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219 Cards in this Set
- Front
- Back
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Which non receptor proteins commonly bind drugs?
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Plasma albumin (most important); beta-globulin and alpha-1-acid glycoprotein
Plasma albumin-acid drugs mostly (approx 2 drug molec per albumin) Beta-globulin and alpha-1-acid glycoprotein=basic drugs >90%=significant if drug is 99% PB and 1% free and the free fraction is active then a change to 97% PB and 3% free = increase of active unbound to to 300% but if drug 23% PB and 77% free = change to 20% PB and 80% free has only insignificant increases |
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Protein binding effects on drug concentration, elimination, clinical signif
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plasma albumin binding is most important; beta-globulin and alpha-1-acid glycoprotein also bind some drugs. Plasma albumin binds, for the most part, acidic drugs (2 molec per albumin molec). Basic drugs may be bound by Beta-globulin and alpha-1-acid glycoprotein. Saturable binding sometimes leads to a nonlinear relationship betw dose and free (active) drug conc. Extensive protein binding slows drug elim (metab and excret by glomerular filtration). Competition betw drugs for protein binding rarely leads to clinically important drug interactions.
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first order kinetics
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(aka dosage dependence) the drug leaves the body at a constant rate or percentage over time. (the reason why half-life is constant)
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zero order kinetics
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alcohol elimination, in which a constant amount (not a percentage) is eliminated over time
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Michaelis-Menton model of kinetics
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(eg phenytoin) dose dependent and flow zero order at high doses and first order once drug levels have fallen.
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Centext-sensitive half-time
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the time to halving of the blood concentration after termination of drug administration by an infusion designed to maintain a constant concentration. Brought about by deficiencies in the standard pharm parameters of halflife for anesthetics.
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the only inorganic molecule that is an inhal anesthetic=?
all the others are? |
Nitrous Oxide; halogenated ethers
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inhal anesthetics work by stimulating ??? receptors which are a channel for ???
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GABA-a receptors are stimulated by inhal anesthetics. They are chloride channels (anion channel permeable to chloride)
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Effect from inhal anesthetics on CMRO2
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decreased consumption of oxygen as a result of decreased cerebral metabolism
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CPP=MAP-ICP
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Cerebral Perfusion Pressure=Mean Arterial Pressure minus Intracranial Pressure
Inhaled anesthetics increase the ICP. They do this by increased cerebral blood flow d/t vasodilation of cerebral vasculature. With low dose, effect is fairly mild and we can compensate by: maintaining control of arterial tone in brain (circle of Willis) = PCO2 ---->mild hypervent decr PCO2=cerebral vasoconstriction (why people pass out with hypervent) incr PCO2=dilate cerebral vessels |
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What are the intracranial compartments
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The cellular compartment
The CSF Compartment The fluid compartment THe blood compartment |
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WHich of the Intracranial Compartments receives most of the Anesthetist's attention
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the blood compartment b/c it is the most amenable to rapid alteration. The blood compartment should be considered as two separate components:
venous: Improve cerebral drainage arterial: decrease CBF |
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The CSF compartment
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There is no pharmacologic manipulation of the CSF space, the time course and magnitude of whihc are relevant to the neurosurgical operating room. The only relevant means for manipulating the size of this compartment is by drainage. A tight surgical field sometimes can be imporved by passage of a brain needle by the surgeon into a lateral ventricle to drain CSF. Lumbar CSF drainage can be used to improve surgical exposure in situations with no substantial hazard of uncal or transforamen magnum herniation
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The fluid compartment of the intracranial compartments
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(intracellular and extracellular) The compartment can be addressed via steroids and diuretics.
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What are the 5 reasons everything goes down when you're getting inhal anesthetics?
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5 reasons:
CNS depression Cardiac Depression Vasodilation decr SVR Decr Baroreceptor axn decr release of cardiac supportive hormones (renin or vasopressin) All anesthetics exhibit all 5 except Nitrous Oxide (not strong enough to do anything with BP even at 70%) |
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Max strength and dose of Epinephrine
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No stronger than 1:100,000 (which contains 0.01mg/ml)
No more than 10ml any 10min period = 0.1mg or 30ml per hour total = 0.3mg |
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1:1000 =
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1mg/ml
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1:10,000=
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0.1 mg/ml
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1:100,000=
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0.01mg/ml
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1:200,000=
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0.005 mg/ml
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Which agents produce tachycardia and why?
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Desflurane and to a lesser extent isoflurane produce tachycardia during initial induction. This is probably due to respiratory irritation and happens more often in young healthy patients. 10-20% incidence. Rapid increase of concentration may also be a factor. (incr catecholamines ---> tachycardia)
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What do inhal anesthetics do to respiratory system?
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ALL ANESTHETICS ARE RESPIRATORY DEPRESSANT AND PRODUCE A DOSE DEPENDENT DECREASE IN RESPIRATIONS (W/ENOUGH THEY'LL BE APNEIC)
All gas anesthetics brochodilate (except N20) all anesthetics cause dose depend respiratory depression (except N20) (higher dose=decr # of breaths)=alteration of central and peripheral chemoreceptors function. Desflurane and (to a lesser extent) isoflurane are respiratory irritants and may cause coughing during induction and emergence (more common in nonsmokers) Depress tidal volume before respiratory rate (opiates are opposite) Hypoxic pulmonary vasoconstriction - anesthetics depress in a dose dependent manner |
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What is the quantity of metabolism of inhal anesthetics
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The only inhal anesthetic that produces metab = sevo 5-7(or 8). Result of free fluoride ion release. May want to avoid in renal patients although most consider it safe.
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Inhaled anesthetic effx on kidneys
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Kidneys slower under anesthesia d/t decrease blood pressure which = decreased blood flow thru glomerulus = decr filtration rate = decr u/o
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Anesthetics in pregnancy? what's okay/not okay? What is the effect in pregnancy?
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All anesthetics except N2O are used in Pregnancy. N2O is contraindicated in pregnancy (teratogenic in animals)
All inhal gases relax the uterus (risk of blood loss - only in intrauterine surgery or c-section; hysterectomy or outside the uterus not effected) low concentrations (i.e. half MAC) used in C-sections. Surgery/Anesthesia during pregnancy carries an increased risk of postoperative miscarriage. |
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Sevo toxic products
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fluoride levels in excess of 50micromol/L is known to cause nephrotoxicity. Serum fluoride concentration often peaks above 50micromol/L but b/c sevo has low b/g solubility and rapid elimination fluoride concentrations fall very quickly after surgery. Renal toxicity not expected from administration.
Compound A - Soda lime or Bara Lime CO2 absorbers react with Sevo at low FGF to cause renal toxicity. |
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carbon monoxide production
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dessicated absorbent and inhaled anesthetic interactions can lead to the production of CO inthe anesthesia circuit (desflurane>>enflurane>isoflurane). Negligible amounts of carbon monoxide are formed from halothane and sevo.
new calcium hydroxide-based CO2 absorbants, such as Amsorb and DragerSorb Free, contain neither NaOH or KOH and thus are chemically inert and do not degrade inhaled anesthetics to CO or degrade sevo to Compound A |
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N2O effect on BP
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No effect on BP with N2O (not strong enough to make BP go down).
ALL ANESTHETICS PRODUCE A DOSE DEPENDENT DECREASE IN BP EXCEPT N2O |
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N2O effect on SVR
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ALL ANESTHETICS CAN CAUSE A DOSE DEPENDENT DECREASE IN SVR (AND VASODILATION) EXCEPT N2O
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Cardiac effx of anesthetics
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cause:
dose dep decr in BP (depressed baroreceptor reflex control of arterial pressure to varying degrees) dose dep decr in SVR dose dep decr in HR (but after initial increase with Des - tachycardia eventually decreases) in normal heart, volatile anesthetics produce dose-related depression in left vent, right vent, and left atrial myocardial contractility; left vent diastolic function, and left vent-arterial coupling. |
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Advantages and disadvantages of N2O
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Advantages:
Analgesia (50% = 15mg morphine IV effx) rapid uptake and elim little cardiac or respir depression nonpungent allows less potent anesthetic to be co-administered decreased fent and anesthetic requirement disadvantages: Expansion of closed air spaces requires high concentration |
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advantages and disadvantages of Isoflurane
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Advantages:
Good muscle relaxation decreased cerebral metab rate minimal biotransformation maintains cardiac output d/t vasodilation inexpensive (most common anesthetic) Disadvantages: Pungent odor Airway irritant |
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Des Advantages/disadvantages
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Advantages:
Rapid uptake and elimination Stable molecules Minimal biotransformation Disadvantages: Airway irritant Low boiling point Sympathetic stimulation (tachycardia) Expensive |
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Sevo Advantages/Disadvantages
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Advantages:
Rapid uptake and elimination Nonpungent Disadvantages: Susceptible to biotransformation Reacts with soda lime (Compound A) Increases serum fluoride concentration Expensive (more than iso but has generic now) |
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Methionine Synthase=
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the enzyme inhibited by chronic long-term exposure to N2O. This enzyme needs B12 (as a cofactor) to function. N20 causes decreased B12 which causes decrease in Purine Synthesis
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Myoclonus can be caused by which 2 induction agents? Why?
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Brevitol and Etomidate = involuntary muscle mvmt which can occur during induction d/t uneven distribution of drug (takes longer to get to one area of the brain than another) lasts 10-20 seconds. I also starred next to ketamine (I think it does too).
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decreases in cortisol side effect of which agent?
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Etomidate
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Absolute contraindications of N2O
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Know deficiency of enzyme or substrate in methionine synthase pathway
potential toxicity from expansion of gas filled space (ie. emphysema, pneumothorax, middle ear surgery, pheumocephalus, air embolism) Raised intracranial pressure |
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Relative contraindications to use of N2O
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Pulmonary HTN
Prolonged anesthesia (>6h) first trimester of pregnancy high risk of postoperative nausea and vomiting |
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Putative relative contraindications of use of N2O (requiring further information)
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Risk of Myocardial ischemia
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Pts at risk from Cobalamin (B12) deficiency
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NUTRITIONAL DISORDERS (elderly, vegans, ETOH), MALABSORPTION DISORDERS (Prolonged use of proton pump inhibitors or H2 receptor antagonists, pernicious anemia, atrophic gastritis, postgastrectomy, whipple procedure, ileal resection, Crohn's disease), INFECTION (bacterial overgrowth, tapeworm)
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How are inhaled anesthetics delivered/elim? What is 'dosage'?
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via pulmonary ventilation. Most useful definition of 'dose' for these drugs is the partial pressure in alveolar gases, which is readily monitored in end-tidal expired gases.
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Inhal anesthetics flammable/metabolized?
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Some early inhaled anesthetic alkanes and ethers were flammable. Halogenation reduces flammability. Fluorination tends to decrease metabolic breakdown.
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Carbon Monoxide in inhaled anesthetics
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All halogenated anesthetics break down, releasing carbon monoxide and heat when they contract desiccated alkaline chemicals, such as those in common CO2 adsorbents. Potential harm to patients from this breakdown can be prevented by proper use and maintenance of anesthesia equipment and by use of less alkaline CO2 adsorbents.
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How do biophysical properties effect inhaled anesthetics?
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biophysical properties incl blood/gas partition coefficients and tissue-blood partition coefficients, determine the speed of drug uptake, distribution among tissue groups, and elimination.
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??? is associated with rapid uptake and elimination via the lungs (of inhaled anesthetics)
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low blood gas solubility
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??? is the alveolar concentration of anesthetics causing loss of response to verbal commands in half of subjects
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MAC awake - whatever concentration where the pt starts opening their eyes. Not really awake and probably won't remember what's being said but responding to verbal commands. At end of case, anesthetic is off, ventilate with 100% O2. Inspired anesthetic is zero, expired will start to decrease since blowing off anesthetic and pt starts waking up.
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??? can be produced by anesthetic concentrations lower than MAC-awake
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Amnesia. Happens in stage 1 low concentration of anesthetic to produce it.
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All potent volatile anesthetics in current use ???? mean arterial pressure in a dose dependent manner.
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decrease
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2 mechanisms that HR increases with use of anesthetic gases
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baroreceptor reflex in response to decreased arterial pressure
direct vagolytic effect on the heart |
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effx of anesthetic gases on RR, TV, inc CO2 and decr O2?
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Volatile anesthetics tend to increase respiratory rate, decrease tidal volume, and blunt ventilatory responses to hypercapnia and hypoxia.
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Airway irritation (which agent causes least which causes most?)
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Desflurane is very pungent, and its use can be associated with airway irritability, bronchoconstriction, and laryngospasm during induction. Sevo causes the least amt of subjective airway irritation (why used in mask induction)
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Cerebral metab with volatile anesthetics
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Volatile anesthetics vasodilate cerebral vessels, increasing blood flow while reducing cerebral metabolic oxygen consumption. Cerebral vascular responses to altered PCO2 are maintained in the presence of volatile anesthetics. Nitrous oxide increases cerebral metabolism.
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effect on hepatic and renal blood flow via volatile anesthetics and N2O
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volatile anesthetics reduce both hepatic and renal blood flow, whereas nitrous oxide does not.
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Does N2O trigger malignant hyperthermia?
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All potent volatile agents (except N2O) may trigger malignant hyperthermia in susceptible individuals
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site of action of immobilization effx of inhaled anesthetics? Site of action of sedation/hypnosis and amnesia?
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immobilizing effx of anesthesia=depression of spinal cord
sedations/hypnosis and amnesia = supraspinal (depressing the brain) |
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what does GABA have to do with inhaled anesthesia?
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volatile inhaled anesthetics enhance inhibitory synaptic transmission postsynaptically by potentiating ligand-gated ion channels activated by gamma aminobutyric acid (GABA) and glycine, extrasynaptically by enhancing GABA receptors and leak currents, and presynaptically by enhancing basal GABA release.
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what does glutamine have to do with inhaled anesthetics?
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inhaled anesthetics suppress excitatory synaptic transmission presynaptically by reducing glutamate release (volatile agents) and postsynaptically by inhibiting excitatory ionotropic receptors activated by glutamate (gaseous agents).
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three factors in uptake from the lungs=
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blood solubility, cardiac output, and partial pressure driving anesthetic from one phase (e.g. lung) into a second phase (e.g. venous blood)
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primary factor that determines the FA/FI ratio?
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Blood solubility (ie. blood gas partition coeff) differs greatly among anesthetics, and solubility is a primary factor that determines the FA/FI ratio and clinically relevant issues such as the rates of induction of and recovery from anesthesia: lower solubility, faster recovery.
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??? is an important mechanism by which pulmonary blood is preferentially redistributed away from poorly ventilated lung regions to those with adequate alveolar ventilation.
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Hypoxic Pulmonary vasoconstriction (HPV) Most inhaled anesthetics attenuate (reduce) HPV in vitro and exert relatively modest inhibitory effects on HPV, shunting, or oxygenation in vivo. Reason we need incr O2 (30%).
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negative inotropic effx of volatile anesthetics=
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r/t alterations in intracellular Ca2+ homeostasis within the cardiac myocyte.
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systemic hemodynamic effx of volatile anesthetics determined by:
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interaction of myocardial effx, direct actions on the arterial and venous vasculature, and alterations in autonomic nervous system activity.
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Coronary Steal from anesthetics
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Volatile anesthetics are relatively weak coronary vasodilators that are not capable of producing coronary steal at typically used clinical concentrations, even in patients with steal-prone coronary artery anatomy.
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inhal anesthetics administered before, during, or immediately after onset of coronary artery occlusion and reperfusion
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exert important cardioprotective effects against reversible and irreversible myocardial ischemia in experimental animals and humans.
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N2O effect on inotropic activity, LVDiastolic fxn, pulmonary and systemic arterial pressure?
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N2O causes direct negative inotropic effx, does not substantially affect left vent diastolic fxn, and produces modest increases in pulmonary and systemic arterial pressure via a sympathomimetic effect. These actions are dependent to some degree on the baseline anesthetic.
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Compound A
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The major base-catalyzed breakdown product of sevoflurane which is a nephrotoxic vinyl ether that induces both dose- and time-dependent renal injury. The threshold for renal injury in rats and humans appears to be approx 150ppm-hours of exposure to compound A (i.e. 50 ppm for 3 hours). The toxic threshold appears to be reached only under clinical conditions of prolonged sevo anesthesia, and changes in glucosuria and enzymuria are observed. Blood urea nitrogen and creatinine levels remain unchanged. To date, no significant clinical renal toxicity has been associated with the use of sevo.
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SEVO - vapor pressure, boiling point, O/G partition coeffic, B/G partition coeffic
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VP at 20C: 157mmHg
Boiling point: 59C O/G: 50 B/G: 0.6 MAC: 2.0 Not stable in moist CO2 absorber (Compound A) Recovered as 2-5% (5-8% for boards) metabolites |
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DES - vapor pressure, boiling point, O/G partition coeffic, B/G partition coeffic
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VP: 669 at 20C
Boiling point: 24C O/G: 18.7 B/G: 0.42 MAC: 5.8 |
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ISO - vapor pressure, boiling point, O/G partition coeffic, B/G partition coeffic
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VP at 20C: 238 mmHg
Boiling Point: 49C O/G: 99 B/G: 1.4 MAC: 1.15 |
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N2O - vapor pressure, boiling point, O/G partition coeffic, B/G partition coeffic
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VP at 20C: 38,770 mmHg
Boiling point: -88 C O/G: 1.4 B/G: .47 MAC: 105 |
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Amount to decrease Volatile anesthetic when admin N2O?
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Anesthetic MAC decreased by 10% for every 10% of N2O. i.e. 50% N2O=decrease MAC of Sevo by 50%
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Thiopental=
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Pentothal
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Methohexital=
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Brevital
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Diazepam=
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Valium
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Lorazepam=
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Ativan
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Midazolam=
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Versed
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Flumazenil=
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Romazicon
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Droperidol=
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Inapsine
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Propfol=
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diprivan, others
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Etomidate=
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Amidate
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Ketamine=
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ketalar
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Barbiturates (5 are on market)
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Phenobarbital (Na Lumnial-antiseisure)
Pentobarbital (Nembutal-sedative in syrup form usually in peds) Secobarbital (Seconal - formerly a sleeping pill) Methohexital (Brevital) Thiopental (Pentothal) |
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oxyanalog=
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Pentobarbital (Nembutal) is the Oxyanalog of Thiopental (Pentothal). This metabolite is the reason for the hangover effect of Thiopental (Pentothal). The thiol group (double bonded Sulfur) oxidizes to a double bonded oxygen and the elimination half-life is 12 hours (x 4 half lives = 48 hour elim)
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Thiobarbiturate=
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contain a sulfur molecule at C-2
Thiopental (Pentothal) - oxydizes to form Pentobarbital (Nembutal) |
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Oxybarbiturate=
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contain an oxygen molecule at C-2
Phenobarbital (Luminal) Pentobarbital (Nembutal) Secobarbital (Seconal) |
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N-Methyl Barbiturates
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Contain a methyl group attached to the Nitrogen molecule at N-1 or N-3
Methohexital (Brevital) |
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Two types of classification of Barbs=
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Chemical (sulfur or oxygen molecule, methyl group)
Duration of action ( Ultra short (30-60min), Short (4-8hrs), Intermediate (8-16hrs), Long (24hrs) |
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Ultra short barbs=
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duration=30-60 min
Thiopental (Pentothal) Methohexital (Brevital) |
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Short Barbs=
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Duration = 4-8 hrs
Pentobarbital (Nembutal) Secobarbital (Seconal) |
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Intermediate Barbs=
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duration 8-16hrs
NONE |
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Long Barbs=
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Duration = 24hrs
Phenobarbital (Luminal) - for seizures once a day |
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Example of Analgesic meds: (he said something about a test question)
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Ketamine, nitrous, dexmetomidine
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distribution phase=
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med leaves blood quickly d/t strong concentration gradient from blood. Initial rapid drop d/t diffusion into tissues (alpha half life). Takes minutes to reach equilibrium (at this point not distributing anymore). Eventually level in blood lower than in tissues (i.e. bile excretion, renal elim, hepatic metab). Causes drug to wear off b/c tissues start dumping back into blood.
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Elimination time of most of our induction meds
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2-3, 4 hour elim time
propofol on the short side of time thiopental long side d/t hangover effect |
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Alpha half life in minutes of:
Thiopental Methohexital diazepam Lorazepam midazolam etomidate propofol ketamine |
=distribution half life
thio-2-4 methohex=5-6 diazepam=10-15 lorazepam=3-10 midaz=7-15 etom=2-4 propofol=2-4 ketamine=11-17 |
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beta half life in hours of:
Thiopental Methohexital diazepam Lorazepam midazolam etomidate propofol ketamine |
Elimination half life:
Thiopental=10-12 (longest 48 hrs to get rid of it) Methohexital=2-5 diazepam=20-40 Lorazepam=10-20 midazolam=2-4 etomidate=2-5 propofol=1-3 (shortest 4-6 hr elim) ketamine=2-3 |
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Protein binding of:
Thiopental Methohexital diazepam Lorazepam midazolam etomidate propofol ketamine |
The only ones that matter are at the 90% cutoff to prevent interaction with other highly-bound drugs. > 90% potential for drug interaction especially in 4 groups: Nutrition problem, liver disease, ESRD, women in last trimester of pregnancy
Thiopental=85% Methohexital=85% diazepam=98%*** Lorazepam=98%*** midazolam=94%*** etomidate=75% propofol=98%*** ketamine=12% |
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Why does a patient wake up from a dose of 140mg of propofol after 5-10 minutes? Where did the drug go?
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Redistribution. When the drug is initially given the whole dose is in the blood stream. Since the concentration gradient favors leaving the blood stream into the tissues, there is a rapid decline in the blood level (alpha half life). Almost none left in the blood at 2 minutes. At that point the drug has been redistributed in the tissue (ie. heart, lungs, kidneys, brain, vital organs) thus the induction of sleep. After one minute the brain level starts to drop off because then the blood level is lower than in the tissue favoring a diffusion gradient back into the blood. As this is happening, the muscles (intermediate group) levels are still rising. In addition, the least amount of blood flow occurs to the fat which is the last to rise (especially since lipid soluble).
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Why does a patient wake up from an induction dose of penothal?
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redistribution!!
following injection, the cardiac output and circulatory flow initially distribute the drug to the brain and upper body, and rapid central nervous system effx begin. As time passes, usually minutes, the drug more evenly distributes throughout the body, lowering the initial high brain concentration, and the patient awakens. Redistribution of the central compartment, not hepatic metabolism, was responsible for awakening. |
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Why does a person go to sleep fast during induction?
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Rapid initial distribution. Wake fast b/c of rapid redistrib out of the brain and into tissues (muscle and fat)
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Why do we care about protein binding?
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Because it could have a potentially exaggerated effect in a pt with low plasma or tissue proteins.
Give 2 drugs together that are highly protein bound i.e. valium 98% and Coumadin 98% - finite number of protein binding sites - competition between both and exaggerate effx of both. |
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four groups of pts with decreased albumin levels:
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i.e. 6% may be free instead of usual 2%. Decrease dose b/c easier to overdose. Valium 98% PB - only 2% free to go to receptor (GABA) and prevent nervousness.
Nutrition problem (malnutrition) Liver disease ESRD Women in last trimester of pregnancy d/t fluid shifts |
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GABA mimetic drugs=
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Benzos, barbs, etomidate, propofol, enflurane, isoflurane, alcohol>>>> except ketamine
Mimic the GABA on the receptor |
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what ion is associated with GABA receptors?
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Chloride - meds work by making the receptor allow chlorine conductance into cell with GABA receptor. Chloride enters the cell hyperpolarizing it (more than -80) and making it more negative (-145) inside therefore it's harder to fire therefore it's inhibited.
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On what receptor does Ketamine work?
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Antagonist. Works on glutamate receptor (excitatory receptor in brain) specifically the NMDA (n-methyl D-aspartate) glutamate receptor, ketamine blocks these. When blocked = depressed
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Flumazinil
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Romazicon - specific antagonist to benzos on the site at GABA. Does not reverse opioids, ethanol, barbituates, general anesthetics. 41 to 79 minutes half life. Can have 'resedation' if give to reverse and don't repeat dose to cover benzo with half life longer than the half life of Flumazinil.
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GABA =
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gamma-aminobutyric acid type A
Have binding sites for: benzos barbs neurosteriods gamma-butyrolactones zinc loreclezole ethanol Gen Anesthetics: etomidate, propofol, isoflurane, enflurane |
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MOA of Barbs
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GABA mimetic Agonist
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MOA of Benzodiazepines
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GABA mimetic Agonist
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MOA Propofol
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GABA mimetic Agonist
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MOA Etomidate
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GABA mimetic Agonist
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MOA Ketamine
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Antagonist; acts via n-methyl-d-aspartate (NMDA) receptor antagonism (glutamate receptor)
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Which AA is associated with NMDA receptors that make them excitatory?
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GLUTAMATE - blocked by KETAMINE
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daytime sedation=
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don't really want sedated - rapidly developing a tolerance (not tired) to sedative effect of benzos - anxiolysis. If come for surgery and on home benzos, dose of benzo won't sedate but will be anxiolytic.
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big diff btw diff benzos?
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duration (half life)
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Alprazolam (trade name, half life, clinical application)
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Benzo used in US: Xanax, 12-15hr, anxiolysis
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chlordiazepoxide(trade name, half life, clinical application)
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Benzo used in US: Librium, 8-18hr, Alcohol w/d, etc
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Clonazepam(trade name, half life, clinical application)
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Benzo used in US: Klonopin, 18.7-39hr, Treatment of epilepsy
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Clorazepate(trade name, half life, clinical application)
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Benzo used in US: Tranxene, 2.4hr, Treatment of epilepsy and etoh w/d
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Desmethyldiazepam (trade name, half life, clinical application)
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Benzo used in US: (Des=removed something or without; diazepam is demethylated to form this), Nordiazepam and Nadar, 20-200hr
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Diazepam(trade name, half life, clinical application)
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Benzo used in US: valium, sedation, induction and maintenance of anesthesia
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Estazolam(trade name, half life, clinical application)
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Benzo used in US: ProSom, 14hrs, Treatment of insomnia
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Flurazepam (trade name, half life, clinical application)
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Benzo used in US: Dalmane; 2-3hrs, Treatment of insomnia
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Lorazepam (trade name, half life, clinical application)
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Benzo used in US: Ativan; 10-22hr; Anxiolysis and sedation
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midazolam (trade name, half life, clinical application)
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Benzo used in US: versed; 1.7-2.6hr, sedation, induction and maintenance of anesthesia
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Oxazepam (trade name, half life, clinical application)
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Benzo used in US: Serax; 3-21hr, Anxiolysis
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Prazepam (trade name, half life, clinical application)
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Benzo used in US: Centrax; 63-70hr; Anxiolysis
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Quazepam (trade name, half life, clinical application)
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Benzo used in US: Doral; 25-41hr; treatment of insomnia
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Temazepam (trade name, half life, clinical application)
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Benzo used in US: Restoril; 10-21hr; Treatment of insomnia
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Triazolam (trade name, half life, clinical application)
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Benzo used in US: Halcion; 2-3hr; Treatment of insomnia
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Flumazenil (trade name, half life, clinical application)
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Benzo used in US: Romazicon; 0.7-1.3hr; Reversal of benzodiazepine agonists
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Zaleplon (trade name, type)
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Sonata; non-benzo receptor agonist (new sleep pills that don't have benzo structure but are NBRAs (gaba mimetic) Don't bind to benzo binding site
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Zoldipem (trade name and type)
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Ambien (most widely used) non-benzo receptor agonist (new sleep pills that don't have benzo structure but are NBRAs (gaba mimetic) Don't bind to benzo binding site
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Eszopiclone (trade name and type)
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Lunesta; non-benzo receptor agonist (new sleep pills that don't have benzo structure but are NBRAs (gaba mimetic) Don't bind to benzo binding site
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Ramelteon (trade name and type)
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Rozerem; Melatonin receptor agonist
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Which allergies are most likely to be a problem with propofol?
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Soybean, Egg or Peanut - since propofol extremely lipid soluble, it is in Lecithin which was originally obtained from eggs. Lecithin has important surfactant properties and is used as an emulsifying agent. WOULD WANT TO GIVE ETOMIDATE or BREVITAL or PENTOTHAL if pt has this allergy.
want to avoid the vehicle that looks like milk |
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What does generic propofol contain that could present a problem to a certain population?
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SULFITES - you don't want to give them to someone with sulfite (food allergy) or ASTHMATICS (d/t multiple allergy). There's no sulfites in original propofol.
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prodrug propofol name and activity
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Lusedra formerly named Aquavan (phospropofol)=prodrug in the more water-soluble form of propofol. Requires 15-20 minutes for onset due to conversion to active form (removing a phosphate and formaldehyde). 50% of pts get paresthesias (pins & needles) in groin.
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the only intravenous anesthetic=
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ketamine (all others are inhalation drugs)
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Other than allergies to eggs, soybean, or peanuts; what concern do we have when using propofol for a long duration (more of an ICU setting thing)?
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BUGS! Bacterial contamination since may have more of a substrate for growth in the milky soln. However, AstraZeneca did start putting small amount of antimicrobial into the med. This preservative (EDTA & sodium metabisulfite) level, in generic and brand name propofol, is below the US Pharmacopoeia minimum std so the manufacturer can still label as "preservative free".
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Class: Thiobarbituates (drug name, available soln, pain on injection (0, +, ++, +++), % soln, concentration, avg sleep dose)
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Thiopental (pentothal); (pka 7.5) sodium salts mixed with anhydrous sodium bicarb (used to buffer the pH up) pH 10.5-11; +++; 2.5% soln=25mg/ml; 4mg/kg avg sleep dose = 280 mg for 70kg pt, would usually give 300mg = 12ml; acid drug so has to be placed in base; tremendously lipid soluble so it goes thru the BBB quickly (why it's so rapid acting)
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N-methylated oxybarbiturate (drug name, available soln, pain on injection (0, +, ++, +++), % soln, concentration, avg sleep dose)
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Methohexital (brevital); pKa 7.9; same as thiopental pH 10-11 (makes it water soluble); 1.5mg/kg dose 70kg=100mg; 1% soln=10mg/ml (10ml for sleep dose); +
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Benzodiazepines (drug name, available soln, pain on injection (0, +, ++, +++), % soln, concentration, avg sleep dose)
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Diazepam (valium) - 0.5% in 40% propylene glycol and 10% alcohol; 0.3-0.5 mg/kg IV; +++ pain
Lorazepam (ativan); 0.4% in propylene glycol; 0.1 mg/kg IV; + pain Midazolam (versed); 0.5% buffered aqueous soln (pH 3.5); 0.2-0.35mg/kg IV; 0 pain |
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Imidazoles (drug name, available soln, pain on injection (0, +, ++, +++), % soln, concentration, avg sleep dose)
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Etomidate (amidate); water soluble at acidic pH, lipophilic at physiologic pH (pKa 4.24); 0.2% soln in 30% propylene glycol (organic solvents) (pH 5); +++; 0.3mg/kg avg sleep dose 21mg avg person; 20mg/vial usually just give the vial of 2ml
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Alkylphenol (drug name, available soln, pain on injection (0, +, ++, +++), % soln, concentration, avg sleep dose)
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Propofol (diprivan); 1% soln in an aqueous emulsion containing 10% soy bean oil, 2.25% glycerol and 1.2% egg phosphatide, EDTA (pKa 11) AstraZeneca; ++ pain ; 2mg/kg; 140mg for 70 kg person=14ml; 1% soln=10mg/ml
generic=watch for formulations containing sulfites (asthma and sulfite allergy); ++ pain fospropofol (Aquavan, Lusedra); Prodrug converted to active propofol; cleaved by alkaline phosphatase to phosphate, formaldehyde and propofol; 0 pain ; 35mg/ml strength vial with 30 ml; avg dose 6.5 mg/kg (would wait 10-15 minutes to see if works, repeat dose @ 25% of original dose) |
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Arylcyclohexyl amines (drug name, available soln, pain on injection (0, +, ++, +++), % soln, concentration, avg sleep dose)
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Ketamine (Ketalar); white crystalline salt 1% or 10% aqueous soln (pH 3.3-5.5; pKa 7.5); 0 pain
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affect on brain from all induction drugs?
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Barbs, propofol, etomidate Decrease CBF, CMRO2, ICP in a dose dependent manner. Except ketamine!
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effect of ketamine on brain blood flow?
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increased by ketamine (CBF, CMRO2, ICP)
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CV effect from induction IV drugs
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IV anesthetics tend to make BP decrease much the same reason that inhal anesthetics cause decrease
propofol > thiopental > etomidate (least amount of BP effx of all induction drugs) (propofol most cardiac depressing of all the induction drugs) Ketamine increases blood pressure and heart rate |
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Mechanisms of decreased BP:
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CNS depression
Direct Cardiac Depression Decreased SVR Baro-receptor depression hormonal changes (decreased hormone rls) |
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which IV induction drug may cause a histamine rls and who would be most effected?
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thiopental (penathal and brevital) (barbs) - small number of people who can have a histamine rls w/barbs and may not want to use with ASTHMA (bronchoconstrict)
Could use propofol or etomidate instead (they don't effect bronchial tone) |
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What agents are acceptable to use for a pt that is susceptible to malignant hyperthermia?
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N20, barbs, propofol, ketamine, etomidate, opiates, amide and ester anesthetics (book pg111)
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which inhal agents increase HR?
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Iso and Des
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what is the effect on CO from inhaled anesthetics (each one)?
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Iso-slightly reduced CO
Des-stabel CO Sevo-Slightly reduced CO |
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Effect on SVR from inhaled anesthetics?
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Iso, Des, Sevo = reduce SVR
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Effect on coronary vasodilation in inhaled anesthetics (for each)?
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Iso=marked
Des=minimal Sevo=moderate |
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Which inhaled agents are respiratory irritant?
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Iso & Des
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Advantages of N2O
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Analgesia
Rapid uptake and elim Little cardiac or respiratory depression Nonpungent allows less potent anesthetic to be admin |
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Disadvantages of N2O
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Expansion of closed air spaces
requires high concentrations Diffusion hypoxia TERATOGENIC |
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Advantages of Iso
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Moderate muscle relaxation
Decreases cerebral metabolic rate Minimal biotransformation no significant systemic toxicity maintains cardiac output because of vasodilation inexpensive |
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Disadvantages of Iso
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Pungent odor
airway irritant fewer negative inotropic effects than halothane Trigger for MALIGNANT HYPERTHERMIA |
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Advantages of Des
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Rapid uptake and elim
stable molecules minimal biotransformation no significant systemic toxicity |
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Disadvantages of Des
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Airway irritant
low boiling point sympathetic stimulation expensive low boiling point and high saturation vapor pressure needs special electrically heated vaporizer rapid increases in inspired concentration can lead to reflex tachy and HTN trigger for MALIGNANT HYPERTHERMIA |
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SEVO advantages
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Rapid uptake and elim
nonpungent excellent for inhalation induction cardiovascular effects broadly comparable to those of iso |
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Sevo disadvantages
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Susceptible to biotransformation
reacts with soda lime increases surm fluoride concentration expensive 3%-5% metabolized, but current evidence is that it causes neither hepatic nor renal toxicity trigger for MALIGNANT HYPERTHERMIA |
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Pentothal (name, Thiobarbiturate/oxybarbiturate/N-methyl barbiturate, duration of action)
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Thiopental; thiobarbiturate (contain a sulfur molecule at C-2); converts to oxyanalog Pentobarbital (Nembutal); considered an ultrashort 30-60 minutes
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Phenobarbital (name, Thiobarbiturate/oxybarbiturate/N-methyl barbiturate, duration of action)
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Luminal; oxybarbiturate (contain an oxygen molecule at C-2); considered a Long Duration of action (24 hours); for seizures once a day
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Pentobarbital (name, Thiobarbiturate/oxybarbiturate/N-methyl barbiturate, duration of action)
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Nembutal; Oxybarbiturate (contains oxygen molecule at C-2); thiopental converts to this; Considered a short acting (4-8hr)
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Secobarbital (name, Thiobarbiturate/oxybarbiturate/N-methyl barbiturate, duration of action)
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Seconal; oxybarbiturate (contain oxygen molecule at C-2); considered Short acting (4-8 hrs)
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Brevital (name, Thiobarbiturate/oxybarbiturate/N-methyl barbiturate, duration of action)
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Methohexital; N-Methyl Barb (contain a methyl grp attached to the Nitrogen molecule at N-1 or N-3); Considered ultrashort acting (30-60 minutes)
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Ketamine, N2O, and Dexmedetomidine ar examples of:
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Analgesics
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Distribution half life of Thiopental in minutes
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2-4
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Distribution half life of Methohexital in minutes
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5-6
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Distribution half life of Diazepam in minutes
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10-15
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Distribution half life of Lorazepam in minutes
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3-10
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Distribution half life of Midazolam in minutes
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7-15
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Distribution half life of Etomidate in minutes
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2-4
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Distribution half life of Propofol in minutes
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2-4
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Distribution half life of Ketamine in minutes
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11-17
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Elimination half life of Thiopental in hours
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10-12 (48 hours =4 half lives to get rid of drug)
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Elimination half life of Methohexital in hours
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2-5
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Elimination half life of diazepam in hours
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20-40 (avg 35) (active metab 7 days)
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Elimination half life of Lorazepam in hours
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10-20
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Elimination half life of Midazolam in hours
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2-4
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Elimination half life of Etomidate in hours
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2-5
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Elimination half life of Propofol in hours
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1-3 (shortest 4-6 hr elim)
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Elimination half life of Ketamine in hours
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2-3
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% of CO and blood flow to brain
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The brain has a high metabolic rate and receives approx 15% of CO. Under normal circumstances, cerebral blood flow (CBF) is approx 50ml/100g/min. Gray matter receives 80% and white matter receives 20% of this blood flow.
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Energy consumption of brain
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Approx 60% of the brain's energy consumpt is used to support electrophysiologic funxn. The remainder of the energy consumed by the brain is involved in cellular homeostatic activities (maintaining the cells, burning glucose, etc)
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CBF is tightly ????? to ?????
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CBF is tightly coupled to local cerebral metabolism. When cerebral activity in a particular region of the brain increases, a corresponding increase in blood flow to that region takes place. Conversely, suppression of cerebral metab leads to a reduction in blood flow.
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Autoregulation in brain=
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CBF is autoregulated and held constant over a mean arterial pressure range conservatively estimated at 65-150 mmHG, given normal venous pressure. There is probably appreciable intersubject variability. CBF becomes pressure passive when mean arterial pressure is either below the lower limit or above the upper limit of autoregulation.
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Chemical regulation of CBF
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CBF is also under chemical regulation. It varies directly with arterial carbon dioxide tension in the PaCO2 range of 25-70mmHg. With a reduction in PaCO2 to below 60mmHg, CBF increases dramatically. Changes in temperature (also changed pressures) affect CBF primarily by suppression of cerebral metab
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Vasodilators/Constrictors effx on CBF
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Systemic vasodilators (NTG, nitroprusside, hydralazine, calcium channel blockers) vasodilate the cerebral circulation and can, depending on mean arterial pressure, increase CBF. Vasopressors such as phenylephrine, norepinephrine, ephedrine, and dopamine do not have significant direct effx on the cerebral circulation (they don't pass the BBB). Their effx on CBF is dependent on their effx on Systemic BP. When mean arterial pressure is below the lower limit of autoregulation, vasopressors increase systemic pressure and thereby increase CBF. If systemic pressure is within the limits of autoregulation, vasopressor-induced increases in systemic pressure have little effect on CBF.
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Effx on CMR from volatile anesthetics
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All modern volatile anesthetics suppress the cerebral metabolic rate (CMR) and, with the exception of halothane, can produce burst suppression of the EEG. At that level, CMR is reduced by about 60%. Volatile anethetics have dose-dependent effx on CBF. In doses lower than the minimal alveolar concentration (MAC), CBF is not significantly altered. Beyond doses of 1 MAC, direct cerebral vasodilation results in an increase in CBF and cerebral blood volume. (by extension cerebral pressure)
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Effect on CMR from barbs, etomidate, and propofol
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Barbs, etomidate, and propofol DECREASE CMR and can produce burst suppression of the EEG. At that level, CMR is reduced by about 60%. Flow and metab COUPLING is preserved and therefore CBF is decreased. Opiates and benzos effect minor decreases in CBF and CMR, whereas katamine can increase CMR (with a corresponding increase in blood flow) significantly.
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Effect on cerebral injury from Barbs, propofol, ketamine, volatile anesthetics, and xenon
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Barbs, propofol, ketamine, volatile anesthetics, and xenon have neuroprotective efficacy and can reduce ischemic cerebral injury. Anesthetic neuroprotection is sustained only when the severity of the ischemic insult is mild; with moderate to severe injury, long-term neuroprotection is not achieved. Administration of etomidate is associated with regional reductions in blood flow, and this can exacerbate ischemic brain injury.
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of all induction drug, which has most heart depression?
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Propofol (also most respiratory depressing); this cardiac depression may be related to the unexplained metabolic acidosis or arrythmias seen in prolonged sedation of peds pts. Decreased cardiac status results in nasty byproducts in the liver.
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Least hear depression of all induction drugs?
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etomidate (also least respiratory depression)
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which three agents are contraindicated in porphyria?
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Pentothal, brevital, and etomidate (induce enzyme ALA synthetase)
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Which agent causes decreased cortisol levels?
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Etomidate supresses 11 beta hydroxylase which decreases cortisol
even with induction dose of etomidate the adrenocorticoids stay down for days after surgery. we usually give it to those who won't tolerate propofol which are usually the sicker patients who would need their steroids, and worry about replacing the steriods (decadrone or cycortef) later. |
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PRIMARY CLINICAL EFFX of KETAMINE (on test)
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Phencyclidine derivative (LSD)
Unconsciousness, amnesia referred to as dissociative anesthesia (doesn't cause s&s of anesthesia)-brain not depressed - non-communitive INCREASES CMR, CBF, ICP, IOP, nystagmus or disconjugate vision Analgesic (decent - why people use small doses i.e. 50mg) increases BP and pulse Potent bronchodilator (catecholamine) Maintains respirations and airway reflexes (note: may be a period of apnea esp with high doses and rapid admin) increases SALIVATION (odd for a sympathomimetic) and respiratory secretions (might give some robinol if not able to suction) Increases muscle tone (no relaxation - require paralytic to keep still) EMERGENCE DELIRIUM, nightmares, hallucinations (even for days - COADMIN Benzo usually prevents) CAUTION in pts with HTN, angina, CHF, inc ICP, Inc IOP, psych disease, airway problems |
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usual dose of ketamine
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induction: 2mg/kg IV; 6mg/kg IM; or orally 6mg/kg
50mg to fuzz up a little (sedation or analgesia) half dose for maintenance |
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Can Ketamine be used in OB?? and Catecholamine with ketamine use:
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Ketamine can be used in OB
indirect sympathomimetic; catecholamine rls is not stimulated directly by ketamine - instead causes a rls of catecholamines which stimulates the receptors. |
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What drug do we give that causes increased salivation and respiratory secretions?
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Ketamine
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Which enzyme is inhibited by etomidate?
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2 negative properties of etomidate:
11 beta Hydroxylase = = decreases cortisol and corticosterone and aldosterone (cortisol/aldosterone synthesis) - adrenal suppression Also causes more post op N/V |
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PONV and drugs cause/prevent:
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N2O, ketamine, and etomidate = EMETIC
PROPOFOL = ANTIEMETIC ketamine in small doses 50mg or so not as much of an effect. |
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Dexmedetomidine is an ??? ???? that produces ???, ???, and ???
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Dexmedetomidine is an nonselective alpha-2 agonist that produces sedation, analgesia, and amnesia.
sympatholytic, sedation, and antinociception effects of alpha-2 adrenoreceptors, ablates memory, minimal changes in respir system, decreased BP and HR d/t effects on the CV system, decreases saliva production, anxiolysis. Used as IV sedation in MAC cases, anesthesia maintenance, sitting neuro cases since can be woken up during case, to check function of some area of body, also to secure an airway with a fiberoptic intubation. |
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best drug to use with acutely elevated ICP
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In the pt with acutely elevated ICP, PROPOFOL provides the greatest margin of safety and ability to reduce ICP. Care must be taken not to compromise CPP through hypotension. High dose barb therapy may be considered in hemodynamically stable severe head injury pts with intracranial hypertension refractory to other ICP-lowering therapies.
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Mannitol for raised ICP
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Mannitol is effective for the control of raised ICP after severe head injury. Limited data suggest that intermittent boluses are more effective than continuous infusion. The effective dose range is 0.25 to 1.0 g/kg. Serum osmolarity should be kept below 320 mOsm/L, and hypovolemia should be avoided.
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hyperventilation in severe traumatic brain injury
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The use of prophylactic chronic hyperventilation (PaCO2 less than 30mmHg) during the first 24 hrs after severe traumatic brain injury should be avoided because it can compromise CBF. Hyperventilation may be used for short periods in acute neurologic deterioration or elective supratentorial craniotomy.
LOW NORMAL PCO2 with PROPOFOL and MANNITOL |
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Ambulatory surgery induction/maintenance agent of choice
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Whenever intravenous access is available in adult pts, propofol offers a definite and clear advantage over thiopentone during ambulatory (usually healthy) surgery. Even when compaired with inhalation agents such as sevoflurane, propofol offers advantages in better and smoother induction of anesthesia and greater pt satisfaction with earlier recovery and therefore should be the natural choice in all but the most exceptional circumstances. (when in doubt, use propofol!)
Maintenance: Early recovery may be delayed by 1-2 min following propofol infusion compared with sevo or des. However, the overall advantages of propofol in terms of reduced incidence of PONV, as well as earlier home discharge, would favor the latter. |
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Choice of inhalation agent in Ambulatory surgery
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Early recovery is faster using des vs. sevo or iso (most use sevo or some des, iso is too slow). However, the time to transfer to phase II is earlier in sevo, and minor complications appear to be equally distributed among the three agents. Therefore factors other than recovery and minor postop complications should be considered when determining the inhalation agent of choice. (Avg pt doesn't go home in 8 minutes-it takes an hour or hour and half regardless of gas.
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What is the rate controlling enzyme that you do not want to stimulate in a pt with porphyria?
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ALA sythetase
Pentothal, Brevitol or etomidate can stimulate it! |
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Droperidol=
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dopamine blocker with extrapyramidal side effx (parkinson's like) Do not give to people who don't have enough dopamine in the first place (parkinson's)
Another = reglan (metoclopramide) |
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Type of drug that Droperidol is and any side effect
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Droperidol is a butyrophenone tranquilizer used as an antiemetic. Negative effect=prolong QT interval and cause arrythmia. obtain 12 lead prior to use.
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