Block 1 Flashcards
1
Q
What does a neurologic exam show?
A
Symmetrical vs asymmetrical function; may identify local lesions within NS
2
Q
Imaging Tools
PET
SPECT
MRI
CT
A
CT; images of brain in slices in 1-10mm thickness
MRI; more detailed image vs CT, uses magnet of H+ and protons
PET; excellent resolution, rates of biological process w/ C14-deoxyglucose
SPECT; poorer resolution than PET, radiotracer where tissue uptake gives image
3
Q
Delirium DSM5
A
Environmental + Medications
Occurs most in older individuals at ICU, nursing homes, or hospice
Can be caused by substance intoxication
4
Q
Epidemiology of migraines?
A
17.1% women and 5.6% men in US have ≥1migraine/yr
After age 12, females are 2-3x more likely to suffer
Highest prevalence in both women and men are aged 30-49
5
Q
Migraine pathophysiology?
A
Activity of trigeminovascular system
Vasodilation and activation of perivascular trigeminal nerve which releases vasoactive peptides
Activates hypothalamus and brainstem
Releases CGRP + PACAP
6
Q
What are the genetic mechanisms behind migraine triggers?
A
Calcium and sodium channels and PP abnormalities that regulate cortical excitability via SEROTONIN release
Increased levels of excitatory AA such as glutamate
7
Q
IHS diagnostic classification of Migraine w/o Aura?
A
≥5 attacks
Lasts 4-72hrs
Lots of sx such as pulsing quality, N/V, photophobia, etc
8
Q
IHS diagnostic classification of Migraine w/ Aura?
A
≥2 attacks
Fulfills criteria for atypical pain or aura
9
Q
What is an aura?
A
Affects 25% of migraineurs
Lasts for 1 hr
Has both “positive” and negative visual effects
Sensory and motor symptoms occur as well
10
Q
Epidemiology of tension headache?
A
1yr prevalence is 31-86%
Peaks in 4th decade and decreases incidence w/ age
Women>Men
Functional impairment occurs in 60% of tension type headache sufferers
11
Q
Pathophysiology of tension headache?
A
May originate from myofascial factors, peripheral sensitization of nociceptors, and heightened sensitivity of pain pathways in CNS
Stimuli such as mental stress, etc
12
Q
How does tension headache present?
A
Bilateral pain in a hatband pattern
No aura
Minor disabilities vs other headaches
Physical activity doesnt affect severity
13
Q
Epidemiology of cluster headaches?
A
Lifetime prevalence is 0.12%
Male:Female ratio is 3:1
Men typically get it in 3rd decade, women at younger age
Predisposition in certain families
65% of pt w/ this headache are current/former tobacco users however cessation doesnt improve the headache :(
14
Q
Pathophysiology of cluster headaches?
A
Modulator = hypothalamus
Secondary activation of trigeminal autonomic reflexes
Alterations in circadian rhythm
15
Q
Clinical presentation of cluster headaches?
A
Daily attacks for 2wks to several months followed by long pain-free intervals
Occurs commonly at night and in spring/fall
Lasts 15 to 180min
16
Q
Migraines are typically (bilateral/unilateral)
A
Unilateral
17
Q
What are the CGRP receptor antagonists used for migraine prophylaxis?
A
Erenumab
Fremanezumab
Galcanezumab
18
Q
What is MIG-99?
A
Used prophylactically for migraines that is extracted of feverfew daisies
19
Q
What are the 1st and 2nd Gen serotonin 5-HT1 agonists? Major differences?
A
Sumatriptan is the only one that is first gen
Everything else is second (rizatriptan, etc)
2nd gen = higher oral bioavailability
20
Q
What functional group is vital for 5-HT1 agonists?
A
Indole group
2 benzene rings with one having an N-H
21
Q
What specific receptors do 5-HT1 agonists target and their MOA?
A
5-HT1B + D
Vasoconstriction of intracranial arteries
Inhibits vasoactive peptides released from perivascular trigeminal neurons
Inhibits transmission thru 2nd order neurons ascending to thalamus
22
Q
Which sumatriptan formulation has significant 1st pass effect? When severe GI symptoms present?
A
1st pass = oral tablet
GI issues = suppositories
23
Q
Triptans vs ergot alkaloids, which have better anti-migraine efficacies?
A
Triptans
24
Q
Which triptans have the longest half life?
A
Naratriptan and Frovatriptan
25
5-HT1 agonist AE?
Paresthesia, dizziness, neck pain
Coronary vasospasms
CI in pt w/ CAD and angina, hemiplegic or basilar migraine
26
What class of drugs are ergotamine and dihydroergotamine (DHE) similar to?
5-HT1 agonists
27
Caffeine can be added to ergotamine to do what?
Improve rate and extent of oral absorption
28
Ergotamine and DHE AE and CI?
N/V
CI in renal/hepatic failure, CAD, uncontrolled HTN, pregnancy or nursing mothers
29
Which receptors do ergotamine and DHE target?
5-HT, alpha, and dopamine 2,3,4
30
CGRP receptor antagonist general info?
Erenumab is the only human antibody, the other two are humanized
PREVENTS migraines
Metabolized by non-sepcific proteolysis (not by CYP)
31
Acupuncture and episodic migraine?
They reported less AE vs those w/ Rx and were less likely to drop out
32
General algorithm for headaches?
If mild/moderate symptoms, use NSAIDs,APAP. If that doesnt work, use fiorcet. If that doesnt work then use Triptans, ergotamine/DHE, CGRPs
If severe symptoms, go straight to Triptans, ergotamine/DHE, CGRPs
33
Non-pharm Headache Tx?
Ice on head
Rest in a dark, quiet area
34
What dose and response rate is used as reference for triptans?
Sumatriptan 100 mg dose and 2 hour response rate
35
What should you NOT take w/ triptans?
MAOIs within 2 wks
36
Lasmiditan (Reyvow®) info
Serotonin 5-HT1F r agonist
Dose: Once daily
Possible serotonin syndrome, Inhibits OCT1 w/ no interaction to sumatriptan
Primary endpoint: no pain for 2 hrs (20-40%)
37
Ubrogepant (Ubrevly®) info
First PO CGRP antagonist for acute Tx. PRN
Taken twice a day, max 200mg/24hrs
Second dose is taken 2hrs after the first dose
Metabolized by CYP3A4, avoid with -azoles
38
Rimegepant (Nurtec ODT®) info
Acute Tx. with/without aura and currently NOT approved for prevention
CGRP antagonist given PO or SL
Mostly metabolized by CYP3A4, avoid with -azoles within 48hrs
39
Pt consideration when using NSAIDs for acute headaches?
Use suppositories for those with N/V
Don't overuse NSAIDs cause it will medication-overuse headaches
40
NSAIDs alone vs Combo products (fioricet)
Which one has a higher chance of medication-overuse headaches?
Combo
41
Safety tips when using ergotamine?
Dont use within 24hrs of triptans
42
Prophylactic regimen therapy for headaches?
Recurrence is predictable? (pregnancy, migraine)
*Use triptan or CGRPs
Healthy or heart issues?
*Beta blockers or verapamil if they are contraindicated not effective
Depression or insomnia?
TCAs
Seizure or bipolar?
Anticonvulsants
None of the above work? Combo products/seek specialist
***go down this list, if anticonvulsants dont work, you may use beta blocker or verapamil then go to last step
43
NSAID therapy info?
Naproxen has the strongest evidence
Use 1-2 days prior to headache and continue using it
Monitor for GI and renal toxicity when using longterm
44
BB therapy info?
Timolol, propranolol, metoprolol
Might raise migraine threshold
BB w/ intrinsic sympathomimetic activity are ineffective
45
Triptan therapy info?
Frovatriptan has established efficacy over naratriptan and zolmitriptan (those only have probable efficacy)
Useful in preventing MENSTRUAL migraine, Use 1-2 days prior to headache and continue using it
46
Antidepressant therapy info?
Amitriptyline, venlafaxine
Downregulates 5-HT2 receptors, increases lvls of norepi, enhanced opioid receptor actions
Limited use due to anticholinergic effects
Caution in BPH and glaucoma and those taking triptans due to serotonin syndrome
47
Anticonvulsant therapy info?
Valproate, divalproex, topiramate
Inhibits GABA, modulates excitatory glutamate, inhibits sodium and calcium channels
Must titrate to avoid AE
Valproate is CI in pregnancy, pancreatitis, and liver disease
48
CGRP and Eptinuzmab (Vyepti™) info?
Galcanuzumab (Emgality™) used for migraine and cluster HA
Preventive drugs
Eptinuzmab is given IV q3months. No interactions w/ sumatriptan
49
What are used in tension HA?
Simple analgesics and NSAIDs
Limit use of NSAIDs for 15 days
Combo 9 days
Butalbital 3 days
50
Abortive therapy for cluster headaches?
Verapamil is first line; takes about a week
Oxygen 100% 12L/hr for 15-30min; caution in those w/ COPD or smoke
SQ or intranasal triptan; 6mg SQ sumatriptan is more effective, but intranasal is better tolerated
IV dihydroergotamine, sublingual or rectal ergotamine can be used as well
Lithium and corticosteroids can be used
51
Pathophysiology of seizures?
Inhibits GABA-A
GABA-B are activated, decreases calcium influx and inhibits neurotransmitter release
Glutamate is the excitatory NT that produces seizures
52
What are the highest RF for SUDEP?
Generalized seizures
Seizures >3/year
53
Which antiepileptic Rx display non-linear PK?
Phenytoin and ethotoin
Valproate when doses >2.5g/day, ethosuximide when doses >1.5g, gaba and pregabalin, and carbamazepine
54
Antiepileptic therapy + special population?
Women = increased drug clearance, secretion of rx in breast milk, fetal malformations
Men = possibility of reduced fertility
Peds = altered PK and need to adjust dose
Geriatric = decrease your dose and many rx interactions
55
Important Rx interaction with valproate?
Lamotrigine
Phenobarbital (increased conc of it)
56
Which antiepileptic drugs dont have any interactions and why?
Gabapentin, pregabalin, Vigabatrin, and Keppra due to renal excretion
57
General AED AE?
Idiosyncratic rxns, blood dyscrasias, SJS/rash, aplastic anemia, pancreatic issues
58
Carbamazepine AE?
Hyponatremia, leukopenia (d/c if WBC<2500), decreased bone density
59
Ethosuximide AE?
N/V, titrate the dose slowly
60
Cenobamate info?
Used for partial onset seizures in adults
DRESS AE
61
Clobazam info?
BZD derivative
Abrupt d/c may cause withdrawal symtpoms
Controlled
62
Eslicarbazepine info?
Pro drug, also better oral absorption vs carbamazepine
Up to 1200mg/day
Hyponatremia
63
Ezogabine AE?
Urinary retention (careful w/ anyone that has BPH or on anticholinergics) and QT prolongation, blue skin discoloration and retina pigment change
64
Felbamate info?
AE = weight loss and anorexia
Limited use and only for those who dont respond to other agents
65
Gabapentin/Pregabalin info?
L-amino acid GI absorption
Pregabalin is a controlled agent and more potent
66
Lamotrigine info?
Pt w/ hx of rash are more likely to have a rash with this Rx
Warning of HLH
67
Oxcarbazepine info?
Prodrug, better oral absorption vs carbamazepine
Can cause hyponatremia
68
Perampanel info?
AMPA receptor antagonist
Causes dizziness and somnolence
69
Phenobarbital info?
Causes delayed development in kids and cognitive impairment in adults, and toxic epidermal necrolysis
Parental product contains propylene glycol and alcohol
70
Phenytoin info?
Do NOT give IM
Uses Michaelis-Menten kinetics
100 mg phenytoin = 92mg phenytoin sodium
Causes gingival hyperplasia and skin issues, ataxia nystagmus
71
Topiramate AE
Can cause kidney stones and metabolic acidosis. Cleft palate in newborns too
72
Valproic acid info?
UGT and beta oxidation
Causes hyperammonemia and platelet issues
73
Vigabatrin info?
S enantiomer is active
Can cause seizures
74
Zonisamide info?
Related to sulfonamide
Can cause decreased sweat, weight loss, and kidney stones
75
What is Dravet Syndrome?
Epilepsy at 1-18 months, variant of SCN1A
Can present in kids or adults
76
How do you treat Dravet Syndrome?
1st line: Valproic acid or Clobazam
2nd line: stiripentol (w/ valproic acid or clobazam) or topiramate or ketogenic diet
3rd line: AED addition or vagus nerve stimulator
77
Lipophilicity and onset of action/duration?
More lipophilic = more rapid onset = shorter duration = high logP
78
What does primidone form?
Phenobarbital + PEMA
PEMA is the weaker anticonvulsant, but is the major metabolite. Is has more toxicity issues
79
Phenobarbital and primidone induce what?
CYP2C
CYP3A
UGT
80
Barbiturate MOA and application?
Increases GABA activity
Partial/generalized tonic-clonic seizures
81
Hydantoins MOA and application?
Inactivates Na channels
Partial/generalized tonic-clonic seizures
82
Succinimides MOA and application?
Blocks T-type Calcium channels
Absence seizures
83
Phenytoin interaction and induction?
90% protein bound which can displace other highly protein bound rx such as Tiagabine
Induces CYP2C, CYP3A, and UGT
84
Phenytoin solubility issues?
It has poor solubility at neutral pH
Absorbs CO2 which causes crystallization, IM injections can be painful
85
Fosphenytoin solubility?
Highly water soluble prodrug
Given as IM or IV and is consistent and predictable
86
Which epileptic drug is not an enzyme inducer?
Ethosuximide even though it is structurally similar
CYP3A4 inducers however can decrease exposure of ethosuximide
87
Which antiepileptic drug is chemically and metabolically reactive at the C10-C11 double bond?
Carbamazepine
88
Carbamazepine metabolism pathways?
Forms an active and reactive metabolite
Active = more toxic than carbamazepine
Reactive = are electrophilic and readily react with thiols
Induces CYP2C, CYP3A, UGT + CYP1A2
89
Carbamazepine AE?
Causes ACHS indicated by fever, rash and hepatotoxicity, blood dyscrasias
90
Whats different about oxcarbazepine vs carbamazepine in terms of metabolism?
2nd Gen analog btw
Doesnt undergo CYP3A4 oxidative metabolism
Also no reactive metabolites, just active only
91
Whats different about eslicarbazepine acetate vs carbamazepine and oxcarbazepine in terms of metabolism?
Prodrug, converts to (S)-licarbazepine (eslicarbazepine)
Produces greater plasma exposure of active metabolite vs oxcarbazepine
92
Gabapentin info?
Not metabolized in human and does NOT bind to proteins
Eliminated renally as unchanged rx
Substrate of L-AA and uses active transport
Transporter protein is saturable and bioavailability is dose-dependent and variable amongst ppl
93
Differences of pregabalin vs gabapentin?
Pregabalin is pretty much the same, but is 3-10x more potent as an anti-seizure rx
94
Differences of gabapentin enacarbil (Horizant) vs gabapentin?
Gabapentin enacarbil (Horizant) is a prodrug which overcomes absorption issues
95
Vigabatrin MOA and AE?
Irreversible (suicide) inhibitor of GABA-transaminase, therefore increases GABA in CNS
Progressive and permanent bilateral vision loss, must be in SHARE program and periodic vision testing
96
Tiagabine metabolism?
Highly protein bound ≥95%
Oxidation via CYP3A4, inducers will reduce the drug
97
BZD metabolism?
Protein bound correlates w/ lipid solubility
EX: diazepam (98% bound with logP=3) vs lorazepam (85% bound with logP=2.4)
Therefore diazepam reaches CNS concentration faster and redistributes into fat faster
98
Valproic Acid metabolism and AE?
Inhibits CYP2C9, UGT, and epoxide hydrolase
Teratogenic! Hepatotoxicity
99
Valproic acid metabolism pathways
Forms active and toxic metabolites!
Can deplete glutathione which leads to toxicity too!
100
Which Rx has BBW given by FDA for aplastic anemia and hepatic failure?
Felbamate; linked to reactive metabolites via glutathione depletion
101
Lamotrigine MOA?
Metabolized by N-glucuronidation, DDI with Rx that induce/inhibit UGT
102
Topiramate metabolism?
Absorbed rapidly via oral route, 70-80% of drug is excreted unchanged in urine
Dose goes down in renal insufficiency
Inhibits CYP2C9
103
Keppra and Brivaracetam metabolism?
Rapid absorption, minimal protein biding, and NOT metabolized by CYP450, UGT, or epoxide hydrolase
Brivaracetam has affinity towards SV2A + Sodium channel blocking activity
104
Zonisamide metabolism?
Half of excreted drug is a a glucuronide conjuagte known as SMAP
Co-adminstration with another CYP3A4 inducing anti-seizure med (phenytoin, carba, etc) will reduce half life and plasma concentration
105
Lacosamide metabolism?
Converts to inactive O-desmethyl metabolic via CYP2C19, excreted 40% unchanged rx
No effect on P450s
106
Rufinamide metabolism?
Major metabolite (78%) is due to carboxylesterase-mediated hydrolysis which can lead to inactive metabolites
Low protein binding, but can be induced by other anti-seizure meds
Valproic acid DDI, increases rufinamide concentration
107
Ezogabine metabolism?
Not metabolized by P450
Pathway includes N-gluc by UGT
108
Perampanel metabolism?
Highly protein bound and metabolized by CYP3A
Discovery led to drug design popularity for AMPA receptors..?
109
Cannabidiol info?
Component of Cannabis sativa plant, NOT psychoactive like THC
Metabolized by 2C19, 3A4, and UGT
Inhibits 2C19
110
Which drug interacts with cannabidiol?
Inhibits 2C19, therefore lacosamide
111
Which anti-seizure meds are NOT metabolized by CYP450?
Keppra + Ezogabine + Rufinimide
112
Which anti-seizure meds are metabolized by N-gluc?
Ezogabine + Lamotrigine
113
Which anti-seizure med needs to be renally adjusted?
Topiramate
114
Which anti-seizure med displaces other Rx?
Phenytoin
115
What is the GABA_a receptor?
Chloride channel
Activating it hyperpolarizes the potential which inhibits action potential
116
What are the glutamate receptors?
Activation increases both sodium and calcium, which causes membrane depolarization, which encourages action potential
117
Do depress neuronal activity, should you open/close what?
Calcium
Chloride
Potassium
Sodium
Close both sodium and calcium
Open both potassium and chloride
118
Lamotrigine
```
Calcium
Chloride
Potassium
Sodium
GABA
Glutamate
```
Sodium inhibition
119
Primadone
```
Calcium
Chloride
Potassium
Sodium
GABA
Glutamate
```
Sodium inhibition, increase GABA
120
Oxcarbazepine
```
Calcium
Chloride
Potassium
Sodium
GABA
Glutamate
```
Sodium inhibition
121
Ezogabine
```
Calcium
Chloride
Potassium
Sodium
GABA
Glutamate
```
Potassium activation
122
Eslicarbazepine
```
Calcium
Chloride
Potassium
Sodium
GABA
Glutamate
```
Sodium inhibition
123
Lacosamide
```
Calcium
Chloride
Potassium
Sodium
GABA
Glutamate
```
Sodium inhibition
124
Zonisamide
```
Calcium
Chloride
Potassium
Sodium
GABA
Glutamate
```
Sodium and T-type calcium inhibition
125
Perampanel
```
Calcium
Chloride
Potassium
Sodium
GABA
Glutamate
```
AMPA (glutamate) receptor antagonist
126
T-channel calcium blockers are useful for which seizure?
Absence
127
Which anti-seizure med undergoes no metabolism and is excreted unchanged by kidney?
Gabapentin
Pregabalin
Vigabatrin
Keppra
128
What are the Rx used for absence seizures?
Ethosuximide and valproate
129
What are the Rx used for status epilepticus?
Phenytoin
Diazepam
Lorazepam
130
Rufinamide AE?
Shortens QT interval
131
BZD MOA?
Bind to GABA_a receptors by opening chloride channels
132
Which BZD can be given rectally?
Diazepam
133
Which barbiturate has the least sedative effects?
Phenobarbital
134
Tiagabine AE?
Increases chance of seizures and status epilepticus
135
Which antiepileptic cause blue skin discoloration and retina pigment changes?
Ezogabine
136
Felbamate
```
Calcium
Chloride
Potassium
Sodium
GABA
Glutamate
```
Sodium inhibition, binds to NMDA, calcium inhibition (not T-type)
137
Divalproex
```
Calcium
Chloride
Potassium
Sodium
GABA
Glutamate
```
Sodium inhibition, reduces T-type calcium
138
Topiramate
```
Calcium
Chloride
Potassium
Sodium
GABA
Glutamate
```
Sodium inhibition, activates potassium, reduces NMDA
139
Carbamazepine concentration levels?
4-12
140
Phenytoin concentration levels?
10-20 *also has unbound levels
141
Valproate concentration levels?
50-100 (some places go up to 150)
142
Phenobarbital concentration levels?
10-40
143
Ethosuximide concentration levels?
40-100
144
Lacosamide AE?
PR interval increase; Get baseline EKG
145
Which Rx can cause kidney stones?
Topiramate and zonisamide
146
Dopamine vs L-dopa
Which one crosses the BBB?
L-dopa
147
What are the excitatory dopamine receptors? Inhibitory?
Excitory = D1 + 5
Inhibitory = D2,3,4
148
What kind of neurotransmitter is dopamine?
Not excitatory nor inhibitory, but a modulatory of neurotransmission
149
Direct/Indirect dopamine pathway
Which one enables and inhibits movement?
Direct = enable
Indirect = inhibit
150
Loss of DA in ____ leads to reduced excitatory input to cortex
Striatum
151
What happens when you take L-dopa PO?
Only 1% reaches brain as DA
Halting conversion of L-dopa to DA in periphery should boost L-dopa taken up into CNS
152
How does carbidopa affect L-dopa?
Extends elimination half life from 1hr to 1.5 hrs
153
Does carbidopa penetrate BBB?
Nope
154
How do you reduce AE chances of carbidopa?
Reduction of peripheral DA concentrations
155
Chronic use of L-dopa leads to what?
Prominent dyskinesias
156
How do you want to affect COMT to enhance DA exposure in CNS?
Inhibit COMT should extend L-dopa
157
What Rx are COMT inhibitors?
Tolcapone and entacapone
158
Main difference between Tolcapone and entacapone?
Tolcapone acts in both CNS and periphery w/ liver problems
Entacapone is just peripherally
159
BBW of COMT inhibitors?
Just tolcapone, acute liver failure
160
What is the cheese effect?
MAOI cant be used w/ L-dopa due to it causing HTN crisis
161
What Rx are MAO-B? Functional group?
Selegiline and rasagiline
Terminal alkyne forms covalent bond with protein
162
By products of MAO-B?
Selegiline can produce amphetamine metabolites (vasoconstrictors) via CYP-mediated N-dealkylation
163
Carbidopa inhibits what?
AADC
164
With Parkinson's, what is missing?
Fewer striatal nerve terminals as decarboxylate L-dopa
165
DA receptor agonists vs L-dopa, which one has a longer duration of action?
DA receptor agonists, also less likely to induce on/off effects and dyskinesias
166
Dopamine receptor agonist AE?
N/V, sedation, vivid dreams, hallucination
167
Ergot alkaloids AE and MOA?
Cardiac issues
Nonselective DA receptor agonists (Serotonin and adrenergic activity)
168
Non-Ergot DA receptor agonist Rx? Which DA receptors do they target?
Pramipexole, ropinirole, rotigotine
Pramipexole and ropinirole = D2
Rotigotine = D1,2,3 as a patch
169
What happens if DA is removed completely?
Increased cholinergic activity leading to extrapyramidal Sx (tremors)
Use muscarinic ACh antagonists for this
170
Muscarinic ACh antagonists for Parkinson's example?
Trihexyphenidyl
Benztropine
Diphenhydramine
171
Structure of Muscarinic antagonists? AE?
Tertiary basic amine + 2x 6 membered rings
AE = sedation and mental confusion
172
What does overactive glutamate transmission in striatum cause? What is used to Tx it? AE?
L-dopa induced dyskinesias
Namenda
Confusion and hallucinations
173
What are used to Tx hallucinations/delusions in parkinsons?
Pimavanserin (04-29-16)
Inverse agonist of 5-HT2a receptors
AE = QT prolongations and avoid in pt developing cardiac arrhythmias
174
What are used to Tx "off" episodes in Parkinson's?
Istradefylline; caffeine derivative and antagonist of Adenosine A2a receptors
175
What are the hallmark features of PD?
Tremors at rest
Rigidity
Bradykinesia
Postural instability
176
What are some environmental and protective factors of PD?
Increased risk: rural areas, well water, heavy metal and hydrocarbon exposure
Decreased risk: cigarette smoking, caffeine consumption, NSAID use
177
L-dopa to Dopamine, whats the enzyme?
L-AAD
178
From DA, what other pathways can it go to?
DOPAC + H2O2 via MAO-B
HVA via COMT
179
What happens if there is a lot of H2O2 present?
Fe 2+ is converted to 3+ which forms OH* radicals
180
General direct and indirect pathway of dopamine + motor function?
Both begin at striatum via SNc's dopamine
Direct = goes straight to GPi, thalamus, then motor cortex
Indirect = stops at GPe first, then subthalamic nuclei, then GPi, thalamus, then motor cortex
181
In PD, what parts of the direct and indirect pathway are affected?
SNc cant provide dopamine to striatum
Direct = loses function from striatum to GPi
Indirect = loses function from GPe to subthalamic nuclei
Both pathways lose function from thalamus to motor cortex
182
How is L-dopa in the body made?
L-tyrosine is converted to L-dopa via TH
183
What correlation does DA have on ACh?
Lowered DA levels will increase ACh which leads to tremors
184
What is the Hoehn and Yahr Severity scale?
0 = no signs
I = Unilateral
II = bilateral, no posturing
III = bilateral, mild posturing
IV = bilateral, postural
V = severe, confined to bed or wheelchair
185
What is the first line Tx for PD? What is used for mild tremors?
Usually Rasagiline
Amantadine and/or anticholinergics (benztropine, trihexyphenidyl)
186
Tx of PD, pt has tremors
≥65yo = carbidopa/levo
<65yo = anticholinergics, then carbidopa/levo
187
Tx of PD, pt has tremors, bradykinesia, rigidity
≥65yo = carbidopa/levo
<65yo = dopamine agonist, then carbidopa/levo
188
Tx of PD, pt has tremors, bradykinesia, rigidity, postural instability/gait
≥65yo = carbidopa/levo and physical therapy
<65yo = dopamine agonist and physical therapy
anything worse than this with Sx, surgery will be needed
189
Amantadine info?
Renal eliminated (decrease dose if CrCl is low)
Causes skin discoloration (molting)
Stimulates DA release, inhibits glutamate
190
How do you Tx end-of-dose- "weaning off"?
Increase dose of carbidopa/levo or switch to ER or inhalation
Add either COMTi, MAO-Bi, or dopamine agonist
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How do you Tx delayed on or "no on" response?
Give carb/levo on empty stomach
Use ODT
Avoid SR
Use apomorphine SQ or l-dopa inhalation
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How do you treat hesitation "freezing"?
Increase carb/levo dose
Give MAO-Bi or dopamine agonist
Physical therapy
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How do you treat peak-dose dyskinesia?
Smaller dose of carb/levo
Reduce dose of dopamine agonist
Add amantadine
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What drug has the "honeymoon period"?
Carb/levo for 5-7 yrs
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COMTi AE?
Only Tolcapone has liver issues
Both have delayed onset of diarrhea and cause brownish-orange urine
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Apomorphine AE?
Severe hypotension when given with serotonin blockers (ondansetron)
Pre dose w/ trimethobenzamide to minimize N/V
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Ropinirole AE?
Can cause pt to suddenly fall asleep, pramipexole does this too
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Pimavanserin info?
Used for psychosis in PD
40mg dose, takes a couple weeks to work
Can cause QTc prolongation!!
