What does FAST check?
- 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
- 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?
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)?
- 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)?
- 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
- Synthetic opioid
- 1 min onset, 30 min duration
- 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
- Low B/G solubility (equilibrates quickly)
- High MAC (not potent)
- Low CV/resp depression
- 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,
- 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?
- CNS depression
- 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?
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
- CV depression
- 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
- 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?
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?
- 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?
- 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
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?
What do you do if you think someone is having a stroke?
- Stop procedure, position UPRIGHT decrease ICP
What is tPA?
- Tissue plsminogin activator to dissolve clots for THROMBOTIC only not for HEMMORHAGIC
- Use within 3 hours