Block 3 Flashcards
Precentral gyrus
Precentral sulcus
Red: Superior frontal gyrus
Blue: Middle frontal gyrus
Orange: Inferior frontal gyrus (A,B,C)
A) Par opercularis
B) Pars triangularis
C) Pars obitalis
Orbitofrontal cortex:
Red: orbital gyri
Blue: gyrus rectus
Red: Postcentral Gyrus
Yellow: intraparietal sulcus
Purple: superior parietal lobe
Orange/green: lateral sulcus
Inferior parietal lobe:
Red: supramarginal gyrus
Blue: angular gyrus
Red: superior temporal gyrus
Green: middle temporal gyrus
Temporal Lobe:
Blue: Inferior temporal gyrus
Red: Occipitotemporal gyrus
Green: parahippocampal gyrus
Orange: uncus (part of parahippocampal gyrus)
Occipital Lobe:
Red: parietooccipital sulcus
Blue: Cuneus gyrus
Green: Lingual gyrus
Red: occipital gyri
Green: preoccipital notch
Visual processing streams:
Red arrow: “Where?”, analysis of motions and spatial relations
Blue arrow: “What?”, analysis of form and color
Occiput regions: Brodmann’s area’s 17 (yellow), 18 (green), and 19 (blue), corresponding to 1’, 2’, and 3’ centers
Cingulate gyrus; contains cingulum, the associational fibers that connect the cingulate gyrus with the parahippocampal gyrus
Language areas:
Red area = Broca’s area
Blue area = Wernicke’s area
Connected by superior longitidunal (arcuate) fasciculus , associational fibers
Orange arrow points to the uncinate fasciculus, associational fibers interconnecting limbic areas (i.e. septal and uncus).
Superior and Inferior occipitofrontal fasciculi; associational fibers interconecting visual areas with association cortices of frontal cortex.
Corpus callosum (yellow); a commissure interconnecting most of cerebral cortex, except portions of temporal lobes
Corpus Callosum;
A) Genu (connects frontal hemispheres)
B) Body
C) Splenium (connects occipital hemipsheres)
D) Rostrum
Anterior commissure; interconnects portions of the temporal lobes, lies anterior to hypothalamus and dorsal to optic chiasm
Posterior commissure; really part of the brainstem, crossing over of pretectal neurons involved in pupillary (consensual) light reflexes, located ventral to pinneal gland
Red: olfactory bulb
Orange: gyrus rectus
Blue: olfactory tract
Red: orbital gyrus
Orange: Uncus
Blue: parahippocampul gyrus
Red: Cingulate gyrus (mood, personality)
Green: corpus callosum
Blue: fornix
Purple: parahippocampal gyrus
Red line over the Uncus
deep to the uncus lies the amygdala (anteriorly, pink arrow) and hippocampus (posteriorly, green arrow)
Red arrow: Amygdala, which is located in same coronal plane as the Basal ganglia (blue arrows)
Amygdala (pink arrow) the center for experiencing fear, anxiety, and rage. Has many inputs/outputs including ventral basal ganglia, mediodorsal nucleus of thalamus, orbital and medial prefrontal cortex.
Red: hippocampal formation, located in same coronal plane as the thalamus (green arrow), in the medial temporal lobe.
Nucleus Accumbens: area of the basal ganglia involved in emotion, reward, and addictive behaviors; this region helps in choosing the appropriate emotional response to a given situation.
Cross section of midbrain:
Yellow = ventral tegmental area, sends dopaminergic inputs to the Nucleus accumbens; centrally this is associated with rewards and addiction
Red = median raphe nucleus
Mammillary bodies (contain mammillary nuclei); considered part of the hypothalamus.
Diencephalic regions of the Limbic System:
Red= anterior thalamic nucleus; receives input from mammillary nuclei and projects to cingulate gyrus
Pink= Medial dorsal nucleus of thalamus; receives input from cortex, amygdala (orange ball below mammillary nucleus), ventral pallidum (n. accumbens), and projects to orbital frontal cortex and medial frontal cortex
Orange= mammillary nucleus (part of hypothalamus)
First line drug tx for partial seizures
carbamazepine and phenytoin
First line tx for generalized seizures
ethosuximide (for pure absence epilepsy)
valproate a traditional med for generalized sz but bad SE profile (fatal hepatoxicity and NT defects), so lamotrigine an alternative.
Drugs specific for partial-sz may make generalized sz’s WORSE (carbamazepine, gabapentin, tiagabine).
MOA for antiepileptic drugs
1) Na+ ch. blockers
2) Ca2+ influx blockers
3) Glutamate antagonists
4) GABA potentiators
Sodium Channel Blockers for epilepsy
Phenytoin, carbamazepine, valproate, lamotrigine, topirimate, Zonisamide
“Val Pro-ate, so she took Phen-phen to metabolize carbs to fit in her lamo top”
Causes use-dependent block of vg-Na+ channels, reducing sustained high rates of repetitive firing by neurons, may block glutamate release (via presynaptic Na+ ch), prevent spread of sz discharges
Ca+ influx blockers, antiepileptic
**-Ethosuximide **blocks rhythmic firing bursts in thalamic neurons seen in absence sz
-Gabapentin: inhibits Ca2+ ch, also a GABA analog
- trimethadone and valproate also reduce Ca2+ currents
Glutamate antagonists, antiepileptic drugs
NMDA receptor antagonists (effective but toxic)
Felbamate (blocks strychnine-insensitive glycine site on NMDA receptor, causes aplastic anemia)
Perampanel: blocks glutamate (AMPA) receptor
Lamotrigine may selectively reduce synaptic release of glutamate
Leviteracetam: may modulate glutamate release
GABA potentiators, antiepileptics
1) Increase affinity of GABA f_or GABAa receptor:_ barbituates (phenobarbital, primidone), benzodiazepines (clonazepam, diazepam, lorazepam, clorazepate),
2) Inhibition of GABA transaminase (slows breakdown of GABA): vigabatrin, valproate
3) GABA agonist: progabide, pregabalin, gabapentin, clobazam
4) Inhibition of GABA transporter: tiagabine
Describe the dose-dependent elimination kinetics of phenytoin
Phenytoin does not have linear elimination kinetics! It has linear kinetics at low doses, but then increases to zero order kinetics at high doses; thus at high doses can rapidly accumulate in blood (become toxic)
Which antiepileptic drugs are inducers of hepatic enzymes?
CYP450 inducers: phenytoin, carbamazepine, phenobarbital, primidone, topiramate, oxcarbazepine
What antiepileptic drug(s) are inhibitors of hepatic enzymes?
What effect do inducers/inhibitors of hepatic enzymes have on other medications?
CYP450 inhibitor: valproate
Inhibitors/Inducers can affect many meds including AED’s, anticoagulants, and antibiotics. Can lower efficiacy of hormonal contraceptives.
Treatment of epilepsy in pregnancy
Safest AED: lamotrigine
Most teratogenic AED: valproate (phenobarbital #2)
Phenytoin
Na+ ch inactivator, narrow spectrum (PS, PC, 2’ gen sz), also used to tx chronic pain, and cardiac arrhythmia, zero order kinetics
SE’s: gingival hypertrophy, may worsen myoclonic and absence sz
Valproate
Na+ ch inactivator, inhib of GABA transaminase, 1st line tx for GTC sz, also tx focal and gen. absence sz’s (broad MOA), also used to tx chronic pain , SE’s include weight gain, tremor, PCOS, and hyperammonemia
Phenobarbital/primidone
increases GABA action, narrow spectrum (PS, PC, 2’ gen sz)
SE’s: sedation, tolerance, dependence, induction of CYP450, cardiorespiratory depression
Carbamazepine
Na+ ch inactivator, narrow spectrum (PS, PC, 2’ gen sz), may worsen juvenile myoclonic epilepsy, also used to tx chronic pain
Blood dyscrasias (agranulocytosis, aplastic anemia), liver toxicity, teratogenesis, induction of CYP450, SIADH, Stevens-Johnson syndromes
Felbamate
a glutamate blocker, potentially lethal side effects are aplastic anemia and acute hepatic failure
Common adverse effects of AEDs
dizziness, fatigue, blurry vision, diplopia, unsteadiness, cognitive issues, mood affects
rarely: Stevens-Johnson syndrome
General PK parameters of AED’s
Essentially complete absorption for all AED’s except gabapentin
AED’s bind to proteins in varying degrees, so total and free fractions of meds can vary significantly (potential for toxicity) so important to monitor serum levels
Most AED’s are metabolized by liver and eliminated by kidneys
Most AED’s follow linear kinetics (exception: phenytoin)
What drugs could you use to tx partial complex sz if unresponsive to phenytoin?
Pretty much anything except ethosuximide or benzo’s, first line tx for partial complex sz is carbamazepine
What is the first line tx for status epilepticus?
status epilepticus is 5+ min of continuous clinical/electrographic sz activity or recurrent sz activity without return to baseline between sz’s.
1st line tx is lorazepam (or diazepam or clonazepam) within 5-10 minutes or emerging SE; at 10-30 minutes out could tx with valproate or phenytoin. If refractory or 30-60 minutes out, tx with **midazolam **or pentobarbital.
Cholinesterase inhibitors
decreases breakdown of ACh in synaptic cleft, increases cognitive fxn, but doesn’t slow progression of dz; SE’s: N/V/D for all
- Donepezil (Aricept) prototypical agent, may cause insomnia
- tacrine
- rivistigmine: may cause HA’s
- galantamine
Memantine
aka Namenda
NMDA antagonist used to tx dementia, tx excitotoxicity, non-cholinergic so can be used with AChE inhibitor, neuroprotective but can cause hallucinations, also dizziness and confusion.
What are the different classes of mood agents?
TCA’s, SSRI’s, MAOI’s, SNRI’s, 5HT2 antagonists, monocycle/unicyclic, and others
Serotonin syndrome
potential SE of any drug that increases 5HT (MAOI, SSRI, SNRI, TCA)—causes hyperthermia, confusion, myoclonus, CV instability, flushing, diarrhea, sz’s. Tx with cyproheptadine (5HT2 receptor antagonist).
Tricycle antidrepressants (TCA)
Imipramine and Despiramine
- poorly tolerated, very sedating, and can be lethal in OD, so not used very much now
- SE’s include anticholinergic effects (tachycardia, urinary retention, dry mouth), alpha1-blocking effects (orthostasis), prolonged QT, sexual side-effects, discontinuation syndrome.
- “Tri-C’s: Convulsion, Coma, Cardiotoxicity”
- tx with NaHCO3 to prevent arrhythmia.
MAOI’s
Phenelzine, Isocarboxazidmare, Tranylcypromine, selegiline
“MAO Takes Pride In Shanghai”
- irreversible action, slows down monoamine metabolism thereby increasing DA, 5HT, and NE
- risk of hypertensive crisis when eating foods with high levels of tyramine.
- Drug interactions with SSRI’s and TCA’s. Causes CNS stim with meperidine.
- Also cause orthostasis, weight gain, sexual side effects, and confusion.
SSRI’s
Fluoxetine (mildly activating, long half-life), Citalopram (sedating), Paroxetine, Fluvoxamine, Escitalopram
- inhibit 5HT transporter;
- 1st line tx for depression; cheap, well-tolerated, broad spectrum of use
- SE’s include increase gut motility, decrease sexual fxn, HA, weight gain, discontinuation syndrome
SNRI’s
Venlafaxine (risk of HTN at high doses), desvenlafaxine, duloxetine (risk of hepatotoxicity), Milnacipran
- target 5HT and NE transporters (not receptors)
- used as 2nd line tx for depression, also tx chronic pain
- SE’s same as SSRI’s plus, HTN, CNS stim.
5HT2 antagonists
no great evidence, but used a lot to tx sleep/depression; SE’s include GI and sedation
**Trazodone**: used to tx insomnia, non-addictive, risk of priapism (“traza**bone**”)
Nefazodone: risk of hepatotoxicity
Bupropion
aka Wellbutrin, a unicyclic antidepressant, resembles amphetamine in structure, stimulating, works on NE and DA; no sexual side effects
Mirtazapine
antidepressant; tetracyclic, and sedating, causes weight gain, no sexual side effects
Lithium
MOA possibly related to inhib of phosphoinositol cascade, used to stabilize mood in BPD, “LMNOP= Lithium SE’s: Movement (tremor), Nephrogenic DI, hypOthyroidism, Pregnancy problems
Valproic Acid (valproate)
AED, also used to tx bipolar disorder
Benzodiazepines
Any drug ending in “-zepam” or “-zolam”
Triazolam (Halcion)
flurazepam (Dalmane)
temazepam (Restoril)
diazepam (Valium)
alprazolam (Xanax)
chlordiazepoxide (Librium)
lorazepam (Ativan)
clonazepam (Klonopin)
midazolam (Versed)
- All benzos potentiate GABA by increasing freq. of Cl- ch opening
- Decrease REM sleep
- older antiepileptic drug
- Most have long t ½ and active metabolites, except “ATOM” (alprazolam, triazolam, oxazepam, and midazolam)
- SE’s: dependence, see additive CNS depression w/ EtOH, less resp depression/coma than barbituates
flumazenil
txs benzo OD, a competitive antagonist at GABA bz receptor
buspirone (BuSpar)
non benzo anxiolytic, stimulates 5HT receptors, non-addictive, not sedating, no interaction w/ EtOH
zoldipem (Ambien)
non benzo anxiolytic used tx insomnia, activates GABA receptor via BZ1 subtype
Typical Antipsychotics
“Haloperidol + -azines,”
- all block D2 receptors which increases cAMP
- toxicities include tardive dyskinesia, constipation, dry mouth, hypotension, sedation, prolonged QT, and neuroleptic malignant syndrome
- “NMS think FEVER: fever, encephalopathy, vitals unstable, enzymes increase, rigidity of muscles”
Haloperidol (Haldol)—high potency, can administer PO, IV, or IM
thioridazine
fluphenazine
trifluoperazine (Stelazine)
chlorpromazine (Thorazine)—low potency
Atypical Antipsychotics
unknown MOA, but varied effects on 5HT2, DA, alpha and H1 receptors; in general has fewer extrapyramidal effects (tardive dyskinesia) and fewer anticholinergic SE’s, though all can cause prolonged QT
“It’s atypical for old closets to quietly risper from A to Z.”
Clozapine (Clozaril)–weight gain, agranulocytosis (need to check CBC’s weekly)
ziprasidone (Geodon)
olanzapine (Zyprexa)—weight gain
quetiapine (Seroquel)
risperidone (Risperdal)—increase prolactin leading to lactation, gynecomastia, irregular menses and infertility
aripiprazole (Abilify)
Lamotrigine
AED; blocks vg-Na+ ch, tx focal, GTC, and gen. absence szs (broad MOA), safest AED to use in pregnancy
Gabapentin
inhibits Ca2+ ch, also GABA analog, txs focal szs, also used to tx chronic pain
Topirimate
blocks Na+ ch, increase GABA action, glutamate (NMDA) receptor blocker, tx PC, PS, and GTC sz (broad MOA), SE include nephrolithiasis, weight loss
Tiagabine
GABA reuptake inhibitor, tx’s PC and PS sz
Zonisamide
Na+ ch blocker, tx partial sz, broad MOA, SE’s include nephrolithiasis and weight loss
Oxcarbazepine
narrow spectrum AED; txs PS, PC, 2’ gen sz
Leviteracetam
unknown MOA, may modulate GABA and glutamate release, broad MOA, tx focal and GTC sz, can cause mood disturbances and other psych effects
Pregabalin
AED, possible GABA activity, also used to tx chronic pain
Lacosamide
narrow spectrum AED: tx PS, PC, 2’ gen sz
Rufinamide
AED used in Lennox-Gastaut syndrome (sx’tic gen epilepsy)
Clobazam
GABA receptor agonist used to tx szs
Ezogabine
AED that activate v-g K+ ch
