein-bound drugs
The nonionized fraction of drug is reabsorbed in the renal tubules, whereas the ionized portion is excreted in urine. |
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Elimination half-life of a drug is proportional to...
inversely proportional to |
Elimination half-life of a drug is proportional to the volume of distribution and inversely proportional to the rate of clearance.
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Repetitive administration of barbiturates....
duration of action becomes more dependent .... |
Repetitive administration of barbiturates saturates the peripheral compartments, so that redistribution cannot occur and the duration of action becomes more dependent on elimination.
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Barbiturates ____________ the cerebral vasculature.
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Barbiturates constrict the cerebral vasculature.
This effect may protect the brain from transient episodes of focal ischemia (eg, cerebral embolism) but probably not from global ischemia (eg, cardiac arrest). |
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The accumulation of morphine metabolites (morphine 3-glucuronide and morphine 6-glucuronide) in patients with renal failure has been associated with 2X
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narcosis and ventilatory depression lasting several days.
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The stress response to surgical stimulation is measured in terms of the secretion of 3 specific hormones
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including catecholamines, antidiuretic hormone, and cortisol. Opioids block the release of these hormones more completely than volatile anesthetics
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Opioids and stress response to surgical stimulation
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The stress response to surgical stimulation is measured in terms of the secretion of specific hormones, including catecholamines, antidiuretic hormone, and cortisol. Opioids block the release of these hormones more completely than volatile anesthetics.
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In sharp contrast to other anesthetic agents, ketamine increases 3X
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arterial blood pressure,
heart rate, and cardiac output. |
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In sharp contrast to other anesthetic agents, ketamine increases arterial blood pressure, heart rate, and cardiac output. These indirect cardiovascular effects are 2X
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These indirect cardiovascular effects are due to central stimulation of the sympathetic nervous system and inhibition of the reuptake of norepinephrine.
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Induction doses of etomidate transiently inhibit 2x
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enzymes involved in cortisol and aldosterone synthesis. Long-term infusions lead to adrenocortical suppression that may be associated with an increased mortality rate in critically ill patients.
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droperidol should be avoided in patients with
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Parkinson disease.
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Elimination implies drug removal by both
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biotransformation and excretion.
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Clearance is measurement of
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measurement of the rate of elimination
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bioavailability
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is the fraction of unchanged drug that reaches the systemic circulation
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an acidic environment favors the absorption of
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acidic drugs (A–+ H+ AH),
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an alkaline environment favors absorption of
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favors basic drugs (BH+ H+ + B).
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Because the veins of the mouth drain into 3X
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superior vena cava, sublingual or buccal drug absorption bypasses the liver and first-pass metabolism.
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venous drainage of the rectum bypasses
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bypasses the liver, first-pass metabolism is less significant than with small intestinal absorption
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Albumin often binds
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acidic drugs (eg, barbiturates), whereas 1-acid glycoprotein (AAG) binds basic drugs (local anesthetics).
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responsible for termination of effect of many anesthetic drugs
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redistribution from the vessel-rich group
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volume of distribution (Vd) and is determined by
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dividing the dose of drug administered by the resulting plasma concentration:
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Biotransformation is
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alteration of a substance by metabolic processes.
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primary organ of biotransformation
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The liver
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The 2 end products of biotransformation
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inactive and water soluble
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depend on biliary excretion
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The kidney
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Elimination half-life of a drug is proportional to the__________ and inversely proportional to the _____________.
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volume of distribution (Vd)
rate of clearance. |
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first-order kinetics
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a constant fraction or percentage of drug is distributed or metabolized per unit of time, regardless of plasma concentration
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zero-order kinetics
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a constant amount of drug may be metabolized per unit of time
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Dose–response curves express the relationship between
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drug dose and pharmacological effect
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dose of drug required to produce a given effect in 50% of the population
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median effective dose (ED50)
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dose that results in death in 50% of the population exposed to that dose.
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median lethal dose (LD50)
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the ratio of the median lethal dose to the median effective dose (LD50:ED50).
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The therapeutic index is the ratio
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Drug receptors are macromolecules—usually proteins embedded into
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cell membranes
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Endogenous substances (eg, hormones) or exogenous substances (eg, drugs) that directly change cell function by binding to receptors
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agonists.
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bind to the receptors but do not cause a direct effect on the cell.
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Antagonists
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bind reversibly to receptors and can be displaced by higher concentrations of agonists.
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Competitive antagonists
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Noncompetitive (irreversible) antagonists
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bind to the receptor with such affinity that even high concentrations of agonists cannot reverse the receptor blockade. Competition of two drugs for the same receptor is one source of drug interactions.
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Receptors affect cell function
2 ways |
either directly (eg, by changing transmembrane ion flux) or by controlling the production of another regulatory molecule (eg, the second-messenger cyclic adenosine monophosphate).
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Barbiturates depress
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reticular activating system—a complex polysynaptic network of neurons and regulatory centers—located in the brain stem that controls several vital functions, including consciousness. In
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In clinical concentrations, barbiturates preferentially affect the function of
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nerve synapses rather than axons.
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Barbiturates suppress
enhance |
suppress transmission of excitatory neurotransmitters (eg, acetylcholine) and enhance transmission of inhibitory neurotransmitters (eg, -aminobutyric acid [GABA]).
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Barbiturates are ________________ derivatives
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barbituric acid
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The sodium salts of the barbiturates are water soluble but markedly ____________
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alkaline
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Biotransformation of barbiturates principally involves __________ to inactive water-soluble metabolites.
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hepatic oxidation
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specific benzodiazepine–receptor antagonist that effectively reverses most of the central nervous system effect of benzodiazepines
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Flumazenil
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Cerebral
Benzodiazepines |
reduce cerebral oxygen consumption, cerebral blood flow, and intracranial pressure
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Benzodiazepines reduce the minimum alveolar concentration of volatile anesthetics as much as 30%
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as 30%
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major types of opioid receptor have been identified
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mu ( , with subtypes -1 and -2), kappa ( ), delta ( ), and sigma ( ).
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opioid agonists and antagonists
dif. |
Although both opioid agonists and antagonists bind to opioid receptors, only agonists are capable of receptor activation.
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Endorphins, enkephalins, and dynorphins
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are endogenous peptides that bind to opioid receptors.
These three families of opioid peptides differ in their protein precursors, anatomic distributions, and receptor affinities. |
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important
Opiate–receptor activation |
inhibits the presynaptic release and postsynaptic response to excitatory neurotransmitters (eg, acetylcholine, substance P) from nociceptive neurons.
The cellular mechanism for this neuromodulation may involve alterations in potassium and calcium ion conductance |
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with intrathecal or epidural administration of opioids the Transmission of pain impulses can be interrupted at
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the level of the dorsal horn of the spinal cord with intrathecal or epidural administration of opioids.
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opioids exert their greatest effect within the ____________________,
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central nervous system
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Most opioids depend primarily on __________for biotransformation.
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the liver
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Morphine undergoes conjugation with _________ to form ______________.
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glucuronic acid
morphine 3-glucuronide and morphine 6-glucuronide. |
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Meperidine is N-demethylated to normeperidine, an active metabolite associated with
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seizure activity
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The end products of fentanyl, sufentanil, and alfentanil are _________.
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inactive.
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The unique ester structure of remifentanil, an ultrashort-acting opioid with a terminal elimination half-life of less than _____________
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10 min
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Meperidine
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Cardiovascular
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opioids __________ cardiac contractility.
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do not depress
Nonetheless, arterial blood pressure often falls as a result of bradycardia, venodilation, and decreased sympathetic reflexes, sometimes requiring vasopressor (eg, ephedrine) support. |
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2 opioids that evoke histamine release
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meperidine and morphine evoke histamine release in some individuals that can lead to profound drops in systemic vascular resistance and arterial blood pressure.
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The effects of histamine release can be minimized in susceptible patients by
3x |
slow opioid infusion,
adequate intravascular volume, or pretreatment with H1 and H2 histamine antagonists |
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Intraoperative hypertension during opioid anesthesia, particularly morphine and meperidine, is not uncommon. It is often attributable to
fixed by |
inadequate anesthetic depth and can be controlled with the addition of vasodilators or volatile anesthetic agents
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apneic threshold—
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the highest PaCO2 at which a patient remains apneic—is elevated, and hypoxic drive is decreased.
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3 Opioids can induce chest wall rigidity severe enough to prevent adequate ventilation
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fentanyl,
sufentanil, and alfentanil |
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________can effectively blunt the bronchoconstrictive response to airway stimulation such as occurs during intubation.
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Opioids
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responsible for a high incidence of nausea and vomiting
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medullary chemoreceptor trigger zone
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most effective opioid for decreasing shivering.
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Intravenous meperidine (25 mg)
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Biliary colic may result from opioid-induced
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contraction of the sphincter of Oddi.
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The stress response to surgical stimulation is measured in terms of
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secretion of specific hormones, including catecholamines, antidiuretic hormone, and cortisol.
Opioids block the release of these hormones more completely than volatile anesthetics. |
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ketamine functionally "dissociates" the
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thalamus (which relays sensory impulses from the reticular activating system to the cerebral cortex) from the limbic cortex (which is involved with the awareness of sensation).
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thalamus fx
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which relays sensory impulses from the reticular activating system to the cerebral cortex)
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limbic cortex fx
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which is involved with the awareness of sensation
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keatmine dissociative anesthesia
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this state of dissociative anesthesia causes the patient to appear conscious (eg, eye opening, swallowing, muscle contracture) but unable to process or respond to sensory input. Ketamine has been demonstrated to be an N-methyl-D-aspartate receptor (a subtype of the glutamate receptor) antagonist. The existence of specific ketamine receptors and interactions with opioid receptors has been postulated.
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Ketamine is biotransformed in the
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liver
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ketamine
Cardiovascular why 2x |
ketamine increases arterial blood pressure, heart rate, and cardiac output (Table 8–8). These indirect cardiovascular effects are due to central stimulation of the sympathetic nervous system and inhibition of the reuptake of norepinephrine.
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ketamine should be avoided in patients with 4x
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coronary artery disease,
uncontrolled hypertension, congestive heart failure, and arterial aneurysms |
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Respiratory
Ketamine |
potent bronchodilator, making it a good induction agent for asthmatic patients
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ketamine
Cerebral |
ketamine increases cerebral oxygen consumption, cerebral blood flow, and intracranial pressure.
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Mechanisms of Action
Etomidate 2x |
Etomidate depresses the reticular activating system and mimics the inhibitory effects of GABA.
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Etomidate
it may have disinhibitory effects on the parts of the nervous system that control |
control extrapyramidal motor activity
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Cardiovascular
Etomidate |
has minimal effects on the cardiovascular system. A mild reduction in peripheral vascular resistance is responsible for a slight decline in arterial blood pressure. Myocardial contractility and cardiac output are usually unchanged. Etomidate does not release histamine.
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Induction doses of etomidate transiently inhibit
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inhibit enzymes involved in cortisol and aldosterone synthesis. Long-term infusions lead to adrenocortical suppression that may be associated with an increased mortality rate in critically ill patients.
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Propofol
Mechanisms of Action |
facilitation of inhibitory neurotransmission mediated by GABA.
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Structure
Propofol |
phenol ring with two isopropyl groups
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mixing lidocaine with propofol
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2 mL of 1% lidocaine in 18 mL propofol
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Cardiovascular
The major cardiovascular effect of propofol |
decrease in arterial blood pressure due to a drop in systemic vascular resistance (inhibition of sympathetic vasoconstrictor activity), cardiac contractility, and preload.
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Mechanisms of Action
Droperidol |
antagonizes the activation of dopamine receptors
in the central nervous system, the caudate nucleus and the medullary chemoreceptor trigger zone are affected. Droperidol also interferes with transmission mediated by serotonin, norepinephrine, and GABA. These central actions account for the tranquilizer and antiemetic properties of droperidol. Peripheral actions include -adrenergic blockade. |
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Prior to administering droperidol,
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a 12-lead electrocardiogram should be recorded. If the QT measures greater than 440 ms for men or greater than 450 ms for women, droperidol should not be given
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