Pharmacological Principles Flashcards
Are ionized or nonionized drugs more readily absorbed?
Nonionized
Why does oral absorption of drugs have the first pass effect,but not the sublingual absorption?
Because the veins of the stomach and small intestine drain directly into the portal system.
The veins of the esophagus and mouth drain into the SVC so drugs absorbed here go into the systemic system first.
What layer of the skin is an effective barrier to small, lipid-soluble drugs (clonidine, nitroglycerin,scopolamine, fentanyl)?
Stratum corneum
What does plasma protein levels affect?
The solubility of the drug in blood, but not the rate of equilibration
What increases the rate of onset of a drug?
High levels of binding in the blood compared to in the tissue because fewer molecules need to transfer into the tissue to reach an effective free drug concentration
What kind of PH does albumin usually bind?
Acidic drugs
What binds basic drugs?
Alpha 1 glycoproteins
What happens to drug solubility if albumin or AAG is decreased in the blood?
The solubility decreases
What conditions increase AAG levels?
Trauma, surgery, infection, MI, chronic pain
What condition decreases AAG levels?
Pregnancy
What drug is administered with its own binding molecules?
Propofol
What is the blood brain barrier made up of?
Pericapillary glial cells and endothelial cell tight junction
What kind of drugs readily pass the blood brain barrier?
Lipophiloc drugs (hypnotics and opioids)
What is redistribution?
The process by which the drug re-equilibration from the tissue to the plasma as drug concentration falls in the plasma.
- delays emergence following prolonged infusions
What is context sensitive half time?
The time required for a 50% decrease in plasma drug concentrations following an infusion
What is the context referring to in context sensitive half time?
Duration of the infusion
What is context sensitive decrement time?
Refers to any clinically relevant decreased concentration in any tissue
What is volume of distribution equation?
Bolus dose/plasma concentration (time)
What is Vdss?
The volume of distribution of 3 compartments
2 peripheral compartments: rapid equilibration (organ and muscle) and slow (fat and skin)
1 central compartment (blood and lung)
What does a small Vdss imply?
High aqueous solubility, stays in the blood (pancuronium)
What does Vdss reflect
.
The volume into which the drug would have to distribute to account for the observed plasma concentration given the dose that was administered
What is phase 1 reaction?
Converts parent compounds into polar molecules through redox reactions or hydrolysis
What is phase II?
Coupled or conjugated parent drugs or phase I metabolites with an endogenous substrate to form water soluble molecules that can be eliminated
What is the extraction ratio?
The fraction of drug that is removed that enters the liver
What is hepatic clearance?
Liver blood flow X extraction ratio
What drug has a high extraction ratio?
Propofol
What kind of clearance does Propofol have?
Flow-dependent clearance
What are capacity dependent drugs?
Methadone and alfentanil
What does capacity dependent mean?
Means the extraction ratio is low. Metabolism depends on the liver enzymes
Dose response curves are typically what shape?
Sigmoidal
What is the equation for drug effect?
Effect = E0 + (Emax-E0) Cgamma/C50 +Cgamma
What is E0?
The baseline effect in absence of the drug
What is E max?
The maximum effect from baseline
What is C50?
The concentration associate with half-maximal effect
What is gamma?
The steepness of the curve (dose response relationship)
What does Emax correlate with?
Efficacy
What does C50 correlate with?
Potency
What gamma value suggests a gradual increase in drug effect with increasing concentration?
Less than 1
What gamma value suggests a rapid increase in drug effect with increasing concentration?
Greater than 4
What is the equation for therapeutic window?
C50 toxicity/c50 desired therapeutic effect
What happens to the central compartment as patients get older?
The central compartment is smaller
What is the volume distribution in a baby.
Larger
Why does an older patient require less Propofol?
Smaller central compartment
Decreased clearance
Why is time to awakening shorter than context sensitive half-time?
Because the decrease in plasma concentration required for awakening is generally less than 50%
What does licorice cause?
Conn syndrome (hypokalemia, hypernatremia, HTN, metabolic alkalosis) by inhibition of 11-beta hydroxyl dehydrogenase, which in turn allows cortisol to activate the Na-K-ATPase channels in the renal proximal tubule like aldosterone usually does
What is decrement time?
The time it takes to reach a certain plasma concentration once an infusion is terminated
Usually equal to infusion duration
What is terminal half life?
Terminal half life is the half life of elimination after the tissue concentration has equilibration with the plasma concentration
What is the time constant?
It is used to calculate how long it takes for a newly dialed concentration of gas anesthetic to equilibration with the gas in the circuit
What is the ED95 for neuromuscular blockers?
The effective dose required to achieve 95% block of a single twitch in 50% of individuals
What is ED95?
The effective dose needed to get the desired effect of 95% of the population
What is the ED95 for rocuronium?
0.3mg/kg
What is efficacy of a drug?
The maximum effect of a drug
What is potency?
The relative dose required to achieve a desired effect
- related to receptor affinity
What is elimination?
The change in plasma concentration of a drug divided by the change in time
What is first order kinetics?
Drug elimination is proportional to drug concentration
Ex: depends on liver blood flow
What is zero order kinetics?
Elimination is independent of drug concentration
Constant elimination
