Systems 4.txt

• Stoke
• Face: smile?
• Arms: raise both?
• Speech: slurred?p
• Time: call 911

Atherosclerosis, hypertension, coagulopathies

• Glioblastoma: intraaxial/intrinsic, (malignant) 1 yr survival, lipid/yellow parenchyma, atypical myosis
• Meningioma: extraaxial/meninges, arachnoidal origin. Slow (benign), NF2, whorls histologically

• Perivenous Demyelinating(automimmune T-cells)
• Waxing/waning neurological
• Multiples saucers: sharply demarcated demylinated lesions
• Dawsons’ fingers: alien finger lesions from ventricles
• Shadow plaque: remyleinated areas w/ thin myelin sheathf
• CSF: oligoclonal bands

Oligoclonal bands?

Remyelinated area of brain (MS)

• Methlyphenidate(MPH) (Ritalin): blocks dopamine reuptake
• Dextroamphetamine/amphetamine (DXTR) (Adderall): blocks Dopamine/NE reuptake, releases Dopamine/NE, and mild MAO inhibition
• Adderall: 12 hour released at 0, 4
• Atomoxetine(Strattera): CYP2D6, unscheduled, NE reuptake inhibitor

• Alpha-2 agonist
• helps moderate ADHD-associated impulsive and oppositional behavior, and may reduce tics, and insomnia.

• Narcolepsy
• Mechanism: Increases DA, NE release and hypothalamic histamine

• Weight loss sympathomimetic
• Stimulates CNS DA/NE -> appetite suppression and activates hypothalamus to stimulate NE release

• Mixed acting adrenergic stimulant
• Anesthesia, herbal

• Anorexia, insomnia/nervousness, constipation
• CV: hypertension, sudden death, abuse liability

• Caffeine, theophylline salts
• Adenosine receptor antagonism
• Phosphodiesterase blockade (PDE IV)-> prolong cAMP (symp activity)
• Histone deacetylase activation
• -> CNS stimulation, EPI CV effects

• Theophylline: Asthma, COPD
• Caffeine: preemie apnea, wakefulness, analgesics
• Adverse: anorexia/nausea, CV stim, SNS insomnia, seizures

• GABA Agonists
• Barbiturates, Propofol, Benzodiazepines, etomidate, ketamine, dexmedetomidine, opiods

• Benzodiazapenes
• Opiods

• Ultrashort barbiturate
• 40 second onset
• 10-15 minute duration
• X: Histamine release

• Ultrashort barbiturate
• More potent than thiopental: shorter distribution/elimination

• Milk of amnesia: potentiates GABA receptors
• Rapid onset/clear recovery (induce/ short anesthesia)
• Painful injection
• Anti-emetic (even subsedative dose)
• X: apnea, respiratory, myocardial depression, peripheral vasodilation, depressed baroreflex response, fatalities for children
• Oil-in water: soybean oil, glycerol, egg lecithin -> allergy, bacteria, dietary lipid

• PCP relative
• Antagonist to NMDA class of glutamate excitatory recepors
• Dissociative: analgesia, amnesia, catalepsy
• Rapid onset/recovery, maintain respiration, bronchodilation, no histamine rls
• X: CV stim (inc HR, BP, CO), emergence delirium, increased airway secretions/reflexes

• Induction of anesthesia
• Inhibit adrenocorticosteroid synthesis
• “wiggle juice”: involuntary myoclonic movements
• rapid onset/recovery
• minimal CV, respiratory depression
• X: nausea

• Midazolam (versed) CYP3a4, 3min on, 45 min duration
• Diazepam (valium) venous irritation, slow metabolism

• newest
• Selective alpha2 agonist (like clonidine)
• Strong analgesia not anesthetic
• Anxiolysis, sedation, bradycardia, anti-shivering, vasoconstriction, analgesia
• X: hypotension, bradycardia

• Analgesia, sedation, euphoria, cough suppression
• Respiraratory depression(decrease CO2 response curve), addiction, nausea, chest wall rigidity

• Slow onset: 15-30 mins
• Long duration: 2 hrs
• Active metabolite: morph6gucuronide
• Mild histamine rls
• Bradycardia (vagal)

• Synthetic opiod similar to atropine
• 2-4 minute onset
• X: histamine rls, MAO inhibitor interaction, asthma

• Synthetic opioid
• 1 min onset, 30 min duration
• CYP3A4
• NO histamine rls, inexpensive
• X: chest wall rigidity
• Derivatives (alfentanil(less potent), sufentanil(more potent), remifentanil(2x potent, SHORTEST DURATION (nonspecific esterases)

Demonstrate N2O as anesthetic, w diethyl ether

• Minimum alveolar concentration: 50% of pts unresponsive to surgical stimulus
• Quantify potency of inhaded anesthetic
• % of gas in mixture
• small = potent (isoflurane)
• large = less potent (N2O)
• MAC awake = .3
• 95% = 1.3 * MAC
• BAR (50% Blocked adgrenergic response) = 1.5)
• Intubation (50% block movement to intubation)= 2* MAC
• Alveolar = Brain concentration after short period of equilibration

• Linear Corr of anesthetic potency and lipid solubility or hydrophobic sites of membrane proteins
• Anesthesia when molar concentration in lipophilic phase
• Oil/gas partition coefficient: lipid solubility corr w anesthetic potency
• Disorder membrane lipids and/or increase membrane volume

• Membrane expansion equaled by body temp inc
• Stereoisomeric differences
• Some non-lipophilic are anesthetics

• Mesencephalic reticular formation: supporting consciousness/alertness
• Depression influences on limbic system are reduced and unconsciousness occurs
• N2O alters most others depress
• Dorsal Lamina of spinal cord: gateway for nociceptive impulses to CNS

• I: Analgesia : dental, some amnesia
• II: Delirium: (no surgery)enhanced reflexes, retching, incontinence, irregular respiration
• III: Surgical Aneshtesia: unconsciousness, no pain reflexis, respiratory/CV depression
• 4 Planes
• 1: dental thoracic
• 2: abdominal
• 3: deep abdominal
• 4: no surgery
• IV: Medullary Paralysis

• Molecules of gas in blood/ molecules of gas in alveolar space
• High=blood holds gas and equilibrates slowly
• Low=blood releases and equilibrates quickly

• Inspired conc, vent rate/depth, CO/regional blood flow, blood solubility, 2nd gas effects
• High CO increases systemic uptake not to brain! Therefore, slows onset.

• Brain receive 7x more blood than avg
• Brain conc closely follows arterial with follows alveolar
• Alveolar partial pressure is the key determinate
• (increasing systemic uptake delays onset)

More fluoride decreases B/G coefficient increasing equilibration speed!

Not so much

Stable, nonflammable, potent, low blood/tissue solubility, no biotransormation, toxicity irritation, minimal CV/resp effects

• Low B/G solubility (equilibrates quickly)
• High MAC (not potent)
• Low CV/resp depression
• Nonflammable

• 1st successful anesthetic
• high B/G solubility (equilibrates slowly)
• low MAC (potent)
• irritating, strong, muscle relax
• flammable, explosive

• Nonflammable but CV myocardial depression and high arrthytmogenic potential
• Hepatic metabolism-> acute hepatitis,

• B/G solubility 1.4 (equilibrates quicly)
• MAC 1.15 (potent)
• Less CV mycocardial depression than halothane, low risk of arrhythmia
• Respiratoroy, moderately irritating

• Desflurane because low B/G solubility (0.42)
• Yet least potent

Sevoflurane(no respiratory irritation)

Volatile agent increase of metabolic rate treated with dantrolene (skeletal muscle Ca2+ channel blocker)

• Bind to benzodiazepine (omega) receptor on GABAa(gamma 2 subunit) receptor complex
• Improves GABA binding to GABA receptor
• Enhanced GABA effect on Cl- channel, increases FREQUENCY of opening
• Many different subtypes therefore different categories.

• Antianxiety
• CNS depression
• Anticonvulsant
• Centrally mediated muscle relaxation
• Anterograde amnesia
• Minimal CV depression
• Inhibits stage 4 sleep (night terrors)
• X: resp depression, drowsiness, paradoxical excitement, IV irritation, Class IV abuse, glaucoma, teratogen(D,X)

• Lots of active metabolites w pharmacokinetic activity.
• CYP450 independent: alprazolam, midazolam, triazolam

• Low pH ring opens -> hydrophilic
• High pH ring closes -> lipophilic -> cross BBB

Flumazenil (romazicon)

• Flumazenil: antagonist
• Summation with CNS depressants
• Modulates opioid analgesia
• Impares metabolism with erythromycin CYP3A4 inhibitors
• Decreased effect w smokers, rifampin, carbamazepine

• Zolpidem (ambien) 2.5 hrs
• Zaleplon (sonata) 1 hour
• Eszopiclone (lunesta) 6 hours
• Stimulate specific BZ1 receptors
• Onset 10-20 inutes

• IV anesthetic (ultrashort): methohexital (brevital), thiopental (pentothal)
• Sedative-hypnotics: pentobarbital (Nembutal, secobarbital (seconal)
• Anticonvulsants: phenobarbital (luminal)

• Bind to GABAa receptor/chloride channel
• Increase GABA effects
• Increase DURATION of GABA opening
• Can act directly on Cl- channel not requiring GABA-> lower safety margin
• Inhibitory on glutamate receptors

• CNS depression: sedation, hypnosis, anesthesia, death
• Antianagesic
• CV depression
• Anticonvulsant
• Resp reflex activity
• Decrease REM
• Liver microsomal stimulation (drug interactions)
• Teratogenesis (predated classification)
• Tolerance, dependence additiction.

5-HT1a receptor partial agonist (antianxiety)

Ramelteon (Rozerem) MT1, MT2 melatonin receptor agonist

• Alcohol sedative
• Metabolized to tricloroethanol
• Similar to halothane -> may predispose arrhythmia

• Sedative-hypnotic
• GABA-ergic
• NMDA antagonism
• Low safety margin, widespread uncontrolled use, avoid w CNS depressant, acetaminophen interaction (induces toxicity of metabolites)
• NAPQI toxic agent of acetomenephen metabolism

N-acetyl-benzoquinoneimine (NAPQI)

• Constant rate as opposed to constant percentage
• Ethanol (alcohol dehydrogenase)-> acetaldehyde (alhdehyde dehydrogenase) -> acetate

Antabuse, makes alcoholics sick, prevents acetaldehyde metabolism

• Hallucination: sense w/o stimuli
• Delusion: false beliefs despite evidence, (presecultion, reference, grandiose)

• Released by sarcoplasmic reticulum after T-tubular action potential depolarization
• Allosterically Regulates thin filament proteins troponin and tropomyosin that cover myosin binding site.

Unilaterally delivered to increase NE and 5-HST release but may affect memory

Elevated cortical 5-HT2 binding

• Drugs change amine activity rapidly but mood changes take weeks
• Drugs: down-regulate amine receptors

• Antidepressents: NE and 5-HT uptake inhibitors, some DA uptake block
• Affinity for H1 and muscarinic alpha-1 and 2 adrenoceptors
• X: cardiotoxicity
• Decrease REM
• Modulates (depressed) stage 4

• Suicide
• May manifest in resp depression and circ collapse
• Interactions w/ anticholinergics, alcohol, CNS depressants, LA & vasoconstrictors.
• Enhance sympathomimetic therefore use epinephrine cautiously and avoid levornordefrin

• MAO A: NY, 5-HT, tyramine
• MAO B: DA

Clinical effect persists after discontinued dosage

• Antidepressant, dec REM, correction of sleep disorder
• X: headach, CNS stim, dry mouth, wight gain, postural hypotention, sexual disturbances
• X: breaksdown endogenous and exogenous monamines which if inhibited could lead to HYPERTENSIVE CRISIS

• SSRI: less severe side effects & wider safety margin
• Fluoxetine (Prozac)
• Sertraline (Zoloft)
• Paroxetine (paxil)

• Anxiety, insomnia, inc appetite, tremors, GI, rashes
• Decreased libido
• Serotonin syndrome: (SSRI & MAOI) fever, agitation, hypertension, hyperthermia, rigidity, myoclonus that could lead to seizure coma and death
• Washout between meds

• Trazodone (desyrel) 1st non-lethal overdose antidepressant
• Yet could cause sedation hypotension, and priapism (boner)
• Bupropriion (wellbutrin): smoking cessation, ADHD
• Seizures, alcoholism

• Venlafaxine(Effexor)
• Duloxetine (Cymbalta): pain of diabetic neuropathy, generized anxiety disorder.

• Lithium salts
• Decrease manic, modulate mood swings, used w/ antidepressant or anticonvulsants or antipsychotics

• Distriubution into body water, slow intracellular entry, no protein binding
• Not metabolized
• Excreted renally about 20% of creatinine
• Therapeutic overdose common: nausea, vomiting, diarrhea, tremor
• Thiazide diureatics decrease exretion of lithium
• Dry mouth therefore don’t use w/ anticholinergics

• Partial D2, 5HT1A agonist
• 5HT2A antagonist

Neuroleptics: block postsynaptic D2 Dopamine receptors which reduces positive symptoms(hallucinations/delusions) yet cannot reduce negative symptoms.

Enlarged ventricles in affected

• Block 5-HT2A serotonin receptors, weakly block D2
• Reduce + symptoms, some mildly attenuate – symptoms

• Extrapyramidal symptoms (EPS)
• Including perioral tremor(rabbit nose) and tardive dyskinesia(facial muscle and limbs involuntary movement (tongue thrust)

Postural hypotension, reflex tachycardia, depressor effects of EPI

• Suppression of dykinesias
• Blurred vision
• Decreased salivation->higher caries
• Constipation

Haloperidol (vs risperidone)

• Diminished EPS (extrapyramidal) including tardive dyskinesia (TD)
• Improved negative symptoms and cognitive/mood
• X: WEIGHT GAIN, tachycardia, orthostasis, sialorrhea, constipation

Overdose of local anesthetic

Medication, vagal stim, ketogenic diet, surgery

Barbituarates, benzodiazepines, hydantoins, succinimides

• Stop treatment, remove objects from mouth, around patient, gently restrain and protect, let run course
• NOTHING in mouth
• Post-ictal: maintain airway, O2, monitor, valium 5-10mg IV or midazolam 2-4 IV or IM if continues or repeats

• Occlusive (88%) – thrombic 81%, emoblitic 7%
• Hemorrhagic (12%) (more fatal and more likely in dental office from HTN)

Transient ischemic attack, neurologic deficit and complete resolution within 24 hrs

• Not within 6 months of stroke
• Confirm antiHTN meds
• Check BP
• Reduce stress
• Judicious EPI

SUDDEN

• Stop procedure, position UPRIGHT decrease ICP
• 911
• O2
• BLS

• Tissue plsminogin activator to dissolve clots for THROMBOTIC only not for HEMMORHAGIC
• Use within 3 hours