Pharmacology EXAM Flashcards
The route of administration associated with the lowest degree of bioavailability is:
intrathecal
By definition, intravenous administration is associated with bioavailability _____%
100%
y. Intramuscular and sublingual administration is associated with______ bioavailability.
60 - 100%
The oil/gas coefficient of an inhaled anesthetic agent best corresponds to the agent’s:
potency
What characteristics of a gas indicates potency?
Oil/gas coefficient
The higher the solubility ______the drug (more or less potent)
More
The antiemetic effects of ondansetron are the result of the drug’s:(MOA)
antagonistic properties at serotonin type-3 receptors
This agent is a Selective serotonin type-3 receptor antagonist
Ondansetron
Drugs used in the preoperative preparation of the hyperthyroid patient,
Methimazole
What is the mechanism of action of Methimazole ?i
Inhibit organification of iodine and synthesis of thyroid hormone
What is the most important goal in managing the hyperthyroid patient?
is to make the patient euthyroid before any surgery, if possible. T
What are 2 THIOUREA derivatives drugs?
Propylthiouracil and Methimazole
What is the mechanism of THIOUREA derivatives drugs?
inhibit organification of iodide and the synthesis of thyroid hormone.
Respiratory insufficiency has been associated with the administration of which drug? (class III antiarrhythmic)
amiodarone
How does Amiodarone affects pulmonary disease?
chronic interstitial pneumonitis, organizing pneumonia, ARDS or a solitary mass of fibrosis.
Prevalence of pulmonary disease with the use of amiodarone?
5 - 15%
Generalized pruritis associated with administration
neuraxial fentanyl
Pruritis mechanism appears to be through interaction with which receptor?
central μ-receptor interaction.
Pruritus associated with ______administration
Intrathecal
Opiates frequently produce a______and a feeling of _______in what areas of the body?
Rash, itching and a feeling of warmth in the area of the face, upper chest, and arms.
Non-HISTAMINE releasing OPIOIDS
FENTANYL
Noncompetitive and nonselective α-blockade can be achieved with the administration of:
phenoxybenzamine
Phenoxybenzamine has what kind of activity at receptors? Phenoxybenzamine is used in the preoperative preparation of patients with pheochromocytoma.
has both α1- and α2-blocking activity.
Phenoxybenzamine The α-receptors are(competitiveness and reversibility)
noncompetitively and irreversibly bound.
Rise and Fall of inhaled anesthetic agent in body compartment? (all brain must be fat)
Alveoli
Brain
Muscle
Fat
Medication to treat Hyponatremic HYPERVOLEMIC CHF ??
Tolvaptan
What is Tolvaptan mechanism of action ?
Inhibit arginine vasopressin receptors
Tolvaptan inhibit arginine vasopressin receptors where in the renal ?
Collecting ducts.
Agents have proven to be safe and efficacious in hyponatremic patients, appearing to have particular value in patients with hypervolemic hyponatremia secondary to congestive heart failure.
Vasopressin receptor blocking agents
Name some vasopressin antagonists?
Conivaptan, Tolvaptan, -Vaptan
The vasopressin receptor antagonists produce a selective
water diuresis without affecting sodium and potassium excretion.
Identify this molecule: CF3-CHF-O-CHF2
Desflurane
Identify this molecule: N=N=O
Nitrous Oxide
Identify this molecule: (CF3)2 - CH- O-CH2F
Sevoflurane
Identify this molecule: CF3- CHCl- O-CH2F
Isoflurane
The onset of action of a local anesthetic agent is closely correlated to its (what properties)
pKa
Since local anesthetic agents need to first _______ to have an effects
gain access to the interior of the neuron to have effect,
Local anesthetic agents with lower pKa,
Lidocaine
Mepivacaine
Prilocaine
Lower pKa have a _______onset of action
more rapid
High pKa have a________ onset of action
Slower
Local anesthetics agents with
Bupivacaine
Tetracaine
Procaine
A patient is undergoing debridement of wounds under hyperbaric conditions. If the pressure in the hyperbaric chamber is 2 atmospheres, the minimum alveolar concentration of desflurane would be expected to be:
3%
MAC as originally defined depends on
atmospheric pressure.
However, when agent concentration is expressed as a partial pressure, MAC becomes independent
of ambient pressure.
MAC, expressed as a percentage,________ with increasing ambient pressure.
decreases
MAC expressed as percentage and relationship with ambient pressure
Inverse relationship
MAC of desflurane @ 1 ATM =
6% of 760 mm Hg = 45.6 mm Hg
MAC of desflurane @ 2 ATM =
45.6 mm Hg / 1520 mm Hg = 0.03 or 3%
What is the CNS effects of Nitrous oxide?
a decrease in cerebrovascular tone, an uncoupling of CBF and (CMRO2)
Nitrous oxide on cerebral vascular tone and CMRO2
decreases cerebral vascular tone significantly and increases CMRO2.
Nitrous and CMRO2 and CBF coupling?
Since the increase in CMRO2 exceeds the elevation in CBF there is an uncoupling of these parameters.
What can you do to ATTENUATE the increase in CBF?
Mild hyperventilation can attenuate the increase in CBF that accompanies the use of nitrous oxide.
Action of succinylcholine on HR? and how?
Succinylcholine may cause bradycardia as a result of its action on cardiac: muscarinic receptors
Succinlycholine has no action on_________ but may cause bradycardia by an action on_______
ganglionic nicotinic receptors; cardiac cholinergic muscarinic receptors.
In considering the two-compartment model of drug distribution, the central compartment comprise what % of the body mass?
Represents approximately 10% of the body mass
In the two-compartment model, the first compartment is termed the and is composed of
central compartment
What is the central compartment composed of ?
intravascular fluid and the highly perfused tissues such as the heart, lungs, brain, liver and kidneys.
The central compartment represents only about _____of the body mass in the adult;
10%; ;
Central compartment receives how much % of the cardiac ouptut?
75% of the cardiac output
Central compartment also referred to as the
vessel-rich group.
Actions produced by opiate agonistic action on the kappa receptor include:
Analgesia, inhibition of ADH release, antishivering
Antishivering opiate agonist through which receptor?
Kappa
Inhibition of ADH release opiate agonist through which receptor?
Kappa
A low-dose infusion of epinephrine would be expected to produce: with skeletal muscles
increased blood flow to the skeletal muscles
With low doses of epinephrine which EFFECT dominate?
Beta dominates, few alpha
The propofol infusion syndrome (PRIS): results in
cardiac and peripheral muscle necrosis
What is the CAuse of PROPOFOL INFUSION syndrome syndrome? PRIS is likely the result of the iSymptoms include Risk factors include
pp 109-110
Inhibition of oxidative phosphorylation by propofol.
What are symptoms of Propofol infusion syndrome (PRIS)
severe metabolic acidosis, Rhabdomyolosis Renal failure Bradycardia and Refractory heart failure.
Risk factors of Propofol infusion syndrome (PRIS)?
young age (children more likely doses greater than 4 - 5 mg/kg/hr, critical illness and an infusion duration greater than 48 hours.
Relief of anginal pain by nitroglycerine is primarily the result of:
decreased preload and cardiac work
Which medication given for angiona causes venodilation and a resultant decrease in preload?
Nitroglycerine
The occupancy theory states that:
the magnitude of a drug’s effect is proportional to the number of receptors occupied
The occupancy theory holds that the magnitude of a drug’s effect is
proportional to the number of receptors occupied.
The duration of action of a local anesthetic agent is closely correlated to its:
degree of protein binding
The duration of action of local anesthetics demonstrates a relationship to
protein binding and lipid solubility.
In theory, drugs that have a high affinity for protein,
attach more firmly to the sodium channel receptor and have a greater duration of action.
Diffusion hypoxia is a potential problem following the administration of:
nitrous oxide
During emergence, when high concentrations of nitrous oxide have been given, Explain the drug exit and its significance on the body?
the drug exits the body quickly and can result in the dilution of normal respiratory gases such as oxygen and carbon dioxide.
How do you prevent the occurrence of diffusion hypoxia with nitrous?
The administration of 100% oxygen for several minutes following the termination nitrous oxide entirely avoids this potential problem.
Ventilatory effects of the volatile anesthetic agents include
Increases in Ventilatory rate, PaCO2, the apneic threshold
What are the effects of Volatile anesthetic agents responsiveness to CO2?
Decrease responsiveness to CO2
The compensatory mechanism for the decreased tidal volume is an________; however, this is
increase in rate; insufficient to prevent an increase in PaCO2.
Hypoxic drive and Volatile agents
Depression of the hypoxic drive occurs with very low concentrations of volatile agents
VA and bronchial tone :
decreased with resultant bronchodilation.
Hydrolysis of succinylcholine by plasma cholinesterase results in the formation of:
succinic acid, choline, succinylmonocholine
Succinylcholine undergoes _______catalyzed ________
Ester Hydrolysis
Plasma cholinesterase
The typical Vd, normalized for the body weight of a 70 Kg adult, would be the
quantity of total body water (42 L) divided by the body weight (70 kg). This results in a Vd of 0.6 L/Kg.
Stimulation of opioid receptors has been shown to:
inhibit adenylate cyclase in the cell
Opioid receptors are what kind of receptors?. This causes in a d
G- Protein Coupled receptors
Opioid receptors are GPCRs , what do they do?
Inhibit the activity of adenylate cyclase inside cells
Opioids receptors are GPCR that inhibit the action of adenylate cyclase which causes what? what about calcium and K+?
decreases conductance of the voltage-gated calcium channels and open potassium channels, resulting in decreased neuronal activity.
Generally absent with low-dose norepinephrine infusions
Positive chronotropic effects
NE infusion at low doses on vascular resistance>
increase in vascular resistance inducing reflex vagal activity
In low doses, norepinephrine show ________the end results is ________
little β2 activity and the end result is largely unopposed α-receptor stimulation.
Why is the chronotropic effect seen with β1-receptor stimulation is generally absent with low-dose norepinephrine?
because of the increase in SVR, which induces reflex vagal activity.
CV and properties of etomidate include: (Select 3) hydrolysis by plasma esterases,, adrenocortical suppression with induction doses
minimal hemodynamic changes with induction
Metabolism of Etomidate is by
hepatic microsomal enzymes and HYDROLYSIS by plasma esterases.
What you should know about Etomidate induction dose?
Adrenal suppression with induction dose
What accounts for the EXTREMETLY short duration of action of Etomidate?
Rapid redistribution
What is the primary clinical advantage of Etomidate?
Hemodynamic stability upon induction
Etomidate action of adrenal hormone is that it ?
Decrease the adrenal hormone levels for up to 24 hours after etomidate administration
What is the cause of Etomidate’s addrenal suppression?
11 Beta-hydroxylase inhibition
Clevidipine: is
highly selective for vascular smooth muscle
What is clevidipine class o
Dihydropyridine L-type CCB
Clevidine is used as an
IV antihypertensive
Why is the good thing about clevidine?
Highly selective for vascular muscle and does NOT AFFECT Myocardial contractility or conduction
The graded dose-response curve has a: hyperbolic shape
Hyperbolic shape
The graded dose-response curve, which is plotted in linear fashion, characterizes
the changes in measured response as an administered dose is increased.
The response curve has a
hyperbolic shape.
When plotted on a logarithmic scale, the dose-response curve takes
on a sigmoid, or ‘S’, shape.
Vasoconstrictive properties are associate with use of what 3 local anesthetics?
pg. 131
cocaine, lidocaine, ropivacaine
What are the only parenterally administered local anesthetics with vasoconstrictive properties?
Ropivacaine and lidocaine
Cocaine also has vasoconstrictive properties because of its
ability to block the reuptake of norepinephrine.
A 23-year-old man is undergoing a thoracotomy for resection of blebs. He is currently has a 500 mL pneumothorax present. If the patient is anesthetized with an anesthetic of desflurane with nitrous oxide and oxygen in a 2:1 ratio, the resultant volume of the pneumothorax will approach:
1500 mL
A compliant airspace, such as a pneumothorax, will
increase in volume during nitrous oxide administration.
Theoretically, at 50% inspired nitrous oxide, the gas bubble would
double in volume.
Theoretically, at 67% nitrous oxide
could triple the volume of a gas bubble
The chemical interaction of sevoflurane with desiccated soda lime has been associated with:
anesthesia machine fires
Sevoflurane can react chemically with desiccated soda lime and yield
excessive temperatures that produce anesthesia machine fires and patient injuries.
The proposed mechanism of Sevoflurane and dessicated soda lime fires?
he proposed mechanism is a dehydrohalogenation of the sevoflurane with the release of hydrogen gas.
3 Causes of increased pseudocholinesterase activity include: thyroid disease
Thyroid disease, nephrotic syndrome and obesity
Cognitively impaired children
Characteristically, drugs with large volumes of distribution are: in terms of Lipid solubility and protein binding
lipid soluble with little protein binding
Drugs that are free, unbound to plasma proteins and lipid soluble
easily cross membranes to tissues and therefore have large calculated volumes of distribution with low plasma concentrations.
Drugs with Large volume of distribution have a _____Plasma concentration
low plasma concentrations
The production of a neurotoxic metabolite has been associated with the use of what opiods?
meperidine
Meperidine is biotransformed by
Liver
Meperidine is biotransformed by the live to
Normeperidine, a neurotoxic metabolite,
Normeperidine half life is
12 - 16-hour half-life.
Repetitive dosing of meperidine can cause accumulation of normeperidine, which may
precipitate tremulousness, myoclonus, and seizures
Low-dose dopamine infusion causes increased urine output as a result of
an increase in renal blood flow
The stimulation of dopamine receptors in the renal artery promotes
an increase in renal blood flow and a resultant increase in glomerular filtration rate and urine output.
Ketamine MOA is
t increases pulmonary compliance in patients with bronchospastic disease.
antagonizes NMDA receptors in the brain,noncompetitively inhibits the NMDA receptor in the brain producing amnesia and a profound analgesic state.
Ketamine on ICP and CBF
Increases ICP ; Increases CBF and CMRO2
Ketamine and Immune system?
Ketamine It inhibits tumor necrosis factor-alpha and interleukin-6, accounting for its antiinflammatory action.
How is Ketamine metabolized?
Ketamine is metabolized by hepatic microsomal enzymes.
Ketamine on the cardiovascular system?
Centrally mediated increase in sympathetic tone with an increase in heart rate and blood pressure.
Ketamine and pulmonary system
It increases pulmonary compliance in patients with bronchospastic disease.
Vasoplegic syndrome has been seen with the induction of anesthesia in patients receiving what class of medication?
ACE inhibitors
What is Vasoplegic syndrome (VS)?
unexpected refractory hypotension resulting from low systemic vascular resistance
The incidence of VS in surgical patients may be as high as 50% in persons receiving
renin-angiotensin system antagonists.
The therapeutic safety margin of a drug is defined as the:
lethal dose in 1% divided by the effective dose in 99% of the population : LD1/ED99
Therapeutic index or margin is
ED
The lower the margin of safety of a drug
the more likely toxic effects will be seen.
Of the following, the rapidity of local anesthetic absorption is the greatest with:
interpleural block
The absorption of local anesthetics generally occurs in the following order of rapidity: Excluding blocks of the airway, (PleuCoCauEBSciSub)
Interpleural block > intercostal block > caudal block > epidural block > brachial plexus block > sciatic-femoral block > subcutaneous blocks.
For LA, the closer the pka is to physiologic pH
the faster the onset of action
How does adding sodium bicarbonate help with local anesthetics?
Raises the pH and increases the concentration of NONIONIZED free base. SPEED up the onset of NEURAL BLOCKADE
Sequence of CLINICAL anesthesia: COMPLETE BLOCKADE OF PERIPHERAL NERVE progresses in the following order:
Vaso-PTProToPreMO
sympathetic block with peripheral vasodilatation and skin temperature elevation Loss of pain and temperature sensation Loss of proprioception Loss of Touch and pressure sensation Motor paralysis
Cardiodepressant potency GREAT to least
Bupi>lidocaine>Chloroprocaine
The more potent,lipid soluble LA will result in ______systemic absorption
Decrease
The greater the lipid solubility of LA the more likely it will
Sequestered in the lipid rich compartment of both the axonal membrane and perineural tissues.
2 LA metabolized to PABA
Procaine and Benzocaine
What is the only Aminoamide LA that is hydrolized to o-toluidine?
Prilocaine
Prilocaine is hydrolized to ______?
O-toluidine
What is the significance of hydrolysis to O-toluidine?
Can oxidize hemoglobin to methemoglobin in a dose dependent fashion, can produce enough to cause cynanosis (methemeglobinemia)
Clinical conditions causing decrease plasma proteins?
Cirrhosis
Newborn
Pregnancy
Leading to decrease binding capacity.
Neonates and microsomal enzymes
Immature hepatic microsomal enzymes leading to decrease elimination of of aminoamide LA.
The greatest degree of anesthetic metabolism is seen with the use of:
sevoflurane
Although approximately____-% of sevoflurane is metabolized, the release of
5%; free fluoride anion does not seem to cause any clinically significant toxicity.
Disruption of DNA synthesis through the inactivation of methionine synthetase has been associated with the prolonged administration of:
nitrous oxide
Administration of Nitrous and DNA
Disruption of DNA synthesis through the inactivation of methionine synthetase
Prolonged or chronic exposure to nitrous oxide can lead to what deficiency of Vitamin?
inactivation of the vitamin B12 component of methionine synthetase. This can disrupt DNA synthesis.
The primary means of rocuronium elimination is:
biliary elimination of unchanged drug
Rocuronium % of renal excretion
Approximately one-third undergoes renal excretion
Rocuronium and renal patients –>
prolonged neuromuscular blockade can be expected in patients with significant hepatic or renal disease
In the two-compartment drug distribution curve shown below, the α-phase is largely the result of:
dispersal of the drug into the tissue compartments
the steep drop from top to bottom
In 2 compartment drugs: what is the first phase of the curve?
The first phase of the curve is the α-phase, or distribution phase, which represents the initial dispersal of drug into the tissue compartments from the central compartment.
Respiratory effects of opiate agonists include: a
.
reduction in the responsiveness of the respiratory centers to increasing PaCO2
All opiate agonists produce a ____________ of respirations via effects on what receptors?
dose-dependent depression of respirations via effects on mu and delta receptors
OPIOIDS reduce the responsiveness of the respiratory centers to
both increasing carbon dioxide and decreasing oxygen levels.
OPIOIDS and the Oxyhemoglobin dissociation curve?
produce a shift to the right of the CO2-response curve
OPIOIDS effects on MV
increase in tidal volume with a decrease in ventilatory rate.
Pharmacodynamic properties of isoproterenol include: (Select 2):
bronchodilation, increased heart rate
Isoproterenol has profound
The profound β1 stimulation of isoproterenol results in both positive inotropic and chronotropic effects
Isoproterenol has profound B1 stimulation resulting in positive inotropic and chronotropic effects which causes what as far as oxygen in the heart?
a dramatic increase in myocardial oxygen consumption.
Isoproterenol is also a potent
bronchial dilator and pulmonary vasodilator.
What is the benzodiazepine with the LONGEST elimination half life?
Diazepam
Diazepam has the longest elimination half-life of the available benzodiazepines, approximately
36 - 50 hours.
Diazepam also exhibits a near-linear relationship between elimination half-life and what patients characteristics?
patient age, which can result in prolonged effect in the elderly.
What is Entacapone action?
inhibits catechol-O-methyltransferase
Ephedra other name is
Ma Huang
Ma Huang (Ephedra)
Think ephedrine because it has sympathomimetic with positive inotropic and chronotropic effects, alpha and beta.
Ginger can
potentiate anticoagulants effet
Ginkgo effects
Inhibits platelet aggregation put the patient at risk for bleeding.
Gingseng can
Lower blood sugar
Can cause hypertension and tachycardia
Gingseng and warfarin
decrease effectiveness of warfarin
Herbs that can potentiate effects of barbuiturates
Valerian
ST John’s Wort action with general
Inducers
May lead to serotonin syndrome
Entacapone and tolcapone are used for the treatment of
Parkinson’s disease.
What are the actions of entacapone and tolcapone?
They are are selective and reversible inhibitors of COMT.
Inhbitors of COMT: Caution should be used when administering
catecholamines as their half-life may be significantly prolonged and effects may be exaggerated.
Reversal of heparin-induced anticoagulation by
protamine sulfate
Chemical antagonism occurs when a drug’s action is
blocked by the antagonist’s chemical binding of the drug.
the chemical binding of rocuronium by
γ-cyclodextrin.
This occurs in the case of positively charged protamine forming an
ionic bond with heparin
The addition of epinephrine, in a concentration of 1:200,000, to lidocaine has been shown to:
result in a more profound block
The addition of a vasoconstrictor to local anesthetics has been shown to reduce _____Allowing for ______
the rate of absorption, allowing more of the drug to stay in the area where it was injected.
What allows for increased neuronal uptake and a longer and more profound block.
Adding vasoconstrictive drugs.
Vasoconstricitive drugs added to LA causes a reduction in the
peak plasma concentration of the drug, thereby reducing systemic toxicity.
As compared to a 40-year-old adult, the required dose (MAC) of inhaled anesthetic agents in a 6-month-old infant is approximately:
increased by 50 - 80%
The MAC or required dose of anesthetics AND AGE: when is highest and lowest?
higher in infants and children and decreases with increasing age.
Infants aged 6 months have a MAC
1.5 to 1.8 times higher than a 40-year-old adult.
The MAC of inhalational agents is decreased by
4% per decade of age over 40 years.
Electroencephalographic evidence of seizure activity has been associated with the administration of:
sevoflurane
Sevoflurane, unlike desflurane, isoflurane or nitrous oxide can predispose patients to
epileptic activity.
Non-specific esterases are involved in the metabolism of which NDNMB:
atracurium
Metabolism of Atracurium is via
Nonspecific esterases and Hofmann elimination are responsible for the metabolism of atracurium.
Cisatracurium undergoes
Hofmann elimination;
Not involved in the metabolism of cisatracurium.
Esterases
2 Drugs that undergo pseudocholinesterase catalyzed phase I hydrolysis include
succinylcholine, chloroprocaine
Drugs that Pseudocholinesterase catalyzed ester hydrolysis? -tigmine
Neostigmine and pyridostigmine
Drugs that undergo pseudocholinesterase catalyzed Ester hydrolysis. LA
Cocaine, procaine, chloroprocaine, tetracaine
For some drugs, although do undergo ester hydrolysis, the hydrolysis is accomplished by
nonspecific esterases.
DRUGS that they hydrolysis is accomplished by NONSPECIFIC ESTERASES
remifentanil, atracurium, esmolol and clevidipine
Endocrine effects of opiate administration during surgery include the increased release of
: vasopressin
Stress response to surgery and Opiates
reduce the stress response to surgery and have an immunosuppressant effect.
OPIOIDS Endocrinologic effects include the release of
vasopressin and inhibition of the stress-induced release of corticotropin and gonadotropins.
OPIOIDS and Release of thyrotropin
Release of thyrotropin is also inhibited.
Primary Pharmacodynamic properties of milrinone include
increased inotropy
What class of medication is milrinone?
Phosphodiesterase type-3 inhibitor, which produces positive inotropic action and vasodilation without producing tachycardia.
Milrinone produces positive inotropic action and ______without ____
Vasodilation ; Tachycardia.
Action of milrinone on Smooth muscle?
In smooth muscle, milrinone causes an efflux of calcium with resultant relaxation and vasodilation.
Flumazenil half life
short half-life as compared to most benzodiazepines
Flumazenil is a
Competitive benzodiazepine antagonist, which produces prompt reversal of benzodiazepine effects. I
Good to remember about Flumazenil
Relatively short half-life and duration of action make the possibility of resedation clinically relevant.
Flumazenil can produce does not
withdrawal reactions in patients who are benzodiazepine dependent.
Limitation of Flumazenil
reverse the actions of ethanol or barbiturates.
The primary antidysrhythmic effect of adenosine: is to
interrupt reentrant AV nodal tachycardia
The primary antidysrhythmic effect of adenosine is to interrupt reentrant AV nodal tachycardia, which most likely relates to its
K+ current rather than Ca2+ current effects.
What is an INVERSE AGONIST ?
A drug that binds to a receptor, resulting in the opposite action of the agonist.
What is an AGONIST?
A drug that binds to a specific receptor and
triggers a response.
What Is A PARTIAL AGONIST?
A drug that activates the receptor, but cannot
produce a maximal response.
What is an ANGATONIST?
A drug that has affinity for the receptor, but
no efficacy.
Maximum dosage guidelines for the infiltrative injection of local anesthetic state that the maximum cumulative (per procedure) dose of lidocaine, without epinephrine, is:
4.5 mg/kg; not to exceed 300 mg dose
If epinephrine is added to the lidocaine, the dose can be increased to
7 mg/kg; not to exceed 400 mg dose.
The anesthetic effect of volatile agents is greatly attenuated or lost if:
the length of the agent’s molecules exceeds 5 carbon atoms
The length of anesthetic molecules is significant in that immobility (anesthetic effect) is attenuated or lost if carbon atom chain length
exceeds a distance of 5 - 6 carbon atoms.
Awakening after an induction dose of propofol is a result of:
. Rapid redistribution from the central compartment to the peripheral compartments produces a quick initial decline. Metabolism plays little role in the initial awakening of the patient.
redistribution of the drug to the peripheral compartment
Rapid distribution following an induction dose of propofol into the brain results in
fast onset of generally one circulation time
LA pka ranges from
7.6 -8.9
Ph LA rangs from
3.9- 6.47
2 highest protein bound LA
Bupivacaine
Ropivacaine
With propofol Rapid redistribution from the central compartment to the peripheral compartments produces
a quick initial decline.
Plays little role in the initial awakening of the patient.
Metabolism
Histamine release has been associated with the use of:
atracurium
Releases modest amounts of histamine.
Atracurium
The rates of rise of the inhalational agents are
Nitrous Desflurane Sevoflurane Isoflurane Halothane
The opioid with the greatest degree of lipid solubility is
Sufentanil (measured by octanol/water coefficient)
Sufentanil vs morphine in potency is approximately
1750 times more lipid soluble than morphine.
When treating maternal hypotension, as compared to phenylephrine, ephedrine
produces an increase in fetal acidosis as a result of causing: an increase in fetal metabolic rate
Ephedrine produces increases in fetal metabolic rate leading to
to fetal acidosis due to beta stimulation, whereas phenylephrine does not.
Mechanism of opioid analagesia in spinal cord
Inhibit the release of substance P from primary sensory neurons, in the dorsal horn attenuation the transmission of painful stimuli from peripheral nerves to the cerebral cortex
Mechanism of opioid analagesia in spinal cord
Act at descending inhibitory pathway s to attenuate painful stimuli.
Dexmedetomidine produces ______With ______causes______in BP and ______in HR.
produces sedation with central sympatholysis, causes a decrease in blood pressure and heart rate
Dexmedetomidine does not
interfere with neurologic monitoring or cause significant ventilatory depression.
Ritonavir: What kind of medication is it?
is a protease inhibitor used in the treatment of HIV infection.
Ritonavir and opioids?
may increase the plasma half-life of fentanyl
Ritonavir can cause changes in the function of the
cytochrome system and may reduce fentanyl clearance and increase its half-life
Ion trapping can occur with the
placental transfer of lidocaine to the fetus as a result of the: lower pH of fetal blood
The lipid-soluble fraction of basic agents such as lidocaine crosses
the placenta easily. However, once there, because of the lower pH of the fetus, the drug becomes more ionized and cannot easily cross the lipid bilayer of the placenta, resulting in accumulation of drug in the fetus.
2 Local anesthetics that have been associated with the production of methemoglobin?
prilocaine, benzocaine
Prilocaine can produce methemoglobin as a result of the
hemoglobin oxidizing effect one of its metabolites, o-toluidine.
Factors shown to INCREASE the minimum alveolar concentration (MAC) of inhaled anesthetics include:
CHYRAH
Chronic alcohol consumption Hyperthyroidism Youth Red Headed Females Acute Amphetamine administration Hyperthermia
Propofol is prepared in a 1% lipid emulsion why?
Because its high pKa
Propofol is prepared in a lipid emulsion as a result of its
Lack of solubility in water, as reflected by its high pKa of 11.
Concerning the pharmacokinetics of neuromuscular blockers in elderly patients:onset and recovery
nset or relaxation is delayed, recovery is delayed
Why is the onset times of NMBAs delayed in the elderly?
The onset times of the NMBAs are generally delayed in the elderly due to slower circulation times.
Why is the onset times of NMBA slows and delayed in elderly? Changes in
hepatic and renal clearance and an increased volume of distribution account for the increased duration.
Vd and elderly
Increase in Vd
During drug metabolism, the products of phase II reactions:
The products of Phase II reactions have little or no biologic activity and are more polar compounds that are more highly ionized and easily extractible by the kidneys.
are more polar compounds than the parent drug
Phase II reactions are also referred to as
synthetic reactions
Phase II reactions are also referred to as synthetic reactions in which the body
actually synthesizes a new compound by donating a functional group. T
The products of Phase II reactions have
little or no biologic activity and are more polar compounds that are more highly ionized and easily extractible by the kidneys.
There is a significant drug interaction that can occur between meperidine and
the first-generation monamine oxidase-inhibiting drugs. Hyperthermia, seizures and death have been reported.
What can happen if you give MEPERIDINE for a patient taking MAOI?
Seizures, hyperthermia and death
Vasodilation in both arterioles and veins, through selective α1-receptor blockade is seen in patients receiving:
Prazosin
Those agents are selective α1-receptor antagonists used the the treatment of hypertension (3)
Prazocin, doxazosin and terazosin
Benefits of selective alpha 1 receptor antagonists areheir
lack of α2-blocking activity indicates that they have no effect on norepinephrine levels and are associated with less tachycardia than seen with the use of nonselective α-blockers.
Effects of Prazosin
Vasodilation in both arterioles and veins, through selective α1-receptor blockade
Concerning the action of local anesthetics, a phasic block refers to:
a faster onset of block in nerves repetitively depolarized
Local anesthetics work faster as the sodium channels are
repetitively depolarized.This is termed as use-dependent or phasic block.
The anticoagulation effect of rivaroxaban is the result of:
inhibition of factor Xa
Direct inhibitor factor Xa are : 2 drugs
rivaroxaban and apixaban, directly inhibit factor Xa
Action of Direct inhibitor of Factor Xa
They prolong the PT and aPTT, but monitoring is not recommended and the INR should not be used
If the absolute value of the pKa - pH of a drug is less than 1, then the drug will be:
partially ionized and partially nonionized
If the absolute value of the pKa - pH is less than 1, regardless of whether the pH is lower or higher than the pKa, the drug will
will be partially ionized (hydrophilic) and partially nonionized (lipophilic
Toxic effects to local anesthetics include:
myotoxicity
When injected directly into skeletal muscle, local anesthetics are
mildly myotoxic
Coagulation and Local anesthetics
depress normal blood coagulation by decreasing platelet aggregation and enhancing fibrinolysis.
When given as a sole inhaled agent, what effect does nitrous have on CV?
increase in systemic vascular resistance, central venous pressure and arterial pressure can be seen with the administration of:
Nitrous oxide activates the
sympathetic nervous system thereby increasing SVR, CVP and arterial pressure.
Fospropofol is converted to propofol through the action of:
alkaline phosphatase
The prodrug, fospropofol, is converted to
active propofol by alkaline phosphatase.
Cholinesterase inhibitors that lack an ester linkage and competitively inhibit the enzyme include:
edrophonium
Edrophonium is a simple alcohol that contains a
quaternary ammonium group.
Because a true chemical bond is not formed, acetylcholine competes with
edrophonium for the binding site of cholinesterase.
For practical purposes, drugs undergoing first-order elimination are regarded as being fully eliminated
he elimination half-life is the time necessary for the plasma content of a drug to drop to half of its prevailing concentration. Clinically a drug is regarded as being fully eliminated when approximately 95% or more has been eliminated. After 5 half-lives a the remaining amount of drug has been reduced to 3.125%.
5 half-lives have past.
For practical purposes, drugs undergoing first-order elimination are regarded as being fully eliminated afterAt this point, the amount of drug remaining is approximately:
3.125%.
What is the elimination half-life?
time necessary for the plasma content of a drug to drop to half of its prevailing concentration
When is thremaining amount of drug has been reduced to 3.125%?
After 5 half-lives
After five half life how do you calculate
(0.5) ^5 = 0.03125 Then you times it by 100 you get 3.125%
Opioids that possess antagonistic effects at the μ-receptor site, while retaining agonistic effects at the κ-receptor site include
nalbuphine and butorphanol
Drugs that are classified as agonist-antagonist opioids.
Both nalbuphine and butorphanol
Main action of the opioids antagonists Nalbuphine or butorphanol?
These drugs act as antagonists at the μ-receptor site while providing agonistic effects at the κ-receptor site.
The rapid termination of effect after the discontinuation of an esmolol infusion is a result of rapid:
hydrolysis by nonspecific plasma esterases
Onset time of Esmolol
2 minutes
Half life of esmolol is about
9 minutes
Esmolol is metabolized by nonspecific esterases found in the
Cytosol of RBCs.
The effects of local anesthetics appear to be the
result of drug binding to receptors in: the inner gate of the sodium channels
Local anesthetics must gain access to
the interior of the neuron to reach their receptor. Once inside the neuron, the ionized fraction binds to the receptor on the inside of the sodium channel.
Bosentan mechanism of action?
reduces pulmonary artery pressure by: inhibiting endothelin
Bosentan is the best studied of the
endothelin antagonists and through this action induces pulmonary vasodilation.
The protein binding of acidic drugs is largely with:
albumin
In the binding of drugs to plasma proteins, What is the most important?
albumin
Plasma albumin binds, for the most part, while basic drugs may be bound by
acidic drugs,
Basic drugs may be bound by
β-globulin and α1-acid glycoprotein.
Treatment of systemic local anesthetic toxicity should include
If cardiac arrest occurs, vasopressin, calcium channel blockers and beta-blockers should be avoided. Lipid emulsion therapy should be administered at the first signs of LAST.
: the administration of lipid emulsion
Treatment of LAST: _________is crucial to preventing hypoxia and acidosis
Prompt airway management
known to potentiate local anesthetic systemic toxicity (LAST).
ACIDOSIS and HYPOXIA
If cardiac arrest occurs with LAST, what are the MEDICATIONS that YOU MUST AVOID?
vasopressin, calcium channel blockers and beta-blockers should be avoided
Lipid emulsion therapy should be administered at the
first signs of LAST
The most marked attenuation of hypoxic pulmonary vasoconstriction is seen with the administration of which GAS?
nitrous oxide
What are the 2 gases that may attenuate the HPV?
Hypoxic pulmonary vasoconstriction is attenuated to some extent by isoflurane administration, but is markedly attenuated or lost by the administration of nitrous oxide.
Pharmacodynamic characteristics of propofol include in the Brain : comment on CBF, CMRO2 and ICP
in cerebral metabolic rate of oxygen consumption, a decrease in cerebral blood flow, an increase in myoclonia
Induction drug that does not cause epileptiform activity on the EEG.
Propofol
Propofol on CV as far as BP , HR, and SVR
causes a decrease in BP, heart rate and SVR.
What is the preferred induction agent for a patient with ASTHMA?
Propofol: No histamine release
Pathologic states associated with resistance to depolarizing neuromuscular blockade include
myasthenia gravis
Myasthenia GRAVIS and SUCC ? What might offset the effect?
Patients with myasthenia gravis are usually resistant to succinylcholine, with larger than usual doses required to produce complete blockade. This effect might be offset by the inhibition of plasma cholinesterase activity provided by pyridostigmine.
Myasthenia Gravis and NDNMB
SENSITIVE TO NDNMB
Zero-order drug elimination
results in the removal of a constant amount of drug per unit time
First-order drug elimination implies that a (think FF)
constant fraction of drug is being eliminated per unit time
This is the most common method of elimination of anesthetic drug
First Order Kinetics
Implications of ZERO order kinetic , is it better than first order kinetics?
This is a much less efficient method of drug elimination and implies saturation of the metabolic or elimination pathway.
Main action of spironolactone
Diuresis, through the competitive inhibition of aldosterone, can be achieved with the administration of:
Aldosterone antagonist By blocking the action of aldosterone, which normally
stimulates Na+ reabsorption and K+ excretion by the collecting duct, spironolactone causes sodium and water loss with potassium retention.
SIGNS OF CYANIDE TOXICITY?
Metabolic acidosis
Increased mixed venous oxygen content
Tachyphylaxis
Tachycardia
When does NITROPRUSSIDE MORE LIKELY to generate Cyanide?
In general, when nitroprusside is administered faster than 2 μg/kg/min, cyanide is generated faster than the patient can eliminate it.
What are the causes of CYANIDE TOXICITY?
may be seen with the high-dose administration of: nitroprusside
Nerve fibers showing the least sensitivity to the effects of local anesthetics are the:
Aα fibers
Aα fibers are responsible for
motor functions and proprioception.
When LAs bind the sodium channel, they render it
impermeable to Na, which prevents action potential initiation and propagation
LA binds more avidly to
Voltage gated Sodium channels in the ACTIVATED (Open) and INACTIVATED (not resting)
What is the Henderson-Hasselbach equation
pKa= pH + log [ BH+ / B]
The basis for classification of LA as either_____ or ______is the ______
Aminoamide or aminoester; nature of the chemical bond.
Only unmyelinated fibers
C fibers
Order of blockade first to last
B Adelta AGamma ABeta AAlpha C fibers
Neurons resting potentioal
-60 to -70mV
NA+ K+ pump how many Na and K+?
3 sodium out
2 K+ in
Conduction move from the one node to the next this is known as
Saltatory conduction
Specialized regions where the voltage gated sodium channels are concentration
Nodes of Ranvier
Sympathetics: sensitivity to LA
Most sensitive to local anesthetic agents (2-4 levels beyond motor)
Pain/touch:sensitivity to LA
moderately sensitive (2-3 levels beyond motor)
Motor fibers: sensitivity to LA
least sensitive
Preganglionic autonomics fibers are
B fibers
The most important physiologic alteration associated with an epidural (as well as a subarachnoid) block is
sympathetic blockade
The most important physiologic alteration associated with an epidural (as well as a subarachnoid) block is sympathetic blockade – T1 to T4 are the
cardioaccelerator fibers which control heart rate and contractility, and their absence leaves one vulnerable to excessive vagal reflexes which can produce sinus arrest.
Hypoglycemic agents that inhibit dipeptidyl peptidase-4 (DPP-4), thereby slowing the
degradation of incretin hormone and improving postprandial glucose control include: sitagliptin
Slow degradation of incretin hormones and improve postprandial hyperglycemia.
Dipeptidyl-peptidase-4 inhibitors, such as sitagliptin [Januvia]
Dipeptidyl peptidase-4 (DPP-4) Inhibitors medicaiton is
Sitagliptin (Januvia)
Improve postprandial hyperglycemia.
Dipeptidyl peptidase-4 (DPP-4) inhibitors such as JANUVIA
Methods of drug delivery that bypass the portal system’s first-pass effect include:
Sublingual
Intravenous
Distal rectal placement
Routes of administration of drugs bypass the pre-systemic, portal systemic first-pass effect and are delivered rapidly to the superior vena cava
sublingual and buccal
Drugs placed in the proximal rectum are absorbed into the
portal system
Agents placed in the distal rectum do not undergo
presystemic elimination.
Routes of administration of drugs bypass the pre-systemic, portal systemic first-pass effect and are delivered to where?
rapidly to the superior vena cava
Etomidate: Induction doses are associated with frequent myoclonic movements secondary to
loss of cortical inhibition.
The mechanism of action of etomidate appears to be
augmentation of GABA gated chloride currents.
Etomidate inhibits
cortisol synthesis resulting in increased morbidity and mortality in ICU patients when used as a prolonged infusion
This drug increase the plasma level of Etomidate as well as prolong the elimination half-life of the drug.
Fentanyl has been shown
As compared with plasma osmolality, hypertonic crystalloid solutions include:
D5 0.45NS
Normal plasma osmolality ranges between
280 - 290 mOsm/L.
Both Ringer’s lactate and D5 0.25NS are isotonic solutions, with tonicities of
273 and 355 mOSm /L respectively.
D5 0.45NS is hypertonic with a tonicity of
406 - 432 mOsm/L.
D5W is hypotonic in relation to plasma, with a tonicity
253 mOsm/L.
