Anesthesia Pharmacology Flashcards
The anesthesia provider should do the following 5 things prior to induction?
- Perform and document a thorough pre anesthesia assessment and evaluation
- Obtain and document informed consent for the planned anesthetic from the patient or legal guardian
- Formulate a patient specific plan for anesthesia care
- Implement and adjust the plan based on the patient’s physiologic response… intervene to maintain optimal physiologic condition
- Monitor, oxygenate, ventilate, CV, temp NMBs, positioning
Pharmacodynamics
- The action of the drug on the body
- “Relationship between the concentration of the drug and the magnitude of effect”
- Nature of the drug (racemic, oral, IV)
- receptors and binding sites
- therapeutic index
Pharmacokinetics
- The effects of the body on the drug
- “Relationship between the drug dose and the time course of drug levels in the bloodstream”- for anesthesia- At the receptor site of desired action*
- binding, permeability, elimination, distribution
Agonists
Cause desired action at the receptor
Antagonists
Have affinity for receptor but NO efficacy
-No action at the receptor
Competitive Antagonism
- shifts agonist-concentration effect curve to the right
- tend to bind at the same site as agonists
Non-competitive antagonists
- May bind irreversibly to the receptor
- Lowers the number of active receptors available
- less effect seen
- tend to bind to another (allosteric) site which changes the desired receptor site
ED/C50 and ED/C95
The dose (concentration) of drug needed to obtain 50% or 95% of the maximal effect
During anesthesia induction, why do we give 2-3 times the ED95 of drugs?
-to achieve rapid onset, knowing it will take a longer time for the effect-site concentration to drop low enough for the effect of that drug to wear off
Potency
- function of affinity for the receptor and function at the receptor
- high affinity with low potency= low potency
- low affinity with higher potency= HIGH potency
Therapeutic Index
Toxic Dose (TD50)/ Effective dose (ED50)
- high TI indicates relatively safe drug
- anesthesia drugs have low TI- less safe
Dissociation constant
- describes the propensity for a drug-receptor complex to break apart
- relatively more important for anesthesia drugs
Clearance
Rate of elimination/ plasma drug concentration
-clearance by an organ is equal to the extraction capability of the organ X the blood flow to the organ
First order Clearance
- clearance of drugs with first order kinetics is constant regardless of plasma concentration
- constant T1/2, 50% decrement per time interval
Zero order Clearance
- clearance of drugs with zero order kinetics is not constant and depends upon plasma concentration
- constant elimination, units eliminated/time (EtOh)
T 1/2 life
- varies directly with the Vd and inversely with clearance
- higher Vd= takes longer to clear
- higher clearance= shorter 1/2 life
Phase 1 metabolism
converts parent drug to more polar substance (hydrophobic to hydrophilic)
Phase 2 metabolism
conjugate drug with polar moiety making it more water soluble and excretable
CYPS: p450, p2D, P3A
response for most drug metabolism
Enzyme induction
- stimulation of drug metabolizing enzymes in the liver, usually phase 1 enzymes
Phase I Reactions- p450 dependent reactions
- P450 dependent reactions (primarily oxidative reactions):
- Hydroxylation- amphetamines, barbs, dilantin, warfarin
-N-deakylation- caffeine, morphine, tehophylline
-O-deakylation- codeine
-N-oxidation- acetaminophen, nicotine
S-oxidation- cimetidine, chlorpromazine
-Deamination, diazepam
Phase I Reactions- p450 Independent reactions
- Amine oxidation- epinephrine
- Dehydrogenation- chloral hydrate, ethanol
Phase I reactions- hydrolyses
- esters, aspirin, procaine, succinylcholine
- amides, indomethacin, lidocaine, procainamide
Phase I reactions- reduction
-clonazepam, dantrolene, nalaxone
Phase II reactions- Glucuronidation
-acetaminophen, diazepam, digoxin, morphine
Phase II reactions- Acetylation
-Clonazepam
Phase II reactions- sulfation
-acetaminophen, methyldopa
Phase II reactions- methylation
-dopamine, epinephrine, histamine, norepi
CYP inducers
- speed up metabolism
- phenobarbital, dilantin, rifampin, carbamazepine, ethanol, barbiturates, st. johns wort
CYP inhibitors
- slow down metabolism
- cimetidine, grapefruit juice, amiodarone, mtronidazole, omeprazole, SSRI’s, diltiazem, erthyromycin
Low molecular weight drugs MW <100
- can get more places and have less specific actions and more side effects
examples: sux, morphine, fentanyl, acetaminophen, NaCl, dextrose
High molecular weight drugs MW >100
- are often poorly absorbed and distributed
examples: rocuronium, cistatcurium, cefazolin, dextran
Plasma binding (Albumin, AAAG1)
-effectively eliminates drugs from the concentration gradient which determine drug movement and action
Water solubility
-is a function of electrostatic charge of the molecules
Lipid Solubility is inversely proportional to:
-to the charge
What aspect is most important in the cessation of our anesthesia drugs?
- redistribution from active sites and removal of administration are most important
- NOT metabolism
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 plasma
- be aware of protein binding effect on Vd
- cardiac output, differential circulation, recirculation and pulmonary intake all effect this
Context sensitive half-times
- time required for plasma concentration of a drug to decrease by 50% after d/c administration
- longer infusions=more drug into tissues
- drug accumulates at different rates based on physiochemical properties of the drug
- drug removed by: redistribution from site of action, metabolism into inactive form, excretion
- beware of active metabolites
Remifentanyl has _______ CSHT
very short, stable context sensitive half time, predictable and rapid emergence
Propofol and fentanyl have _____CSHT
longer CSHT, less predictable and longer emergence
Active metabolites
-codeine and tramadol designed as prodrugs with active metabolites which cause desired action
4 major options for anesthesia
- Monitored Anesthetic Care (MAC) with or without local anesthesia
- Peripheral nerve block (inter scalene, femoral) with or without a MAC
- Regional (conductive) anesthesia (spinal or epidural)
- General anesthesia (with or without intubation, LMA, I gel, mask)
What are the 4 major components associated with providing general anesthesia?
- Anxiolysis
- Analgesia
- Hypnosis
- Paralysis
MAC
- support VS, monitor respiratory depth and pattern
- provide other meds as needed
- physical and physiological support
Is MAC= conscious sedation?
No, an unconscious patient is not in a MAC state
Peripheral Nerve Blocks
- Good for extremity anesthesia
- Allow for conscious patient
- Beneficial if unable to perform more invasive anesthesia
- Unpredictable sensory and more effects
- Verify with surgeons*
Regional Anesthesia- Spinal/Subarachnoid block (SAB)
- rapid placement
- rapid onset high quality sensory and motor blockade
- less pain during surgery, some residual after
- less PONV
Regional Anesthesia- Epidural/Caudal
- lower risk for PDPH?
- less systemic hypotension than SAB
- extended blockade via indwelling catheter
- post operative analgesia
Potential increased risks with SAB, epidural/caudal
- hypovolemia
- increased ICP
- coagulopathy
- sepsis
- infection at puncture site
- pre-existing NM disease
General Anesthesia- 4 stages
- Induction
- Airway management
- Maintenance
- Emergence
