USMLE Step 1 Web Prep Dopamine, Parkinsonism, Schizophrenia

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Opioid Analgesics: Mechanisms of Action

Act partly via receptors for endogenous opiopeptides - G-protein linked and include (mu ! (delta " (kappa # $ffects depend on receptor su%type &it' &'ic' drugs interact as full agonists! partial agonist! or antagonists# (i)ed agonist-antagonists activate kappa receptors - antagoni*e mu receptors# Activation of presynaptic receptors ion c'annels +a,- influ) t'roug' voltage-regulated .- efflu) mem%rane neurotransmitter release

Activation of postsynaptic opioid receptors 'yperpolari*ation in'i%ition#

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SLIDE 2 of 9

Analgesic Actions of Opioids

/pioid-analgesics " endogenous opiopeptides act on receptors in t'e peria0uaductal gray region of t'e mid%rain activation of descending pat'&ays to 1ap'e nuclei transmission in pain pat'&ays 2 supraspinal analgesia# /pioid receptors are also located presynaptically on primary afferents (type + " A fi%ers in t'e dorsal 'orn of t'e spinal cord# 1eceptor activation release of su%stance 3! an e)citatory transmitter in primary afferents in pain pat'&ays 2spinal analgesia#

Fig IV-

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Opioid Analgesic #ha$macolog% &A'

Analgesia: pain tolerance " perception " reaction to pain5 6aria%le efficacy: morphine 7 meperidine 7 methadone > nal%up'ine > 'ydrocodone > codeine > propo)yp'ene 8edation! dro&siness! possi%le eup'oria! s'ort-term memory loss# 1espiratory depression: response to p+/, via depression of %rain stem respiratory center 2 ma9or pro%lem in /:# +ardiovascular: cere%rovasodilation releases 'istamine ;3#
SLIDE ( of 1"

intracere%ral pressure5 morp'ine

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Opioid Analgesic #ha$macolog% &)'

3upils: miosis (not meperidine # G< tract: peristalsis constipation! or clinical use in diarr'eal states! (eg! lope$amide " dip'eno)ylate # 8moot' muscle: tone of %iliary! %ladder " ureter - possi%le spasms (not

meperidine 5 tone of vasculature " uterus# +oug' suppression: independent of analgesia (eg! de*t$ometho$phan =ausea " emesis: stimulation of +>? in area postrema# 8ee >a%le <6-5 in te)t#
SLIDE + of 1"

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Mi*ed Agonist-Antagonists

Nalbuphine " pentazocine: analgesia compared &it' morp'ine! %ut less respiratory depression " a%use lia%ility Acute >o)icity: e)tensions of p'armacodynamic actions /:: c'aracteristic triad: pinpoint pupils! respiration " coma# (anagement of /:: patent air&ay - ventilation - <6 nalo)one >olerance: marked for analgesia! eup'oria " respiratory depression! %ut minimal for miosis " constipation# +ross-tolerance is t'e rule#
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Ad,e$se Effects of Opioid Analgesics

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Opioid-Analgesic Dependence

3syc'ological " p'ysical components# Bit'dra&al or a%stinence syndrome: an)iety! lacrimation " r'inorr'ea! s&eating! ya&ning! goose%umps! 'otCcold flas'es! muscle cramps " spasms! G< distress and DpainE# <ntensity of symptoms depends on drug! mode of administration! dosage " time from a%rupt discontinuance# (anagement oral methadone! %uprenorp'ine! or clonidine! &it' gradual dosetapering# (et'adone maintenance programs#
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Dopamine . /0S 0e1$ot$ansmission &A' 0ig$ost$iatal t$act

<n <n 3arkinsonGs :isease! nigrostriatal degeneration loss of :A neurons results in e)cessive A+' activity e)trapyramidal dysfunction5 :A antagonists pseudo-3arkinsonism (reversi%le 5 :A agonists dyskinesias Hunctions: regulation of affect! reinforcement! psyc'omotor activity " sensory perception# :rugs t'at :A functions psyc'omotor activity " reinforcement and! at 'ig' doses! may cause psyc'oses# :A antagonists psyc'omotor function#
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Mesolim2ic-Mesoco$tical 3$acts

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Dopamine . /0S 0e1$ot$ansmission &)' 312e$o-Inf1ndi21la$ 3$act

+ell %odies in 'ypot'alamus pro9ect to anterior pituitary " release :A prolactin# :A agonists (eg! pergolide - 1) 'yperprolactinemia# :A antagonists gynecomastia " amenorr'ea-galactorr'ea#

+'emoreceptor >rigger ?one

Activation of :A receptors emesis# :A agonists (eg! apomorp'ine are emetic " :A antagonists (eg! proc'lopera*ine are antiemetic#
SLIDE 9 of 1"

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3a2le IV- 4 Dopamine 5ecepto$ S12t%pes

8u%type :1A :1; :,A :,; :,+ +'aracteristics Hormerly :1 Hormerly :5 Hormerly :, Hormerly :4 Hormerly :4 cA(3 cA(3 cA(3 cA(3 cA(3