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35 Cards in this Set
- Front
- Back
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Excitatory Pathway Potential |
Influx of Ca+ and Na+ to depolarize the cell |
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Inhibitory Pathway Potential |
Influx of anions Cl- to hyperpolarize the cell |
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Ionotropic receptors |
Ligand binding opens the connected channel directly, fast, short duration of action (milliseconds) |
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Metabotropic receptors |
G protein coupled receptors that use second messenger to open channel, slower bc more steps, longer duration (seconds-minutes) |
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Neurotransmitters Amino Acids |
Glutamate-excitatory GABA-inhibitory Glycine |
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Glutamate |
Excitatory - released by Ca+ exocytosis - binds to glutaminergic receptors - increases Ca+ in post synaptic cell - cleared from synaptic cleft by glutamate transporters into glial cells (modified to glutamine) - transported back to nerve cell and converted to glutamate |
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GABA/Glycine |
Inhibitory - released from vesicles - bind to pentameric receptors - GABA preserved through reuptake mechanisms |
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GABA MOA |
CNS - interacts w/ receptors in cerebral cortex, Promotes action of GABA - Increases conductance of membranes to Cl- ions, hyperpolarizes cell, Increases affinity of inhibitory neurotransmitters (IPSP), Need to be lipid soluble to be absorbed in BBB. |
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BZD's Sedative Effect |
Alpha-1 subunit of GABA (most abundant) |
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BZD's Anxiolytic effect |
Alpha-2 subunit |
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Characteristics of BZD's |
Synergistic effect - increases GABA effect No analgesic properties Low toxicity w/ built in ceiling effect Highly lipid soluble and bound to plasma proteins |
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Characteristics of BZD Ring |
Benzene Ring 7 member diazepine ring - potency and biotransformation are effected with changes to this ring |
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Benzos Kinetics - ADME |
A- orally and parenterally D- lipid soluble rapid penetration BBB M- Phase 1 oxidation in liver (3A4 metabolism), Phase 2 glucuronidation E- eliminated in urine |
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Safety of Benzos |
Minimal resp depression/cardiac depression when admin alone, Ability to antagonize (flumazenil) |
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Midazolam |
Imidazole ring - H2O soluble at low pH w/ open ring, pH>4 closes ring and becomes highly lipid soluble Potent BZD - short acting, cons sedation, induce anesthesia, more amnesia than sed, used for sz |
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Midazolam Kinetics |
CYP3A4 at liver and small intestine Half life 1-4 hrs Large Vd which increases in obese and seniors Clearance 4 hours, prolonged sedation in pts w renal and liver dysfunction |
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Midazolam ADRs |
COPD - vent depression Apnea w rapid admin of large doses Hypoxemia and decreased art oxygen w fent Decreased swallowing refelx and upper airway activity |
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Diazepam |
Long acting BZD (active metabolites) Available oral and parenteral Common uses: preop, anxiety, muscle spasms, status epilep |
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Diazepam Kinetics |
A- GI tract abs 1hr, 30 min in child, highly lipid soluble, rapidly penetrates BBB D- Highly protein bound, Large Vd M- Hepatic metabolism, Half life 30 hrs, active emtabolites E- elimintated in urine |
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Lorazepam |
Med duration BZD, Oral and parenteral Most potent sedative and amnesic than vers and val. Use anxiety, insomnia, preop sed |
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Lorazepam Kinetics |
A- Slow onset D- Low Vd, less lipid soluble (hydrophilic) M- Liver E- Kidney urine |
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Flumazenil |
Competitively binds w BZD receptor with decreased effect Reverses CNS of BZDs and other hypnotics - Zdrugs Short acting, may require mult doses for OD |
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Flumazenil Dose/Admin/ADR |
titrated from 0.2mg IV DOA- 30-60 min avoid in sz pts w/ bzds ADR - fatigue, HA, N/V, hiccups, Agit, Palpitation, vertigo, confusion, convulsions |
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Dependence of BZD's |
Common at therapeutic doses when drug is discontinued after tx lasting >6months Common sx of withdrawls - rebound effect 1-2 days of short acting 2-5 days of long acting |
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Geriatric Population |
Diazepam is metabolized by oxidative metabolic pathways Aging and liver disease decreases the effect of this metabolic pathway Cognitive decline in elderly pop is faster with long term bzds |
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Barbituates |
Derivative of barbituric acid Older less commonly used, still used as anticonvulsant Derivatives - sulfur at 2nd oxygen = thiobarb More lipid soluble, easily crosses BBB, greater hypnotic action, rapid onset, shorter duration Sulfur molecule can increase risk of histamine release - asthmatic flareup |
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Barbituates MOA |
Effects rate of dissociation of GABA from receptor by decreasing it Increases DOA in which chloride channel is open Can mimic action of GABA by directly activating Cl channels It does both open channel and increase time channel open |
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Barbituates Kinetics |
A-Thiobarbs readily absorbed from GI, Less lipid soluble barbs less available from GI D- Highly bound to plasma, not readily available to tissue (less lipid soluble greater Vd)? M- Oxybarbiturates by liver primarily E- Urine primarily |
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Barbituates Clinical Uses |
Induction of anesthesia, Tx of ICP,
Other uses decline: lack of specificity, BZDs better tolerated, Greater liability, high risk for drug interactions |
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Tx of ICP w/ Barbituates |
Decreases CBV w cerebral vascular constriction and decrease in CBF Induces depression of Cerebral metabolic oxygen requirements by 35% Side effect w high dose hypotension |
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Tolerance and Physical Dependance of Barbituates |
Tolerance to sed effects sooner than anticonvulsants Tol increases: therapeutic index (TI) decreases - lethal dose more readily achieved Rapid increase in tolerance, what increases TI |
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ADRs of Barbituates |
Anaphylactic 1:30,000 - thiobarbs contain sulfur mediate histamine rel, alternatives for asthmatic pts N/V, Hyperactivity in peds SJS - Stephen Johnson Syndrome |
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Zolpidem |
Highly available orally (70%) Metabolized prim by liver t1/2 - 2 hours Short DOA Strong sedation effects - primary affinity for Alpha-1 Subunit Little tolerance/withdrawal observed |
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Zaleplon - Sonata |
Low Oral availability (30%) - less efficacy than zolpidem Metabolized in liver and peripheral tissues t1/2 is 1 hour, Short DOA, indications at bedtime or when waking up at middle of night Eliminated in Urine |
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Eszopiclone - Lunesta |
High oral availability (80%) Metabolized by liver Eliminated in urine t1/2: 6 hours, longer DOA than other two Efficacy similar to Zolpidem
R enantiomer has greater incidence of ADRs when given wo S enantiomer - nausea, bad dreams, anxiety |
