Exam 3 Flashcards
(132 cards)
1
Q
this type of antidepressants share a common 6-7-6 tricyclic structure and have a similar pharmacologic profile for reuptake inhibition and adverse effects arising from blocking receptors like H1, M1, alpha 1
A
tricyclic antidepressants
2
Q
which type of tricyclic antidepressant (secondary/tertiary) are more selective for SERT?
A
tertiary
3
Q
which type of tricyclic antidepressant (secondary/tertiary) are more selective for NET?
A
secondary
4
Q
which type of TCA (secondary/tertiary) has less sedation/orthostatic hypotension/dry mouth/urinary retention/constipation?
A
secondary
5
Q
which type of TCA (secondary/tertiary) has more sedation/orthostatic hypotension/dry mouth/urinary retention/constipation?
A
tertiary
6
Q
all antidepressants in this class have an ionizable amine
A
SSRIs
7
Q
which 3 SSRIs are enantiopure?
A
paroxetine, escitalopram, sertraline
8
Q
how does the relationship between venlafaxine (SNRI) and TCAs align with their mechanisms of action for depression?
A
selectivity of venlafaxine is closer to NET than SSRIs so more similar to TCAs in that sense
9
Q
all of these antidepressants contain a piperazine ring attached to an aryl (aromatic ring) group
A
arylpiperazine antidepressants
10
Q
this SSRI has a relatively long half life which is a desirable feature for management of depression, it has an active metabolite which helps give it a longer half life, tapering off/washing out will take longer than for other antidepressants
A
fluoxetine
11
Q
which chemical feature of TCAs contributes most to adverse effects arising from receptor blockade as compared with non-TCA antidepressants?
A
shape of the TCA structure (planar)
12
Q
disorder of mood and emotion, often comorbid with anxiety, recurring episodes of dysphoria (sadness that is disproportionate and prolonged) and negative thinking especially about one’s self/life
A
major depression (unipolar depression)
13
Q
normal sadness that is healthy/normal to feel when something bad happens
A
reactive/exogenous/secondary depression
14
Q
type of depression characterized by increased appetite and hypersomnia
A
atypical depression
15
Q
- depressed mood, much greater in intensity and duration that reactive depression
- anhedonia (inability to experience pleasure)
- increase/decrease in appetite
- insomnia/hypersomnia
- increase/decrease in psychomotor activity
- fatigue/loss of energy
- loss of self esteem
- diminished ability to think, concentrate, make decisions
- suicidal thinking
need 5 of these symptoms and one of the 5 has to be depressed mood or anhedonia
can’t be caused by drugs, medications, etc
need to present for at least 2 weeks and significantly affects daily life
A
major depression general features
16
Q
when a loved one dies it’s normal to be sad for longer than 2 weeks, no longer used because people weren’t getting treatment
A
bereavement exclusion
17
Q
hypothesis that depression is the result of low monoamine levels (NE, 5HT, DA), originated more than 50 years ago with reserpine (side effect of depression –> irreversibly binds to VMAT, vesicles can’t store neurotransmitters and neurotransmitters are depleted), antidepressants increase monoamine function, depressed patients have low levels of metabolites of NE and 5HT suggesting low utilization of these transmitters
SHORTCOMING - antidepressants which target monoamine systems don’t work acutely but require several weeks of administration, many work to block reuptake which starts working as soon as it reaches the brain - CLINICAL LAG
A
monoamine hypothesis
18
Q
- depressed patients have higher than normal cortisol levels which is in response to higher than normal ACTH levels which is in response to higher than normal CRF
- pituitary and adrenals are enlarged due to hypersecretion
- primary dysfunction probably has to do with abnormalities in the hypothalamus (produces too much CRF and has too many CRF producing cells, might be due to genetic variations between individuals)
- circadian rhythm of cortisol release is flatter and higher in depression (cortisol levels stay high regardless of time)
A
HPA dysfunction in depression
19
Q
- hippocampus (through glucocorticoid receptors) exerts inhibitory control over CRF release by the hypothalamus
- when glucocorticoid levels are high for prolonged periods of time hippocampal neurons become damaged and unresponsive (loss of dendrites and spines, decrease in neurogenesis)
- consequence of the damage is that the hippocampus can’t inhibit the hypothalamus which leads to even greater glucocorticoid levels which leads to more damage, etc.
- evidence for this process is that depressed patients have reduced hippocampal volume and antidepressants/ECT both reduce CRF levels
could be a reason why antidepressants take a few weeks to change mood
A
glucocorticoid hypothesis of depression
20
Q
regular neurons can’t go through mitosis but neurons in the _______ can still be reformed through neural progenitor cells, could be a reason why antidepressants take a few weeks to change mood
A
hippocampus
21
Q
dendritic atrophy in the hippocampus is related to reductions in ___________ that occurs with stress, chronic antidepressant treatment increase these levels in the brain, stress that occurs while antidepressants are administered does NOT reduce these levels in the brain
A
brain-derived neurotrophic factor (BDNF)
22
Q
increases in stress lead to increases in glucocorticoids which _____ (increases/decreases) BDNF leading to atrophy and decreased survival of neurons/increased vulnerability
antidepressants increase NE and 5HT which _______ (increases/decreases) BDNF leading to increased survival and growth of neurons
A
decreases, increases
23
Q
this type of receptor is Gi coupled, inhibitory, and acts as negative feedback for neurotransmitter release
A
presynaptic autoreceptors
24
Q
this structure is responsible for reuptake of NE or 5HT
A
transporters
25
antidepressants block which type of structure on the presynapse and prevent reuptake?
transporters
26
the effect of blocking reuptake transporters can _______ (increase/decrease) the amount of neurotransmitter binding to presynaptic autoreceptors
increase
27
with long term treatment with antidepressants, this takes place and is asymmetrical (only happens on the PRESYNAPTIC autoreceptors) and what is this called?
downregulation of autoreceptors, asymmetrical desensitization
28
this class of antidepressants block serotonin and NE reuptake, block 5HT and NE transporters, no difference in clinical efficacy or lag
TCAs
29
this happens when patient sees improvements in appetite and sleep when starting a TCA, if see this response within first few weeks it is a good sign that the antidepressant will work
trigger response
30
people with depression will have elevated mood (but not euphoria), people without depression will have no mood elevation and it will even produce drowsiness, secondary are less sedating than tertiary which can be desired in patients with insomnia
CNS effects of TCAs
31
principle effects are anticholinergic (dry eye/mouth, tachycardia, blurred vision, etc.), desipramine minimal, amitriptyline strongly, some alpha blocking activity which can cause some orthostatic hypotension
ANS effects of TCAs
32
orthostatic hypotension due to alpha blocking, arrhythmias (not a good choice for people with cardiovascular history)
cardiovascular system effects of TCAs
33
these drugs are well absorbed after oral administration, widely distributed with long half lives (20-80 hours, want all day all the time effects), active metabolites which help with long half life, dosing starts as divided doses throughout the day and progresses to one dose at bedtime since they can be sedating
kinetics/metabolism of TCAs
34
1500 mg (2 week supply) of these drugs can be lethal so need to have caution especially in patients with suicidal ideation, toxicity will present as ANS symptoms
TCA toxicity
35
which TCA can be used for OCD?
clomipramine
36
which TCA can be used for enuresis (bedwetting in children)?
imipramine
37
which TCA can be used for anxiety?
doxepin
38
these drugs are much more selective for blocking serotonin reuptake than TCAs, lose selectivity at higher doses though (will see some blocking of NE), no difference between the different drugs in the class in terms of clinical efficacy
SSRIs - fluoxetine, citalopram, escitalopram, fluvoxamine, sertraline, paroxetine, vortioxetine
39
sexual dysfunction (delayed/impaired orgasm, loss of libido, ED), GI distress (N/V, sertraline diarrhea, paroxetine constipation), CNS agitation/restlessness (fluoxetine in particular)
adverse effects of SSRIs
40
this can occur when 2 or more serotonergic drugs are used together, muscle rigidity, seizures, fever, rare but potentially fatal
serotonin syndrome
41
fluoxetine and paroxetine inhibit which CYP450 enzyme? what interactions are there with these because of this?
CYP2D6, 2D6 substrates have interactions (most TCAs and SSRIs, many antipsychotics, beta blockers, tamoxifen which needs to be converted to active form by 2D6)
42
panic disorder, anorexia/bulimia, chronic headaches/migraines, premenstrual dysphoric disorder (PMDD)
other uses for fluoxetine besides depression
43
no statistical/clinical differences in efficacy, drop out rate lower for SSRIs because they generally have more manageable side effects, SSRIs safer on overdose (TCAs have more fatalities with overdose), SSRIs safe in pregnancy (fluoxetine, amitriptyline Class C avoid in pregnancy, paroxetine Class D can cause defects), when discontinuing must taper dose of SSRIs that have short half life
TCAs vs SSRIs
44
SSRIs with a ______ (long/short) half life will cause more withdrawal symptoms during discontinuation
short
45
SSRIs with a _______ (long/short) half life don't necessarily have to be tapered, "self taper"
long
46
- reuptake inhibitors of both 5HT and NE, some claims of faster onset that are not well founded
- side effects: minimal effects on muscarinic and alpha receptors, fluoxetine like SEs (N/V, sexual dysfunction), increase blood pressure similar to TCAs
SNRIs - venlafaxine, desvenlafaxine, duloxetine, levomilnacipran
47
this drug is a 5HT reuptake blocker that has a metabolite that is a 5HT antagonist, not a very effective antidepressant, very sedating so used as a sleep aid, minimal anticholinergic side effects, headache and GI upset are common, priapism and orthostatic hypotension
trazodone
48
this drug is an alpha 2 antagonist, 5HT antagonist, and H1 antagonist (at inhibitory autoreceptors in noradrenergic synapse, NE levels in synapse will go up and at inhibitory heteroreceptors), when these receptors are blocked with this drug there will be increases in 5HT in synapse because the 5HT neuron has alpha 2 heteroreceptors, very sedating (must be taken at bedtime) and increased appetite leading to weight gain
*BLOCK alpha 2 get MORE neurotransmitter release*
*NE can regulate 5HT through its action at alpha 2*
mirtazapine
49
this drug is a NE and DA reuptake inhibitor, DA reuptake due to similar structure to amphetamine, side effects are stimulant side effects like loss of appetite and insomnia, good for patients with hypersomnia and increased appetite
bupropion (NDRI)
50
work by blocking the action of the enzyme monoamine oxidase (MAO), which is responsible for breaking down neurotransmitters like serotonin, dopamine, and norepinephrine in the brain, inhibit MAOA and MAOB pretty evenly, side effects (liver - hepatotoxicity unrelated to dose, CNS - happen at high frequency, insomnia, tremors, convulsions, CVS - decreased BP and orthostatic hypotension OR hypertension
MAO inhibitors - tranylcypromine, isocarboxazid, phenelzine
51
this can happen when patients take MAOIs, tyramine (found in processed meats/cheeses, wine) displaces NE in storage vesicles but normally MAO will break this down, when taking an MAOI tyramine won't be metabolized in gut so more tyramine reaches the brain and NE is released into the cytoplasm, NE is released into synapses, causes increased BP (hypertensive crisis)
tyramine effect
52
serotonin syndrome when added to SSRI/SNRI, 2 week washout for drug class switches, meperidine (opioid agonist and 5HT reuptake inhibitor), generally risky
MAOI drug interactions
53
antagonist of the NMDA receptor (a glutamate receptor) used for induction and maintenance of anesthesia, sub-anesthetic doses reduce depression symptoms 4 hours after infusion in treatment resistant patients (symptoms like suicidal ideation and negative self talk went away), time of onset is after perceptual disturbances have abated and drug is essentially gone from the brain, antidepressant effects persist for 3-7 days, limitations (dissociative anesthetic with abuse potential)
ketamine
54
in the prefrontal cortex stress causes decreased BDNF (dendrites and spines atrophy) which leads to synaptic dysconnectivity (cortical neurons not as connected to whatever neuron they connect with), glutamate synapses are deficient in specialized synaptic proteins and AMPA receptors, this drug enhances translation of mRNA for BDNF and AMPA subunits and increases insertion of AMPA receptors into the postsynaptic membrane (complex but quick process), synaptic connectivity is restored and depression symptoms remit, dendritic spine density is increased
*this drug enhances translation of BDNF and AMPA which leads to restoration of synaptic connectivity and dendritic atrophy that is seen in depression*
ketamine MOA
55
approved March 2019, S enantiomer of ketamine, nasal spray, patient has to be monitored after administration of this drug, approved for when symptoms not treated with other antidepressants
esketamine
56
hormone made by ovaries, adrenal glands, neurons, largest quantity in the placenta, precipitous decline after childbirth, decline may be related to postpartum depression
allopregnanolone
57
these agents act at the non-benzodiazepine sensitive GABAA receptors, allopregnanolone
brexanolone (60 hour IV infusion), zuranolone (PO daily for 14 days)
58
periods of mania and periods of depression
mania:
- feeling of faultlessness
- bursting with energy
- no need for sleep
- excessively talkative
- racing thoughts and ideas
- unlimited confidence
- impulsive decision making (foolish business decisions, reckless driving, shopping sprees, sexual indiscretions)
- some patients can channel the mania into high levels of productivity and creativity
- onset in 20s
- periods of mania could be seen as a "good" thing in patient's eyes but will be followed by periods of depression
bipolar disorder
59
periods of major depression, periods of mania (symptoms for 1 week, hospitalization, arrest, etc), or mixed periods (depression + 3 mania symptoms for 1 week)
bipolar I disorder
60
periods of hypomania (3 symptoms for 4 days without hospitalization) and major depression
bipolar II disorder
61
periods of hypomania and depression that doesn't qualify as major depression
cyclothymic disorder
62
what medications can trigger manic episodes when depression is initially diagnosed?
SSRIs/TCAs
63
- approved for treatment of mania, onset of action is 7-10 days, effective in 70-80% of patients (high rate of efficacy)
- inhibits the phosphatases that are involved in recycling of IP3 to PIP2 which limits the amount of PIP2 that can be acted on by PLC (Gq coupled receptor)
- GI side effects (N/V), tremors and hypothyroidism, polyuria, polydipsia *OCCURS WHEN LEVELS ARE TOO HIGH*
- readily and almost completely absorbed from GI tract
- effective plasma level ranges from 0.6-1.3 mEq/L, toxic is greater than 1.5 (VERY NARROW therapeutic index)
- interaction with Na+ handling
lithium
64
this drug prevents ADH from acting in the collecting duct of the nephrons, ADH normally helps concentrate the urine (passing less liquid so more concentrated with ions, this drug inhibits this so less concentrated urine)
lithium
65
- has kidney origin, polyuria/polydipsia, lithium induced
- give a thiazide diuretic so going to urinate less than before, thiazide acts at distal tubule and causes Na+ secretion which increases Na+ reabsorption at the proximal tubule, transporters in proximal tubule that reabsorb Na+ don't known difference between Na+ and Li+ so Li+ is reabsorbed back into the blood
- there is only an effect of Li+ on ADH when Li+ is in the urine in collecting duct
- thiazide diuretic treatment can overall be good if patient is experiencing this condition but BAD if Li+ levels are already good for patient, could now experience Li+ toxicity if thiazide is added
nephrogenic diabetes insipidus
66
carbamazepine (mania/mixed), valproic acid (mania/mixed), lamotrigine (maintenance)
anticonvulsants (mood stabilizers) for bipolar disorder
67
aripiprazole (mania/mixed, maint), quetiapine (mania/mixed, depression, maint), risperidone (mania/mixed, maint), olanzapine (mania/mixed, maint), lurasidone (depression), cariprazine (mania/mixed, depression)
atypical antipsychotics for bipolar disorder
68
two functional categories --> sympathetic postganglionic fibers (diameter of capillaries, sweat) and primary sensory afferents
cutaneous nerve
69
this type of neuron has Aβ fibers (light touch and movement), Aδ fibers (respond maximally to pain), C fibers (respond maximally to pain)
primary sensory afferents (primary afferent nociceptors)
70
which fibers of primary sensory afferents have μ opioid receptors?
Aδ and C fibers
71
which fiber of primary sensory afferents is myelinated, speeds conduction, hurts right away
Aδ fibers
72
which fiber of primary sensory afferents is not myelinated, throbbing/more chronic pain
C fibers
73
where along the ascending pathway are there μ opioid receptors?
all along the pathway, opioids stimulate the μ opioid receptors all along the ascending pathway
74
pain causes _________ (hyperpolarization/depolarization) and an action potential, receptors are specific to the type of pain (chemical, mechanical, thermal)
depolarization
75
what is the main NT associated with pain transmission in the dorsal horn of the spinal cord?
glutamate
76
when pain is transmitted, what channels open allowing influx of ions?
calcium (presynaptic), calcium and sodium (postsynaptic)
77
what type of protein are μ opioid receptors coupled to (which G protein)?
Gi
78
when opioids are bound to μ opioid receptors, what happens to calcium movement? what does this mean in terms of pain signaling?
less influx, less calcium influx means less glutamate release which means less pain signals
79
when opioids are bound to μ opioid receptors, what happens to K+ movement at the postsynaptic neuron? what does this mean in terms of polarization?
K+ efflux meaning hyperpolarization of the postsynaptic neuron
80
opioids _______ (inhibit/stimulate) the ascending pain pathway through a "double whammy" effect --> act on pre and postsynaptic neurons
inhibit
81
opioids _______ (inhibit/activate) the descending pathway
activate
82
opioids turn _____ (on/off) the tonically active GABAergic neuron which activates the descending pain pathway which inhibits pain transmission
off
83
descending pathway _______ (stimulates/inhibits) pain transmission through release of Enkephalin which acts at μ opioid receptors to (stimulate/inhibit) pain transmission which is useful when we need to do hard things
inhibits, inhibit
84
any naturally occurring extract from the poppy plant that acts at opioid receptors
opiate
85
all agents, natural and synthetic, that have morphine like actions
opioid
86
this type of receptor is located in the brain and spinal cord - responsible for analgesia, sedation, euphoria
brain stem neurons - responsible for respiratory depression (proximal cause of death in opioid overdoses) and inhibition of peristalsis (resulting in constipation)
μ opioid receptors
87
this type of receptor is located in the brain, spinal cord, GI tract - responsible for analgesia, inhibition of peristalsis
kappa opioid receptors
88
this type of receptor is located in the brain and spinal cord, very similar to μ in function and effects
delta opioid receptors
89
these ligands have physiological functions of analgesia, regulation of respiration, regulation of peristalsis, stress, reward
cellular functions - inhibitory, hyperpolarizes cells and decreases NT release through increasing K+ efflux and decreasing Ca2+ influx
endogenous opioid ligands
90
- analgesia: mainly activates μ receptors, relieves moderate to severe pain without loss of consciousness or other sensory systems at a therapeutic dose, selective for pain signaling, more effective against continuous dull pain than sharp intermittent pain
- diminishes the neurophysiological and psychological (emotional reactions to being in chronic pain) components of pain
analgesic effect of morphine and other opioids
91
mood: if patient has pain it will produce euphoria, if patient does not have pain it will produce drowsiness, apathy, dysphoria (EXCEPTION: heroin)
effects on mood of morphine and other opioids
92
- respiration: decreases breathing by decreasing sensitivity of respiratory center to CO2 (neurons don't respond to changes in CO2 in blood), not a problem at therapeutic dose, cause of death in OD
effects on respiration of morphine and other opioids
93
opioids like morphine suppress cough by inhibiting cough center in brain stem, little correlation between analgesic effect and antitussive effect, antitussive effects may be due to action at what type of receptors?
sigma
94
caused by opioids' direct stimulation of the chemo trigger zone (CTZ), uncommon in patients confined to bed but more common in ambulatory patients
nausea/vomiting associated with opioids
95
opioids stimulate the oculomotor nerve, little tolerance to this effect, *differential diagnosis - unique from other sedatives*
miosis (constriction of pupils) associated with opioids
96
therapeutic doses of opioids have no major effect, can cause peripheral vasodilation and baroreflex inhibition leading to _______ (increase/decrease) in BP, orthostatic hypotension may occur, mainly a concern in patients with low blood volume
decrease, CV effects of morphine and other opioids
97
opioids _______ (inhibit/stimulate) peristalsis/intestinal secretions, constipation is a side with no development of tolerance (so even if someone uses opioid chronically they may get tolerance to pain relief but not constipation), constriction of biliary sphincter (gall stones)
inhibit
98
morphine and other opioids are generally well absorbed through which routes of administration?
SC, IM, PO
99
morphine ______ (does/doesn't) accumulate in tissues and _______ (does/doesn't) penetrate the brain easily
doesn't, doesn't - penetrates brain enough to work though
100
significant first pass effect with these drugs, major metabolic pathway is conjugation with glucuronic acid (glucuronidated metabolite is the one excreted), eliminated by glomerular filtration of the glucuronide
morphine and other opioids
101
at which position is the glucuronide metabolite of morphine active?
position 6
102
at which position is the glucuronide metabolite of morphine inactive?
position 3 and positions 3+6
103
the half life of morphine is ______ (increased/decreased) in kidney disease and M-6-gluc can accumulate leading to potential opioid toxicity
increased
104
morphine causes mental clouding, miosis, vomiting, decreases respiration which ______ (improves/worsens) intracranial bleeding
worsens - cerebral blood vessels dilate to compensate making brain bleed worse
105
morphine inhibits respiration and ______ (inhibits/stimulates) histamine release leading to bronchoconstriction
stimulates
106
some of these drugs enhance analgesic effects of morphine but also enhance CNS depression
TCAs and anticonvulsants
107
don't want to mix opioids with what drug class because too much CNS depression?
benzodiazepines
108
this develops over 2-3 weeks of using morphine, minimized by small doses with long intervals, this happens across opioids because they act at the same receptor (this doesn't "start over" when switched to a new opioid)
tolerance to opioids
109
this occurs when patient's physiological homeostasis is dependent on the opioid, invariably accompanies tolerance, withdrawal symptoms are generally opposite the acute effects, time of onset, intensity, and duration related to half life (drugs with long half life don't really see withdrawal, natural taper off), cellular and systems level explanations
physical dependence
110
this occurs because euphoria can promote compulsive use of opioids, substance abuse/dependence rarely occurs if used properly, tolerance and withdrawal symptoms do NOT indicate addition according to DSM-V criteria
psychological dependence
111
the acetyl groups that are added to morphine structure in heroin _______ (increase/decrease) lipophilicity for faster onset
increase
112
what enzyme metabolizes heroin to morphine?
plasma esterase
113
this drug is not a very strong μ receptor agonist, most of its analgesic effect comes from its metabolism to morphine
codeine
114
glucuronidated codeine/morphine metabolites are all cleared by the kidneys, kidney disease leads to _______ (increased/decreased) accumulation of M-6-gluc, leading to _______ (increased/decreased) effect/toxicity
increased, increased
115
ultra CYP2D6 metabolizers means _______ (increased/decreased) metabolism of codeine to morphine for ______ (increased/decreased) effect
poor CYP2D6 metabolizers means ________ (increased/decreased) metabolism of codeine to morphine for ________ (increased/decreased) effect
increased, increased
decreased, decreased
116
this drug is a μ agonist, mostly similar to morphine but NOT antitussive though (doesn't really bind to sigma receptors), thought it would be good for post-surgery, less constipation (more crosses the BBB so less stays in GI), large doses over a short period of time can cause tremors and convulsions due to one of its metabolites, not recommended for longer than 48 hours, blocks serotonin reuptake (don't use with MAO-Is, serotonin syndrome very likely)
meperidine
117
these 2 drugs are μ agonists that are very lipophilic, very potent, rapid onset because of lipophilicity, quicker recovery because of redistribution into the fat/muscle (not because of metabolism), used preoperatively as an anesthetic adjuvant, also used for post-op pain
fentanyl, sufentanil
118
this drug is approved to treat diarrhea because opioids have constipation effect, tablet also has atropine in it to help both with diarrhea and prevention of abuse
diphenoxylate
119
this drug is used to treat diarrhea, not absorbed by the GI tract, doesn't penetrate the BBB (won't experience analgesia), not very soluble so difficult to inject
loperamide
120
this drug is a full μ agonist, used as an analgesic or to treat opioid addiction, long duration of action, oral route slowly enters the brain
methadone
121
someone using heroin bounces around between being high and being sick which means the patient's whole day is revolving around finding and using heroin, this drug maintenance therapy to help patient be more functional - more time in normal range than bouncing between high and sick, counting on slow entry into the brain (can't inject this drug and have the same effect)
methadone
122
this drug has analgesia via inhibition of reuptake of NE and 5HT, very weak μ agonist, used for moderate acute and chronic pain (similar in efficacy to codeine + acetaminophen), not as effective as morphine for severe pain, drowsiness, dizziness, seizures with large doses especially in patients with history of seizures or on drugs that lowers seizure threshold like SSRIs/TCAs/MAOIs, nausea, vomiting, constipation (less than codeine), decreases respirations but less than morphine, drug interactions (TCAs, SSRIs, MAOIs serotonin syndrome, carbamazepine increases metabolism so much that the dose may need to be doubled)
tramadol
123
kappa agonist, μ partial agonist, sigma agonist, comparable analgesia to morphine, slows respiration but can't stop it, few effects on GI tract, sedation, dizziness, psychotomimetic at high doses, combination product with naloxone - won't do anything if patient is taking orally but if the patient injects the drugs then naloxone will prevent opioid from working, added to discourage abuse
pentazocine
124
lipophilic partial μ agonist, causes some respiratory depression, because this drug has a high affinity it cannot be reversed by naloxone, partially reverses respiratory depression caused by full agonist, FDA approval to be used like methadone, SUBOXONE is this drug with naloxone to prevent abuse
buprenorphine
125
this drug antagonizes all opioid receptors, reverses analgesia/constipation/miosis/euphoria/respiratory depression - rescue agent, causes withdrawal syndrome in people with opioid addiction (no effect in others), used IV/IM/SC/intranasally to treat opioid intoxication/overdose
naloxone
126
orally active opioid antagonist, not completely destroyed by first pass, can be used to treat alcohol use disorder by preventing the rewarding properties, methyl version of this drug is charged in the GI, can hang out longer in GI, can help with constipation, won't decrease opioid ability to relieve pain
naltrexone and methylnaltrexone
127
non-opioid analgesic, blocks voltage gated Ca2+ channels, good for nerve pain
gabapentin
128
non-opioid analgesic, blocks Na+ channels on neurons responsible for pain, diabetic neuropathy
carbamazepine
129
non-opioid analgesic, MS, phantom limb syndrome
lamotrigine
130
non-opioid analgesic, alpha 2 agonist
clonidine
131
non-opioid analgesic, increase NE and 5HT, work a little better than SSRIs in this case suggesting that NE is more responsible for pain relief
TCAs
132
primary sensory afferents express Nav1.8, this drug decreases Na+ current through this selectively, decreases action potentials (decrease in frequency of action potentials to decrease pain signaling), binds and stabilizes closed can't be opened conformation of Nav1.8
suzetrigine
