Basic Pharmacological Principles

Question 1

Pharmacokinetics definition

Answer 1

The relationship between drug dose and drug concentration at the site of drug action

Question 2

Pharmacodynamics definition

Answer 2

A description of what the drug
does to the body, including the relationship between drug concentration and pharmacologic effect

Question 3

What are the processes that govern pharmacokinetics?

Answer 3

The processes of absorption,
distribution, and elimination (metabolism and excretion)

Question 4

How to calculate the volume of distribution?

Answer 4

Amount of dose (mg)
/
Concentration (mg/L)

Question 5

How can clearance be expressed mathematically

Answer 5

Clearance = Q(Cin - Cout)
Cin

• Q is the blood flow to
  metabolic organs;
• Cin is the concentration of drug delivered to metabolic organs;
• Cout is the concentration of drug leaving metabolic organs.

OBS: The fraction of inflowing drug extracted by the organ is (Cin − Cout)/Cin and is called the extraction ratio (ER)

Clearance is defined in units of flow, that is, the volume completely cleared of drug per unit of time (e.g., L/min)

Question 6

What is the utility of back-end kinetics?

Answer 6

Using estimates of distribution volume and clearance, back-end kinetics is a useful tool that describes the behavior of intravenous drugs when administered as continuous infusions. Back-end kinetics provide descriptors of how plasma drug concentrations decrease once a continuous infusion is terminated

Question 6

What is the dynamic range of a drug?

Answer 6

the concentration range where changes in concentration lead to a change in effect

Question 7

What is the potency of a drug?

Answer 7

Potency describes the amount of
drug required to elicit an effect. The C50 is a common parameter used to describe potency. For drugs that have a concentration-versus-effect relationship that is shifted to the left (small C50), the drug is considered to be more potent, and the reverse is true for drugs that have a concentration-versus-effect relationship shifted to the right

Question 8

What is efficacy?

Answer 8

Efficacy is a measure of drug effectiveness once it
occupies a receptor. Similar drugs that work through the
same receptor may have varying degrees of effectiveness
despite having the same receptor occupancy. For example, with G protein–coupled receptors, some drugs may bind the receptor in such a way as to produce a more
pronounced activation of second messengers, causing more of an effect than others. Drugs that achieve maximal effect are known as full agonists and those that have a less-than-maximal effect are known as partial agonists

Question 9

Whats is the isobole?

Answer 9

A term used to characterize the continuum of drug
concentrations across various combinations of drug pairs
(X in combination with Y).

The isobole is an isoeffect line for a selected probability of effect.

A common isobole is the 50% isobole line. It represents all possible combinations of two-drug effect-site concentrations
that would lead to a 50% probability of a given effect.

Other isoboles are of more clinical interest. For example,
the 95% isobole for loss of responsiveness represents the
concentration pairs necessary to ensure a 95% probability of unresponsiveness.

Question 10

Ideal body weight equation

Answer 10

Male: 50 kg + 2.3 kg for each 2.54 cm over 152 cm

Female:
45.5 kg + 2.3 kg for each 2.54 cm over 152 cm

Question 11

Lean body mass equation

Answer 11

Male:
1.1 × TBW − 128 × (TBW/Ht)^2

Female:
1.07 × TBW − 148 × (TBW/Ht)^2

TBW, total body weight in kg
Ht, height in centimeters

Question 12

Fat free mass equation

Answer 12

Male:
(9.27 × 103 × TBW)/
(6.68 × 103 + 216 × BMI)

Female:
(9.27 × 103 × TBW)/
(8.78 × 103 + 244 × BMI)

TBW, total body weight in kg
BMI, Body mass index

Question 13

Corrected body weight equation

Answer 13

IBW + (TBW - IBW) × 0.4

Question 14

Which dosing scalars are recomended for propofol in obese patients?

Answer 14

authors recommend LBM
for bolus dosing (i.e., during induction) and TBW or corrected body weight (CBW) for infusions

Question 15

Which dosing scalars to use for midazolam, ketamine, etomidate, dexmedetomidine and barbiturates in obese patients?

Answer 15

Although not clinically
validated in obese patients, bolus doses probably should
be based on TBW, and use of other dosing scalars will
lead to inadequate effect.

For dexmedetomidine, dosing
according to TBW can lead to excessive sedation and
lower oxygen hemoglobin saturations in obese patients.
Clinical pharmacology research in obese patients suggests that the FFM scalar may be a better choice for bolus dosing.

In contrast, continuous infusion rates should be dosed to IBW. Remimazolam, an ultra-short-acting benzodiazepine, has recently become available. At
this time, an appropriate selection of weight scalars
in obese patients is unknown, which warrants future investigation

Question 16

Which dosing scalars to use for remifentanil in obese patients?

Answer 16

For an obese patient, dosing scaled to FFM or IBW
resulted in almost identical remifentanil effect-site
concentrations as in the lean patient dosed according
to TBW.

Unlike propofol, dosing remifentanil to CBW leads to higher plasma concentrations compared with levels achieved when dosing to TBW in a lean individual.

Question 17

To obtain equipotent doses of remifentanil and propofol in patients aged 20 and 80 years, how much to reduce the dosage of these drugs?

Answer 17

To achieve equipotent doses of remifentanil in 20- and 80-year-olds, the dose for the 80-year-old should be reduced by 55%.

A similar analysis for propofol recommends that the dose for an 80-year-old be reduced by
65% compared with that of a 20-year-old