-
What does FAST check?
- Stoke
- Face: smile?
- Arms: raise both?
- Speech: slurred?p
- Time: call 911
-
What are stroke risk factors?
Atherosclerosis, hypertension, coagulopathies
-
What are the names/features of the most common brain cancers?
- Glioblastoma: intraaxial/intrinsic, (malignant) 1 yr survival, lipid/yellow parenchyma, atypical myosis
- Meningioma: extraaxial/meninges, arachnoidal origin. Slow (benign), NF2, whorls histologically
-
Describe MS.
- 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
-
What are the CSF findings of MS?
Oligoclonal bands?
-
What is shadow plaques?
Remyelinated area of brain (MS)
-
What are the phrmacotherapies for ADHD?
- 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
-
What does adding clonidine do for ADHD?
- Alpha-2 agonist
- helps moderate ADHD-associated impulsive and oppositional behavior, and may reduce tics, and insomnia.
-
What is modafinil(Provigil)?
- Narcolepsy
- Mechanism: Increases DA, NE release and hypothalamic histamine
-
What is Phentermine (Adipex-P)
- Weight loss sympathomimetic
- Stimulates CNS DA/NE -> appetite suppression and activates hypothalamus to stimulate NE release
-
What is ephedrine?
- Mixed acting adrenergic stimulant
- Anesthesia, herbal
-
What are the adverse effects of sympathomimetic stimulants?
- Anorexia, insomnia/nervousness, constipation
- CV: hypertension, sudden death, abuse liability
-
What are xanthine derivatives mechanisms?
- Caffeine, theophylline salts
- Adenosine receptor antagonism
- Phosphodiesterase blockade (PDE IV)-> prolong cAMP (symp activity)
- Histone deacetylase activation
- -> CNS stimulation, EPI CV effects
-
What are the uses and side-effects of xanthine derivatives?
- Theophylline: Asthma, COPD
- Caffeine: preemie apnea, wakefulness, analgesics
- Adverse: anorexia/nausea, CV stim, SNS insomnia, seizures
-
What is the mechanism of IV anesthetics?
- GABA Agonists
- Barbiturates, Propofol, Benzodiazepines, etomidate, ketamine, dexmedetomidine, opiods
-
Which IV anesthetics have antagonists?
-
Features of thiopental (pentothal)?
- Ultrashort barbiturate
- 40 second onset
- 10-15 minute duration
- X: Histamine release
-
Features of Methohexital(Brvital)?
- Ultrashort barbiturate
- More potent than thiopental: shorter distribution/elimination
-
Features of Propofol?
- 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
-
Ketamine (Ketalar) features?
- 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
-
Etomidate (amidate) features?
- Induction of anesthesia
- Inhibit adrenocorticosteroid synthesis
- “wiggle juice”: involuntary myoclonic movements
- rapid onset/recovery
- minimal CV, respiratory depression
- X: nausea
-
What are the IV Benzodiazepines?
- Midazolam (versed) CYP3a4, 3min on, 45 min duration
- Diazepam (valium) venous irritation, slow metabolism
-
What class of drugs is dexmedetomidine (Precedex)?
- newest
- Selective alpha2 agonist (like clonidine)
- Strong analgesia not anesthetic
- Anxiolysis, sedation, bradycardia, anti-shivering, vasoconstriction, analgesia
- X: hypotension, bradycardia
-
What are the common features of opiods?
- Analgesia, sedation, euphoria, cough suppression
- Respiraratory depression(decrease CO2 response curve), addiction, nausea, chest wall rigidity
-
Unique features of morphine?
- Slow onset: 15-30 mins
- Long duration: 2 hrs
- Active metabolite: morph6gucuronide
- Mild histamine rls
- Bradycardia (vagal)
-
Features of meperidine?
- Synthetic opiod similar to atropine
- 2-4 minute onset
- X: histamine rls, MAO inhibitor interaction, asthma
-
Fentanyl?
- 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)
-
What did Morton do that Wells failed?
Demonstrate N2O as anesthetic, w diethyl ether
-
What is the MAC?
- 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
-
What is the Meyer-Overton Rule?
- 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
-
What are the criticisms of the lipid theories of inhaled anesthetics?
- Membrane expansion equaled by body temp inc
- Stereoisomeric differences
- Some non-lipophilic are anesthetics
-
Where do inhaled anesthetics affect?
- 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
-
What are the Guedel’s Stages of anesthesia?
- 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
-
What is the blood:gas partition coefficient?
- Molecules of gas in blood/ molecules of gas in alveolar space
- High=blood holds gas and equilibrates slowly
- Low=blood releases and equilibrates quickly
-
What factors affect the onset of inhaled anesthetics?
- 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.
-
How is brain plasma conc and alveolar conc related?
- 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)
-
What does Fluoride substitution do to B/G coefficient?
More fluoride decreases B/G coefficient increasing equilibration speed!
-
Does the liver affect metabolism of inhaled anesthetics?
Not so much
-
What are the desired properties of inhaled agents?
Stable, nonflammable, potent, low blood/tissue solubility, no biotransormation, toxicity irritation, minimal CV/resp effects
-
N2O features?
- Low B/G solubility (equilibrates quickly)
- High MAC (not potent)
- Low CV/resp depression
- Nonflammable
-
Ether features?
- 1st successful anesthetic
- high B/G solubility (equilibrates slowly)
- low MAC (potent)
- irritating, strong, muscle relax
- flammable, explosive
-
Why is halothane not used?
- Nonflammable but CV myocardial depression and high arrthytmogenic potential
- Hepatic metabolism-> acute hepatitis,
-
Isoflurane?
- B/G solubility 1.4 (equilibrates quicly)
- MAC 1.15 (potent)
- Less CV mycocardial depression than halothane, low risk of arrhythmia
- Respiratoroy, moderately irritating
-
Which is the fastest onsetting inhaled analgesic?
- Desflurane because low B/G solubility (0.42)
- Yet least potent
-
What is used for inhalation induction?
Sevoflurane(no respiratory irritation)
-
What is malignant hyperthermia?
Volatile agent increase of metabolic rate treated with dantrolene (skeletal muscle Ca2+ channel blocker)
-
What is the mechanism of action of benzodiazepines?
- 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.
-
What are the pharm effects of benzodiazapenes?
- 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)
-
What are the important features of benzodiazepine metabolism?
- Lots of active metabolites w pharmacokinetic activity.
- CYP450 independent: alprazolam, midazolam, triazolam
-
What about midazolam structure makes it unique?
- Low pH ring opens -> hydrophilic
- High pH ring closes -> lipophilic -> cross BBB
-
What is the benzodiazepine antagonist?
Flumazenil (romazicon)
-
What are th interactions with benzodiazepines?
- Flumazenil: antagonist
- Summation with CNS depressants
- Modulates opioid analgesia
- Impares metabolism with erythromycin CYP3A4 inhibitors
- Decreased effect w smokers, rifampin, carbamazepine
-
What are the selective BZ1 receptor agonists?
- Zolpidem (ambien) 2.5 hrs
- Zaleplon (sonata) 1 hour
- Eszopiclone (lunesta) 6 hours
- Stimulate specific BZ1 receptors
- Onset 10-20 inutes
-
What are the uses of barbiturates?
- IV anesthetic (ultrashort): methohexital (brevital), thiopental (pentothal)
- Sedative-hypnotics: pentobarbital (Nembutal, secobarbital (seconal)
- Anticonvulsants: phenobarbital (luminal)
-
How do barbiturates work?
- 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
-
What are the pharm/toxic effects of barbiturates?
- 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.
-
How does Buspirone (Buspar) work?
5-HT1a receptor partial agonist (antianxiety)
-
What is the only nonscheduled prescription drug for insomnia?
Ramelteon (Rozerem) MT1, MT2 melatonin receptor agonist
-
What does chloral hydrate do?
- Alcohol sedative
- Metabolized to tricloroethanol
- Similar to halothane -> may predispose arrhythmia
-
Ethanol features?
- 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
-
What is the toxic agent of acetaminophen toxicity?
N-acetyl-benzoquinoneimine (NAPQI)
-
How is alcohol metabolized?
- Constant rate as opposed to constant percentage
- Ethanol (alcohol dehydrogenase)-> acetaldehyde (alhdehyde dehydrogenase) -> acetate
-
What is a aldehyde dehydrogenase blocker?
Antabuse, makes alcoholics sick, prevents acetaldehyde metabolism
-
What is the differences between hallucinations and delusions?
- Hallucination: sense w/o stimuli
- Delusion: false beliefs despite evidence, (presecultion, reference, grandiose)
-
What is the role of calcium in skeletal muscle?
- Released by sarcoplasmic reticulum after T-tubular action potential depolarization
- Allosterically Regulates thin filament proteins troponin and tropomyosin that cover myosin binding site.
-
What does ECT shock do?
Unilaterally delivered to increase NE and 5-HST release but may affect memory
-
What is the most common finding of post mortem depression?
Elevated cortical 5-HT2 binding
-
What are the problems with monamine hypothesis of depression?
- Drugs change amine activity rapidly but mood changes take weeks
- Drugs: down-regulate amine receptors
-
What are the features of tricyclics?
- 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
-
What are the side effects of tricyclics?
- 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
-
What does MAO A and B break down?
- MAO A: NY, 5-HT, tyramine
- MAO B: DA
-
What is unique about the pharmacokinetics of MAOIs?
Clinical effect persists after discontinued dosage
-
Efffects of MAOI?
- 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
-
What is the most commonly prescribed antidepressant today/
- SSRI: less severe side effects & wider safety margin
- Fluoxetine (Prozac)
- Sertraline (Zoloft)
- Paroxetine (paxil)
-
What are the adverse effects of SSRIs?
- 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
-
What are the 2nd generation nonselective MA reuptake blocker?
- Trazodone (desyrel) 1st non-lethal overdose antidepressant
- Yet could cause sedation hypotension, and priapism (boner)
- Bupropriion (wellbutrin): smoking cessation, ADHD
- Seizures, alcoholism
-
What are the 3rd gen, nonselective MA reuptake blockers?
- Venlafaxine(Effexor)
- Duloxetine (Cymbalta): pain of diabetic neuropathy, generized anxiety disorder.
-
What are the treatment of bipolar disorder?
- Lithium salts
- Decrease manic, modulate mood swings, used w/ antidepressant or anticonvulsants or antipsychotics
-
What are the pharmacokinetics of Lithium salts?
- 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
-
What does aripiprazole (abilify) do?
- Partial D2, 5HT1A agonist
- 5HT2A antagonist
-
What do most antipsychotic drugs target?
Neuroleptics: block postsynaptic D2 Dopamine receptors which reduces positive symptoms(hallucinations/delusions) yet cannot reduce negative symptoms.
-
What did the MRI brainscans of twins show with schizophrenia?
Enlarged ventricles in affected
-
What is the target of atypical antipsychotics (clozapine, risperidone)?
- Block 5-HT2A serotonin receptors, weakly block D2
- Reduce + symptoms, some mildly attenuate – symptoms
-
What are side effects of the dopamine blockade?
- Extrapyramidal symptoms (EPS)
- Including perioral tremor(rabbit nose) and tardive dyskinesia(facial muscle and limbs involuntary movement (tongue thrust)
-
What are the effects of a a-adrenergic receptor blockade?
Postural hypotension, reflex tachycardia, depressor effects of EPI
-
Effects of cholinergic receptor blockade?
- Suppression of dykinesias
- Blurred vision
- Decreased salivation->higher caries
- Constipation
-
Which drug considerably raises risk for tardive dyskinesia?
Haloperidol (vs risperidone)
-
Why use 2nd generation/ novel atypical antipsychotics(clozapine)?
- Diminished EPS (extrapyramidal) including tardive dyskinesia (TD)
- Improved negative symptoms and cognitive/mood
- X: WEIGHT GAIN, tachycardia, orthostasis, sialorrhea, constipation
-
In the dental setting what can precipitate a seizure?
Overdose of local anesthetic
-
What are the treatments of epilepsy?
Medication, vagal stim, ketogenic diet, surgery
-
Which medications are used for epilepsy?
Barbituarates, benzodiazepines, hydantoins, succinimides
-
What do you do if someone has a seizure?
- 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
-
What are the kinds of strokes?
- Occlusive (88%) – thrombic 81%, emoblitic 7%
- Hemorrhagic (12%) (more fatal and more likely in dental office from HTN)
-
What is TIA?
Transient ischemic attack, neurologic deficit and complete resolution within 24 hrs
-
What are stroke pt treatement guidelines?
- Not within 6 months of stroke
- Confirm antiHTN meds
- Check BP
- Reduce stress
- Judicious EPI
-
What is the defining charactrerisitcs of stroke?
SUDDEN
-
What do you do if you think someone is having a stroke?
- Stop procedure, position UPRIGHT decrease ICP
- 911
- O2
- BLS
-
What is tPA?
- Tissue plsminogin activator to dissolve clots for THROMBOTIC only not for HEMMORHAGIC
- Use within 3 hours
|
|