Week3 lectures (sans Dementia Day) Flashcards
1
Q
blocking this dopamine pathway, would result in worse negative sx (mesocortical/mesolimbic/nigrostriatal/tubuloinfundibular)
A
mesocortical
2
Q
blocking this dopamine pathway, would result in ↓ positive sx (mesocortical/mesolimbic/nigrostriatal/tubuloinfundibular)
A
mesolimbic
3
Q
blocking this dopamine pathway, would result in EPS or NMS (mesocortical/mesolimbic/nigrostriatal/tubuloinfundibular)
A
Nigrostriatal
4
Q
blocking this dopamine pathway, would result in high prolactin (mesocortical/mesolimbic/nigrostriatal/tubuloinfundibular)
A
tubuloinfundibular
5
Q
circuit for reward/motivation includes (3)?
A
ventromedial PFC, Nucleus Accumbens/Ventral Striatum, Thalamus
6
Q
lesion in the reward/motivation circuit would cause (sx type)?
A
negative sx (apathy/amotivation)
7
Q
Hallucination/Delusions from ↑DA can be improved with
A
dopamine blockers
8
Q
Mania (euphoria/grandiosity) can be treated with
A
Antipsychotics (lithium + Valproic acid too, via other MOAs)
9
Q
Antipsychotics mostly block ____ in the _____ DA pathway, EXCEPT pimvanserin
A
block D2 rcps; mesolimbic DA pathway
hint: useful for 1˚+ 2˚ psychosis and mood stabilziation; ↓DA –> ↓noise
10
Q
D2 blocks in the nigrostriatal pathway lead to (2)
A
- extrapyramidal sx (EPS)
- tardive dyskinesia (TD)
hint: motor SE (invol movemnt)
11
Q
Acute dysotnia (eg. torticollis), 2˚parkisnonism, akathisia are eg’s of _______ seen with what drugs?
A
extrapyramidal sx seen with antipsychotics (first gen)
12
Q
toritcollis, oculogyric crisis (upwards eye deviation), and Opithotinus (arched back/neck) are eg’s of? How do you treat?
A
acute dystonia tw anticholinergic agentics (IV/IM benztropine)
13
Q
why can’t anticholinergics be used in 1˚ parkinsons (older popn)?
A
adverse cognitive SEs; use DA agonists instead
14
Q
steps for treating 2˚ parkinsonism (3)
A
- dc/↓ antipyschotics
- if not, switch to SGA w/lower D2 potency
- if not, tw with benztropune/amantidine to ↑DA
15
Q
steps for treating Akathisia (1st line/2nd line)
A
1st = propranolol (CNS β blocker) 2nd = benztropine (antiAch)
16
Q
steps for treating tardive Dyskinesia (3)
A
- dc/↓ antipyschotics
- if not, switch to SGA w/lower D2 potency
- if not, tw with VMATi
17
Q
Valbenzaine, tetrabenazine, deutetrabenazine are eg’s of (drug class)? MOA?
A
VMATi; block DA packaging and release into synapse
18
Q
indications for VMATi (2)? what can it NEVER BE used for?
A
- TD
- HUntington’s CHorea
Never use for antipsychotic
19
Q
Hyperthermia, unstable ANS/vitals, muscle rigidity, rhabdomyolysis + ↑CPK, confusions are all signs of (syndorme)?
A
NMS (Neuroleptic Malignant Syndrome
20
Q
what 4 receptors do low pot FGA’s target, causing a mess?
A
- D2 dopamine rcp –> EPS
- H1 histamine rcp –> sedation + ↑appetite/wt
- AntiAch-M –> dry mouth, blurred vision, constipation
- Noradrenergic 𝛂1 rcp –> ortho hypotn
21
Q
Haloperidol and FLuphenzaine are (high/low) potency FGAs?
A
high potency FGAs
22
Q
Chlorpromazine + Thioridazine are (high/low) potency FGAs?
A
low potency FGAs
23
Q
Atypicals/SGA mechanism of action?
A
lower affinity D2 blockade + 5HT2a rcp antags
hint: cant AUGMENT (not replace) anitD’s
24
Q
SGA that cause severe metabolic SE (2)? zap
A
clozapine + olanzapine
25
SGA that cause intermediate metabolic SE (2)? PQR
Palepridone, Quetiapine, Risperidone
26
SGA that cause minimal metabolic SE (2)? (from LAZI + PIPs)
Aripirazole, Ziprasidone
27
dirty SGA that has activity on NDMA***, D1, nictoinic rcps; useful for refractory schizophrenia and suicide risk reduction
Clozapine
28
Dirty SGA that causes metab SE, agranulocytosis (watch WBCs), seizures, sedation, sialorrhea
Clozapine
29
This SGA is a partial D2 agonist/antag w/5HT1 agonism (antidepressant)? rips and pips
Aripirazole
30
DA is removed formt he sunapse by ____, destroyed in the neurons by _____, destroyed in the synapse by ______. (COMT, MAOab, DAT)
dat removes; MAOab internally destroys; COMT externally destroys
31
Valine substition for this genes --> agrresive DA breakdown --> too little DA
COMT
32
```
Hyperfunctioning DA results in what in the following pathways?
Mesolimibic
Mesocortical
NIgrostriatal
Tuberoinfundibular
```
Mesolimibic - addiction
Mesocortical - hypervigilence
NIgrostriatal - dyskinetic movment
Tuberoinfundibular - hypoprolactinemia
33
This drug used for Parkinson's Pyschosis is an inverse agonist (= below baseline) of 5HT2a glutamate neurons with no DA efx
Pimvanserin
hint: inh 5HT2a rcps on cortical glutamate neurons --> ↓stimulation --> ↓downstream mesolimbic*** DA firing
34
This drug blocks VMAT (↓DA) + used for htn (↓NE); causes depression, ↓ BP, ↓ psychosis. (Pimvanserins/Reseprine/Tetrabenazine)
Reserpine
35
Newer gen VMATi that ↓ choeric movemt + used for HD Chorea (Pimvanserins/Reseprine/Tetrabenazine)
Tetrabenazine
36
Valbenzaine and Deutetrabenzine block ____ (rcp type), ↓ synaptic DA?
VMAT2
37
Parkinson's DA enhancing pro-drug that crosses BBB; high doeses cause dyskineisa + hallucinations/psychosis (Levadopa/Carbidopa)
Levodopa
38
Parkinson's DA enhancing combo-drug that prevents peripheral DA activity; ↓fatigue, dizziness, nausea and hot flashes, etc (Levadopa/Carbidopa)
Carbidopa
39
Prescribe these 2 drugs to treat dperession caused by low DA state via the 1C pathway
l-methylfolate + s-adenosyl methionine
hint: ↑ 1C cycle --> ↑ neuronal DA prodn
40
Effectiveness and Purity are concnersn for _____
Complimnetary alternative Medicien
41
TT alleles for what enzyme results in lower DA prodn
MTHFR (methyl folate prodn)
42
ADHD stimulants that block and reverse DAT, ↑ VMAT2 DA ejection
Amphetamines (dextro-/lisdexam-phetamine + mixed salts)
43
ADHD stimulants that block DAT more aggresively than bupropion
Methylphenidate
stims have greater DA, NE, NRI SEs
44
Class IV stimulants for treating narcolepsy, apnea, shiftworks fatigue (but not ADHD) (2)
Modafinil + Armodafinil
45
Modafinil and Armodafinils may lower birth control effectiveness; cause addiction; or appetite + weight loss. How?
↑ p450-3A4 enzymes lower OCP;
↑DA in the mesolimbic pathways --> addiction (psychosis at hig doses);
↑ NE --> apetite and weight loss
46
stimulants that ↑ histamine activity in TMN (alertness) and ↑ orexine activity (wakefulness, requires DAT; may manipulate post-syn NE rcps (amphetamines/finils)
Modafinial + Armodafinil
47
Isocarboxid, phenelzine, tranycypromine, selgeine can all treat _____ (dz) viah ___ (mech)?
depression;
| MAOa/b inh
48
low dose MAOb and high dose MAOa/b inh for Parkisnons + Depression
Selegiline
49
MAOb inh used for Parkinsons
Rasagaline
hint: MAOb more sgf for DA
50
MAOi SEs include hypotn, dizziness, insomnia, wt gain via antagonism of what 2 rcp's
𝛂1 + histimine1 rcp antagonism
51
MAOi for depression primariy targets MAOa which interferes with ___ (2 NTs) breakdown.
5HT + NE
hint: basis for drug-drug interaction
52
how may a Hypertensive crisis leading to a heart attack/stroke occur
↑↑↑ NE --> ↑↑↑BP --> HC
eg ingesting tyramine or adding and NE agonist --> release NE --> HC
53
how may seratonin syndrome occur?
adding aggressive 5HT drug (antiD, narc, antiH1) --> toxic 5HT levels in CNS --> SS
hint: tremor, muscle spasm, unstable vitals, hyperthermia, delirium, coma and death
54
2 COMTi drugs for Parkinsons and SEs
Entacapone (nausea + fatigue)
Tolcapone (liver failure/∆lfTs)
hint: ↑synaptic DA
55
Bromocriptine, Pramipexole, Ropinerole, and Apomorphine injections treat Parkinsons and RLS via____ (MOA)
phasic D2 agonism** to ↑DA activity
hint: common SEs = nausea, fatigue, dizziness, and mania
56
Aripiprazole and the pips treat Schizophrenia and Depression via____ (MOA)
tonic D3 partial* agonism to ↑ alertness and energy
57
Used to treat Parkinson's and Influenza* by releasing DA, blocking DAT and stimulating D2
Amantidine
hint: SE = pyschosis, insomnia, seizures
58
DSM5 insomnia criteria (4)
1. CC of dissatification with sleep quality or qty
2. causes distress or impairs life/functioning
3. 3+ nights/wk for 3+ mo
4. not due to substance/meds/mental disorder
59
Excess of NTs at night can lead to insomnia (4)
1. NE (locus ceruleus)
2. 5HT (raphe nucleus)
3. DA (vent tegmental area)
4. Histamine (tuberomamillary nucleus)
60
Defc of NTs at night can lead to insomnia (3)
1. GABA
2. melatonergic tone
3. adenosinergic tone
61
Psych cause for insomnia where short REM sleep latency, repeated nightime awakenings, and wkaing too early occurs?
MDD
62
Psych cause for insomnia where manic and hypomanic have problems falling/staying asleep (and usually don't feel tired) occurs?
Bipolar Disorder
63
Psych cause for insomnia dt nightmares/trouble falling asleep occurs?
Generalized anxiety disorder/PTSD
64
Sleep deprivation hits what 3 areas of the brain the hardest?
ant cingulate gyrus, prefontal Cortex, thalamus
65
steps to tx insomnia (3)
1. dx, consent, education
2. behavioral counseling (sleep hygiene)
3. Meds
4. Mgt (risk of addiction)
66
Pharmocodynamic MOA of BZRAs and BZs
positive allosteric modulation of GABAa rcp --> sensitized Cl- pores (↑opening duration + frequency) --> ↑hyperpolz
67
___(drug class) stimulate wake cts where NE, 5HT, DA, and ACh are made. These are targets for ↓ arousal
orexins
68
antagonizing 5HT2a creates ____(effect)
deeper sleep patterns
69
antagonizing 5HT1d and 7 promotes ____(effect)
more accurate circadian clock
70
antiD's can also target ____(rcp), to ↓arousal --> sedation --> sleep initiation
H1 rcp (histamine)
71
how would you dx and tx the following: xs datyime sleepiness/cant maint wakefulness; not dt medical/substance issues; affecting daily life.
hypersomnia;
tw stimulants (cafeine, methylphenidate, amphetamine, modafinil/armodafinl)
tw hygeine (morning- light/excercise/meal or strategic naps)
72
how would you dx and tx the following: abrupt sleep attacks; cataplexy; hyno-pompic/gogic hallucination; ↓↓REM latency; sleep paralysis
narcolepsy
tw stimulants or armodafinil (if defc orexin rcps)
73
how would you dx and tx the following: partner complains of snoring/gasping/coughing; obese/overwt pt; yields insomnia/hypersomnia
sleep apnea
tw CPAP, dental devices, surgery, impantable device for hypoglossal stim.
74
how would you dx and tx the following: yields in-/hypersomnia dt sleep wake cycle mistmatch/shift/syncrhony advanced (elderly) vs delayed (jetlag/shiftwork)
CRSD (circ rhythm sleep disorder)
tw benzos, melatonin, exercise, stimulants, or light tx
75
how would you dx and tx the following: 1) unconscious leg movements 2) creeping sensations, conscious movements occurs
1) nocturnal myoclonus
2) RLS
tw D2 rcp agonists (pramipexole, ropinirole)
76
how would you dx and tx the following: long frightening dreams where pt is awake, alert, oriented and remembers dreams vividly; occurs during REM
Nightmare Disorder
tx: Self-limiting
77
how would you dx and tx the following: Pt is awake disoriented, not consolable, has no emmory, dreams are vague if remembered; happens in 1st 1/3 of the night in NREM stage (3 or 4)
Sleep Terror disorder
tx: self limiting
78
how would you dx and tx the following: teeth frinding in stage 2 of sleep
Sleep rel bruxism
tw mouth guard/bite plate
79
how would you dx and tx the following: occurs during sleep, pt can awaken confused but orients; but will not remember the event
sleeptalking/walking (somn-iloquy/ambulism)
tx: self limiting
80
how would you dx and tx the following: 1) atonia during REM --> violently act out dreams
2) rocking head back and forth /left and right while asleep
1) REM sleep behaviro disorder tw D2 agonists
| 2) Jactatio capitis nocturna/sleep related head banging; tx = self limiting
81
hyperthyroidism and pheochromocytoma are organic causes of anxiety disordrs dt increased ___(NT)
↑NE levels
82
neurogbio factors contributing anxiety ↑ ____(2 NTs) and ↓ ____ (2NTs)
↑NE + Glutamate;
| ↓5HT + GABA
83
1. xs worry about 1+ event, for 6+ months
2. can't control worry
3. 3/6 sx
4. sgf impairments
5. no other explanation
list the DSMV criteria for GAD (5)
84
AntiD's for GAD + MOA
SSRis: escitalopram/Paraoxteine;
SNRis: Venlafaxine/Duloxetine;
MOA: ↑NE/5HT --> desentiize rcps
85
5HT agonist for GAD + MOA
Buspirone;
MOA: 5HT1a ag --> ↓5HT actiivty --> downregn --> ↑5HT output
hint: ↓sex/wt gain SEs
86
2nd line Rx for GAD dt addiction/fall/apnea risk + MOA
BZs;
MOA: GABAa PAM --> ↑Cl+ channel openings
87
Abrupt, unexpected surge of intense fear/discomfort (minutes) with 4/12 sx
Panick Attack (DSMV)
88
1. Recurrent, unexpected attacks
2. 1+ attack --> 1+ mo of (concern of attacks + maladaptive behavior change)
3. no other sx explanation
Panic Disorder (DSMV )
89
1. fear/anxiety abt 2/5 situations
2. fear of inability to escape situation
3. situation always produces fear
4. Avoids situations
5. fear out of propn to actual danger
6. 6+ mo
7. sgf impairment
8. ø other explanation
Agoraphobia (DSMV)
90
Therapy tx for Panic Disorder (2)
CBT (flooding/desnesitizn) + Psychodynamic Tx
91
Meds for Panic Disorder (3)
1. Fast BZs like alprazolam (emergency)
2. SS/NRis (1st line long term)
3. intermediate/long BZ's (2nd line long term dt addiction)
92
1. 6+ mo's
2. sgf impairment
3. marked fear for specific obj/situation
4. obj/situ always provokes fear
5. actively avoids obj/situ
6. fear out of propn
7. ø other sx explanation
Tx?
Specific phobia (DSMV)
93
vocal tics, motor tics, ± OCD
Tourrette's Disorder
94
repetitive motor movements ≠ compulsion
temporal lobe epilepsy
95
rigid, moralisitc workaholic pt who is list/pattern oriented w/ no insight into behavior. Wont's have discret, repetitive behaviors to undo anxiety
OC Personality D (OCPD)
96
Comorbidt's of OCD (3)
MDD (1/3)
Tourrettes (2/3)
high suicide risk
97
OCD PsychoTx (2)
- CBT (exposure + response)
| - ACT (acceptance + commitment)
98
OCD PharmaTx (4)
1st line = high dose/duration SSRi
2nd = CLimpriamine (TCA for OCD)
3rd = AntiPsy's/antiD's
hint: BZ don't work!!!
99
Tx for Social ANxiety Disorder (social Phobia)
PsychoTx: CBt, ACT
1st line: SS/NRis's (Paroxetine/Venafaxine ER)
2nd: MAOi's (Phenelzine, Tranylcypromine)
100
1st line Rx for performance social anxiety (public speaking) ONLY?
Beta Blockers (propranolol)
101
3 chrs of local anesthetic?
1. reversible
2. blocks nerve impuslse transmission
3. ø efx on consciousness
102
first lcoal anesthetic?
Cocaine
hint: Incan use --> eye surgery --> jaw nerve block --> brach plex --> spinal anesthia
103
Cocaine was followed by ____ in 1901 and ____ in 1928
Procaine (unstable/allergy inducing);
| Tetracaine (high vol tox)
104
This anesthetic, mde in 1942, was more effective/longerlasting/lower risk than its predecessors, and could be diluted/stored with Epi
Lidocaine
105
Why is the inside of the neuron negative? (3)
1. ↑ ⊖ cytoplsamic proteins
2. K+ efflux thru leak channels/impermb to Na+ ions
3. Active Na/K pumps (3 Na+ out/2 K+ in)
106
preemptive analgesia
nerve block before incision
107
Local anesthetics bind reversibly to the ____ part of the Na+ channel to inactivate it
intracellular
hint: ↑excitation threshold/↓impulse conduction
108
critical length in myelinated nerves is
2-3 Nodes of ranvier
109
name the state of the Na+ channel:
| ø stimulus
resting (closed but modifiable)
110
name the state of the Na+ channel:
| immediately on depolz
active
111
name the state of the Na+ channel:
refractory to repeat stimulus
transitions ms's after opening
inactivated (closed + non modifiable)
112
Na+ Blockade deps on (2)
voltage and time
hint: ↑ during active state + rapid fire axons
113
name the 3 parts of local anesthetic mol
- aromatic rign (lipophilic; potency)
- intermediate link (ester/amide)
- terminal 3˚ amine (hydrophilic wk base; on/off switch)
114
Cocaine, Procaine, Tetracaine, Chlorprocaine, and Benzocaine are all eg's of
esters broken down by esterases
hint: "one eyed esther has allergies"
115
Lidocaine, Bupivacaine, Ropicaine, Mepivacaine are all eg's of
Amides
hint: amides have two I's
116
how does a LA repond to infected tissue; when bicarbonate is added
- ↓effectiveness dt acidic/infected env;
| - ↑potency/faster onset bc less ionized form can cross CM --> activate
117
onset of action depends on (2)
pKa + lipid solb
118
duration of action deps on
plasma protien binding to 𝛂1 GP
hint: rel to lipid solb
119
list the order of Nerve block sensitivity by nerve type: A𝛂, Aβ, A𝛅, C
C(pain w/chem) > A𝛅 (pain) > Aɣ (muscle tone) > Aβ (touch) > A𝛂 (propio/P) > motor
120
what is more senstive than C fibers?
B fibers (pregangiolonic SNS)
hint: vasomotor for viscero-/sudo-/pilo-motor
121
Epi (↑/↓) absorbtion?
epi decreases abs
hint: ↑HR after epi = probable bv insertion
122
rapid* metabolism to water solb metabolites is impaired by abnormal ____(gene/enz)
psuedocholinesterase that break down esters
hint: occurs in plasma
123
How are intrathecal esters metabz?
abs into blood bc CSF lacks pseudocholinesterase
124
slow metabolizm by _____ (enz)may be impaired by liver dz (liver tox); or prolongd by ↓hepatic flow/CHF/Vasopressor use
Carboxyl esterases or CYP450 enz's that break down amides
125
COntinuous spinal catheter use results in pt reporting severe back pain, loss of motor control, sensory deficits (saddle anesthesia). Bladder and bowel control is also lost. what happened?
Cauda Equina syndrome
hint: also occurs with high dose lidocaine (neurotoxic acc'm of LA in caudal space after admin to a restricted subarachnoid space) --> conduction failure, membrane/cytosk/axonal transport dmg, ↑intracell Ca+, apoptosis
126
Pt in surgery for lithotomy reports brief, severe pain (dysesthesia). Dx? what 3 drugs were most likely used? (lidocaine, Bupivicaine, Procaine, Chlorprocaine, Mepivacaine)
Transient Neurologic Sx;
| lidocaine, Procaine, Mepivacaine
127
circumoral numbness, dizziness, tinnitus, blurred vision, and CNS excitation are all early signs of
systemic toxicity
128
how does bupivicaine cause cardiotox
binds Na+ channels in the heart --> ↓myocard contractn + refractory period
129
intrinsic props that ↑ potential for CNS tox (2)
↓prot binding + clearance
130
extrinsic props that ↑ potential for CNS tox
metabolic acidosis
hint: ↑CBF + ↓plasma prot binding --> ↑PCO2
131
all LAs are vasodilators (± cardiac arrest) except (2)
Cocaine + Ropivacaine
