COCO Study Guide Flashcards
MAC Additive properties
drug effects sum together
Racemic Mixture
When 2 enantiomers are present in equal proportions. Thiopental and etomidate are racemic mixtures.
Synergism
When 2 drugs interact to produce a greater effect than the some total of the 2 drug’s effects.
Division of cardiac output - Central Compartment
Central compartment gets rapid uptake of drug and includes intravascular fluid, and highly perfused tissues such as the brain, heart, lungs, kidneys, and liver.
The central compartment receives 75% of CO and makes up 10% of body mass.
Division of cardiac output - Peripheral Compartment
Peripheral compartment gets slower uptake and includes less vascular tissues like fat, bone, and inactive skeletal muscle.
pH for ionization
Basic drugs will ionize at a ph lower than their pK values, while acidic drugs will ionize at a pH greater than their pK.
pKa
The pH at which a molecule or drug is 50% ionized
Pharmacokinetics
What the body does to drugs
Absorption, distribution, metabolism, elimination. Combined with drug dosing, pharmacokinetics determines concentration of drug at its target.
Pharmacodynamics
What drugs do to the body
Study of intrinsic sensitivity or responsiveness of receptors to a drug and mechanisms by which these effects occur.
Agonist
A drug that produces its clinical effect by binding to a receptor and activating it.
Direct Agonist
Binds directly to the receptor to trigger a physiological response
Indirect Agonist
Produces its effect by increasing the endogenous substrate (NT or hormone)
Antagonist
Drugs that bind to receptors without activating them and simultaneously prevents agonists from stimulation said receptor.
Competitive Antagonist
A receptor inhibitor that competes for binding sites. Can be overcome by increasing the concentration of the agonist to out compete.
Non-Competitive Antagonist
A receptor inhibitor that cannot be overcome by increasing concentration of agonist (irreversible).
Hyperactive
unusually low doses that produce pharmacological effect
Hypersensitive
Allergy to a drug or substrate
Hyporeactive
Tolerant of said drug, requiring large doses to evoke effects
Tachyphylaxis
Tolerance that develops acutely with only a few doses
Prodrug
Molecule that is not pharmacologically active until after it has been metabolized and transformed.
Antagonistic Effect
When 2 drugs interact to produce an effect lesser than the sum of the 2 drugs.
Midazolam (First Pass Metabolism)
Midazolam given PO undergoes first pass metabolism. Midazolam given IV doesn’t undergo first pass metabolism.
Flumazenil Metabolism
Flumazenil is a specific, competitive antagonist of benzodiazepines. It has a shorter half life than benzodiazepines which can result in a resedation effect after it is metabolized. It is metabolized by hepatic enzymes which account for the quickness.
Midazolam Drug Interacions
Benzos exert a synergistic sedative effect on other CNS depressants including alcohol, barbiturates, opioids, and inhaled and injected anesthetics. It is especially potentiative of ventilatory depressant effects of opioids.
Clinical effects of Benzos
Sedation, anxiolysis, anticonvulsant, anterograde amnesia.
Premedication of Benzos in children
Kids get a 0.5mg/Kg (15 mg maximum) dose of midaz 30 minutes before surgery.
Contraindications for Acute Intermittent Porphyria
Do No Use barbiturates such as thiopental in patients with this disorder. It will inhibit the enzyme Porphobilinogen Deaminase used to synthesize heme which can cause problems with heme synthesis. Use Benzodiazepines instead.
Thiopental Induction Dose
3 - 5 mg/Kg
Onset = 30 - 40 seconds (peaks at 1 minute)
Duration = 5 - 8 minutes
Protein Binding = Approximately 80% bound to plasma protein (Albumin)
Thiopental Burst Supression
Barbiturates work well to lower the CMRO2 which lowers the cerebral blood flow to injured or operable areas of the brain. Can flat line an EEG.
Mechanism of action - Barbiturates
Barbiturates interact with inhibitory NT, and GABA in the CNS. They decrease the rate of dissociation of GABA from GABA receptors, thus increasing the open time of the chloride channels. This results in hyperpolarization of the cell.
Thiopental effects on HR and BP
Can lead to decreased systolic BP and a compensatory increase in HR. Histamine release can also lead to decreased BP.
GABA
Gamma Aminobutyric Acid (NT)
pH of Thiopental
10.5, which is very basic, making it bacteriostatic because bacteria doesn’t grow well in high pHs. When mixed with acidic drugs such as Fentanyl crystals will form.
Barbiturate side effects
Cardiovascular: decreases systolic BP with compensatory HR increase
Histamine Release: Can lead to low BP
Heat Loss: due to vasodilation
Ventilation: low TV and Low RR is dose dependent. Apnea with induction dose.
Laryngeal Response: Laryngo/Broncho-spasm possible even with induction dose.
EEG: Low CMRO2 up to 55%
SSEP: not affected
Hepatic/Renal: lowers the blood flow to these organs
Placenta: will transfer to baby, but won’t affect baby
Tolerance: Happens sooner, lower therapeutic index
Intra-Arterial: BAB because high pH leads to thrombophlebitis
Supply of Thiopental
24 mg/ml
Thiopental Pharmacokinetics
very lipid soluble so fast uptake and easily crosses the BBB and quickly redistributes, highly protein bound, slow metabolism (wake up hungover), metabolism in liver to water soluble, inactive metabolites, renal clearance of inactive water soluble metabolites.
Thiopental Stability
Supplied as an anhydrous powder. In this form it is good indefinitely. When drug is mixed in solution at room temp it is good for 1 week and good for 2 weeks when refrigerated.
Propofol in the ICU
Extended use of Propofol can lead to hyperlipidemia so it should not be used longer than 3 days.
MAC dose of Propofol
GA and TIVA cases = 100 to 200 mcg/Kg/min
Propofol properties
Oil at room temperature, insoluble in aqueous solution, 98% protein binding
Etomidate properties
Water soluble at an acidic pH and lipid soluble at physiological pH, 35% glycerol, racemic mixture, 76% protein binding
Ketamine properties
Derivative of PCP, low protein binding of 27%
Side effects of Propofol
Allergic reaction to eggs, may decrease convulsant activity, abuse, bacterial growth, pain on injection (glycerol)
Propofol effect on CNS
Lowers the CMRO2, lowers ICP, Lowers CBF, can flatline the EEG and cause anterograde amnesia
Propofol effect on cardiovascular system
Lowers SBP through vasodilation, Increases HR slightly, probably through compensatory efforts
Propofol effect on pulmonary system
Lowers RR, Lowers TV = dose dependent, bronchodilation, hypoxic pulmonary vasoconstriction mechanism still intact.
Propofol effect on Hepatic/Renal system
No adverse side effects, but green urine with prolonged infusion
Propofol effects (Other)
Lowers IOP, Lowers responsiveness to DL
Etomidate effect on CNS
Lowers CMRO2 (35-45%), Lowers CBF, can flatline the EEG but also increases excitatory spikes in EEG, which can induce a seizure soe use with caution in seizure patients.
Etomidate effect on Cardiovascular system
Stability - minimal changes
Etomidate effect on Ventilation
induction dose probably won’t cause apnea - SV possible
Etomidate side effects
Pain on injection, myoclonus, adrenocortical suppression (inhibits 11-B-Hydroxylase), which leads to decreased cortisol, induces PONV and can rarely cause hiccups.
Ketamine effect on CNS
Increased ICP due to increase in CMRO2, and increase in CBF*** - can cause excitatory spikes in EEG. OK to use when monitoring SSEPs.
Ketamine effect on Ventilation
Causes no depression in ventilation (SV), increases secretions, causes bronchodilation
Ketamine effect on Cardiovascular system
Increases BP (systolic > diastolic), increases HR, increases CMRO2, increases CO, is a myocardial depressant, cardiac rhythm (increase in catecholamines can lead to arrhythmias)
Ketamine treatment for emergence delirium
Benzodiazepines
Propofol additives
1% propofol
10% soybean oil
2.25% glycerol
1.2% purified egg phosphatide
Drugs that interact with GABA receptors
Benzodiazepines
Thiopental
Propofol
Etomidate
Drugs that do not interact with GABA receptors
Ketamine - instead it interacts with NMDA, opioids, MAO and muscarinic receptors
Induction Analgesia
Ketamine is the only induction drug that has analgesic effects
Etomidate dose
IV induction dose = 0.2 - 0.6 mg/Kg
Onset = 30 seconds (peaks at 1 minute)
Duration = 3 - 5 minutes
