Neuro (3) Flashcards
(173 cards)
1
Q
What modulated cerebral blood flow?
A
- Cerebral metabolic rate
- CPP
- PaCO2
- PaO2
- Various drugs/pathology
2
Q
How is CPP calculated?
A
MAP-ICP
3
Q
With autoregulation CBF is approx _____mL/____g brain tissue per minute
A
50mL/100g brain tissue per minutes
750mL/min
4
Q
What percent of cardiac output makes up cerebral blood flow?
A
15%
5
Q
What makes up the brain and spinal cord compartment?
A
*Neural tissue
*Blood
*CSF
6
Q
What is the brain/SC compartment enclosed by?
A
Dura mater and bone
7
Q
What is the combined volume of brain tissue, CSF, and intracranial blood?
A
1200-1500mL
8
Q
When the intracranial volume is 1200-1500mL what is ICP maintained at?
A
5-15mmHg
9
Q
What is the Monro-Kellie Hypothesis?
A
Any increase in one compartment of intracranial volume (tissue, CSF, blood) MUST be offset by a decrease in another component→ prevents elevated ICP
10
Q
What happens to homeostatic mechanisms when ICP increases?
A
Homeostatic mechanisms increase MAP to maintain CPP
11
Q
What happens if ICP is elevated and homeostatic mechanisms cant keep up to maintain CPP?
A
Cerebral ischemia occurs
12
Q
The intracranial vault is considered _____________
A
Compartmentalized
13
Q
___________ barriers separate the brain contents
A
Meningeal
14
Q
What is the Falx cerebri?
A
A reflection of dura that separates the 2 cerebral hemispheres
15
Q
What is the tentorium cerebelli?
A
Reflection of dura that is rostral to the cerebellum and separates supratentorial and infratentorial spaces
16
Q
What are herniation syndromes categorized based on?
A
Region of the brain affected
17
Q
Can there be increased ICP in just one area of the brain?
A
Yes, increases in contents of one are can cause regional increases in ICP
extreme cases the contents can herniate into different compartments
18
Q
What is subfalcine herniation? What structures can be compressed?
A
Herniation of hemispheric against the flax cerebri
*often compressing branches of the anterior cerebral artery, creating a midline shift
19
Q
What is transtentorial herniation? What structures are compressed?
A
Herniation of the supratentorial contents against the tentorium cerebelli
*causes brainstem compression in rostral to caudal direction
20
Q
What are common S/S of transtentorial herniation?
A
*AMS
*Ocular reflex defects
*Hemodynamic/resp compromise
*Death
21
Q
What is uncal herniation?
A
Subtype of transtentorial herniation wjere uncus herniates over the tentorium cerebelli
22
Q
What is the uncus?
A
Medial portion of temporal lobe
23
Q
What are S/S or uncal herniation?
A
- Ipsilateral oculomotor nerve dysfxn
- Pupil dilation
- Ptosis
- Lateral deviation of affected eye
- Brainstem compression
- Death
24
Q
What can cause herniation of cerebellar tonsils? Where do the structures herniate through?
A
Elevated infratentorial pressure→causes cerebellar structures to herniate through foramen magnum
25
What are S/S of cerebellar tonsil herniation?
*Meduallary dysfxn
*Cardiorespiratory instability
*Death
26
Which number is subfalcine herniation?
1
27
Which number is transtentorial herniation?
2
28
Which number is cerebellar herniation?
3: Cerebellar contents through foramen magnum
29
Which number is showing herniation out of the cranial cavity? What can cause this?
4: Caused by trauma
30
What are causes of increased ICP?
*Tumors
*Intracranial hematomas
*Blood in CSF
*Infections
31
How do tumors lead to increased ICP?
*D/t size
*indirectly by causing edema in tissue
*obstructing CSF flow
32
Tumors involving the ____ ventricle commonly cause obstruction of CSF flow
3rd
33
How does blood in CSF cause increased ICP?
Seen with subarachnoid hemorrhage
*Obstruct CSF reabsorption
*granulation can exacerbate increased ICP
34
What specific infections commonly lead to increased ICP through development of edema or obstruction of CSF reabsorption?
*Meningitis
*Encephalitis
35
List methods to decreased ICP:
*Elevate head (encourage jugular venous outflow
*Hyperventilation (lower PaCO2)
*EVD (CSF drainage)
*Hyperosmotic drugs (draw fluid across BBB)
*Diuretics (systemic hypovolemia)
*Corticosteroids (↓ swelling, enhance BBB integrity)
*Propofol: Cerebral vasoconstrictor (↓CMRO/CBF)
*Surgical decompression
36
What are key take aways from a neuro assessment?
* Know basic path for neuro disorders
* Know pt baseline neuro deficits
* Review imaging/neuro testing
* Review current meds
* Eval potential risk/benefit of anesthetics
* Pre op measures to optimize pt condition
* Clear pre op documentation of factors above and have rationale for chosen anesthetic plan
37
Which neurological disorders discussed in lecture are genetic?
*Multiple Sclerosis
*Myasthenia Gravis
*Lambert eaton syndrome
*Myasthenia syndrome
*Muscular Dystrophies
*Myotonic dystrophies
38
_________: progressive, autoimmune demyelination of central nerve fibers
MS
39
What is the onset for MS? What are risk factors?
20-40y/o onset
Female, 1st deg relative, Epstein Barr Virus, other autoimmune disorders, smoking
40
What are exacerbation triggers for MS?
*Stress
*Elevated temps
*Postpartum period
41
What are S/S of MS? What is the cure?
S/S: Motor weakness, sensory disorder, visual impairment, autonomic instability, sx vary d/t site of nerve demylination
Tx: no cure, manage with steroids, immune modulators, targeted antibodies (IVIG)
42
What are preanesthetic considerations for a patient with MS?
* Assess existing deficits
* PFT
* CBC,BMP,LFT
* Pre op steroids if long term steroid use
* Critical temp management (temp changes can cause exacerbation)
* Avoid SUCCs
43
What are acceptable anesthetic options for pt with MS?
Ga, regional, peripheral nerve blocks
avoid succs (hyperkalemia, upreg nAch receptors)
44
What is the pathophys of myasthenia gravis? When is muscle weakness exacerbated?
* Autoimmune antibodies generated against nAch receptors at skeletal muscle end plate
* Effects skeletal muscle (not smooth or cardiac muscle)
*Muscle weakness exacerbated with exercise
45
______ hyperplasia is common in MG. What can be done to improve symptoms associated with this?
Thymic hyperplasia (10%)
90% pt improvement after thymectomy
46
What are exacerbation triggers for MG?
* Pain
* Insomnia
* Infection
* Surgery
47
Treatment for MG:
*Acetylcholinesterase inhibitors→pyridostigmine
*Immunosuppressants
*Steroids
*Plasmapheresis
*IVIG
48
What are preanesthetic considerations for patients with MG?
* PFTs
* Reduce paralytic dose (avoid prolonged muscle weakness)
* Caution with opioid (resp compromise)
* Pyridostigmine may prolong Succs and ester LAs
* pre op steroids if on long term
* Discuss w/pt about increase risk for post op resp support/vent until fully recovered from anesthesia
49
Why do we want to check LFTs on some of these patients?
*On immunosuppresant meds that can cause liver function impairment
50
What labs do we want to pay attention to if a patient is on steroids?
*Glucose and electrolytes
51
What is the pathophysiology of Eaton-Lambert Syndrome?
Antibodies against VG Ca2+ channels (P type)
* reduce Ca2+ influx into presynaptic cell
* decrease Ach release from presynaptic cell at NMJ
52
>60% of Easton Lambert syndrome are associated with _______________.
Small cell lung carcinoma (paraneoplastic syndrome)
53
What are S/S or eaton-lambert syndrome? What is the treatment?
* Progressive limb-girdle weakness
* dysautonomia
* oculobulbar palsy
* proximal muscle weakness (Improved with repeated use)
TX: 3-4 diaminopyridine (K+ channel blocker), Azathioprine, Acetylcholinesterase inhibitors, steroids, plasmapheresis, IVIG
54
What are preanesthetic considerations for ELS?
* Know existing deficits
* PFTs
* VERY sensitive to all NMB
* MORE sensitive to ND-NMB than MG pts
* extreme caution of NMB and opioid dosing
* discuss with pt potential for resp support post anesthesia
55
What is the pathophys of muscular dystrophy?
* Hereditary disorder causing breakdown of dystrophin-glycoprotein complex
* leads to myonecrosis, fibrosis, skeletal muscle membrane permeability
56
How many types of MD are there? What is the most common and severe?
* 6 types
* Duchenne MD
57
What patient population is affected by duchenne MD? What is the average lifespan?
* Occurs only in boys (autosomal recessive)
* onset 2-5 y/o
* wheelchair bound by 8-10
* Lifespace 20-25y/o→ cardiopulmonary complications
58
What are S/S of muscular distrophy?
* Progressive muscle wasting w/o motor/sensory abnormalities
* Kyphoscoliosis
* Long bone fragility
* Respiratory weakness
* Frequent pna
* EKG changes
elevated CK d/t muscle wasting
59
What are preanesthetic consideration for patient with muscular distrophy?
* CBC,BMP, PFT, CK
* Pre op EKG, echo
* cautious with ND NMBs
*avoid succs and volatiles (exacerbate membrane instability)
* MH card with dantrolene available
* regional better than GA (avoids triggers)
60
What can be triggered by succs and volatiles in patients with muscular dystrophies? What type of anesthetic would be better for these pts?
Hypermetabolic syndrome (similar to MH)
* Can lead to rhabdo, hyperkalemia, vfib, cardiac arrest
Consider low dose roc and TIVA for GA, OR Regional anesthesia
61
Prolonged contraction after muscle stimulation:
Myotonia
62
What is the most common for of myotonia? When is the onset?
Myotonic dystrophy→ onset 20-30s
63
What are S/S of myotonic dystrophy>
*Muscle wasting in face, masseter, hand, pre-tibial muscles
*may also affect pharyngeal, laryngeal, diaphragmatic muscles
*cardiac conduction may be affected (20% have mitral valve prolapse)
64
What is myotonia congenita?
Mild form of myotonic dystrophy that only involves skeletal muscles
65
What is central core disease? What are S/S?
*Rare
*core muscle cells lack mitochondrial enzymes
S/s: proximal muscle weakness and scoliosis
66
All myotonias are triggered by __________ and __________
Stress
Cold temps
67
What can myotonias be treated with?
*No cure
*S/S management with Quinine, Procainamide, steroids
68
What are preanesthetic considerations for myotonic dystrophies?
* Know extent of cardiac and pulm abnormalities
* assess heart and breath sounds
* Aspiration risk (GI hypomotility)
* High endocrine abnormalities
* Keep pts warm (avoid flare ups)
* Optimize preop resp status
* avoid succs d/t fasciculations
* caution with opioids (post op resp depression)
* Increased risk for post op weakness
69
What are the 3 major dementia syndromes?
* Alzheimers (70%)
* Vascular dementia (25%)
* Parkinsons (5%)
70
Which preop dementia meds may impact anesthetic?
*acetylcholinesterase inhibitors
*MAOIs
*Psych meds
71
Why might TIVA be better for patients with dementia? Why is regional preferred over GA?
GA with volatiles increases risk for post op delirium
Regional preferred over GA to decrease opioid requirements
72
What is the cause of Parkinsons? What is the biggest risk factor?
Unknown cause
Advanced age= biggest risk factor
73
What is pathophys of parkinsons?
* Degeneration of dopaminergic fibers of basal ganglia
* Motor neurons become over stimulated
74
What is the triad of symptoms associated with parkinsons?
*Skeletal muscle tremor
*Rigidity
*Akinesia
Rhythmic pill-rolling, facial rigidity, slurred speech, difficulty swallowing, respiratory difficulty, depression, demential
75
What is the treatment for parkinsons?
*Levodopa (crosses BBB)
*Anticholinergics
*MAOIs (inhibit dopamine degradation)
* Deep brain stimulator
76
What are preanesthetic considerations for parkinsons?
* Assess severity (attn to degree of pulmonary compromise
* Review home meds (interactions with anesthesia)
*labs/PFT
* EKG/echo
* aspiration (dysphagia, dementia)
* Continue PO levodopa
* Avoid reglan, phenothiazines, butyrophenones
*Avoid demerol in on MAOI
* Disable deep brain stimulator
* use of bipolar cautery if used
77
Why is PO levodopa continued in preop?
Avoids unstable extreme EPS such as chest wall rigidity
78
Common symptoms for brain tumors:
- increased ICP
- Papilledema
- Headache
- AMS
- Mobility impairment
- Vomiting
- Autonomic dysfunction
- Seizures
79
____ are the most common CNS glial cells
Astrocytes
80
What are the primary brain tumors, and least aggressive astrocytomas? Often found in young adults with new onset seizures
Gliomas
81
Which brain tumors are mostly benign, good outcomes if resectable, and in children and young adults?
Pilocytic astrocytomas
82
Which brain tumors are poorly differentiated and usually evolve into glioblastoma multiforme?
Anaplastic astrocytoma
83
Which brain tumors carry a high mortality, usually require surgical debulking and chemo, and life expectancy is weeks?
Glioblastoma multiforme
84
Usually benign, arise from dura or arachnoid tissue;
Good prognosis with surgical resection:
Meningiomas
85
Noncancerous brain tumors, varying subtypes;
transsphenoidal or open craniotomy for removal is usually curative:
Pituitary adenomas
86
Usually benign schwannomas involving the vestibular component of CN VIII within the auditory canal;
good prognosis w/resection +/- radiation:
Acoustic neuromas
87
These brain tumors can vary widely in origin and symptoms; outcomes are generally less favorable:
Metastatic carcinomas
88
Radiation damage may lead to ____ and ___.
lethargy and AMS
- Chemotherapy may also have neurological effects
89
What are two common medications that patients with brain tumors are on?
- Steroids to minimize cerebral edema (continue them)
- Anticonvulsants
90
What medication is given to reduce intracranial volume and pressure in brain tumor patients?
Mannitol
91
In patient's with brain tumors, ____ ____ may manifest on EKG, labile HR and BPs
Autonomic dysfunction
92
What diagnostic testing would you consider for patients with a brain tumor?
CBC, BMP (glucose), EKG, CT/MRI
93
____ is the leading cause of death and disability worldwide
Stroke
94
Strokes are characterized by sudden neurologic deficits resulting from:
- Ischemia (88% of cases)
- Hemorrhage (12% of cases)
95
Blood is supplied to the brain from:
- internal carotid arteries
- vertebral arteries
96
The internal carotid arteries and vertebral arteries from the ___ that provides collateral circulation to multiple areas of the brain
Circle of Willis
97
Occlusion of a vessel that perfuses a region of brain, causing brain cell necrosis:
Ischemic stroke
98
Sudden focal vascular neurologic deficit that resolves within 24 hours
Transient ischemic attack
99
___ of patients who experience a TIA will subsequently suffer a stroke
1/3
100
If stroke is suspected, a ______ is needed to distinguish ischemic stroke from intracerebral hemorrhage
STAT non-contrast CT
101
Causes of ischemic stroke are categorized according to the TOAST classification into 5 groups:
1. Large artery atherosclerosis (e.g. carotid stenosis)
2. Small vessel occlusion (e.g. lacunar stroke)
3. Cardioaortic embolic (e.g. emboli from atrial fibrillation)
4. Other etiology (e.g. stroke due to hypercoagulable states or vasculopathies)
5. Undetermined etiology
102
What is the initial recommended treatment for an ischemic CVA?
PO aspirin
103
What is the time window for giving tissue plasminogen activator?
3-4.5 hours post onset
104
Performed in interventional radiology, allowing for angiographic fluroscopy during administration of thrombolytics or thrombectomy:
Revascularization
105
Assessment prior to revascularization:
- avoid any delay in treatment
- focus on baseline neuro assessment, ability to safely lay flat, and CV function
- determine whether procedure could be done under sedation or if secure airway necessary
- Patients with ischemic stroke often have CV risk factors and valvular disease that could impact vasoactive drug choices and hemodyamics
106
What is a hemorrhagic CVA?
Bleeding inside the cranial vault that impairs perfusion of the brain
107
Hemorrhagic stroke is ___ more likely to cause death than ischemic stroke
4x
108
What are the two most reliable predictors of outcome for a hemorrhagic CVA?
- Blood volume
- Change in LOC
109
What does it mean that the cranial nerves are susceptible with MG?
Common Ocular Sx: Diplopia, ptosis
Bulbar involvement: can cause laryngeal weakness (resp insufficiency and aspiration risk)
110
Conservative treatment of hemorrhagic CVA:
- reduction of ICP
- BP control
- Seizure precautions
- Monitoring
111
Protocols for cerebrovascular disease:
- New anticoagulant for thrombus = no elective cases w/in 3 months
- Anticoagulants for CVA prophylaxis = consult prescriber to establish protocol
- Close monitoring of coag status
- High risk patients that pause LA anticoags will need SA coags
- If regional is planned, d/c anticoags for sufficient time to safely perform block
112
Pre-op assessment for cerebrovascular disease:
- Assess orientation, pupils, bilateral grip strength, LE strength
- Ask about headaches, tinnitus, vision/memory loss, bathroom issues
113
What diagnostic testing would you get for a patient with cerebrovascular disease?
- Imaging = Carotid US, CT/MRI head and neck, echo
- Preop EKG
- CBC, BMP, possible T&C
- Cerebral oximetry is possible
114
What do aceytlcholinesterase inhibitor drugs prolong?
* Succs
* Ester local anesthetics
115
Majority of cerebral aneurysms not ____ before rupture
diagnosed
116
Only ___ of aneurysm patients have symptoms before rupture
1/3
117
What are symptoms of cerebral aneurysms?
- Headache
- Photophobia
- Confusion
- hemiparesis
- coma
118
Risk factors for cerebral aneurysms:
- HTN
- Smoking
- Female
- Oral contraceptives
- Cocaine use
119
Diagnostics for cerebral aneurysms:
- CT/angio
- MRI
- Lumbar puncture w/ CSF analysis if rupture suspected
120
How soon should interventions be performed for cerebral aneurysms for best outcome?
72 hours
121
Pre-anesthesia considerations for cerebral aneurysms:
- CT/MRI
- EKG
- Echo
- CBC, BMP, T&C w/ blood available
- BP control, mannitol (to avoid rupture)
- seizure prophylaxis
122
Surgical treatment for cerebral aneurysms:
- Coiling
- Stenting
- Trapping/bypass (very large aneurysms)
*neurosurgeon may be on standby in case of intra-op rupture/SAH
123
What causes post-SAH vasospasms?
Free hgb triggers inflammatory mediators which reduce nitric oxide availability and increase endothelin 1, leading to vasoconstriction
124
When are patients at risk for vasospasms?
3-15 days post SAH
125
Treatment for post-SAH vasospasms:
Triple H therapy - Hypertension, hypervolemia, hemodilution
126
What are some interventional treatments for post-SAH vasospasms?
Balloon dilation and direct injection of vasodilators to relieve the spasm
127
For post-SAH vasospasms, to avoid complications of hypervolemia, ____ is the initial main treatment
hypertension
128
Pre anesthesia interventions for post-SAH vasospasms:
Same as aneurysm, although normally less invasive --
- CT/MRI
- EKG
- Echo
- CBC, BMP, T&C w/ blood available
- BP control, mannitol
- seizure prophylaxis
129
Aneurysm grading for prognosis:
*Hunt and Hess classification will gauge the mortality of the patients (won't have to use this)
130
What is an arteriovenous malformation?
Arterial to venous connection without intervening capillaries - creates an area of high flow, low resistance shunting
- believed to be congenital
131
Symptoms of AVM:
Range from mass-effects to hemorrhage
132
What is the most common location for AVMs?
Supratentorial
133
Diagnostic testing for AVM:
- angiogram
- MRI
134
Treatment for AVM:
- Radiation
- Angio-guided embolization
- Surgical resection (higher mortality)
135
Pre-anesthesia considerations for AVM:
- H&P
- review meds
- imaging
- CBC, BMP, T&C, EKG, echo
- BP control, mannitol?
- Seizure prophylaxis
- CVC or 2 large bore IVs, aline
136
AVM grading system
Spetzier-Martin: ranges different severities
137
Congenital brain abnormalities result from defects in the development or structure of the ___
CNS
138
Are congenital brain abnormalities often hereditary?
Yes
139
Congenital brain abnormalities may be diffuse or confined to specific ____ ____
Neuronal structures
140
What is chiari malformation?
Congenital displacement of the cerebellum
141
Downward displacement of the cerebellum:
Type 1 chiari malformation
142
Downward displacement of cerebellar vermis, often associated with myelomeningocele
Type 2 Chiari malformation (arnold chiari)
143
Rare, occipital encephalocele with downward cerebellar displacement
Type 3 chiari malformation
144
Cerebellar hypoplasia w/o displacement of posterior fossa contents
Type 4 chiari malformation
145
Symptoms of chiari malformation:
- Headache
- Extending to shoulders/arms
- Visual disturbances
- Ataxia
146
Treatment for chiari malformation:
Surgical decompression
147
Pre-anesthesia considerations for chiari malformation:
- Review H&P
- Deficits
- Imaging
- CBC, BMP, T&C
- May hyperventilate to decrease ICP
- Large bore IV x2 or CVC, aline
148
What is Tuberous Sclerosis?
AKA "bourneville disease
- genetic disease causing benign hematomas, angiofibromas, and other malformations that can occur anywhere in the body
149
Tuberous sclerosis lesions of the brain include:
Cortical tumors and giant cell astrocytomas
150
Tuberous sclerosis often involves co-existing tumors of what?
Face, oropharynx, heart, lungs, liver, and kidneys
151
Presentation for tuberous sclerosis likely includes:
Mental retardation and seizure disorders
152
Anesthesia considerations for tuberous sclerosis:
Airway compromise, cardiac and/or kidney involvement
153
What the heck is Von Hippel-Lindau Disease?
Genetic disease process involving formations of benign tumors of the CNS, eyes, adrenals, pancreas and kidneys
154
Von Hippel-Lindau disease are commonly associated with what?
Pheochromocytoma
- take into account exaggerated HTN
155
Types of neurofibromatosis:
Type 1 = most common
Type 2
Schwannomatosis (rare)
156
Anesthesia considerations for neurofibromatosis:
- Account for increased ICP, airway issues, scoliosis, possibility of pheo
157
What would you want to avoid in patients with neurofibromatosis?
Neuraxial anesthesia due to high likelihood of spinal tumors
158
What is hydrocephalus?
- Excessive CSF accumulation, causing ↑ICP, leading to ventricular dilatation
- Accumulation of CSF is due to an imbalance btw CSF production and absorption
- Can be congenital or acquired d/t meningitis, tumors, trauma, or stroke
159
Are symptoms of hydrocephalus acute or chronic?
Can be both
160
What is the main treatment for hydrocephalus?
Mainly diuretics - furosemide and acetazolamide decrease CSF production
161
Other treatments for hydrocephalus:
- Diuretics
- Serial lumbar punctures (temporary)
- Majority of cases require surgical treatment (VP shunt or ETV)
162
What is the difference in a VP shunt and ETV?
VP shunt = drain placed in ventricle of the brain and empties into the peritoneum
ETV (endoscopic third ventriculostomy) = catheter placed into the lateral ventricle that drains into the peritoneal space, right atrium or pleural space (rarely)
163
VP shunt malformation occurs most frequently in the ___ ___ of placement and have a ___ failure rate
1st year; high
164
How are traumatic brain injuries categorized?
- "penetrating" or "non-penetrating" depends on breech of dura
- severity categorized by GCS
165
When does primary injury occur in TBIs?
Occurs at the time of insult
166
Secondary injuries from TBI:
- Neuroinflammation
- Cerebral edema
- Hypoxia
- Anemia
- Electrolyte imbalances
- Neurogenic shock
167
Pre-anesthesia considerations for TBI:
- Review co-morbidities,
- degree of injury
- Imaging
- Labs
- Neuro exam
168
Interventions for TBIs:
- C-spine stabilization, IV access, CVC, aline
- Uncrossmatched blood if no time for T&C
- Refrain from NGT/OGT (potential for basal skull fx)
- Intra-op iSTAT labs, pressors, bicarb, calcium, blood products
169
What is a seizure?
Transient, paroxysmal, synchronous discharge of neurons in the brain
170
What transient abnormalities can cause seizure disorders?
- Hypoglycemia
- Hyponatremia
- Hyperthermia
- Intoxication
*in these cases, treating the underlying disease is curative
171
What is epilepsy?
Recurrent seizures d/t congenital or acquired factors
172
Antiepileptic drugs decrease ____ excitability/ ___ inhibition
Neuronal; Enhance
173
Pre-anesthesia considerations for seizure disorder:
Determine source of seizures and how well they are controlled
- want anti-seizure drugs on board before incision
- Review home drugs
- Phenytoin, tegretol, barbiturates are enzyme-inducers (pts on these meds require higher doses of hepatically-cleared medications)
