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117 Cards in this Set
- Front
- Back
Mecamylamine (Inversine)
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Ganglionic Blocker Crosses CNS easily, and acts to block nicotinic receptors in the brain, as well as at the ganglia. In the brain, this blockade tends to decrease dopamine and norepinephrine release from specific neurons as well as modulating neuroendocrine responses.
Tourette’s syndrome |
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ADVERSE REACTIONS OF MECAMYLAMINE (INVERSINE)
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N/V, anorexia, constipation, mydriasis, syncope, weakness and fatigue, among others.
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GANGLIONIC BLOCKERS
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*only nicotinic ganglionic blockers can completely block the transmission through ganglia.
Depolarizing type blockers initially stimulate the ganglia like ACh then block due to persistent depolarization |
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HEXAMETHONIUM
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GANGLIONIC BLOCKER
doesn't stimulate the receptor, it acts by competing for ACh binding site only (non depolarizing) |
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TRIMETHAPHAN
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mechanistically acts like curare does at the NMJ, competitively blocking ACh from getting to receptors on the ganglia
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Symptoms of ganglionic blockade
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: increased bloodflow to the skin (warm and pink), decreased sweating, inhibited lacrimation and salivation, mydriasis and cycloplegia, decreased GI tone and motility, hypotension, urinary retention, constipation, and hypoglycemia.
These symptoms are due to blockade of the predominant tone on each tissue, allowing the non-predominant autonomic effects to override and be expressed. |
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Non-Depolarizing blockers
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Agents in this class act as (somewhat) competitive antagonists of ACh at the neuromuscular junction. This blocks the ability of ACh to stimulate the muscle at the motor end plate, resulting in muscle weakness (at lower doses) or paralysis (at higher doses).
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Succinylcholine
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Can cause transient sinus bradycardia accompanied by hypotension, cardiac arrhythmias, tachycardia, and possible cardiac arrest by increased vagal stimulation.
Can cause also cause hyperkalemia. Pre-treatment with anticholinergic agents, e.g., atropine, may reduce the occurrence of bradyarrhythmias. Also possesses significant histamine-releasing properties. Rxns at mast cells. |
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potentiate neuromuscular blockade with the nondepolarizing agents.
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lithium, calcium salts, magnesium salts, inhalational anesthetics, local anesthetics, certain antibiotics, quinidine, procainamide, lidocaine, and others
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histamine-releasing properties
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atracurium, cisatracurium, and succinylcholine) have precautions for use in asthma or cardiac disease, and may be associated with increased cardiopulmonary adverse effects including flushing, hypotension, sinus tachycardia, urticaria, wheezing, and bronchospasm.
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Sugammadex (Bridion???)
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designed as a reversal agent for Rocuronium
also works fairly well with vecuronium and pancuronium structure is a complex cyclodextrin ‘cage’ with high lipophilicity that binds the neuromuscular blocker and allows removal. |
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AROMATIC GROUP
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lipophillic
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WHY ALKALINIZE A LOCAL ANESTHETIC PRIOR TO INJECTION?
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it will increase the onset time by increasing the pH of the solution, therefore increasing the number of unionized particles that will be able to cross the membranes better.
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DIAMINE
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two ionizable groups on the molecule each group has a different pka, you need to worry about the highest pka
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AMINE
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hydrophillic group
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INCREASING LIPID SOLUBILITY
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decreases onset time and increases duration
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LOCAL ANESTHETIC MOA
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All agents act to decrease the permeability of the membrane to sodium ions.
These agents bind to sites in the Na+ channel of the voltage gated Na+ channels, thus inhibiting Na+ inflow during depolarization. Low conc. of LA's decreases both the rate of rise and the height of the action potential. Higher concentrations can abolish it totally. Firing threshold is also increased, and total propagation time is increased. In myelinated fibers, this occurs only at the Nodes of Ranvier. |
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AT WHAT STAGE OF THE SODIUM CHANNELS DO LA BIND?
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The trick with the local anesthetics is to get them into the closed inactivated state and block them
. In the inactivated stage the beta subunit turns and plugs the channel causing it to become inactivated. |
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NA CHANNELS MADE UP OF?
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Sodium channel made up of an alpha subunit comprised of 4 additional subunits, and additional beta subunits.
The alpha subunit contains the sodium pore Local anesthetics bind to the closed, inactivated channel stabilizing it in that form. |
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WHICH NERVES ARE AFFECTED FIRST IN LA?
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Small diameter nerves are affected first, then larger diameter nerves due to the number of channels to be blocked (greater in large fibers).
More rapidly stimulated fibers are also blocked first due to more frequent opening of Na+ channels, and the ability of the LA's to get into channel to bind (sensory fibers tend to be triggered more frequently than motor fibers, and so tend to be blocked first). Usually, autonomic fibers are affected first, then sensory, then motor. |
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LA RECOVERY
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Recovery is in reverse order
where motor neurons will come back first, then sensory, then autonomic. |
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ONSET OF ANESTHESIA FASTEST WITH WHICH LA?
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lidocaine and prilocaine
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ONSET OF ANESTHESIA IS SLOWEST WITH WHICH LA?
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procaine and tetracaine
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SHORTEST DURATION OF ACTION OF THE LA?
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procaine and chloroprocaine (15-30 min)
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INTERMEDIATE DURATION OF ACTION OF LA'S?
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lidocaine and prilocaine 30-90 min
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LONG DURATION OF ACTION OF LA
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tetracaine 2-3 hours
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Local hypersensitivity reactions more common with
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ester type
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LA'S THAT CAN CAUSE METHEMOGLOBINEMIA
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oxidize hemoglobin
prilocaine, benzocaine, lidocaine, cetacaine |
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Benzocaine (Oragel) (many other tradenames)
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Poorly water soluble, so topical use only.
Excessive absorption may lead to methemoglobinemia. pKa ~ 3.5 sunburn after sunburn. |
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Procaine (Novocaine)
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First synthetic local anesthetic.
Slower onset with short duration and weak potency. Fairly low systemic toxicity. Best for infiltration and nerve block. Use superceded by better agents (amides). |
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Chloroprocaine (Nesacaine)
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Rapid onset, short duration.
Low systemic toxicity. Used in high concentration solutions (since toxicity is low). For infiltration, nerve block, IV and epidural use. |
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Tetracaine (Pontocaine)
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Ten times more potent than procaine, but also ten times more toxic.
Long duration with slow onset. Major use is in spinal anesthesia, where the barriers decrease diffusion and decrease toxicity risk. Also effective topically, but absorption across mucous membranes limits its use. |
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Cocaine
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C-II controlled substance derived from the leaves of the coca plant.
Too toxic for uses other than topically. (cardiac toxicities) Unique agent that has potent vasoconstrictive activity and addiction liability in addition to it’s LA effect. Used topically on mucous membranes, such as nasal cavities or oropharyngeal cavities prior to surgery, and packed post-op to decrease bleeding and pain. |
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Cetacaine (Cetylite)
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Topical agent for local skin disorders and is used on various mucous membranes (except the eye).
Cetacaine is a mixture of Benzocaine, Tetracaine, and Butyl Aminobenzoate used topically, rectally or as a spray to inhibit the gag reflex (during bronchoscope exam, etc). |
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Lidocaine (Xylocaine)
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Most commonly used local anesthetic.
Rapid onset with intermediate duration. Causes vasodilation, so many formulations include EPI. Useful for most types of application |
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Prilocaine (Citanest)
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Similar to lidocaine in properties, but less vasodilation.
Rapid onset, intermediate duration. Least toxic of the amides, but can still cause methemoglobinemia. |
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MORE LIKELY TO CAUSE METHEMOGLOBINEMIA
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amides
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Mepivacaine (Carbocaine)
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Uses Similar to lidocaine.
Used for infiltration, nerve block, epidural. Not effective topically. Not used in obstetrics because biotransformation in fetus is prolonged. Racemic mixture, structurally similar to Bupivacaine and Ropivacaine |
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Bupivacaine (Marcaine)
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Long duration, with slower onset.
High potency. More toxic than Lidocaine (cardiotoxic). Used for infiltration nerve block, epidural and spinal anesthesia. Most likely to cause adverse effects. |
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Articaine (Septocaine)
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Only available in U.S. in combination with EPI.
Similar to Lidocaine - short duration, rapid onset. Used for dental and periodontal procedures. Low systemic toxicity due to rapid breakdown (it has an ester group in addition to an amide). Only used with epi b/c the drug is removed from the area so quickly. Articaine is BOTH an ester and an amide. |
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Ropivacaine (Naropin)
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Long duration, similar to Bupivacaine, but less cardiotoxic.
Actually an S-isomer, whereas the structurally similar bupivacaine is racemic, with the more cardiotoxic R-isomer. Less lipid soluble, and more rapidly metabolized than Bupivacaine. Uses are similar to Bupivacaine (infiltration, nerve block, epidural, spinal). |
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Pramoxine (Proctofoam)
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Topical agent for relief of hemorrhoids, rectal pain and itching of skin disorders (pruritus).
Weak potency (will not totally abolish gag reflex). Mixed in combination with many products (ex. Hydrocortisone, calamine). |
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SHIFTS OXYGEN DISSOCIATION CURVE TO THE LEFT
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decreased PaCO2, decreased temp, increased pH, decreased 2,3-dPG, fetal Hgb, CO, methemoglobinemia
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SHIFTS OXYGEN DISSOCIATION CURVE TO THE RIGHT
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increased PaCO2, increased temp, decreased pH, increased 2,3-dPG
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HYPOXIC EFFECTS
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Increased ventilation
sympathetic stimulation (tachycardia, but decreased peripheral vascular resistance – local effect) pulmonary vasoconstriction to optimize V/Q impaired CNS function anerobic metabolism, increased lactic acid, decreased ionic gradients – increased cell H+, Ca++, Na+ cell death |
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Hypocarbia (resp alkalosis)
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constrict cerebral vessels, and decrease brain size somewhat – used in neurosurgery
cardiac surgery uses to decrease air (insoluble N2) around heart not normally used to increase respiration |
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Nitric Oxide
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use can cause large pulmonary vasodilation with minimal systemic effects (binds and inactivates oxyhemoglobin)
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Paraldehyde
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, control DT’s in alcohol therapy
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GABA RECEPTOR COMPLEX
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pentameter, 5 proteins, chloride channel, benzos, steroids, barbs, picrotoxin
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Normal sleep characterized by at least 2 phases:
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Slow wave sleep (SWS) in which the EEG shows mainly high-voltage synchronous activity
Rapid eye movement sleep (REM) in which skeletal muscles are relaxed (inhibited) and the eyes move back and forth rapidly. Accounts for ~ 25% of sleep. |
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Hypnotic sleep differs
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SWS patterns are altered and shortened
REM sleep is depressed Total sleep time is prolonged |
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The more lipid soluble agents (higher partition coefficient) of barbituates
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usually have the more rapid onset and shorter duration
Short duration because of redistribution. |
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BARBS MOA
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Bind to GABAA receptor complex
Location is different from benzodiazepine binding site Decreases the dissociation rate of GABA from its binding site, thus increasing the duration of action of GABA at the receptor, and increasing chloride conductance. (altering the affinity) While Barbiturates have been reported to be able to mimic the action of GABA at the GABAA receptor, this is minimal, and major effects require GABA. Also inhibits excitatory glutamate AMPA receptors |
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Barbiturates
Chemistry and SAR |
Barbituric acid, which has no sedative powers is the parent compound
Exists in keto and enol forms (tautomers) Addition of various functional groups onto position 5 alters sedative/hypnotic properties Replacement of C-2 oxygen with sulfur results in the thiobarbiturates (greater lipid solubility) Addition of a phenyl group at C-5 enhances anticonvulsant activity (ex.-Phenobarbital) Addition of a methyl group to the ring N atom shortens duration of action (ex.- Methohexital |
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LONG DURATION BARBS
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Phenobarbital (Luminal) (epileptic disorders)
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INTERMEDIATE DURATION BARBS
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Pentobarbital (Nembutal)
Secobarbital (Seconal) |
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SHORT DURATION BARBS
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Methohexital (Brevital)
Thiopental (Pentothal) |
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IONIZATION OF BARBS
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Barbiturates are weak acids
Usually packaged as sodium salt, which is the basic form High pH of solution makes itself bacteriostatic Stability of solutions limited to a couple weeks after opened and exposed to air due to precipitation of acid form caused by CO2 in air altering pH of solution |
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BARBS METABOLISM
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. Potent enzyme inducers, induce their own metabolism.
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Barbiturates
Metabolism |
Most metabolized to a large extent
Primary metabolic pathway is hydroxylation to inactive metabolites Some only slowly metabolized (ex.- phenobarbital, t1/2 = 86 hrs) N-glucosylation also occurs (to a larger extent in oriental populations). Potent inducers of the hepatic microsomal enzyme system. Results in an increase metabolic rate of barbiturates as well as other drugs normally metabolized by this system (ie.- oral anticoagulants, phenytoin, TCA’s, etc.) PHASE I REACTIONS |
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Barbiturates
Use in Pregnancy |
Fetal blood levels usually well under maternal levels, but placental transfer does occur
Fetal elimination much slower than mother |
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BARBS PRIMARY USES
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Therapeutic/diagnostic aids in psychiatry
Reduction of cerebral edema following surgery, head injury or cerebral ischema. Antiepileptic use. |
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Thiopental (Pentothal)
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-ultra short acting induction 10-15secs, metabolized P450, 1/2 life 6 hours, redistribution, repeated admin can lead to increased duration of action, lowers pain threshold thus increasing sensitivity to pain, very poor skeletal muscle relaxant effects, depresses myocardium and relaxes vascualr smooth muscle--> so decreases BP
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Methohexital (Brevital)
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Similar to thiopental, but three times as potent
metabolized faster (due to less lipid solubility) mainly via P-450 oxidation loss of effect still mainly due to re-distribution recovery is faster than thiopental with multiple doses |
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INSOMNIA AGENTS
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Zaleplon (Sonata) – potency = 1
Zolpidem (Ambien) – potency = 1 Eszopiclone (Lunesta) – potency = 7X similar to Benzodiazepines in action on GABAA receptor complex bind to specific GABA receptor (alpha-1) subpopulations better and have greater effects on sleep (alpha-2 agonists anti-anxiety and anticonvulsant effects) all have relatively short half-lives (< 8 hours) thus do not interfere with next day’s activities |
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Propofol (Diprivan)
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Acts by interaction with GABAA receptor, decreasing the rate of GABA dissociation from the receptor.
Fairly selective with few perceivable effects at other receptors Very low water solubility, so prepared in emulsion vehicle. Vehicle contains soybean oil and egg lecithin use care in patients with egg allergies Reactions rare – due to proteins in egg white, not yolk Diprivan contains disodium edenate as preservative (EDTA) Generic formulation contains sodium metabisulfite and care should be observed in patients with sulfite allergies |
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Fospropofol (Lusedra)
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propofol prodrug recently approved by the FDA which is cleaved to propofol on administration by endothelial alkaline phosphatases
Water soluble with little or no pain on injection This will take a little longer than propofol |
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PROPOFOL ANESTHESIA
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Induction in 15-30 seconds, but must be given more slowly than Thiopental due to vessel irritation at injection site.
To minimize pain on injection larger veins should be used Pre-administration of 1% lidocaine also used to minimize pain co-mixing with lidocaine may increase risk of pulmonary embolism due to breaking emulsion and the formation of soybean oil droplets Awakening time faster than with other IV induction agents Less occurrance of hang-over, in fact many reports of elevated post-op mood Rapidly distributes to brain (high blood flow). Also possesses antiemetic, antipruritic, and anticonvulsant actions. |
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PROPOFOL METABOLISM
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Termination of anesthesia due to redistribution to fatty tissues and metabolism.
Hepatic and extrahepatic P-450 oxidative metabolism and phase II glucuronide and sulfate conjugation High levels of lung cell uptake but released mainly unchanged Duration of effect typically 5-10 minutes. Half life of 2-3 hours, so it does not accumulate as much as Thiopental, and can be used for maintenance by continuous infusion. Easily crosses placenta to fetus, but is rapidly metabolized by fetus. Liver and renal disease do not appear to appreciably affect elimination. Highly protein bound (95% - 99%) |
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PROPOFOL EFFECT ON VITALS
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Does not increase pain sensitivity.
Blood pressure is decreased due to decreased cardiac output and vascular resistance. Blood pressure is decreased more than seen with Thiopental by inhibition of sympathetic vasoconstriction Increased risk of bradycardia-related death, due to inhibition of cardiac sarcolemmal calcium release Depresses ventilation, with apnea reported in approximately 30% of patients. This effect may be enhanced by opioids. Does not trigger malignant hyperthermic crisis. |
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PROPOVEN
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Propoven (different vehicle formulation – more lipids, but no preservative, so short vial life) approved by FDA
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PROPOFOL SIDE EFFECTS
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bradycardia, pain, hypertriglyceridemia all attributed to lipid emulsion vehicle
allergic reactions lactic acidosis (more common with long term infusion) |
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Etomidate (Amidate)
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Structure unlike any other anesthetics.
Mechanism believed to be via GABA-activity enhancement like barbiturates and benzodiazepines. Exact site on GABAA receptors still not clear More selective for GABAA receptors than the barbiturates A weak base, it is 99% unionized at physiological pH Mixed with propylene glycol for injection. Approximately 75% protein bound Vd is large (tissue distribution) Reaches peak brain concentration within one minute following IV administration Rapid recovery due to rapid lipid redistribution and partly due to metabolism Metabolized rapidly mainly via hydrolysis of side chain ester group by plasma esterases and hepatic P-450 system |
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ETOMIDATE EFFECTS ON VITALS
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Induction as rapid as Thiopental, with emergence in 5-10 minutes.
Elimination half-life of 2-5 hours Minimal cardiovascular effects. Better choice than barbiturates or propofol for patients with cardiac instabilities Less ventilatory depression than with barbiturates or propofol Occasional apnea on rapid administration High incidence of myoclonus on rapid IV induction (>80%). If administered really fast. Depresses steroid (cortisol) synthesis in adrenals, so is not recommended for long term use. Increased risk in sepsis and hemmorrhage. |
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Dexmedetomidine (Precedex)
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a novel agent for the control of stress, anxiety and pain
classed as an alpha-2 agonist usually used in combination with agents such as propofol, opioids, and benzodiazepines when used alone, it produces sedation with the ability to rouse the patient, allowing the medical staff to communicate with the patient if needed negative feedback alpha 2 receptor |
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Dexmedetomidine (Precedex)
METABOLISM |
Vd ~ 118 liters, t1/2 ~ 2 hrs, Cl ~ 39 L/hr
Approximately 95% protein bound metabolism almost complete mainly via glucuronidation and P-450 hydroxylation dosage adjustment may be required in hepatic disease pharmacokinetics unaltered by age administered via continuous IV infusion |
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Midazolam (Versed)
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Usually used as an adjunct, but it can be used for induction (approximately 60 seconds) and maintenance.
Duration of effects approximately 15 minutes. Usually used with opioid (i.e. fentanyl) for longer durations. Synergistic and pain relief Minimal cardiovascular effects. Good amnesic. 95% plasma protein bound (similar to other benzodiazepines) |
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Ketamine (Ketalar)
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Similar to PCP (Phencyclidine).
Can be used IV or IM. Rapid induction with IV duration of approximately 15 minutes. Stimulates the cardiovascular system: increases heart rate, cardiac output, and blood pressure. Good analgesic and amnesic. Blocks glutamate excitatory NMDA receptors in CNS. Highly lipid soluble but minimal protein binding Triggers catalepsy (dissociative anesthesia), which is the appearance of being awake, even though they do not respond. Recovery phase characterized by CNS stimulation, so keep patient in quiet area. NMDA the only ones with ligand and gated receptors. |
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Ketamine (Ketalar)
METABOLISM |
N-demethylated (P450) to Norketamine, which has approximately 25% of Ketamine’s activity
Further metabolized by hydroxylation (P450) to hydroxynorketamine (inactive) Glucuronated and excreted in urine. |
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Ketamine (Ketalar)
USES |
Used for induction and maintenance.
Potentially very dangerous, especially if unprepared and poorly trained. Dangers presented with these are based on the potential of overdosing the patient and the irrevocable nature of IV administration. Comes out of IM quicker than other drugs that are given IV |
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Benzodiazepines
Pharmacokinetics |
Varying half-lives ranging from 1 hour for midazolam to more than 24 hours for diazepam.
Many metabolized via microsomal N-demethylation (diazepam), but some (oxazepam) eliminated rapidly primarily via glucuronide conjugation. Midazolam is metabolized rapidly mainly via microsomal hydroxylation. Due to liver metabolism, half-lives can be greatly altered in patients with liver disease or patients taking other drugs which induce or inhibit metabolism. Diazepam not only has a long parent half-life, but is converted into several active metabolites which also increase the period of clinical effect. Benzos are potent enzyme inducers. Decrease the half life. |
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Benzodiazepines
Mechanism of Action |
Act on specific receptor sites located at the interface of the α and γ subunits of the GABA receptor in the CNS.
Enhance the ability of GABA to bind to its receptor, thus increasing the ability of the chloride ionophore to admit more chloride ions into the cell, resulting in hyperpolarization which makes them more resistant to excitation. Receptors found almost exclusively on post-synaptic regions in the CNS, which explains their minimal effects in other areas of the body (except effects caused via CNS control). Receptor density greatest in cerebal cortex and areas associated with memory formations. Memory effects (amnesia) seen after use. GABA either on pre or post synaptic neurons. Hippocampal region responsible for memory formation lower part of the frontal cortex. NT for memory formation ACh. (usually cholinergic) Ionophoric channels need to bind at two different places to open the channel. |
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Benzodiazepines
Effects on other tissues |
Caused by action in the CNS
Mild cardiovascular effects, which are normally seen as a minor decrease in systemic blood pressure and vascular resistance. Heart rate may decrease or increase somewhat, probably reflexively. Transient apnea is a potential problem, especially with rapid IV infusion of diazepam, and respiratory support should be available. Induces relaxation of spastic skeletal muscle activity via central inhibition. |
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PRIMARY EXCITATORY AND INHIBITORY RECEPORS IN THE SPINAL CORD
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glycine – inhibitory, and aspartic acid – excitatory in the spinal cord)
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Benzodiazepines
Miscellaneous |
Crosses placenta well, and leads to fetal depression.
Not used as anesthetics, but adjunct to balanced anesthesia. Use allows decrease in dose of other anesthetics. Abuse potential relatively high, and long-acting agents (diazepam) can lead to true physical dependance. |
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BENZOS THAT READILY LOOK LIKE BENZOS
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Chlordiazepoxide (Librium) - (oral)
Clorazepate (Tranxene) - (oral) |
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Actions (Ethanol
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Locally cause dehydration of cell protoplasm (astringent).
Cooling effect on skin due to rapid evaporation. Increases cutaneous blood flow when applied topically, and is used as a counterirritant and rubifacient. This effect also partly responsible for the usefullness of alcohol rubs to lower body temperature. Injections near nerves blocks conduction by decreasing Na+ and K+ conductance (high doses required). Bactericidal effect by disruption of cell membranes. Potent CNS depressant . |
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CNS Actions (Ethanol)
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Decreases mental and physical abilities by a “top down” CNS depression, similar to other general anesthetics.
While effects are well correlated to plasma concentration, the effects are greatest of the “up-swing” of the plasma concentration curve. Small therapeutic window as a general anesthetic, and so is not used for this purpose. Raises pain threshold and causes euphoria. Depresses medullary sensing of plasma CO2 levels, and thus may affect respiration. Anticonvulsant activity, but only at concentrations that depress other CNS functions. |
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Other Actions (Ethanol)
Cardiovascular |
Relatively minor in moderate amounts, however cutaneous vasodilation via central mechanism common.
Central temperature control mechanisms depressed in high doses, which causes a strong loss of body heat, and can be potentially fatal in cold weather. High plasma concentration causes cardiac depression by both central and direct mechanisms |
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Other Actions (Ethanol)
Skeletal Muscle |
Small doses increase total work ability via central mechanisms, but larger doses decrease work and are also damaging to the muscle directly.
Similar to rhabomylysis with large doses. Real hard core alcoholics |
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Other Actions (Ethanol)
GI Tract |
Increases gastric blood flow and secretions (up to approx. 20% conc.) increases hunger.
High concentrations cause severe gastric irritation and erosion. Vomiting due to large ingestions due to local irritant effect. |
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Other Actions (Ethanol)
LIVER |
Increases synthesis of fat in liver, leading to “fatty liver” seen in alcoholics.
Cirrhosis seen in long-term abuse. Hallmark of liver cancer. Ethanol helps solubility of lipid soluble drugs. Irritation also alters how compounds are dissolved. |
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ETHANOL METABOLISM
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Ethanol is converted via alcohol dehydrogenase (a liver enzyme that contains zinc, and requires NAD as a cofactor) to acetaldehyde.
Acetaldehyde converted by another liver enzyme, aldehyde dehydrogenase, to acetic acid, which can then be used as an energy source. Methanol converted via same enzymes to formaldehyde then formic acid. Formaldehyde damages retinal cells and leads to blindness (15 ml dose of methanol). Formic acid can not be utilized by body, and build-up leads to acidosis, which can be fatal. Treatment of methanol toxicity with large doses of ethanol to ‘tie-up’ metabolizing enzymes until excreted in urine. Newer agent (fomepizole, Antizol) is an inhibitor of alcohol dehydrogenase and may replace ethanol use. |
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PANCURONIUM
METABOLISM |
-primarily renal, some biliary, may accumulate in renal failure
amino-steroidal long acting |
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ROC AND VEC
METABOLISM |
-primarily biliary, some renal
Roc no active metabolites Vec metabolite 3-desacetyl has 1/2 the activity both are amino steroidal intermediate acting |
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ATRACURIUM AND CISATRACURIUM
METABOLISM |
ester hydrolysis and Hoffman elimination
Laudanosine metabolite has CNS excitation may accumulate in renal/hepatic failure |
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INTERACTION WITH NMB
ANTIARRHYTHMIC (QUINIDINE, PROCAINAMIDE, LIDOCAINE) |
ENHANCED NMB ACTIVITY
both non-dep and dep |
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INTERACTION WITH NMB
ANTIBIOTIC |
prolonged resp depression, excessive blockade
both |
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INTERACTION WITH NMB
ANTIEPILEPTICS (CARBAMAZEPINE, FOSPHENYTOIN, PHENYTOIN) |
more rapid recovery time following NMB admin
NON DEP may need higher/more freq doses of NMB agent |
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INTERACTION WITH NMB
APROTININ (TRASYLOL, BAYER) |
prolonged NMB activity
DEPOLARIZER use lowest dose possible to achieve adequate blockade |
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INTERACTION WITH NMB
AZATHIOPRINE |
DEP- enhanced NMB activity
NON DEP- reversal of NMB activity |
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INTERACTION WITH NMB
CALCIUM CHANNEL BLOCKERS |
BOTH
enhanced NMB activity use lowest possible dose |
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INTERACTION WITH NMB
CORTICOSTEROIDS |
-NON DEP- muscle weakness, decreased NMB activity
DEP- prolonged NMB activity |
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INTERACTION WITH NMB
CYCLOPHOSPHAMIDE |
DEP- enhanced or prolonged sux induced apnea
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INTERACTION WITH NMB
DIGOXIN |
BOTH- risk of cardiac arrhythmias
specifically with sux |
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INTERACTION WITH NMB
INHALATION ANESTHETICS (ENFLURANE, ISOFLURANE) |
BOTH- enhanced NMB activity
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INTERACTION WITH NMB
LITHIUM |
BOTH- prolonged NMB activity
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INTERACTION WITH NMB
MAG SALTS |
-BOTH- enhanced NMB activity
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INTERACTION WITH NMB
REGLAN |
BOTH- prolonged NMB activity
specifically with mivacurium |
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INTERACTION WITH NMB
ORAL CONTRACEPTIVES |
-BOTH- prolonged NMB activity especially sux
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INTERACTION WITH NMB
OXYTOCIN |
BOTH- enhanced NMB activity
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INTERACTION WITH NMB
TACRINE |
DEP- prolonged NMB activity
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INTERACTION WITH NMB
TERBUTALINE |
DEP- enhanced NMB activity
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INTERACTION WITH NMB
TRICYCLIC ANTIDEPRESSENTS |
NON DEP- risk of ventricular arrhythmias
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POTENTIATION OF NMB
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NEURO DISEASE- myasthenia gravis, Eaton-Lambert syndrome
ELECTROLYTE-hypermag, hyponatremia, hypokalemia, hypocalcemia ACIDOSIS- (conditions that prolong metabolism- atypical plasma cholinesterase, renal and hepatic disease) |
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ANTAGONISM OF NMB
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NEURO DISEASE- hemiparesis or paraparesis, demyelinating lesions, peripheral neuropathies
OTHER- hypercalcemia, alkalosis, burn injury |
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INCREASED RISK FOR CARDIAC ARRHYTHMIAS OR CARDIAC ARREST WITH SUX
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ACUTE PHASE OF INJURY FOLLOWING- major burns, multiple trauma, spinal cord injury, extensive denervation of skeletal muscle, upper motor neuron injury
OTHER- hyperkalemia, dig toxicity |