Final Exam Flashcards
1
Q
goals of therapy for depression
A
alleviate the signs and symptoms
2
Q
types of depression
A
reactive (60%)
MDD (25%)
Bipolar Affective (15%)
3
Q
physiological signs of depression
A
decreased sleep, appetite changes, fatigue, psychomotor dysfunction
4
Q
psychologic symptoms of depression
A
dysphoric mood, worthlessness, guilt, loss of interest/pleasure
5
Q
cognitive symptoms of depression
A
decreased concentration, suicidal ideation
6
Q
Drug induced depression
A
antihypertensive and cardiovascular agents, sedative hypnotics, anti-inflammatory and analgesics, steroids, anti-Parkinson, anti-neoplastics, neuroleptics
7
Q
onset of action of anti-depressant drugs
A
biochemical effects within hours; clinical changes are not seen for weeks
8
Q
MOA for MAOIs (monoamine oxidase inhibitors)
A
MAO-A inhibitors- blocks the degradation of NE and 5HT causing more NE and 5HT to be released from the vesicles into the synapse
MAO-B inhibitors - block the break down of dopamine
9
Q
Non-selective MAO inhibitors; used for treatment resistant depression; irreversible inhibitors
A
Phenelzine (Nardil)
Tranylcypromine (Parnate)
10
Q
MAO-B selective inhibitors; used for Parkinson’s; reversible inhibitors
A
Selegiline (Eldepryl/Ensam)
11
Q
MAO-A selective inhibitors; not used in the US; reversible
A
Moclobemide (Manerix)
12
Q
MAO inhibitors SE
A
headache, drowsiness, dry mouth, weight gain, orthostatic hypotension, sexual dysfunction
13
Q
MAO inhibitors drug interactions
A
cause hypertensive crisis; otc cold medications, TCAs, SSRIs, L-DOPA
14
Q
reuptake blockers site of actions
A
allosteric
15
Q
indications for tricyclic antidepressants
A
depression, panic disorder, chronic pain, and enuresis; warning: patients more likely to commit suicide or self harm 2 weeks into treatment
16
Q
tertiary amines
A
inhibit both NET and SERT and are antagonists at H1, M, and A1 receptors
17
Q
side effects of tertiary amines
A
sedation, autonomic side effects, weight gain, cardiovascular conduction disturbances
18
Q
tertiary amine drugs; have a three-ring structure
A
Imipramine (Tofranil)
Amitriptyline (Elavil)
Clomipramine (Anafranil)
Doxepin (Adapin)
19
Q
Secondary amines drugs
A
Desipramine (Norpramin)
Nortriptyline (Pamelor)
Protriptyline (Vivactil)
Maprotiline (Ludiomil) (NET inhibitor)
20
Q
Secondary amines info
A
Better at inhibiting NET than SERT
Less sedation, anticholinergic, autonomic, weight gain, and cardiovascular SE than tertiary amines
21
Q
Side effects of all TCAs (general)
A
anticholinergic, CV, neurological, weight gain, look for suicidality
22
Q
SSRIs drugs
A
Fluoxetine (Prozac)
Fluvoxamine (Luvox)
Paroxetine (Paxil)
Sertraline (Zoloft)
Citalopram (Celexa)
Escitalopram (Lexapro)
23
Q
side effects of SSRIs
A
N/V, HA, sexual dysfunction, anxiety, insomnia, tremor
24
Q
SSRI discontinuation
A
brain zaps, dizziness, sweating, nausea, insomnia, tremor, confusion, vertigo
25
serotonin syndrome symptoms
hyperthermia, muscle rigidity, restlessness, myoclonus, sweating, shivering, seizures, coma
26
s/o to buspirone MOA
5HT1A (serotonin 1A) agonist
27
SSRI and 5HT1A partial agonists
vilazodone (Viibryd)
vortioxetine (Brintellix)
28
Serotonin-norepinephrine reuptake inhibitors (SNRIs)
Venlafaxine (Effexor)
Desvenlafaxine (Pristiq)
Duloxetine (Cymbalta)
Milnacipran (Ixel)
Levomilnacipran (Fetzima)
29
NE selective reuptake inhibitors
- reboxetine (Vestra) (not used in US)
- Atomoxetine (Strattera)
30
NMDA antagonists
glutamate antagonists; act as channel blockers (ketamine and scopolamine, esketamine)
31
treatment for PPD
fluoxetine, paroxetine, and venlafaxine, CBT, brexanolone
32
Brexanolone MOA and info
re-sensitizes GABA-A receptors after pregnancy
33
Filbanserin (Addyi)
for hypoactive sexual desire disorder; agonist at 5HT1A and 5HT2A/C antagonist
34
pharmacotherapy of bipolar
mood stabilizers, atypical antipsychotics, CCBs
35
Lithium MOA
ion; depletes PIP2 and Gq receptor signaling (PLC and IP3)
36
anticonvulsants used for bipolar mood stabilizers
Valproic acid and sodium valproate, carbamazepine/oxcarbazepine, lamotrigine, topiramate
37
risk of recurrence in depression
1 episode: 50-60%
2 episodes: 70%
3 episodes: 90%
38
recurrence info
- risk becomes lower over time as duration of remission increases
- persistent mild symptoms during remission is a predictor of recurrence
- function deteriorates during the episode and goes back to baseline upon remission
39
diagnostic info
at least one of the symptoms must be depressed mood or loss of interest or pleasure in doing things
40
DSM-5 Criteria SIG E CAPS
difficulty sleeping, interest decreased, guild, energy loss, concentration difficulties, appetite change, psychomotor agitation, suicidal ideation
41
Self-administered rating scales
PHQ-9; Patient Health Questionnaire (Primary care)
QIDS-SR-16: Quick inventory of Depressive Symptomatology Self-Report (psych practice)
Mood disorder questionnaire (MDQ) (used to rule out bipolar)
42
Goals of treatment for depression
- reduce or eliminate signs/symptoms of depression
- restore occupational/psychosocial functioning to baseline
- reduce the risk of recurrence/relapse
- reduce the risk of harmful consequences/suicidal ideation
43
risk of suicidality
boxed warning for suicidality in all patients 24 and younger; counsel them
44
clinical factors for bipolar
- depression is the mood pole experienced most; often misdiagnosed
- alcohol and substance use common in bipolar
- anxiety disorders are common comorbidities
45
DSM-5 classification
- Bipolar 1 disorder: > = 1 manic episode
- Bipolar 2 disorder; major depressive and hypomanic episodes
46
pharmacotherapy for bipolar
mood stabilizers and antipsychotics
47
lithium use and dosing
very effective for bipolar 1; associated with decrease in suicidality, but has a narrow therapeutic index = dangerous and can be fatal in overdose
- use 1:1 conversion for different dosage forms
48
lithium SE and other
may cause hypothyroidism, teratogenic; causes cardiac structural abnormality (avoid use in first trimester)
49
Lithium monitoring
need to keep sodium levels and water levels consistent; renally eliminated; do not use with NSAIDs
50
Valproate info
- several dosage forms; 1:1 conversion but ER dosage form less bioavailable
- risk for GI ulcerations in the syrup and capsule
- serum levels 80-125mcg/mL
51
Valproic acid AE
- unsafe in pregnancy; neural tube defects & negative IQ effects
- may cause PCOS
- anorexia, N/V/D, dyspepsia, ulceration, thrombocytopenia, platelet dysfunction, weight gain, hyperammonemia
52
Valproate monitoring
- pregnancy test, LFTs, and CBC
- Serum concentration
- serum ammonia (if needed)
- interacts with lamotrigine (stevens-johnson syndrome)
53
other mood stabilizers
- carbamazepine: thrombocytopenia/hematologic effects
- oxcarbazepine: CYP3A4 inducer, hyponatremia
-lamotrigine: for depressive episodes only
- topiramate: weight loss, heat intolerance, metabolic acidosis/kidney stones, teratogen (cardiac structural defects)
54
Antipsychotics
atypical antipsychotics can be used as monotherapy or can be used in combination with other mood stabilizers (valproate or lithium)
- monitor for weight gain, tardive dyskinesia, etc.
55
which bipolar meds cannot be used in pregnancy
valproic acid, carbamazepine, topiramate, lithium (first trimester)
- often choose to use atypical antipsychotics in pregnancy
56
AB fibers
fastest, identify touch and pressure and innervate the skin
57
AS fibers
fast; identify sharp/prickly pain "first pain"
58
C fibers
pain, temperature, touch, pressure, itch, dull/aching pain
59
role of substance P
vasodilation, degranulation of mast cells, release of histamine, inflammation and prostaglandins, increase sensitization (ex: sunburn)
60
neuropathic pain causes
increased AMPA and NMDA expression and sensitivity
61
inflammatory pain
throbbing, pulsating,
62
neuropathic pain
stabbing, shooting, burning, tingling
63
visceral pain
squeezing
64
CYP 3A4 opioids
makes opioids starting with nor
65
morphine
bioavailability is 25%
CYP 3A4 and 2D6
66
fentanyl
potent af
67
opioids that are full agonists
fentanyl
hydromorphone and oxymorphone
morphine
hydrocodone
oxycodone
68
non-phenanthrene opioids
tramadol; mild opiate- has SNRI properties
meperidine (demerol)- used to treat rigors; metabolized by 3A4; neurotoxic
69
opioids with NMDA block
methadone (blocks ion channel glutamate receptor; blocks pain signal in spinal cord)
prolongs QTC interval
70
opioids used for anti-diarrheals
diphenoxylate/atropine (lomotil)
loperamide (Imodium) - no BBB access
Eluxadoline (Viberzi) Mu/Kappa agonist; delta antagonist
71
buprenorphine MOA
partial Mu agonist, weak k agonist, and sigma antagonist
72
adverse opioid effects
tolerance/hyper-algesia: euphoria, respiratory depression, urinary retention, nausea
no tolerance: itch, constipation, miosis
73
methadone MOA
slow acting full agonist, provides relief from withdrawal, NMDA antagonist
74
buprenorphine
partial agonist to reduce withdrawal and euphoric symptoms
75
naltrexone MOA
ER IM injection or daily PO; will cause withdrawal, full antagonist
76
Naloxone MOA
antagonist, rapid onset, short half life
77
Naltrexone MOA
antagonist, PO with 4 hour half life
78
Neonatal Abstinence Syndrome symptoms
tremors, yawning, poor feeding, sweating in 24-48 hours after birth; serious withdrawal caused by heroin and other opiates including seizuresp
79
pharmacologic neonate abstinence syndrome treatment
morphine sulfate, SL buprenorphine, clonidine
80
Mu
endorphins (Mu-ey like reed)
81
Kappa
Dynorphins (kappa delta)
82
Delta
Enkephalins (keflex after delta dental)
83
orphanin/ORL1
nociceptin/orphanin (orphans are noice)
84
pain pathway
mediators recruit inflammatory cells: eicosanoids: arachadonic acid metabolites, prostaglandins (redness, heat, pain), thromboxanes, leukotrienes (swelling), cytokines (pain)
85
COX 1 protects stomach lining when expressed in the GI system
through PGE-2 and PGI-2
86
Aspirin MOA
irreversible inhibition of COX-1
87
Other NSAIDS MOA
competitive inhibitors of COX-1 and COX-2
88
reyes syndrome
vertigo/tinnitus, respiratory alkalosis, metabolic acidosis
89
aspirin overdose tx
increase urinary excretion; dextrose, sodium bicarbonate
90
misoprostol use
PGE-1 analog; protects GI lining
91
enolic acid nsaids
meloxicam; cox-2 selective at low doses; used for arthritis
92
NSAIDS AEs
peripheral edema, GI bleeding, inhibition of uterine motility
93
AE for acetaminophen
hepatic necrosis; do not take with alcohol
94
COX-2 selective inhibitors
reduce ulcers and GI bleeds, higher risk of blood clots, stroke, and heart attacks (reduced PGI2 formation)
95
contraindications to NSAIDS
CKD, PUD, GI bleed history.
other issues: inc. CV risk, interferes with bone healing, asthma exacerbations
96
sodium channel blockers that can be used for pain
SNRIs, Duloxetine, Venlafaxine, Milnacipran, lamotrigine, carbamazepine, amitriptyline, gabapentin, pregabalin
97
DEA schedule 1
no medical use; marijuana, THC, LSD
98
schedule 2
medical use; high abuse; cocaine and PCP
99
schedule 3
moderate abuse and dependence risk; marinol (THC)
100
schedule 4
low abuse and dependence; benzos
101
schedule 5
lower risk; cough suppressants; lomotil
102
opioids MOA
act on Mu opioid receptors
103
LSD aand mushrooms MOA
act on serotonin receptors 2a and 2c
104
marijuana, K2, and spice MOA
cannabinoid receptor agonists
105
Caffeine MOA
adenosine receptors
106
cocaine/amphetamine MOA
act on dopamine transporter
107
nicotine MOA
act on ionotropic ach receptors; agonist
108
PCP; ketamine MOA
ionic NMDA receptor antagonist
109
benzos and barbiturates
positive allosteric modulators of ionic GABAa receptors
110
neuronal plasticity changes
rewarding substances cause relative increase in glutamatergic AMPA receptors
111
withdrawal symptoms
goose bumps, muscle spasms, grand mal seizures, delerium tremens
112
physical dependence
tolerance
113
psychological dependence
addiction
114
pain pneumonic
PQRSTU
Palliative or precipitating
quality of pain
region of pain location
severity of pain
time
impact on U (daily activities)
115
objective pain assessment
behavioral changes
mydriasis
pallor
sweating
tachycardia
tachypnea
116
acute pain
<3 months
117
chronic pain
>3 months
118
goals of therapy
correct underlying cause of pain
minimize pain and symptoms
improve quality of life and activities of daily living
limit pharmacotherapy side effects
119
step therapy: step 1
non-opioids: tylenol and NSAIDS
adjuvant therapy: Gabapentinoids, SNRIs, tricyclic antidepressants, skeletal muscle relaxants, antiepileptics, topical agents
120
tylenol patient considerations
available PO, liquid, IV solution, suppository
dosing 325-1000mg PO q4-6H (max 3-4g/day)
liver disease max 2g/day
pediatrics max dose 75mg/kg/day
121
side effects of NSAIDs
GI bleeding, nephrotoxicity, fluid retention, increased CV events
122
Aspirin patient considerations
formulations: chewable tab, ec tab, suppository
adult dosing: max 4g/day
avoid in children
avoid for pain in patients taking blood thinners
123
Ibuprofen patient considerations
formulations: cap/tab, suspension, IV solution
adult dosing: max 3200mg/day
child dosing: max 40mg/kg/day
124
Diclofenac patient considerations
formulations: cap/tab, IV solution, suppository, topical, patch, eye drop
Dosing: 50mg PO q8h or 2-4g QID
Pearls: minimal systemic effects with gel
Can be used with CKD and CVD
125
Naproxen patient considerations
formulations: cap/tab, suspension
dosing: adults max 1000mg/day
126
Ketorolac patient considerations
formulations: tab, eye drop, IV/IM, nasal spray
adult: 15-30mg IV q6h or 10mg PO q6h
pediatric: 0.5mg/kg q6h
pearls: max duration of use is 5 days
127
celecoxib patient considerations
capsule/solution
200mg PO BID
Cox-2 selective; less GI effects (caution in CVD)
128
gabapentin and pregabalin patient considerations
uses; fibromyalgia, neuropathy, post-op pain
- formulations: tabs/caps, solution
- dosing: gabapentin (max 3600mg/day), lyrica (max 600mg/day)
- SE: sedation, dizziness, drowsiness, edema
- pearls: renally adjusted, titrate dose up, start low and titrate
129
venlafaxine and duloxetine considerations
uses: fibromyalgia and neuropathy
dosing: venlafaxine (max 225mg/day)
duloxetine (max 60mg/day)
SE: nausea, HA, HTN, sedation, weakness
avoid duloxetine in CrCl<30, renally adjust venlafaxine
130
TCAs:
Amitriptyline and nortriptyline (pamelor) considerations
uses (off-label): fibromyalgia, neuropathy, migraine prophylaxis
dosing: max 150mg/day
SE: anticholinergic, sedation
last line option due to SE
131
Muscle relaxants:
cyclobenzaprine, baclofen, methocarbamol, carisoprodol, and tizanidine considerations
uses: musculoskeletal pain/spasms
formulations: parenteral (methocarbamol and baclofen)
dosing: cyclobenzaprine (max 30mg daily)
baclofen (max 80mg daily)
carisoprodol (max 1050 daily)
methocarbamol (max 8g/day)
tizanidine (max 24mg/day)
SE: sedation/drowsiness, dizziness, dry mouth, vision changes
short term use <3 weeks
132
antiepileptics: carbamazepine (Tegetrol)
use: neuropathic pain
dosing: 200-400mg daily in 2-4 doses (max 1200mg/day)
hypersensitivity reaction with HLAB*1502 allele
autoinduction of hepatic enzymes (levels fall over first few weeks of use)
133
lidocaine
formulations; patch, injection, topical cream or gel
dosing; remove after 12 hours
SE: hypotension, arrythmia
pearls: tachyphylaxis with continuous use
12 hour break between patches, local effect
134
capsacian
uses: muscle/joint pain, neuropathic pain
lotion/gel/cream, patch
apply 3-4 times per day or 1 patch for 8 hours
SE: skin irritation/pain
pearls: do not get in eyes, wash hands after applying, can be used for vomiting
135
recommendation for NSAIDs and aspirin >=325mg/day in adults>65
Not recommended
136
Indomethacin and ketorolac in adults >65
do not use
137
skeletal muscle relaxants in adults >65
avoid
138
SNRIs, TCAs, and carbamazepine in adults >65
use with caution
139
opioids with benzos in adults >65
avoid combination
140
opioids with gabapentin/pregabalin in adults >65
avoid unless transitioning from opioid to gabapentin or using gabapentin to reduce opioid dose
141
anticholinergic medications
minimize the number of anticholinergic drugs in older adults. why? cognitive decline, delerium, falls, and fracture risk
142
antiepileptics, gabapentinoids, antidepressants, antipsychotics, benzos, z drugs, opioids, and skeletal muscle relaxants
avoid use of three or more together
143
medications to use in the elderly to minimize side effects
- tylenol
- diclofenac, capsaicin, lidocaine
- SNRIs
- gabapentinoids
144
opioid antagonsit
naloxone
145
opioid weak agonists
codeine, tramadol
146
opioid full agonists on exam
morphine
hydrocodone
oxycodone
meperidine
fentanyl
methadone
147
opioid overdose signs
- sedation/unconsciousness
- pinpoint pupils
- decreased respiratory rate
- bradycardia
- hypotension
- pale and clammy
148
opioid withdrawal signs
- insomnia/agitation
- dilated pupils
- increased respiratory rate
- tachycardia
- hypertension
- sweating
149
who should have naloxone?
- history of overdose
- history of SUD
- high opioid dosages
- concurrent benzo use
150
opioid withdrawal onset
short acting (heroin): 8-24 hours after last dose; duration of 4-10 days
long acting: (methadone): 12-48 hours after last use; duration of 10-20 days
151
opioid withdrawal treatment
clonidine for symptoms (htn, sweating, vomiting, anxiety)
buprenorphine/suboxone
methadone
152
codeine patient considerations
tablet and cough syrup
metabolized to morphine via cyp 2D6
not recommended in breast feeding mothers or children under 12
153
tramadol considerations
capsule, tablet, solution
risk of serotonin syndrome w/ other serotonergic meds
- renally dose adjusted
CYP3A4 and 2D6
154
morphine
- oral, injectable, and suppository formulations
- may cause itching
- accumulates in renal dysfunction
- avoid with AKI or CKD
- do not take with alcohol
155
hydromorphone
oral, injectable, and suppository
boxed warning for dosing errors
156
hydrocodone/acetaminophen
oral tablets and solutions
caution with CYP3A4 inhibitors and extra acetaminophen
157
Oxycodone/APAP
oral tabs and solutions; no IV
abuse deterrent formulations
caution CYP 3A4 and acetaminophen
158
Fentanyl/Duragesic
SL/buccal, lozenge, injectable, and patch
monitor 3A4
less hypotension
only for opioid tolerant patients (morphine 60mg/day for one week)
159
fentanyl patches counseling
do not cute (may cause overdose) and do not let it get too warm
160
methadone (methadose)
last time treatment for chronic pain; can be used for opioid detox
oral, solution, and injectable
only opioid with QTC prolongation warning
long half life
161
meperidine (demerol)
injectable, oral, tablet
avoid in elderly and renal impairment
warning with CYP 3A4, do not use with MAOIs, metabolized by liver, accumulation leads to delerium and seizures, not commonly used
162
potential side effects
seizures and serotonin syndrome
163
natural opiates
morphine
codeine
164
semi synthetic opiates
hydromorphone
oxycodone
oxymorphone
hydrocodone
buprenorphine
165
synthetic opioids
fentanyl
methadone
meperidine
tramadol
166
when are non-opioid therapies preferred?
for subacute and chronic pain
167
what type of opioid should be used when starting opioid therapy and how much?
IR dosage forms in the lowest effective dosage
168
when to taper/reduce opioids
- when the patient requests a dosage reduction
- no clinically meaningful improvement in pain or function
- doses over 50 MME/day without benefit or use concurrently with benzos
- signs/sx of SUD
- experiences overdose or adverse event
- warning signs for overdose risk
169
how to reduce opioid doses
decrease by 10% per month is patient has been on it more than one year
decrease by 10% per week if it has been weeks to months
170
hospital orders for acute pain
can only have one order for each severity of pain
171
fibromyalgia recommended treatment
pregabalin or duloxetine
other: TCAs, gabapentin, venlafaxine
172
neuropathic pain recommended tx
firs line: SNRIs, gabapentin/pregabalin
second line: topical lidocaine, TCAs
173
nicotine mechanism
nicotine is membrane penetrable at physiologic pH (is a weak base)
not degraded by acetylcholinesterase; longer duration of action than Ach
174
why is there a higher success for quit rate for varenicline than NRT?
varenicline is a partial agonist; reduces cravings and takes away the reward
175
why doesn't Phenylephrine work?
extensive first pass metabolism inactivates it; the nasal spray does work
176
caffeine + amphetamine
fenethylline
177
Cocaine MOA
- DAT, SERT, and NET antagonist
DAT>SERT>NERT
prevents dopmine reuptake, increases DA concentration, increases duration of DA action
178
Meth, ecstasy, and bath salt MOA
resemble exogenous DA and NE and compete for reuptake
push out DA from vesicles
amphetamines are MAOis
Activate trace amine associated receptor (TAAR1)
- phosphorylates DAT and induces reverse transport function
179
synthetic cathinones effect
mild euphoria and excitement; similar to strong coffee
180
synthetic cathinones
designer drugs; similar to nutmeg. bath salts, molly,
181
clinical effects of meth abuse
neurologic: delerium, tremor
psych; anxiety, paranoia, hallucinations, delusions, repetitive behavior
ENT: dental decay
CV: tachycardia, hypertension, vasospasm
skin: diaphoresis
(basically all anticholinergic effects except for sweating)
182
using methamphetamine causes down-regulation of dopamine receptors
causes withdrawal symptoms
183
sympathomimetic toxidrome
MATHS
Mydriasis
Agitation, arrythmia, angina
Tachycardia
Hypertension, hyperthermia
Seizure, sweating
184
acute cannabis intoxication perceptual
temporal slowing, auditory, visual, or tactile illusions, de-personalization.
185
acute cannabis intoxication affective
euphoria, disinhibition, anxiety, emotional lability
186
acute cannabis intoxication physical
tachycardia, hypotension, conjunctival injection, dry mouth, increased appetite
187
acute cannabis intoxication cognitive
suspiciousness or paranoid ideation, impaired judgement, impaired reaction time, and impaired attention
188
what comprises the endocannabinoid system?
CB1 and CB2 receptors, anandamide and 2-AG ligands, EMT transporter, and enzymes
189
what do endocannabinoids and phytocannabinoids do?
serve as retrograde regulators of neurotransmission inhibiting the release of GABA and glutamine
190
THC vs synthetic cannabinoids action on CB1R
THC is a partial agonist
synthetics are full agonists
191
In the brain, the CB1 receptor has more expression than the CB2 receptor
low levels of CB2 on respiratory centers of the brainstem, decreasing the likelihood od respiratory depression and coma
192
CB2 and Cb1 expression in periphery?
CB2>>CB1
CB2 on lymphocytes
CB1 in liver
193
Marinol about
Dronabinol; synthetic delta 9 THC in sesame oil; for loss of appetite
causes tachycardia and red eyes
194
Nabilone about
Cesamet
THC mimetic; anti-emetic and used for chronic pain
195
CBD pharmacology and use
low affinity for CB receptors
may antagonize THC at CB1
no euphoric effects; most commonly used for pain
196
cannabinoid hyperemesis syndrome treatment
cannabis cessation
benzodiazepines
haloperidol
capsaicin cream
197
phenethylamine molecular target
increase release of serotonin>DA, NE
198
what are the classical psychedelic drugs derivatives of?
phenethylamine, tryptamine
199
Classic psychedelic target
Serotonin 2A receptor
200
MDMA MOA
stimulates serotonin release
201
psychedelic AE; short term physiologic
tachycardia, hypertension, tremors, dry mouth, nausea, hyperthermia
202
psychedelic AE; acute dysphoric reaction
terrifying thoughts, fear of insanity, fear of losing control, fear of death
203
psychedelic AE; psychotic reations
flashbacks, enduring changes in personality, exacerbate underlying psychotic disorder, instigate prolonged psychotic disorder, rate of psychosis after LSD1 to 5%
204
potential therapeutic uses
cancer related psychological distress
PTSD
depression
SUD for alcohol
205
dissociative psychedelic MOA
NMDA antagonists, disinhibition of glutamate release, inhibition of GABA release
206
ionotropic glutamate receptors
NMDA receptor antagonist; induce anesthesia and analgesia
207
Dextromethorphan
serotonin reuptake inhibitor; NMDA receptor antagonist
208
phencyclidine
NMDA antagonist more potent than ketamine (D2 receptor agonist) associated with severe dissociation and analgesia, psychotic reactions, violence, and suicide
209
muscimol MOA
GABAa agonist that acts on channels. benzos and alcohol are allosteric modulators. This is orthosteric
210
alkyl nitrates
nitric oxide release; smooth muscle contraction, relaxes anal sphincter, enhanced erections and euphoria. may also cause methemoglobinemia
211
volatile solvents of abuse
toluene, acetone, benzene, butane
212
acute effects of volatile solvents
locomotor stimulation, euphoria, exhilaration, CNS depression, slurred speech, disorientation, weakness, sedation
213
effects of repeated exposure of volatile solvents
lipid accumulation: adipose tissue, lipid-rich organs
214
risks of inhalant abuse
asphyxiation, suffocation, convulsions, coma, choking, fatal injury, development of fatal arrythmia, and neurotoxicity
215
alcohol metabolism
90% in liver by alcohol dehydrogenase (ADH), microsomal ethanol oxidizing system (MEOS) only at high concentration and involves CYP2E1 (low affinity for alcohol), then metabolized by aldehyde dehydrogenase
216
fomepizole
alcohol dehydrogenase inhibitor; slow formation of formaldehyde and toxic metabolites
217
metabolism of acetaldehyde
metabolized by aldehyde dehydrogenase
218
disulfiram (antabuse)
strong inhibitor of ALDH2; irreversible inhibitor with effect persisting up to 14 days. Causes a strong hangover.
219
targets of alcohol
- allosteric activator of GABAa receptors (inhibitory)
- NMDA receptor inhibitor
Alpha7 nicotinic receptor
causes neurotransmitter release; enkephalins (dopamine), serotonin/NE, Ach, increases CNS and blood ACTH levels
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blood alcohol level measurement
0.1% = 100mg/dL = 100mg%
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Driving limit
0.08%
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pharmacologic actions of low levels of alcohol
30-60mg/dL = euphoria, disinhibition, talkative
60-90mg/dL = analgesia
80-120mg/dL = CNS stimulation; mood swings/aggression
100-200mg/dL = CNS depression; slurred speech, ataxia, sedation, loss of motor control, irrational behavior
300-500mg/dL = respiratory paralysis, coma, death
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acute cardiovascular effects
vasodilation, reduced BP, increased HR
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moderate use CV effects
reduced risk of coronary disease; increased HDL
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Heavy/Chronic use CV effects
cardiomyopathy, arrythmias, hypertension, hemostasis
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physiological effects of alcohol consumption
hypothermia (possibly lethal), chronic gastritis, appetite stimulant (low dose), appetite depressant (high dose)
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long term AEs in liver
increased fat metabolism, fatty liver leading to cirrhosis, vitamin deficiencies, small intestine damage = diarrhea, edema, ascites, effusions
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long term AEs in blood
anemia, gastritis, folic acid deficiency
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long term AEs cancer
liver cancer or mouth, larynx, esophagus, stomach
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Drug interactions with alcohol
CNS depressants, aldehyde dehydrogenase inhibitors (antimicrobials), (sulfonylureas), acetaminophen, aspirin
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teratogenic effect of alcohol
fetal alcohol syndrome:
- facial dysmorphology, low birth weight, decreased brain size, mental retardation, lower testosterone and sperm quality
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alcohol withdrawal
anxiety, insomnia, seizures, N/V, tactile hallucinationsa
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alcohol withdrawal treatment
benzos, phenytoin, electrolytes, clonidine, guanfacine
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FDA approved treatments for alcoholism
disulfiram (causes flushing, throbbing, headache, N/V, sweating, hypotension, confusion)
Acamprosate (NMDA receptor antagonist/GABA antagonist)
Naltrexone (Revia) (opioid receptor antagonist)
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off-label treatments
topiramate, baclofen, varenicline
