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98 Cards in this Set
- Front
- Back
5 methods to increase DA tone
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1) Increase availability of precursor (L-DOPA)
2) Enhance DA release 3) Direct DA agonists 4) Inhibiting breakdown of DA via COMT inhibitors 5) Inhibiting breakdown of DA by MAO-B inhibitors |
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L-DOPA --> DA by what enzyme?
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DOPA decarboxylase
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L-DOPA: cause of side effects
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95% of it is used peripherally --> massive amounts of peripheral DA
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L-DOPA: side effects
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excessive peripheral DA results in
A) Nausea/vomiting - stim. of area postrema B) orthostatic htn C) Cardiac irregularities D) Dyskinesias E) Psych and behavioral problems F) Somnolence G) Impulse control problems H) On-off response |
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On-off response: defn
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fluctuations between severe dyskinesia and akinesia, possibly from rising and falling levels of L-DOPA.
(Controlled release formulation of L-DOPA (Sinemet) helps with this) |
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Cardiac irregularities in L-DOPA: What is cause?
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Stimulation of β1-adrenergic receptors by massive DA in heart
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3 important drug interactions with L-DOPA
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1) Pyridoxine (B6): enhances peripheral decarboxylation of L-DOPA
2) MAO-inhibitors: can result in hypertensive crisis 3) Antipsychotics: block stim of DA receptors |
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Amantadine: MOA
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NMDA-channel blocker. Thought to cause increase DA release.
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Amantadine: problems
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Tolerance rapidly develops
Used to help patients thru exacerbation times |
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Ergot derivatives like bromocriptine: MOA
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Stimulate D2 DA receptors on postsynaptic membrane.
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Ergot derivatives like bromocriptine: problems
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less dyskinesia, but more mental side effects (hallucinations)
Causes N/V |
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Ropinirole: MOA
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D2 DA agonist (non-ergot)
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Pramipexole: MOA
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D3-selective DA agonist
Acts selectively on D3 presynaptic inhibitory autoreceptors. |
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Apomorphine: MOA
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injectable, non-ergot DA agonist to treat periods of immobility in advanced PD
Must be taken with antiemetics |
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pramipexole is also approved for _______
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restless legs syndrome
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Entacapone: MOA
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COMT inhibitor - reduces metabolism of DA and L-DOPA
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T/F Entacapone must be given with L-DOPA
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T
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Selegiline: MOA
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MAO-B inhibitor. Prevents breakdown of DA (and theoretically prevents formation of neurotoxins in CNS.)
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Selegiline: added benefits
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MAY slow progression of PD. But once it's D/Cd, patients rapidly deteriorate.
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Why is it safe to give selegiline with L-DOPA?
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Because it inhibits MAO-B, which preferentially metabolizes DA (Not NE, 5HT, or tyramine)
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Rasagiline: MOA
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MAO-B inhibitor (like selegiline)
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trihexyphenidyl: MOA
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Anticholinergic (antimuscarinic).
Greater blockage of muscarinic ACh-Rs in central rather than peripheral sites. |
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trihexyphenidyl: Side effects
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Related to peripheral anticholinergic action: Dry mouth, blurred vision, tachycardia, constipation.
Also have CNS effects including confusion and hallucinations. |
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benztropine: MOA
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antimuscarinic, central > peripheral.
<b>also blocks re-uptake of DA</b>, acting to block excess cholingeric tone and enhance DA tone. enztropine antagonises the effect of acetylcholine, decreasing the imbalance between the neurotransmitters acetylcholine and dopamine, which may improve the symptoms of early Parkinson's disease. |
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There is a loss of neurons containing what (4) in the striatum in HD?
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GABA
ACh Substance P Enkephalin |
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2 approaches to HD treatment
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1) Reduce DA
2) Enhance ACh |
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Antipsychotic drugs: MOA for HD
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DA receptor antagonists
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tetrabenazine: MOA
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vesicular monoamine transporter-2 (VMAT-2) inhibitor. Results in reduced stores of NE, 5HT, and especially DA.
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tetrabenazine: side effects/risks
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Can worsen depression.
Carries increased risk of suicide. |
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What types of antidepressants should be used in HD?
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Those with NO anticholinergic properties - ex, fluoxetine, carbamazepine
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Wilson’s Disease: pathophys
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Mutation in gene that results in <b>accumulation of Copper in organs</b> especially affecting liver and brain.
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Wilson’s Disease: tx
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CHELATING CU2+ to relieve symptoms.
Penicillamine is the chelator. |
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Triethylenetetramine/trientine: MOA
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The hydrochloride salt of triethylenetetramine, referred to as trientine hydrochloride, is a chelating agent, and is used to bind up and remove copper in the body to treat Wilson's disease, particularly in those who are intolerant to penicillamine.
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Penicillamine: MOA
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effective chelator of Cu2+
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Penicillamine: toxicities/side fx
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Drug-induced lupus
Nephrotic syndrome |
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Rotigotine: MOA and use
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non-ergoline dopamine agonist indicated for the treatment of Parkinson's disease (PD) and restless legs syndrome (RLS)
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MAO-B inhibitors used in PD
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Rasagiline
Selegiline |
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Spasticity: defn
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increased muscle tone due to flexor or extensor muscle spasms caused by an increase in velocity-sensitive stretch reflexes
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Stretch reflex: defn
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muscle contraction in response to stretching within the muscle. It is a monosynaptic reflex which provides automatic regulation of skeletal muscle length.
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_____ regulate how sensitive the stretch reflex is by tightening or relaxing the fibers within the spindle.
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Gamma motoneurons
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stretch reflex is aka
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myotactic reflex, deep tendon reflex, knee-jerk reflex
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T/F Drugs acting "centrally with little sedation" are effective for spasticity.
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F. They may act merely thru sedation but are for ACUTE MUSCLE SPASMS ONLY
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Benzos: MOA at spinal cord level
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act at the BNZ (benzo) receptor at the GABA-BNZ-Cl-ionophore complex, at least partially at the spinal cord level, to increase affinity of GABA receptor for GABA.
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Which benzo is useful for acute muscle spasms?
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Diazepam
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Baclofen: MOA
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GABA-B agonist.
Acts at level of spinal cord in reflex circuit involving g-motoneurons. |
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Baclofen: indications
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spasticity associated with MS and traumatic SCI
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Baclofen: side effects
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If withdrawn rapidly, can cause seizures and hallucinations
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Tizanidine: MOA
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centrally acting α2 adrenergic agonist.
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Tizanidine: indications
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Spasticity, cramping, and tightness of muscles caused by MS, diplegia, back pain, or certain other injuries to the spine or central nervous system.
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Dantrolene: indications
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Spasticity of CEREBRAL origin.
Ie, MS, cerebral palsy, hemiplegics, paraplegics. Also good for malignant hyperthermia. |
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Dantrolene: particularly effective for _______ movements
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athetoid (involuntary convoluted, writhing movements of the fingers, arms, legs, and neck)
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Dantrolene: MOA
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Binds to ryanodine receptor (within intracellular Ca2+ channel), inhibits release of Ca2+ from SR, thus interfering with excitation-contracting coupling.
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Dantrolene: side effects
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Generalized muscle weakness
hepatotoxicity |
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Botulinum toxin: MOA
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inhibits release of ACh at NMJ
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Botulinum toxin: indications (re: movement disorders)
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cervical dystonia
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Tizanidine: metabolism
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CYP1A2 (potential drug interactions)
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A 70-year-old male reports prowlers in his house, although his wife never sees anyone. He is being treated with Sinemet (l-dopa + carbidopa) for Parkinson’s disease. What should be added?
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Clozapine
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hypnosis: defn
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drowsiness and induction of sleep
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Most sedative-hypnotics act involving the ______ receptor
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GABA-A
Specifically, the GABA-benzo-chloride ionophore complex. |
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T/F Most sedative-hypnotics have the capacity to produce a withdrawal syndrome.
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T (physical dependence)
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T/F Most sedative-hypnotics exhibit an analgesia effect.
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F
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Binding of agonist to GABA receptor results in influx of ___ ions
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Cl-
results in hyperpolarization (more difficult to conduct AP) |
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Barbiturates: binding site and implications
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Bind to a site within the Cl- channel, increasing duration of channel open time.
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Benzos: binding site and implications
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Bind to BNZ receptor, increasing affinity of GABA receptor for its ligand.
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Why are benzos more safe than barbiturates?
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Benzos rely on GABA present endogenously, wherease barbiturates OPEN THE CHANNEL DIRECTLY.
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GABA-Benzodiazepine-Cl- Ionophore Complex: Structure and Subunits
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Five subunits. Most commonly two α, two β, and one γ.
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T/F Barbs exist as tautomers at physiological pH.
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T
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tautomer: defn
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isomers (structural isomers) of organic compounds that readily interconvert by a chemical reaction called tautomerization
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____ of barbiturates determines onset and duration of action.
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Lipid solubility
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Barbiturates: What does Tissue Redistribution determine?
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duration of action
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Barbiturates: Metabolism
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Metabolism by CYPs (many); then excreted by kidneys
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Barbiturates: absolute contraindication
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Acute intermittent porphyria
δ-aminolevulinic acid (ALA) synthetase |
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Barbiturates: CNS effects
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1) Hyperalgesia
2) Decrease in REM sleep 3) Respiratory depression |
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T/F barbiturates reduce cerebral metabolism and hence cerebral blood flow.
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T
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T/F Benzos affect metabolism of other drugs similarly to barbiturates.
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F
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Benzos: excretion
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Water-soluble glucuronides by kidneys
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Benzos: distribution
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lipid solubility determines onset of action.
Many have active metabolites which play a role in duration of action. |
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Benzos: metabolism
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Many are metabolized by liver microsomal enzymes (CYPs) to ACTIVE METABOLITES that can accumulate.
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Lorazepam: metabolism and excretion
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Directly glucuronidated and then excreted.
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Benzos: sleep effects
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decrease stage 4 sleep
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Benzos that have the least effect on REM sleep that were developed to treat insomnia
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Triazolam
Flurazepam |
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Benzos used to induce sleep or maintain anesthesia
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Diazepam
Lorazepam Midazolam |
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Zolpidem, zaleplon, eszopiclone: MOA
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Non-benzo drugs that bind selectively to one benzo receptor subtype.
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Zolpidem, zaleplon, eszopiclone: indication
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Short-term treatment of insomnia
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competitive benzo antagonist that can be used in OD situations
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flumazenil
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T/F Flumazenil does not reverse effects of Zolpidem, zaleplon, eszopiclone
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F (These bind to a benzo receptor)
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Barbiturates vs Benzodiapines: Sleep effects
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Barbiturates: decrease REM sleep Benzodiapines: decrease stage 4 sleep
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When treating insomnia, rule out _______ first.
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sleep apnea
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methohexital : MOA
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binds to a distinct site which is associated with Cl− ionophores at GABAA receptors.[1] This increases the length of time which the Cl− ionopores are open, thus causing an inhibitory effect.
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methohexital : indication
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induction of anesthesia
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Propofol : uses
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Rapid induction of anesthesia
Rapid uneventful recovery Anti-emetic properties Apnea and bradycardia |
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Propofol : side effects
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Apnea and bradycardia
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Dexmedetomidine: MOA
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selective α2 agonist
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Dexmedetomidine: indications
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use as adjunct to anesthesia, reduces heart rate and blood pressure associated with intubation
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Ramelteon: MOA
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Melatonin receptor agonist
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Advantages of Dexmedetomidine:
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Cardiovascular stability - attenuates hypertension and tachycardia
No respiratory depression Patients are often arousable and responsive Reduces anesthetic and opioid requirements |
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Disadvantages of Dexmedetomidine:
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Sympatholysis with hypotension and bradycardia
Transient hypertension may occur during loading infusion Nausea |
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phenobarbital overdose: tx
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Alkalinization of urine plus supportive therapy
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