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422 Cards in this Set
- Front
- Back
What are the two major types of ion channels?
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1. Voltage Gated
2. Ligand Gated |
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Where are voltage gated channels concentrated?
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They are concentrated on the axons of nerve cells.
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Voltage gated ion channels include what channels?
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They include the sodium channels responsible for action potential propagation.
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Cell bodies and dendrites also have voltage sensitive ion channels for what?
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Potassium and calcium.
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Ligand gated ion channels are also called what?
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ionotropic receptors
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Ionotropic receptors respond to what?
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Chemical neurotransmitters that bind to receptor subunits present in their macromolecular structure.
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Neuturtansmitters also bind to G protein coupled receptors. What are these called?
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Metabotropic receptors.
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Metabotropic receptors (G-Protein coupled receptors) can do what?
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Modulate volatage gated ion channels.
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What is a "Global but reversible depression of CNS function" called?
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Anesthetized state
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General Anesthesia includes what four things?
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1. Amnesia
2. Immobility 3. Inhibition of reflexes 4. Skeletal Muscle Relaxation |
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How many stages of anesthesia are there?
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Four
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Stage 1 of Anesthesia is?
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Analgeisa with or without amnesia
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Stage 2 of Anesthesia is?
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Excitement (Delirium)
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Stage 3 of Anesthesia is?
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Surgical Anesthesia
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How many planes does stage 3 of anesthesia have?
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Four
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What two ways are general anesthetics administered?
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IV and Inhalation
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What are the two types of inhaled general anesthetics?
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Nitrous Oxide and Volatile Liquids
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Can Nitrous Oxide produce stage III anesthesia on its own?
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NO!!!
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Why is it that Nitrous oxide can not produce stage three anesthesia on its own?
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Low potency
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What is the maximal safe concentration of Nitrous Oxide?
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70%
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What are the four types of Volatile Liquid Inhaled Anesthetics?
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Isoflurane, halothane, desflurane, and sevolfurane
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How are volatile liquids administered?
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They are vaporized with air; or oxygen as a carrier gas.
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There are six categories of IV general anesthetics. What are they? HINT: BBOPKM
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Barbiturates, Benzodiazepines, Opiods, Propofol, Ketamine and Misc.
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What is the method of action for the general anesthetics?
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Involves suppression of neuronal communication in critical brain areas.
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Since the MOA for general anesthetics involves suppression of neuronal communication in critical brain ares, what are the two ways this occurs?
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By either increasing Action Potential Threshold or By interfering with synaptic transmission.
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General Anesthetics bind to the ________ receptor and potentiate _______ transmission?
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GABAa
GABA |
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When GABA transmission is potentiated what does this cause to happen?
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An increase in Cl- influx, which in turn increases membrane hyperpolarization, ultimately inhibiting neuronal activity.
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What happens when you have a low concentration of a general anesthetic?
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Indirect effect on GABAa receptor
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What does this indirect effect of low concentration general anesthetics do to GABA?
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It enhances the efficacy of the endogenous GABA
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High concentrations of general anesthetics do what?
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Directly activate GABAa channels.
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What other methods of action might general anesthetics have involving K+ and Nicotinic Na+ channels?
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An increase of K+ efflux can occur which would cause hyperpolarization. There can also be a decrease in the duration of opening of nicotinic Na+.
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What three general anesthetics function by inhibiting NMDA receptors?
HINT: K,NO,X |
Ketamine, nitrous oxide and xenon.
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Potency of Inhalational general anesthetics is directly proportional to?
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Lipid Solubility.
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Increased Lipophilicity =
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Increased Potency
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The potency of an inhaled general anesthetic is measured by?
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Minimum alveolar concetration of anesthetic or the MAC
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If you have a high Oil/gas partition coefficient?
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You have a high potency.
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If you have a low MAC you have?
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A high potency due to a higher lipid solubility.
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The alveolar concentration of an anesthetic that is required to prevent a response to a standarized painful stimulus in 50% of patients.
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MAC
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MAC =
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ED50
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What is the usual effective MAC range?
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0.5-1.5 MAC
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When are MAC values lowered?
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In the elderly and hypothermia
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With inhaled anesthetic, brain anesthetic concentration is directly correlated to?
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Blood anesthetic concentration.
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During Induction:
Highly _______ (2)exert the greatest influence? |
Perfused Organs
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Highly perfused organs are?
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The brain, heart, liver, kidneys, lungs, and spleen
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During Maintenance: The rate of drug transfer is dependent on? (two things)
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Drug tissue Solubility
Blood Flow |
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What is the major route of elimination for all inhalational anesthetics?
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Lungs
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What is the most important thing regarding elimination of an inhaled anesthetic?
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Blood:Gas partition coeffecient
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Which is eliminated faster? Blood insoluble agents, or blood soluble agents.
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Blood insoluble agents are eliminated faster.
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All inhaled anesthetics ____ MAP in direct proportion to their ______?
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Decrease
Alveolar Concentration |
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What inhaled anesthetics decrease BP by decreasing CO?
HINT: H, E |
Halothane and Enflurane
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Isoflurane, desflurane, and sevoflurane do what to the cardiovascular system?
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Decrease BP and PVR
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What inhaled anesthetic decreases SA node firing leading to bradycardia?
HINT: Hal |
Halothane
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What two inhaled anesthetics cause sympathetic activation leading to tachycardia?
HINT: D, I |
Desflurane and Isoflurane
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How do inhalation anesthetics, except Nitrous Oxide, affect the respiratory system?
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They decrease tidal volume and increase respiration rate. They decrase ventilatory response to low 02 so must ventilate mechanically until breathing restored. Pooling of mucus leads to atelectasis/pneumonia. Suctioning/early ambulation are required.
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How do inhalation anesthetics affect the brain?
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They decrease metabolic rate, they increase cerebral blood flow due to a decrease in vascular resistance.
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In what brain condition should inhaled anesthetics be used with caution?
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Increased Inter-Cranial Pressure, caution also in head trauma.
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________ seen on EEG (CNS depressent effect) up to 1-1.5 MAC but higher may predispose to _______.
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Burst Firing
Seizures |
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How do inhaled anesthetics affect the kidneys?
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They decreased glomerular filtration rate and decrease renal blood flow.
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In the liver, inhaled anesthetics decreased _______ to 15-45% normal.
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Hepatic blood flow.
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This inhaled anesthetic causes liver damage at low 02 levels, and usually after repeat exposure. What is the name of this toxicity?
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Halothane
Halothane Hepatitis |
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What types of proteins are created in the process of halothane metabolism and what does this lead to?
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Trifuoroacetylated proteins are generated, this leads to antibody formation, autoimmune hepatitis which results in liver transplant.
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Sevoflurane degradation by CO2 absorbents release ___________ which causes ____________.
HINT: VE, PTN |
Vinyl Ether
Proximal Tubular Necrosis |
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What is a genetic disorder of skeletal muscle where mutations on ryanodine receptors (L-type voltage gated Ca2+ channel) or SR leads to increase in free Ca2+?
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Malignant Hyperthermia Syndrome
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In patients that this occurs in what are they receiving when this occurs?
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Muscle relaxants and inhaled anesthetics (especially halogenated).
|
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Malignant Hyperthermia involves what symptoms?
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Hyperthermia, Tachycardia, HTN, Muscle Rigidity and Contractions, and Metabolic Acidosis
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What is the suggested Rx for metabolic hyperthermia syndrome?
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Dantrolene, cooling, restore pH to 7.4
|
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How does dantrolene work against this syndrome?
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It blocks ryanodine.
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This inhaled anesthetic sensititizes the heart to catecholamines by increasing automaticity leading to cardiac arrhythmias.
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Halothane
|
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When using halothane what are two drugs you must use with extreme caution?
HINT: EPI and Cat |
Use EPI and other catechomalines with extreme caution.
|
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This drug causes seizures, especially at higher concentrations?
HINT: En |
Enflurane
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In what kind of patients should enflurane be avoided?
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Epileptics
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Nitrous oxide can decrease methionine synthase activity leading to what?
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Megaloblastic anemia.
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Intravenous anesthetics are combined with what to increase cardiovascular stability?
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Opiods
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The short acting barbiturate, Thiopental is used for ______ and ___________?
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Induction and Short Surgeries
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If you have a large dose of the short acting barbiturate thiopental, what can occur?
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Myocardial depression
|
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In what situation is thiopental, a short acting barbiturate, used for specifically in large doses?
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Brain Trauma. Due to the decrease in cerebral blood flow it can help lower blood loss.
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What are three benzodiazepenes that are used as pre-op medications?
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Diazepam, lorazepam, and midazolam
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Midazolam, a benzodiazepene, is the ______ and it is placed in a ___________ so it results in __________?
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Most common
water soluble preparation less irritation |
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What reverses the effects of Midazolam, a benzodiazepene?
HINT: Flu |
Flumazenil
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Flumazenil is a ________, that reverses ________.
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Benzodiazepene antagonist
Midazolam |
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Flumazenil has a _________ meaing that ___________.
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Short t1/2
multiple doses may be required for desired affect |
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With the opiods _____ and _____, N20 and Benzodiazepenes are used. This is especially useful in high risk patients.
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Morphine and Fentanyl
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Increased _______ and Increased _______ are used in patients undergoing cardiac surgery or if patients have cardiac problems.
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Increased doses of opiods with increased doses of Benzodiazepenes
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What is one of the complications that can occur from using increased opiods?
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Chest wall rigidity during surgery which leads to impaired breathing.
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What is a opiod agonist that reverses respiratory depression?
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Naloxone
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What opiods have a very fast induction?
HINT: Alf, Rem |
Alfentanil and remifentanil
|
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What causes remifentanil to have a very fast recover
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Remifentanil is metabolized by esterases, which leads to fast recovery
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When you give fentanyl (an opiod) with droperidol (like haldol) and N20, neuroleptanesthesia occurs. What is this?
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It is a dissociative anesthesia
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What is a drug that has a very fast onset and recovery, quicker ambulation, less nausea and vomiting, and patient feels better overall. This drug is also used in conscious sedation.
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Propofol
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Propofol causes what problems in kids?
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Acidosis, especially in kids with respiratory infections
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Etomidate is best for patients with compromised _______ function?
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cardiac
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Etomidated causes minimal _____ and _______ depression.
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CV and respiratory
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This drug is not ______, so you must use with _______?
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analgesic
opioids |
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What drug causes dissociative anesthesia, related to PCP, it is an NMDA receptor blocker so it effects glutamate and it is lipophilic so it has a very fast distribution?
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Ketamine
|
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Ketamine should be avoided in patients with ?
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Head Trauma
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Ketamine acts as a ______. It is good in _______ patients.
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Cardiac Stimulant
Increased Risk Elderly |
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Ketamine can cause Emergence Phenomenon which leads to illusions, disorientation, excitation and hallucinations in PACU. How do you combat this?
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Combine the drug with Benzodiazepenes.
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What was the first local anesthetic?
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Cocaine
|
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Local anesthetics prevent ______ from generating leading to no _____ release further leading to the prevention of nerve conduction.
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Action Potential
Neurotransmitter |
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What are the first neurons to be affected by local anesthetics?
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small, unmyelinated neurons
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MOA of Local Anesthetics are all the same.
Local anesthetics bind to the ________, decreasing _______ into the neuron, which inhibits ________ and ________ generation. |
voltage gated Na channels
Na influx depolarization action potential |
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In order to gain entrance into the neuron, the local anesthetic must be in its ______ form?
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Un-ionized form
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In order to bind to its site of action, and block the Na channel, the local anesthetic must be in its ______ form?
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Ionized
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What are the routes of administration for local anesthetics?
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Topical, Infiltration, or Regional Block
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What type of formulations should always be used with spinal and epidural anesthesia?
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Those that contain no preservatives and also those that contain vasoconstrictors
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Avoid using spinal or epidural anesthesia in patients that are on ____?
|
LMWH = Low Molecular Weight Heparin
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Local anesthetics are weak bases with pKa's between ______. Buffering the local anesthetic solution by increasing the _______ increases penetration to the site of action.
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8.0-9.0
Unionized Aspect |
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Local Blood Flow can affect the _____ of local anesthetics.
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absorption
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Vasoconstriction of the local blood vessels __ drug removal, __ duration of action, and __ systemic toxicity.
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Decreases
Increases Decreases |
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Local anesthetics are often mixed with ____ as a vasoconstrictor?
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EPI
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What conditions do you not use vasoconstrictors with local anesthetic?
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PVD, Raynauds, "end artery areas" such as fingers and toes, also spinal/epidural sites. Also, caution should be taken with patients with pre-existing cardiovascular diseases.
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The local anesthetic esters contain the suffix _____ .
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-caine
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The ester local anesthetics are? (5 of them) Hint: C, B, P(N), Ch, T
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Cocaine, Benzocaine, Procaine, Chloroprocaine, and Tetracaine
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The amide local anesthetics contain the suffix ______, plus an extra _ in the rest of their name.
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- caine
- i |
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The amide local anesthetics are?
Hint: L, M, D, B, R, P |
Lidocaine, Mepivacaine, Dibucaine, Bupivacaine, Ropivacaine, Prilocaine
|
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How are the ester local anesthetics metabolized?
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They are rapidly hydrolyzed by plasma and tissue esterases.
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A special caution with ester is that some patients have atypical plasma cholinesterase enzyme with leads to an
|
increase duration of action.
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Hydrolysis of ester type local anesthetics results in the formation of _____.
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PABA
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PABA hypersensitivity can occur in patients who are given?
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Ester type local anesthetics
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PABA can inhibit the actions of _____, therefore you should avoid using _____ on patients taking sulfonamide antibiotics.
|
Antibiotics
ester local anesthetics |
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Amide local anesthetics are metabolized via ____ and ____ by liver microsomal enzymes.
|
Dealkylation
Hydrolysis |
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If a patient has liver impairment, caution should be taken with amide local anesthetics because?
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The liver microsomal enzymes are what metabolize amide local anesthetics. Also, in the process of metabolism, active metabolites can be formed.
|
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Cocaine is isolated from?
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The leaves of the Erythroxylon coca tree.
|
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When is cocaine actually used as a local anesthetic?
|
It is used topically in eye and nose surgeries.
|
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What causes cocaine to have intrinsic vasoconstrictor properties?
|
Its ability to block NE uptake.
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Benzocaine is for _____ use only. It is poorly absorbed due to its low _______, this also means that it has low systemic toxicity.
|
Topical
water solubility |
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What is the prototype of the ester local anesthetics?
|
Procaine
|
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Procaine does not work ______.
|
Topically
|
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Procaine has a _____ onset of action, and a _____ duration of action.
|
Short
Short |
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Chloroprocaine is structurally similar to ______. Chloroprocaine is _____ potent than ______, but _____ toxic.
|
Procaine
More Procaine Less |
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What ester local anesthetic is used in obstetrics because of its short duration of action and margin of safety?
|
Chloroprocaine
|
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What drug is more potent than Procaine, but also more toxic?
|
Tetracaine
|
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Tetracaine is commonly used in _____ anesthesia. It has a ____ onset of action and a _____ duration of action.
|
Spinal
Slow Long |
|
What is the most commonly used amide local anesthetic?
|
Lidocaine
|
|
Lidocaine, apart from being used as a local anesthetic, can also be used as an ?
|
Anti-Arrhythmic
|
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Compared to procaine, lidocaine is ______ potent, ______ onset, and ______ duration of action.
|
More
Faster Longer |
|
Lidocaine works in what ways?
HINT: Routes of Administration |
Topically, infiltration, and by spinal and epidural routes of administration
|
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When lidocaine is given as an anti-arrhythmic how is it administered?
|
Via IV
|
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Mepivacaine is similar to _____, but has a ______ onset, and a _______ duration of action.
|
Lidocaine
Quicker Prolonged |
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Mepivicaine is not used _____.
|
Topically
|
|
Dibucaine is used ?
|
Topically
|
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This drug is commonly used epidurally during labor because it alleviates pain, but it does not affect the motor function of the abdominal muscles?
|
Bupivacaine
|
|
Bupivacaine can sometimes have a rare incidence of?
|
Cardiotoxicity
|
|
This drug has a decreased cardiovascular toxicity compared to Bupivacaine? This drug is also less potent than Bupivacaine, so you need a higher drug concentration.
|
Ropivacaine
|
|
This drug has a longer onset of action than lidocaine, but has a similar duration of action. IT is 40% less toxic than lidocaine.
|
Prilocaine
|
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Prilocaine is metabolized by the liver and yields _______ . Accumulation of this metabolite can lead to _______?
|
Orthotoluidine
Methemoglobinemia (Hb3+) |
|
What is the rare occasion that local anesthetics become toxic?
|
When given in very high doses and administered systemically.
|
|
CNS effects of local anesthetic toxicity include agitation, anxiety, shaking, and seizures. This is treated with?
|
IV diazepam
|
|
Systemic toxicities of local anesthetics lead to?
|
Depression: Sleepiness, respiratory depression, myocardial insufficiency, and systemic hypotension (effects due to medullary depression), Decreased cardiac conduction, pacemaker activity, and strength of contraction, hypotension due to the effects on vascular smooth muscle, and if given via the spinal epidural route, then hypotension is due to inhibition of sympathetic output.
|
|
The skeletal muscle relaxants are made up of two dissimilar drug groups, what are they?
|
Neuromuscular blockers and spasmolytic (antispasmotic) drugs
|
|
Neuromuscular blockers are used as?
|
Paralytic agents during surgery for muscle relaxation and intubation. This allows for a "lighter" general anesthesia.
|
|
Neuromuscular blockers do not enter the ______, and they act on the ________.
|
CNS
Motor end plate |
|
Most of the spasmolytic drugs act in the ______.
|
CNS
|
|
Spasmolytic drugs decrease _______ caused by neurological or moter end plate disease.
|
excessive muscle tone
|
|
Neuromuscular blockers produce blockade of the __________ causing paralysis of ________.
|
Neuromuscular junction
skeletal muscle |
|
All neuromuscular blockers are given ______.
|
IV
|
|
What is the prototype for the non-depolarizing neuromuscular blockers?
|
Tubocurarine
|
|
What is the only depolarizing neuromuscular blocker in the United States?
|
Succinylcholine
|
|
The MOA for succinylcholine, a depolarizing NMB = succinylcholine (anectine) is an ______ at the _______ receptor.
|
Agonist
Nicotinic |
|
Succinycholine, depolarizing NMB, initially causes _____ and ______. Normal sustained muscle contraction requires cycles of ______/_______.
|
Twitches
Fasciculations Depolarization/Repolarization |
|
Succinylcholine, depolarizing NMB, is given by continuous _______.
|
Infusion
|
|
Succinycholine, depolarizing NMB, causes continous depolarization "flickering" of ______ receptors. This leads to Phase I Block also known as ______.
|
Nicotinic
Flaccid paralysis |
|
Succinlycholine, depolarizing NMB, Phase I is followed by Phase II which is gradual _______, and desensitization.
|
Repolarization
|
|
What is considered a kind of secondary MOA for succinylcholine, a depolarizing NMB?
|
It can also "plug up" the Na+ channel
|
|
What is the MOA for a non depolarizing NMB?
|
They block the nicotinic receptor at the end plate.
|
|
When a non-depolarizing NMB blocks the nicotinic receptor at the end plate what happens?
|
Competitive inhibitors prevent opening of the Na channel.
|
|
Some non-depolarizing NMB cause _____ of the channel pore at ______ concentrations.
|
Blocking
Higher |
|
What is a way to overcome non-depolarizing NMB?
|
Increasing ACh in the synapse by administering AChEIs
|
|
What determines the t1/2 life for a non-depolarizing NMB?
|
The route of metabolism
|
|
If a Non-Depolarizing NMB has a short duration it is metabolized by ______.
|
Plasma Esterases
|
|
There is a caution for Non-depolarizing NMB for patients in ____ and ____ failure because these patients have low ____ levels/activity.
|
Renal and Hepatic
Esterase |
|
With non-depolarizing NMB, one breakdown product can accumulate, enter the _____, and cause ______.
|
CNS
Convulsions |
|
The short duration non-depolarizing NMB, that are metabolized by Plasma Esterases, are? Hint: 3 of them, A, C, M
|
Atracurium - can have spontaneous chemical degredation
Cistracurium (Nimbex) Mivacurium (Mivacron) |
|
What are the two intermediate duration non-depolarizing agents?
HINT: Two of them, R, and V |
Rocuronium (Zemuron)
Vecuronium (Norcuron) |
|
Rocuronium (Zemuron) and Vecuronium (Norcuron), the two intermediate duration non-depolarizing NMB, are metabolized in the _____ and excreted in the ______.
|
Liver
Bile |
|
Long duration non-depolarizing NMB, include these four drugs.
HINT: D-T, D, Pan, Pip |
D-Tubocurarine
Doxacurium (Nuromax) Pancuronium (Pavulon) Pipecuronium (Arduan) |
|
Most of the long duration non-depolarizing NMB are _____ eliminated.
|
Renally
|
|
What Non-depolarizing NMB agents have a steroid nucleus?
HINT: 2 Intermediate and 2 Long Duration = R, V, Pan, Pipe |
Rocuronium (Zemuron)
Vecuronium (Norcuron) Pancuronium (Pavulon) Pipercuronium (Arduan) |
|
There is a caution with the non-depolarizing NMB with a steroid nucleus. They can metabolize to a _______ metabolite that can accumulate over several days.
|
3-Hydroxy
|
|
Succinylcholine, a depolarizing NMB = ______ molecules attached. Very rapidly metabolized by ___________. Inactivation by diffusion away from _______. Duration is less than _____.
|
2 Ach
Plasma Cholinesterase End Plate 8 Minutes |
|
Succinylcholine, a depolarizing NMB, Phase I blockade is ?
|
Depolarizing
|
|
The succinylcholine, a depolarizing NMB, has a spreading, sustained depolarization leading to _______. This cannot be overcome by AChEIs. AChEIs actually augment the blockade.
|
Flaccid Paralysis
|
|
Phase II blockade, for Succinylcholine, a depolarizing NMB, is ________.
|
Desensitizing
|
|
Phase II blockase, for succinylcholine, a depolarizing NMB, can be overcome by?
|
AChEIs
|
|
With NMB, full respiratory paraylsis occurs so the patient must be?
|
Ventilated
|
|
Non depolarizing NMB, cause motor weakness leading to _______. Larger muscles are affected _____, recover _____. This muscle is the last of all to be affected?
|
Paralysis
later faster Diaphragm |
|
The depolarizing NMB, succinylcholine, has evident _______, paralysis occurs in the ______ leading to the _______. There is very rapid paralysis, less than ____.
|
Fasciculations
Extremities Trunk One Minute |
|
Tubocurarine, a non-depolarizing NMB, has partial autonomic ganglia blockade. This has a cardiovascular effect leading to _____ and _____
|
Hypotension
Tachycardia |
|
Succinylcholine, a depolarizing NMB, can cause what cardiovascular affects?
|
First bradycardia (stimulates vagal ganglia) and then tachycardia and hypertension (stimulates sympathetic ganglia)
|
|
What non-depolarizing NMB can cause histamine release? This can cause bronchospasm, hypotension, and excessive bronchial secretions.
|
Tubocurarine
|
|
What dangerous effect can succinylcholine, depolarizing NMB, cause? HINT: Potassium
|
Hyperkalemia, succinylcholine can release K from inside the cells. K is normally situated inside the cells.
|
|
This drug is conraindicated in patients with Burns, spinal cord injuries, peripheral nerve dysfunction, muscular dystrophy, heart failure, cardiac arrhythmias and Increased interoptic pressure - especially narrow angle glaucoma?
|
Succinylcholine
|
|
Succinylcholine and Tubocurarine, when combined with general anesthetic can cause what life threatening problem?
|
Malignant Hyperthermia
|
|
Drug interactions for NMB, that cause prolonged NMB, involve what drugs?
HINT: Antibiotics, Heart, Anesthesia |
Aminoglycoside antibiotics, antiarrhythmic agents, and inhaled anesthetics (especially isoflurane)
|
|
Reversing the non-depolarizing NMB, you use _____, because they compete with NMB.
|
AchEI (neostigmine, pyridostigmine)
|
|
With reversal of NMB, patients must _______ before leaving the O.R., and show a sufficient response to a _____ before extubation. Train of four: ____ impulses over ____ seconds.
|
breathe independently
peripheral nerve stimulator Four Two |
|
What is given in pre-reversal of NMB and why?
|
Atropine is given to counter act any negative effces of AChEIs, such as bradycardia and salivation.
|
|
Spasmolytic drugs are effective in ____ excitatory or enhancing _____ synapse actions.
|
Decreasing
Inhibitory |
|
Spasmolytic drugs affect the 1A motorneurons which are _____ neurons, that go from _____ to _____.
|
Afferent
Muscle Spinal Cord |
|
Diazepam, a benzodiazepene, augments _____ activity at ______ chloride channels.
|
GABA
GABAa |
|
Diazepam produces presynaptic inhibition of _______? What is the major problem with this?
|
1A motorneurons
Sedation |
|
Baclofen (Lioresal), a spasmolytic drug, is an _____ at _____ receptors. It Hyperpolarizes via increased ____ efflux. This can decrease sedation.
|
agonist
GABAb K+ |
|
What is a problem, and a concern, with Baclofen (Lioresal), a muscle relaxant?
|
Problem: Can increase seizures
Concern: Taper down when discontinuing the drug |
|
What is a spasmolytic drug, that is an a2 agonist, but works via imidazoline receptors? HINT: T
|
Tizanidine (Zanaflex)
|
|
Tizanidine, a spasmolytic drug, causes an increase in both ___ and ___________ in spinal cord.
|
Pre and Post synaptic inhibition
|
|
What are the problems with Tizanidine, a spasmolytic.
|
Drowsiness, hypotension, and dry mouth
|
|
Dantrolene, a spasmolytic drug, acts in ______ to decrease the release of ____ from the ____.
|
Skeletal muscle
Ca Sarcoplasmic Reticulum |
|
Botulinum toxin (Botox), used sometimes as a spasmolytic drug, types __, ___, and ___, prevent release of ______ vesicles. The effects of these injections can last up to ____ months.
|
A,B, and F
Cholinergic Six |
|
What is the prototype for acute local muscle spasm?
|
Cyclobenzaprine (Flexaril)
|
|
Acute local muscle spasm drugs, such as cyclobenzaprine (flexaril), are ____ that act in the brain stem/cord. They have ____ and _____ actions. These drugs are similar to ______.
|
Sedatives
Sedative and Antimuscarinic Tricyclic Antidepressants |
|
What is the most important class of sedative hypnotics and anxiolytics?
|
Benzodiazepines
|
|
Benzodiazepenes can also be used for the treatment of _____ and _____?
|
Seizures and Anxiety
|
|
What is the mechanism of action for benzodiazapenes and Barbiturates?
|
They potentiate the action of GABA at GABAa receptors.
|
|
BDZs bind specifically to their own recognition site on the ______ receptor/Cl- ______ complex.
|
GABAa
Ionophore |
|
BDZs bind specifically to their own recognition site on the GABAa receptor/Cl-ionophore complex. This leads to an increase in the ________ of Cl- channel opening (increased Cl- influx) by promoting the binding of _______
|
Frequency
GABA |
|
Increased GABA binding = increased ______ influx = _______ leading to increased inhibitory transmission. GABAa receptor has __ subunits from __ classes.
|
Cl-
Hyperpolarization 5 8 |
|
You need a minimum of alpha-2, Beta-2, and gamma subunites for what?
|
So chloride channels can function.
|
|
BDZ drugs in the brain are classified as either ?
|
BZ1 or BZ2
|
|
Zalepon and Zolpidem, newer drugs, not BDZs, they are a part of the Misc. class, they bind to what selectively?
|
BZ1
|
|
Barbiturates prolong the ______ of opening of the ___ channel by binding to their specific site on the _____ receptor.
|
Duration
Cl- GABAa |
|
Barbiturates at increased concentration can block _____ receptors and _____ channels.
|
Glutamate
Na+ |
|
What is a major inhibitor NT in the brain? HINT: G
|
GABA
|
|
GABA is the boss. It controls the __ channel?
|
Cl-
|
|
BDZs are ineffective without ____ present?
|
GABA
|
|
BDZs increase the ______ of channel opening?
|
Frequency
|
|
Barbiturates increase the _______ of openness.
|
Duration
|
|
Advantages of BDZs:
Relatively high __ Low incidence of ___ Slow elimination, active metabolites lead to long _____ __ _____, and better compliance Low risk of ________, minor withdrawal symptoms. |
TI
DDIs Duration of Action dependence |
|
Disadvantages of BDZs:
__________ dependence ______ metabolites Amnesia Cost Additive ___ depression |
Psychological
Active CNS |
|
Absorption of BDZs:
P.O. is _______ IM absorption of BDZ is ______ |
Variable
Erratic |
|
All BDZs cross the _____?
|
Placenta
|
|
Metabolism for BDZs?
|
Hepatic, extensive metabolism. No induction of liver microsomal enzymes.
|
|
Which BDZ has the longest t1/2?
HINT: D |
Diazepam (20-90) hours
|
|
What BDZ has the shortest t1/2?
HINT: T |
Triazolam (1-5) hours
|
|
Due to its long t1/2, Diazepam, a BDZ, should not be given to ?
|
The elderly and liver patients
|
|
Many BDZ phase I metabolites are active: Some metabolites have longer ___ than parent.
|
t1/2
|
|
There are nine BDZ, what is the most common suffix, what are the three BDZs that don't have this suffix named?
|
-epam, Triazolam, Alprazolam, Chlordiazepoxide
|
|
Barbiturates are given orally for _______ use?
|
Hypnotic
|
|
IV administration of barbiturates is given for control of __________ or to induce ________?
|
Seizures
Anesthesia |
|
What is the one barbiturate that is partially excreted unchanged?
|
Phenobarbital
|
|
What are the ultra-short acting barbiturates? HINT: T, Meth
|
Thiopental
Methohexital |
|
What are the short acting 1-4 hour barbiturates? HINT: S, H, Pent
|
Secobarbital
Hexobarbital Pentobarbital |
|
What are the intermediate acting 6-8 hour barbiturates? HINT: Amo, But
|
Amobarbital
Butabarbital |
|
What are the long acting 10-12 hour barbiturates?
HINT: Bar, Phe, Metha |
Barbital
Phenobarbital Methabarbital |
|
In the elderly and patients with liver disease two things can happen, what are they?
|
Drug Accumulation
CNS depression |
|
In chronic barbiturate users:
Induction of liver microsomal enzymes leads to an increase in _______ metabolism, and development of _______. |
Hepatic
Tolerance |
|
Barbiturate elimination is via the ______, much drug may be reabsorbed from the _____ ______.
|
Kidney
Renal Tubule |
|
You can alkalinate the urine of a patient to enhance elimination of barbiturates by using what?
|
NaHCO3
|
|
What is the only barbiturate that doesn't accumulate in the body when given daily? HINT: HEX
|
Hexobarbital
|
|
Sedatives are ____ dependent?
|
Dose
|
|
Pharmalogical Effects: Hypnosis:
Essentially no psychomotor ______, good if _____ ______. These produce _____ at a somewhat higher dose. Patients fall asleep faster. _ ___ sleep for insomniacs, tolerance with over two weeks use unless you are treating _____. |
Depression
giving everyday Sleep Decreased REM Anxiety |
|
What two barbiturates are used for anesthesia, are highly lipophilic and are short acting due to rapid redistribution? HINT: Thi, Met
|
Thiophental
Methohexital |
|
What two BDZs act as anesthesia adjuncts, have longer lasting effects, and are reversed with flumazenil? HINT: D, M
|
Diazepam
Midazolam |
|
Most of the sedative/hypnotic drugs can decrease the spread of _______ activity in the brain?
|
Seizure
|
|
What BDZs are good for treating seizures? HINT: 4 of them, N, L, Cl, and D
|
Nitrazepam
Lorazepam Clonazepam Diazepam |
|
What two barbiturates are good in treating seizures? HINT: P, Meth
|
Phenobarbital
Methabarbital |
|
What is a prodrug of phenobarbital, a barbiturate?
|
Methabarbital
|
|
What drugs in combination are good for muscle relaxation? HINT: Car, Benz
|
Carbamates
BDZs |
|
What is the method of action for the combination of Carbamates and BDZs?
|
Decrease neuronal transmission, believe to inhibit 1A activity
|
|
What drugs are primarily responsible for overdose deaths in the sedative-hypnotic/anxiolytic drugs?
|
Barbiturates, due to respiratory arrest. This is due to effects on the medullary respiratory center.
|
|
What problems can result cardiovascular from the sedative-hypnotic/anxiolytic drugs?
|
Hypovolemia, CHF, and decreased cardiac contractility
|
|
______ is common with both BZDs and Barbiturates? You can increase dose if necessary.
|
Tolerance
|
|
Cross tolerance with other sedative/hypnotic drugs can occur, also can occur with ____.
|
ETOH
|
|
Cause of tolerance in these drugs is unknown?
|
Barbiturates
|
|
Abrupt D/C, of sedative/hypnotic drugs, leads to generalized ____ withdrawal symptoms. These withdrawal symptoms may include what?
|
CNS
REM rebound, insomnia, agitation, excitation, tremulousness, weakness, delierium, high risk of seizure and death. |
|
What is one of the most important reasons that you have to withdrawal a patient slowly from sedative/hypnotic drugs?
|
The high risk of seizures.
|
|
What are the four newer sedative-hypnotic drugs?
HINT: Bus, Zol, Zal, Esz |
Buspirone (Buspar)
Zolpidem (Ambien) Zaleplon (Sonata) Eszopiclone (Lunesta) |
|
What is Buspirone used for?
|
Anti-Anxiety
|
|
Buspirone has no strong sedative effets, it is not hypnotic, anticonvulsant, or a muscle relaxant. it is a partial agonist at _____ receptors. It has no effect on ___ or ___ binding sites. it is not useful in ____ _____.
|
5HT1a
GABA BDZ Panic Attacks |
|
Zolpidam (Ambien), is not structurally related to ___.
|
BDZs
|
|
Zolpidem (Ambien) is a hypnotic (___-________) that facilitates ____ inhibition.
|
BZ1-selective
GABA |
|
Zolpidem (Ambien) is used for the treatment of ______. it decreases ____ sleep. It is not a muscle relaxant or an anticonvulsant. Respiratory depression is seen with an increased dose, especially with ____?
|
Insomnia
REM ETOH |
|
Zolepidem (Ambien) is less likely to produce tolerance than BDZs, you have to decrease the dose for _____, _______, and patients taking _______.
|
Elderly
Liver Disease Cimetidine |
|
Zaleplon (Sonata) is like _____ but has a t1/2 of _______. it is rapidly metabolized by _____ _____ and ______.
|
Ambien
1 Hour Aldehyde Oxidase CYP450 |
|
Zaleplon (Sonata) decreases _____ _____, which makes it good for patients with difficulty _____ _____, but may not be useful in maintaining _____.
|
Sleep latency
Falling Asleep Sleep |
|
Eszopiclone (Lunesta) is the newest non-___ hypnotic believed to act at the ___-___ receptor.
|
BDZ
GABA-BDZ |
|
Eszopiclone (Lunesta) has a rapid onset (peak levels _ __ after dose) and a t1/2 of _ __.
|
1 hr
6 hrs |
|
Eszopiclone (Lunesta) is used for the treatment of ______, and its pharmalogial effects and side-effects are similar to ____.
|
Insomnia
BDZs |
|
Older, Hardly ever used drugs:
Alcohols: Chloral hydrate (Noctec): Is metabolized by the ____ to _________ ____ (a toxic metabolite that accumulates) |
Liver
Trichloracetic Acid |
|
Piperidinediones:
Glutethimide (Doriden): Now a schedule II drug due to _______/________ |
High abuse/addiction potential
|
|
What are the carbamates?
|
Meprobamate (Miltown, Equanil)
|
|
What are the most commonly used drugs for anxiety states?
|
BDZ of intermediate/long t1/2
|
|
When diagnosing anxiety you have to determine if anxiety state is _______ or ______.
|
Secondary
Situational |
|
What is a good drug for panic/phobic attacks? HINT: A(X)
|
Alprazolam (Xanax)
|
|
Buspirone is a great drug for anxiety, but it takes what? And it is not good for what?
|
It takes a week for the effect to begin.
It is not good for panic attacks. |
|
when treating anxiety you have to use ____ doses for ____ periods. Caution patients about addictive effects with ____, and other _____ ____, ex. antihistamines.
|
Low
Short Alcohol Sedative Drugs |
|
What drugs are best for sleep disorders, and what do you have to do on D/C? HINT: Est, Tri, Zol, Zal
|
BDZs with short t1/2 estazolam (pro-som), triazolam (halcion), Zolpidem (ambien) and zelplon (sonata)
Taper drugs on D/C or pt. can get rebound insomnia. |
|
What is a barbiturate, used as a pre-anesthetic agent?
|
Thiopental
|
|
What two BDZs are used as components of anesthetic mixtures?
|
Diazepam (Valium), Midazolam (Versed)
|
|
What are two drugs, BDZ and Barbiturate, used as anticonvulsants?
|
Clonazepam (Klonopin), Phenobarbital
|
|
Diazepam lorazepm (Ativan) is used for ____ _______.
|
Status Epilepticus
|
|
Diazepam et al. can be used as?
|
Muscle relaxants.
|
|
Chlordiazepoxide (Librium), diazepam can be used for ______ ________/________.
|
Alcohol withrdawal/detoxification
|
|
Flumazenil (Romazicon) is a competitve antagonist of what?
|
BDZs and Zolpidem
|
|
Decrease doses of hypnotic/sedatives in what patients?
|
Cardiovascular
Respiratory Liver Disease Sleep Apnea |
|
Higher doses of hypnotic/sedatives can cause what?
|
Lethargy, drunkeness, and behavioral problems (aggression)
|
|
What is a major problem with Flumazenil if given to patients who are long term users of BZDs, and have developed a dependence on BZDs?
|
It will precipitate withdrawal syndrome.
|
|
Is there a direct antidote for barbiturates?
|
NO!
|
|
What is the DSM-IV Criteria for diagnosing depression?
|
5 or more symptoms for at least 2 weeks and represent a change from previous functioning.
|
|
How long does it take for improvement to be seen with tricyclic antidepressants or MAOIs?
|
Even they they act fairly quickly, it takes like 2-3 weeks for these drugs to show signs of clinical improvement.
|
|
What are the four classes of anti-depressants?
|
Tricyclic antidepressants
Heterocyclics: 2nd and 3rd Gen. SSRIs MAOIs |
|
All four classes of the antidepressants ptentiate the central action of __, __ or both?
|
NE
5-HT = Seratonin |
|
What types of antidepressants have three rings and a similar strucure as phenothiazines (antipsychotics)?
|
Tricyclic Antidepressants
|
|
What are the two prototypes of tricyclic antidepressants?
HINT: IMI, AMI |
Imipramine (IMI; Tofranil)
Amitryptiline (AMI; Elavil) |
|
Imipramine and Amitriptyline, tricyclic antidepressants, are second favorite drugs to use compared to what other type of antidepressant?
|
2nd Favorite to SSRIs
|
|
Tricyclic antidepressants, MOA, block the re-uptake of __ and ___ by presynaptic nerve terminals. This increases __ and ___ available to interact with post synaptic receptors.
|
NE
5-HT NE 5-HT |
|
What are one of the dangers when using TCAs compared to SSRIs?
|
TCAs are very toxic and can be used successfully to perform suicide. If concerned for a patient it is best to give them a week's worth of an SSRI and then re-evaluate the patient.
|
|
TCAs are well absorbed __, they have widespread distribution and are highly bound to plasma proteins.
|
PO
|
|
TCAs have long half lives and can be problematic in overdose. They are highly toxic at higher blood levels. An example of this is ______ that has a t1/2 of ____.
|
Protriptyline
80 Hours |
|
TCAs are metabolized via ______ (demethylation), then glucuronidation. Many have active _______.
|
CYP450
Metabolites |
|
The CNS effects of TCAs:
In _________ individuals, feelings of dysphoria, anxiety and sedation, and difficulty concentrating and thinking. ____ ________ are corrected, and some _____ can be experienced. |
Non Depressed
Sleep Disturbances Sedation |
|
Dry mouth, blurred vision, constipation, and urinary retention (due to blockade of muscarinic cholinergic receptors) are the results of what types of effects caused by TCAs?
|
Anticholinergic Effects
|
|
TCAs can cause what kind of cardiovascular effects?
|
Postural (orthostatic) Hypotension (due to peripheral a blockade)
Tachycardia (due to cardiac muscarinic receptor blockade and inhibition of NE reuptake) |
|
What type of serious toxicity can occur because of TCAs, and should be avoided in such patients?
|
Cardiotoxicity
Cardiac patients |
|
TCAs can also cause excessive sweating, weight gain, transition to manic excitement, can precipatate glaucoma, esp. in elderly with ____ _____ _____.
|
Narrow Angle Glaucoma
|
|
TCA is a common drug used in suicide attempts. It can cause SEVERE ________ _____.
|
Anticholinergic effects
|
|
What is the treatment for overdose of TCAs
|
Gastric lavage, activated charcoal, NaHCO3, diazepam and/or physostigmine (AChEI)
|
|
What are a few other indications for the use of TCAs?
|
Enuresis
Agorophobia OCD Neurogenic Pain |
|
What drug must you never use with TCAs?
|
MAOIs, this leads to hyperpyrexia, convulsions, and death. Also Seratonin Syndrome
|
|
What syndrome, a rare but fatal drug interaction, is due to excessive 5-HT and results in HTN, Tachycardia, Hyperthermia, and Myoclonus
|
Serotonin Syndrome
|
|
Is there a specific antidote for Serotonin Syndrome?
|
No
|
|
What is the only treatment for serotonin syndrome?
|
Supportive treatment and discontinuing precipitating drugs. May also give cyproheptadine. Cyproheptadine is an antihistamine that blocks some serotonin receptors. BDZs can help control symptoms.
|
|
What are the second generation Heterocyclics or atypical antidepressants. HINT: Amo, Mapro, Traz, Bupro
|
Amoxapine (Asendin):NE reuptake blocker
Maprotiline (Ludiomil):NE reuptake blocker Trazodone (Desyrel):5-HT reuptake blocker Bupropion (Wellbutrin):??? |
|
What is Trazodone (Desyrel), a second generation heterocyclic/atypical antidepressant is used for what by exploiting its side effect?
|
It is used for insomnia, due to the fact that it causes drowsiness.
|
|
What are the third generation Heterocyclic/Atypical antidepressants?
HINT: Ven, Mir, Nefaz |
Venlafaxine (Effexor): Blocks reuptake both of NE and 5-HT, but 5-HT more
Mirtazapine (Remerol):5-HT reuptake blocker plus it increases amine release (a2 blocker) Nefazodone (Serzone):5-HT reuptake blocker |
|
Amoxapine (Asendin), a second generation heterocyclic antidepressant, has a __ antagonist effect which means it has a _________ effect?
|
DA = Dopamine
Antipsychotic |
|
Amoxapine (Asendin), a second generation heterocyclic antidepressant, can cause what types of symptoms?
|
Akathisia, parkinsonism, tardive dyskinesia, and amenorrhea-galactorrhea syndrome can occur.
|
|
Maprotiline (Ludiomil), a second generation heterocyclic antidepressant, is a strong __ reptake blocker. It causes decreased sedation, antimuscarinic effects vs. older TCAs.
|
NE
|
|
Trazodone (Desyrel), a second generation heterocyclic antidepressant, is a selective blocker of ________ uptake with only weak effects on catecholamine uptake. It is a good hypnotic but has a side effect in men which is _______. This drug may be best given to women
|
Serotonin
Priaprism |
|
Bupropion (Wellbutrin, or Zyban), a second generation heterocyclic antidepressant. What is Wellbutrin used for? What is Zyban used for? What is there a high risk of when using this drug, especially in increased doses?
|
Wellbutrin = Depression tx
Zyban = Smoking tx Seizures |
|
Nefazodone (Serzone), a third generation heterocyclic antidepressant, Is like trazodone but less sedating. There are fewer _____ _____ _____ vs. other SSRIs, but this drug is a ____ inhibitor so there are a lot of DDIs.
|
Sexual side effects
CYP450 |
|
Venlafaxine, a third generation heterocyclic antidepressant, is like ____ at low doses. At higher doses it can _ pulse, and BP. So it is sympathomimetic.
|
SSRIs
Increase |
|
Mirtazapine (Remerol), a third generation heterocyclic antidepressant, has strong __________ effects: It is more sedating than other heterocyclics. It can cause what physical change?
|
antihistamine
weight gain |
|
SSRIs = She flew plains to central florida every day.
|
She = Sertraline (Zoloft)
Flew = Fluoxetine (Prozac) Planes = Paroxetine (Paxil) to Central = Citalopram (Celexa) Florida = Flovoxamine (Luvox) Every = Escitalopram (Lexapro) Day = Duloxetine (Cymbalta) = an SNRI |
|
What was the first SSRI? It had minimal autonomic toxicity.
|
Fluoxetine (Prozac)
|
|
SSRIs have fewer side effects than ___, and ________?
|
TCAs
Heterocyclics |
|
Fluoxetine (prozac), an SSRI, has a t1/2 of ______, and also has _____ metabolites. Fluoxetine is a ______ inhibitor causing many DDIs.
|
2-9 days
Active CYP450 |
|
What are other indications for SSRI?
HINT: PA, SP, Bul, WL |
Panic Attacks
Social Phobias Bulimia Weight Loss |
|
Adverse reactions and DDIs of SSRIs include nausea, decreased libido, sexual dysfunction, Seratonin syndrome with ____? This combination is a deadly one.
|
MAOIs
|
|
SSRIs are very safe in comparison to ___ and ____, it is the drug of choice for ________.
|
TCA
MAOIs Depression |
|
MAOIs = TIP
|
Tranylcypromine (Parnate)
Isocarboxazid (Marplan) Phenelzine (Nardil) |
|
All of the MAOIs have a long duration of action. What is the DOA for Tranylcypromine, Isocarboxazid, and Phenelzine?
|
7 days
2-3 weeks 2-3 weeks |
|
MAOIs are irreversible ______.
|
Inhibitors
|
|
All of the MAOIs have ________ effects.
|
Sympathomimetic
|
|
The MOA for MAOIs is that they block _______ ________ of ________ and 5-HT by MAO (A and B isoforms; non-selective)
|
Oxidative Deanimation
Catecholamines |
|
Type A MAOIs typically block reuptake of what three things?
|
NE, 5-HT, Tyramine
|
|
Type B MAOIs typically block reuptake of what?
|
Dopamine
|
|
What type of MAOI, A or B, is known for having an antidepressant effect?
|
MAOa, Type A
|
|
Inhibition of MAOa, prevents _______ of NE, 5HT in neuronal cytoplasm which leads to an _ in molecules surviving to enter vesicles leading to _ molecules being released into the synapse
|
degradation
increase increase |
|
Adverse reactions of MAOIs
|
Postural hypotension
Liver toxicity DDIs with TCA and SSRIs which can cause Serotonin syndrome |
|
What is something that must be done in order to avoid problems with TCA, SSRI or Meperidine?
|
You have to allow for at least a 2 week wash out period. If this is disregarded death can result.
|
|
MAOIs can cause dangerous drug-food interactions. What specific problem can result?
|
Tyramine hypertensive crisis
|
|
PTs on MAOIs should avoid eating what foods?
|
Aged cheeses, red wine, beer, pickled herring, chicken liver, snails, yeast, chocolate, coffee, canned figs, fava beans, avocados and bananas
|
|
With this type of seizure the patient doesn't lose consciousness when the seizure starts.
|
Partial Seizures
|
|
What type of seizures occur when a patient loses consciousness instantaneously at the start of the seizure?
|
Generalized Seizures
|
|
Simple Partial Seizures, Complex Partial Seizures, and Partial Seizures secondarily generalized are examples of what type of seizures?
|
Partial Seizures
|
|
The etiology of seizures is usually ______. Although, seizures can be considered to be ______ due to channelopathies.
|
Idiopathic
Genetic |
|
Causes of seizures can stem from ______ _______ _____ : Head trauma (acute), or CNS infections/tumors. Post Traumatic Epilepsy can occur after ____ years. Neurochemical/Metabolic disorders can cause epilepsy, such as ____ ____ ____. Also _________ diseases.
|
Elevated Intercranial Pressure
3-5 years Low Blood Sugar Neurogenitive |
|
SEIZURE MECHANISMS:
"____ ____" by neurons occurs. An influx of _____ causes an opening of voltage dependent __ channels. There are bursts of action potentials. This causes a hypersynchronization and recruitment of neighboring ______. |
Burst Firing
Ca Na Neurons |
|
The key to preventing seizures is to prevent ________.
|
Hypersynchronization
|
|
Primary generalized seizures start in the _____ and then spread out.
|
Thalamus
|
|
Partial Seizures:
Pt is not _______, at least at outset. Localized onset that is determined by symptoms or EEG. The focus is in the brain; often the temporal lobe. It may spread or not. |
Unconscious
|
|
What are the three types of partial seizures?
|
Simple Partial
Complex Partial Partial with secondary generalization |
|
Simple partial seizures are characterized by?
|
Patient remains conscious, has sensory, autonomic, motor or psychic symptoms.
|
|
Complex partial seizures are characterized by?
|
Patient is conscious initially, may become confused. Motor symptoms start regionally, may spread unilaterally or bilaterally. Automatisms and Aura.
|
|
What is Aura?
|
Smelling something, bright flashes, etc. This gives a patient an indication to find a safe place to lay down.
|
|
Generalized Seizures
|
Generalized Tonic-Clonic (Grand Mal)
Absence Seizures (Petit Mal) Lennox-Gastaut Syndrome (variant absence) Myoclonic Seizures Atonic Seizures Unclasssified Infantile Spasms |
|
GTC: Gran Mal is characterized by?
|
Ca 2+ channel blockers, tonic = rigid, clonic = jerking motions; urinary incontinence.
|
|
Characteristics of Absence Seizure (Petit Mal)?
|
Brief 10-45 seconds, with a loss of conscious. Staring, pause in converation. Minor motor symptoms. More common in children. Characteristic 2.5-3.5 Hz spike and wave pattern on EEG. These are seen a lot in the elderly.
|
|
Lennox-Gastaut Syndrome is characterized by?
|
Triad of seizure types - GTC, atonic and absence. Slow wave on EEG, Poor prognosis: due to brain abnormality. This is usually seen with children who have brain malformations.
|
|
Myoclonic Seizures are characterized by?
|
Jerking (single or repetive), Often seen in combination with other seizure types. Early Adolescence (JME), In AM, good prognosis with drugs.
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Atonic seizures are characterized by what?
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Sudden loss of postural tone. Dropping/falling down. Dangerous: Head injury/wear helmets.
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Status Epilepticus is characterized by?
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Motor or "absence continuing", medical emergency, antiseizure drugs include anesthetics and ventilator.
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AEDs are usually taken for ____. Thus toxicity and DDIs are a major concern.
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Years
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AED MOAs = Repress repetitive firing in _____ ___, or block the _____ of abnormal electrical activity to adjacent neurons.
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epileptic foci
spread |
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Phenytoin (Dipehnylhydantoin; Dilantin) Very effective for ______ and _____. MOA = Voltage-dependent __channel blocker. Blocks high frequency repetitive firing by stablizing the inactive state of the Na channel. Does not block normal firing.
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Partial
GTC Ca |
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Phenytoin PK is _____! Zero order elimination in the therapeutic range. It is non-linear, oral bioavailability variable, undergoes ___-____ metabolism, 97-98% _____ bound.
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Horrid
First-Pass Protein |
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Phenytoin has DDIs with drugs that compete for ___ ____ binding sites.
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Plasma Protein
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Phenytoin is metabolized by CYP___ and ___, so inducers therof cause increased elimination and therapeutic failure. Inhibitors thereof cause slowing of elimination and toxicity.
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2C9
3A4 |
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The adverse reactions of Phenytoin include ______, ataxia, _______ hyperplasia. Idiosyncratic reactions include rash, lymphadenopathy, and in rare cases agranulocytosis.
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Diplopia
gingival |
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What is a water soluble pro-drug of Phenytoin? It is expensive but worth it.
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Fosphenytoin (Cerebyx)
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Carbamazepine (CBZ; Tegretol) is very effective for _____ and ______ seizures?
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Partial
Generalized TC |
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Carbamazepine (CBZ; Tegretol) blocks voltage dependent __ channels. It is an inducer of CYP___. It causes many drug interactions. It is also used for trigeminal neuralgia and bipolar disorder
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Na
3A4 |
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The adverse reactions of Carbamazepine (CBZ; Tegretol) includes Diplopia, _____, idiosyncratic agranulocytosis, and _____ anemia.
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Ataxia
Aplastic |
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Oxcarbazine (Tileptal), is similar to _____, but less ____.
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Carbamazepine
Potent |
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Oxcarbazine (Trileptal) blocks voltage dependent __ channels. It is safer and has fewer idiosyncratic reations. It has less CYP___ induction.
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Na
450 |
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This is the oldest anti-epileptic drug; it is effective but highly sedative?
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Phenobarbital (Pb)
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Phenobarbital is a _____ enhancer.
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GABA
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What seizures might be worsened by the use of Phenobarbital?
HINT: A, A |
Absence and Atonic
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What anti-epileptic drug is metabolically converted to phenobarbital? This drug has a voltage dependent __ channel blockade.
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Primidone
Na |
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Diazepam (Valium), is used for ____ _____ rectally.
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Status Epilepticus
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Lorazepam (Ativan) is used for ____ ____ and has a longer duration than ______.
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Status Epilepticus
Diazepam |
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What benzodiazepam is useful in combating absence and myoclonic seizures? It is potent and has a long acting effect. Although it can be sedative.
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Clonazepam
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Clorazepate dipotassium (Tranxene) has an adjunctive use for complex _____ seizures.
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Partial
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Lamotrigine (Lamictal) is for ____, ____ and ______ seizures.
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Partial
Absence Myoclonic |
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Lamotrigine (Lamictal) blocks voltage dependant __ channels. It may act on Ca channels. The ARs are the usual CNS effects that include what?
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Na
Ataxia, Droginess |
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Lamotrigine can cause rashes, especially in ______.
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Children
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Topirimate (Topamax) has _ possible MOAs.
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3
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Topirimate (Topamax) is bested for partial and GTC seizures, as well as ______ and _____-_____.
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Absence
Lennox-Gastaut |
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What are the three MOAs for Topirimate (Topamax)?
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Blocks voltage dependent Na channels
May enhance GABA action Decreased effect of Kainate (excitatory amino acid analog) on AMPA receptor. |
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What are the ARs for Topiramate (Topamax)?
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The usual CNS effects, plus nephrolithiasis.
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Zonisamide (Zonegran), is a sulfonamide. This means that there is a danger of this causing a ____ that could lead to _____-______ syndrome
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Rash
Steven's-Johnson's |
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What is Zonisamide (Zonegran) used for?
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Partial and GTC seizures, myoclonic and infantile spasms
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What is the MOA for Zonisamide (Zonegran)?
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Blocks voltage dependent Na channels.
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Levetiracetam (Keppra) has an unknown MOA. It is an adjunct for ____ seizures. It is not metabolized by CYP___, so it means there are fewer DDIs with its use.
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Partial
450 |
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Felbamate (Felbatrol), is a very ____ drug.
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risky
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Felbamate is toxic and can cause ___ _____. It is reserved for refractory cases and has restricted prescribing.
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aplastic anemia.
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Gabapentin (Neurontin), considered an ___ __ ___ is an amino acid like GABA itself. Its MOA is unknown. It is a adjunctive drug for ___ and ___ seizures, it is also used for ______ pain. It has minor side effects that include sleepiness, dizziness and ataxia.
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Add on Drug
Partial and GTC Neuropathic |
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Tiagabine (Gabatril) is a _____ uptake inhibitor. It is adjunctive for ____ seizures. It has minor ARs and idiosynycratic rash.
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GABA
Partial |
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Vigabatrin (Sabril), is an irreversible ___-_ inhibitor. It is for ____ seizures. It has renal elimination which means that it less likely to have ___. It can cause drowsiness, etx. psychosis.
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GABA-T
Partial DDIs |
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What is a major AR of Vigabatrin (Sabril)?
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It can cause irreversible visual field damage.
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Who should you never give Vigabatrin to?
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Someone who is a Psych patient.
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Ethosuximide (Zarontin) is the DOC for what kind of seizures?
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Absence
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What is the MOA for Ethosuximide (Zarontin)?
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It decreases T-currents (calcium); pacemaker in thalamus
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What is a DDI for Ethosuximide (Zarontin)?
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Valproate inhibits ethosuximide metabolism
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ARs for Ethosuximide (Zarontin) include GI pain, the usual rash, and in rare cases ____-_____ ______.
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Steven's-Johnson's Syndrome
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Valproic acid/Valproate (Depakene; Depakote [SR]) is the DOC for _____ in combination, ___, and ______ seizures.
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Absence
GTC Myoclonic |
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What is the MOA for Valproic acid/Valproate?
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It isn't fully known but it may be a calcium channel blockade.
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The DDI's for Valproic acid/Valproate include what?
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it inhibits metabolism of PHT, CBZ, PB, LTG, also displaces PHT from plasma proteins.
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The ARs of Valproic acid/Valproate are usual, plus idiosyncratic ______.
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Hepatotoxicity.
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The formation of toxic metabolites occur, you have to monitor the LFTs of this anti-epileptic drug. The rule of thumb for administering this drug is "start low, go slow".
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Valproic acid/Valproate.
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Valproic acid/Valproate can cause what tetratogenic problem?
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Fetal Hydration Syndrome
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What are the other three treatments for epilepsy?
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Ketogenic Diet
Surgery Vagal Nerve Stimulation. |