Unit 4 - Pharm 1 Flashcards
What does the volume of distribution (Vd) describe?
The relationship between the administered dose of a drug & the plasma concentration that results.
What are the two assumptions made about the volume of distribution (Vd)?
- The drug distributes instantaneously (Full equilibration occurs at time = 0)
- The drug is not subjected to biotransformation or eliminated before it fully distributes
When is a drug assumed to be lipophilic based on its volume of distribution?
When Vd exceeds total body water (>0.6 L/kg or > 42 L).
What is an example of a lipophilic drug?
Propofol.
When is a drug assumed to be hydrophilic based on its volume of distribution?
When Vd is less than total body water (< 0.6 L/kg or < 42 L).
What is an example of a hydrophilic drug?
Rocuronium.
How does a higher volume of distribution (Vd) affect the loading dose?
The higher the Vd, the higher the loading dose that must be given to achieve its effect.
What is the bioavailability of IV medication?
1, since it is directly injected into the bloodstream.
What factors affect volume of distribution (Vd)?
- Drug concentration (Molecular size, ionization, protein binding)
- Patient characteristics (Pregnancy & burns)
What does clearance measure in pharmacokinetics?
The volume of plasma that is cleared of drug per unit time.
Which organs are most important for drug clearance?
- Liver
- Kidney
- Organ independent (Hofman elimination & ester hydrolysis in the plasma)
What is the relationship between clearance (CL) and drug dose?
CL is directly proportional to drug dose, extraction ratio, & blood flow to the target organ.
How does clearance (CL) relate to half-life and drug concentration?
CL is inversely proportional to half-life & drug concentration.
How is steady-state concentration maintained in plasma?
The infusion rate or dose interval must equal the rate of drug clearance by metabolism & elimination.
How many half-times does it generally take to achieve steady-state?
Five half-times.
What does a two compartment model illustrate?
The biphasic decrease of a drug’s plasma concentration after a rapid IV bolus.
What does the alpha phase represent in a two compartment model?
Distribution from the central compartment (the plasma) to the peripheral compartment (the tissues).
What does the beta phase represent in a two compartment model?
Elimination from the central compartment.
What does elimination half-life measure?
The time it takes for 50% of the drug to be eliminated from the body after a rapid IV dose.
What is context-sensitive half-time?
The time required for the plasma concentration to decline by 50% after the infusion is stopped, taking infusion duration into account.
What is ionization in the context of pharmacology?
The process where a molecule gains a (+) or (-) charge, affecting its ability to diffuse through lipid membranes.
What factors determine ionization of a drug?
- The pH of the solution
- The pKa of the drug
What is the pKa of a drug?
The pH where 50% of the drug is ionized, and the other 50% is non-ionized.
How does acidic urine affect drug excretion?
Acidic urine favors reabsorption of acidic drugs and excretion of basic drugs.
What is the effect of maternal alkalosis on drug ionization in the fetus?
Increases non-ionized drug in maternal circulation, leading to more drug trapped in the fetus.
What are the three phases of drug metabolism?
- Phase 1: Modification
- Phase 2: Conjugation
- Phase 3: Elimination
What is the primary metabolic organ in the body?
The liver.
What does hepatic clearance depend on?
The product of liver blood flow & hepatic extraction ratio.
What is the significance of the P450 system in drug metabolism?
It is the most important mechanism of drug biotransformation in the body, carrying out most phase 1 biotransformation.
What are enzyme inducers?
Substances that stimulate the synthesis of additional enzymes, increasing drug clearance.
What is renal clearance determined by?
The drug’s polarity & the pH of the ultrafiltrate.
What is the effect of hydrophilic drugs in the ultrafiltrate?
They tend to be eliminated in the urine.
What is the role of plasma in drug metabolism?
Plasma is an important site of drug metabolism, specifically hydrolysis.
What is pharmacodynamics?
Explains ‘What the drug does to the body,’ focusing on the relationship between effect-site concentration & clinical effect.
What does the dose-response curve illustrate?
The relationship between the drug dose & its clinical effects.
What does potency refer to on the dose-response curve?
The dose required to achieve a given clinical effect.
What does a left-shift on the dose-response curve indicate?
Increased affinity for the receptor, higher potency, and lower dose required.
What is potency defined as?
The dose required to achieve a given clinical effect
It is influenced by absorption, distribution, metabolism, elimination, and receptor affinity.
What do ED50 and ED90 represent?
The dose required to achieve a given effect in 50% and 90% of the population, respectively
These are measures of potency.
What does a left-shift in the dose-response curve indicate?
Increased affinity for receptor, higher potency, lower dose required
This means that a smaller dose is needed to achieve the same clinical effect.
What does a right-shift in the dose-response curve indicate?
Decreased affinity for receptor, lower potency, higher dose required
This means a larger dose is necessary to achieve the same clinical effect.
What is efficacy defined as?
The ability of a drug to elicit a given clinical effect
The height of the plateau in the dose-response curve represents efficacy.
What occurs once a drug dose reaches maximum efficacy?
Additional administration increases the risk of toxicity
This highlights the importance of dosing within safe limits.
What does the slope of the dose-response curve indicate?
How many receptors must be occupied to elicit a clinical effect
A steep slope implies that most receptors must be occupied for a clinical response.
True or False: A steep slope in the dose-response curve implies that small increases in dose have little effect.
False
A steep slope means small increases in dose can lead to significant clinical effects.
What is individual variability in pharmacology?
Differences between pharmacokinetics & pharmacodynamics between patients.
What is a full agonist?
A substance that instructs the receptor to produce its maximal response
Examples include NR, dopamine, propofol, and alfentanil.
What is a partial agonist?
An agonist-antagonist that can only partially activate a cellular response
Example: Nalbuphine.
What does an antagonist do?
Binds to a receptor and prevents an agonist from binding
It does not activate the receptor.
What is competitive antagonism?
Reversible antagonism that shifts the dose-response curve to the right
Examples include atropine and non-depolarizing neuromuscular blockers (NDNMB).
What is non-competitive antagonism?
Irreversible antagonism that shifts the dose-response curve down
Examples include aspirin and phenoxybenzamine.
What is an inverse agonist?
Binds to the receptor and causes an opposite effect to that of a full agonist
Example: Propranolol.
What is synergism in drug interaction?
1 + 1 = 3
This means the combined effect of two drugs is greater than the sum of their individual effects.
What is the effective dose 50 (ED50)?
The dose that produces the expected clinical response in 50% of the population
It is a measure of potency.
What does the lethal dose 50 (LD50) refer to?
The dose that produces death in 50% of the population.
What is the therapeutic index (TI)?
A measure of drug safety, the ratio between either LD50 or TD50 to ED50.
What does a narrow therapeutic index indicate?
A narrow margin of safety
Examples include volatile anesthetics (VA) and chemotherapy.
What is stereochemistry?
The study of the three-dimensional structure of molecules.
What does chirality refer to in stereochemistry?
It deals with molecules that have a center of three-dimensional asymmetry
It results from carbon binding to four different atoms.
What are enantiomers?
Chiral molecules that are non-superimposable mirror images of one another.
What is a racemic mixture?
A mixture containing two enantiomers in equal amounts
Example: Racemic epinephrine.
What are the cardiovascular effects of Propofol?
Decreased blood pressure, decreased systemic vascular resistance, decreased venous tone, and decreased myocardial contractility.
What are the respiratory effects of Propofol?
Shifts CO2 response curve down and to the right, causing respiratory depression and/or apnea.
What are the CNS effects of Propofol?
Decreased cerebral O2 consumption, decreased cerebral blood flow, decreased intracranial pressure, and decreased intraocular pressure.
What is Propofol infusion syndrome?
A high mortality rate syndrome associated with prolonged high-dose Propofol administration
Risk factors include high doses and duration over 48 hours.
What is the risk of bacterial contamination with Propofol?
Propofol increases the risk of bacterial contamination
Syringes must be discarded within 6 hours and infusions within 12 hours.
What are the cardiovascular effects of Ketamine?
Increased sympathetic tone, increased cardiac output, increased heart rate, increased systemic vascular resistance, and increased pulmonary vascular resistance.
What are the respiratory effects of Ketamine?
Bronchodilation and maintenance of respiratory drive.
What are the CNS effects of Ketamine?
Increased cerebral O2 consumption, increased cerebral blood flow, and increased intracranial pressure.
What is emergence delirium associated with Ketamine?
Presents as nightmares and hallucinations
Risk factors include age >15 years, female gender, and high doses.
What are the cardiovascular effects of Etomidate?
Hemodynamic stability with minimal change in HR, systemic vascular resistance, or cardiac output.
What is a key side effect of Etomidate?
Myoclonus and suppression of adrenocortical function.
What are the cardiovascular effects of Barbiturates?
Hypotension primarily due to venodilation and decreased preload.
What is Dexmedetomidine known for in terms of respiratory effects?
It does not cause respiratory depression.
What is the effect of Benzodiazepines at induction doses?
Decreased blood pressure and systemic vascular resistance.
What is the role of Flumazenil?
A competitive antagonist of the GABA-A receptor used to reverse sedation effects of benzodiazepines.
What are the three groups of inhaled anesthetics?
Ethers, alkanes, & gases
At atmospheric pressure & room temperature, which inhaled anesthetics exist as liquids?
Ethers & alkanes
What is the chemical structure of ethers?
R-O-R’
What is the chemical structure of alkanes?
R-H
Which inhaled anesthetic is identified by having 3 fluorine atoms?
Halothane
How many fluorine atoms does isoflurane contain?
5 (+ 1 Cl-)
What is the vapor pressure?
The pressure exerted by a vapor in equilibrium with its liquid or solid phase inside a closed container
How does temperature affect vapor pressure?
Vapor pressure is directly proportional to temperature
What is the boiling point?
The temperature where matter transitions from a liquid state to a gas state
What does Dalton’s law of partial pressure state?
The total gas pressure in a container is equal to the sum of partial pressures exerted by each gas: P total = P1 + P2 + P3
What is the blood: gas partition coefficient (λ)?
Describes the relative solubility of an inhalation anesthetic in the blood vs. in the alveolar gas
What is the blood: gas partition coefficient for desflurane?
0.42
What is the relationship between alveolar partial pressure (FA) and brain partial pressure?
Alveolar partial pressure ~ blood partial pressure ~ brain partial pressure
What are the three factors that determine anesthetic uptake into the blood?
- Agent solubility
- Partial pressure difference between the alveoli & blood
- Cardiac output
What does the FA/FI curve illustrate?
The speed at which FA equilibrates with FI (Speed of induction)
What does high solubility of an anesthetic indicate about its onset?
Slower equilibration of FA/FI → Slower onset
What is the primary way inhaled anesthetics are eliminated from the body?
Elimination from the alveoli
What percentage of sevoflurane is metabolized in the body?
2-5%
What is the concentration effect in anesthesia?
The higher the concentration of inhalation anesthetic delivered to the alveolus (FA), the faster its onset of action
What does the second gas effect imply?
Administering one gas during anesthetic induction will hasten the onset of a second gas
What is diffusion hypoxia?
Movement of N2O from the tissue back to the alveoli during emergence, diluting alveolar O2 & CO
How does a right to left shunt affect induction with a volatile agent?
Slower induction
What is the blood: gas partition coefficient for nitrous oxide?
0.46
What is the minimum alveolar concentration (MAC)?
The concentration of inhalation anesthetic that prevents movement following a painful stimulus in 50% of the population
What is the MAC for isoflurane?
1.2%
What is the Meyer-Overton rule?
Lipid solubility is directly proportional to the potency of an inhaled anesthetic
What is the primary site of action for general anesthetics in the brain?
GABA-A receptor
What cardiovascular effects do halogenated anesthetics have?
- Reduce MAP in a dose dependent fashion
- Decrease contractility
- Decrease SVR
What effect does nitrous oxide have on MAP and SVR?
Increases MAP & SVR by SNS activation
How do halogenated anesthetics affect PaCO2?
Cause hypercapnia through depression of the central chemoreceptor & respiratory muscles
What is the significance of the ‘reverse Robin Hood’ effect?
Blood flow is preferentially directed to healthy tissue at the expense of diseased tissue
What is the effect of sevoflurane on systemic vascular resistance (SVR)?
Reduces SVR the least
What is the risk associated with prolonged exposure to nitrous oxide?
Megaloblastic anemia, neuropathy, immunocompromise, impaired DNA synthesis
What is the effect of inhaled anesthetics on the ventilatory response to CO2?
Increased apneic threshold – decreased ventilatory response to CO2
What is the effect of halogenated anesthetics on PaCO2?
Hypercapnia through depression of the central chemoreceptor & respiratory muscles, altered respiratory pattern, increased apneic threshold, relaxation of upper airway tone, decrease of pulmonary muscles, and bronchodilation.
Key points include decreased tidal volume, increased respiratory rate, and net decrease in ventilation.
How do halogenated anesthetics affect the respiratory pattern?
Decreased tidal volume, increased respiratory rate, and decreased effective ventilation.
This results in an increased dead space to tidal volume ratio.
What is the impact of halogenated anesthetics on ventilatory response to CO2?
Increased apneic threshold and decreased ventilatory response, shifting the CO2 response curve down & to the right.
This leads to impaired respiratory drive.
What is the consequence of relaxation of upper airway tone due to halogenated anesthetics?
Leads to upper airway obstruction.
This occurs due to muscle relaxation of genioglossus or tensor palatine.
What happens to FRC when pulmonary muscles are decreased by halogenated anesthetics?
Decreases functional residual capacity and the effectiveness of ventilation.
What is the risk associated with impaired peripheral chemoreceptors after anesthesia?
Risk of hypoxemia, particularly with a PaO2 < 60 mmHg.
This impairment can last for several hours.
At what MAC does impaired response to acute hypoxemia occur?
0.1 MAC.
This does not impair the response to PaCO2.
Which halogenated anesthetic is thought to impair hypoxic drive the least?
Desflurane.
It is the best choice for patients relying on hypoxic drive, such as those with emphysema or sleep apnea.
What is the relationship between CMRO2 and cerebral blood flow under halogenated anesthetics?
Dose-dependent reduction in CMRO2 and increase in cerebral blood flow and volume.
At >0.5 MAC, CBF increases while CMRO2 decreases.
What MAC level is required to produce an isoelectric state?
1.5-2.0 MAC.
This reduces CMRO2 by 60%.
What is the effect of sevoflurane at high concentrations?
Can produce seizure activity, exacerbated by hypocapnia.
This is more common with pediatric inhalation induction.
What are SSEPs used to monitor?
The integrity of the dorsal column (medial lemniscus).
The posterior spinal arteries perfuse this region.
What do MEPs monitor?
The integrity of the corticospinal tract.
The anterior spinal artery perfuses this region.
When should you be concerned about nerve ischemia during evoked potential monitoring?
When amplitude decreases by >50% or latency increases by >10%.
What is the best anesthetic technique to preserve evoked potentials?
TIVA without N2O.
Some institutions only use TIVA when evoked potentials are monitored.
What is the recommendation for volatile agents when monitoring evoked potentials?
Use <0.5 MAC and supplement with IV agents but avoid N2O.
Which evoked potentials are most sensitive to anesthetic agents?
Visual evoked potentials.
Which evoked potentials are most resistant to the effects of anesthetics?
Brainstem auditory evoked potentials.
What other factors affect amplitude and latency of evoked potentials?
Hypoxia, hypercarbia, and hypothermia.
When can muscle relaxers be used during evoked potential monitoring?
Only with SSEP; they should not be used when monitoring MEPs.
What is the ‘wake up test’ in the context of evoked potentials?
Cut the anesthetic and allow the patient to wake up, then ensure everything is intact before putting them back under.
