Week 1 - Anesthesia Pharm Flashcards
Roles of the Anesthesia Provider
Perform and document a thorough preanesthesia assessment and evaluation
Obtain/document informed consent for planned anesthetic
Formulate a pt-specific plan for anesthesia care
Implement and adjust plan based on pt’s physiologic response… intervene to maintain optimal physiologic condition
Monitor: oxygenation, ventilation, CV, temp, NMBs, positioning
Define Pharmacodynamics
The action of the drug on the body
“Relationship between the concentration of drug and the magnitude of effect”
Nature of the drug, receptors/receptor sites, inert binding sites, MOA, therapeutic/toxic effect
Define Pharmacokinetics
The effect of the body on the drug
“Relationship between the drug dose and the time course of drug levels in the bloodstream” - at the receptor site of desired action
Binding, permeability, henderson-hasselbach, distribution, elimination
Agonists vs Antagonists
Agonists: cause desired action at receptor
Antagonists: have affinity for receptor but NO efficacy (no action at receptor)
Competitive Antagonist vs Non-Competitive Antagonist
Competitive: antagonism shifts agonist concentration effect curve to the right (binds to same site as agonists - effect is which ever has higher concentration)
Non-Competitive: antagonists may bind irreversibly to the receptor. Lowers number of active receptors available, less effect seen, tend to bind to another site which changes the desired receptor site
ED/C50 and ED/C95
The dose (concentration) of drug needed to obtain 50% and 95% of maximal effect
Lower ED50 = more potent drug
During anesthesia induction we frequently give 2-3x the ED95 to achieve rapid onset
Define Potency of a Drug
A function of affinity for the receptor and function at the receptor
High affinity with low potency = low potency
Low affinity with high potency = HIGH potency
Define Therapeutic Index
Toxic Dose (TD50) divided by Effective Dose (ED50)
High TI indicates relative safety of a drug – the higher the TI the safer the drug
Define Dissociation Constant
Describes the propensity for a drug-receptor complex to break apart
Define Clearance
Rate of Elimination divided by Plasma Drug Concentration
Clearance by an organ = extraction capability of the organ X blood flow to the organ
Zero Order Kinetics vs First Order Kinetics
Zero Order: clearance of drug is constant and NOT dependent upon plasma concentration (Unit/Time)
First Order: clearance of drug is proportional to the plasma concentration (% Eliminated/Time) - basis of the half-life model of drug metabolism
How does half-life vary with Volume of Distribution and Clearance?
Directly with Vd and inversely with clearance
Higher Vd takes longer to clear
High clearance = shorter half-life
What are the phases of metabolism?
Phase I: converts parent drug to more polar (hydrophobic –> hydrophilic)
Phase II: conjugate drug with polar moiety making it more water soluble and excretable
CYP iso’s: P450, P2D P3A(4,5), (50% CYP rxn) responsible for most drug metabolism
Enzyme Induction: stimulation of drug metabolizing enzymes in the liver; usually phase I enzymes
Metabolism - Phase I Reactions
Oxidation, Reduction, Hydrolysis
Metabolism - Phase II Reactions
Makes drugs water soluble for excretion
Glucuronidation, Acetylation, Glutathione Conjugation, Glycine Conjugation, Sulfation, Methylation
CYP inducers vs CYP inhibitors
CYP inducers: phenobarbital, dilantin, rifampin, carbamazepine, ethanol, barbiturates, St. John’s wort
CYP inhibitors: cimetidine, grapefruit juice, amiodarone, metronidazole, omeprazole, SSRI’s, diltiazem, erythromycin
Lower molecular weight drugs vs High molecular weight drugs
LMW: <100, can get more places and have less specific actions and more side effects
HMW: >1000, are often poorly absorbed and distributed
Define Plasma Binding
Drug bind to proteins in the blood
Effectively eliminates drug from the concentration gradient which determines drug movement and action
What affects the cessation of action of most anesthesia medications?
Redistribution from active site and removal of administration
Metabolism is relatively unimportant in the cessation
Volume of Distribution
Units of drug in body/Units of drug in plasma
Low Vd means most of the drug is in the plasma and very little has moved elsewhere
High Vd means drug moves throughout the body and less remains in the plasma
What are Contact Sensitive Half-Times?
Time required for plasma concentration of a drug to decrease 50% after discontinuing administration
Longer infusion, more drug into tissues, absorbed and held
Drug accumulates at different rates based on physiochemical properties of the drug
Remifentanil has very short/stable CSHT - predictable, rapid emergence
Propofol and Fentanyl have longer CSHT - less predictable, longer emergence
What are the four major options for anesthesia?
1) Monitored Anesthetic Care (MAC) with or without local anesthesia (Deep monitored Anesthesia)
2) Peripheral Nerve Block with or without a MAC
3) Regional (conductive) anesthesia (Spinal or Epidural)
4) General anesthesia (with or without intubation, LMA, iGel, Mask, etc)
How do you determine which anesthetic to do?
Preferences of pt, surgeon, anesthesia provider
Coexisting diseases of pt
Site of surgery/Body position during surgery
Likelihood of reflux or aspiration
Suspected airway issues
Expected (not scheduled) duration of procedure
Anticipated recovery location and time
What are the components to general anesthesia?
Anxiolysis
Analgesia
Hypnosis
Paralysis
Decrease Somatic and Autonomic Systems
