Lecture 5: Pharmacokinetics I

Comprehensive practice questions covering pharmacokinetics (ADME), pharmacodynamics, diffusion, pH effects on drug trapping, routes of administration, and drug transporters based on the lecture transcript.

How is pharmacokinetics defined in relation to the drug and the body?

What the body does to the drug

What are the two potential consequences of a drug concentration being too low or too high?

Too low: no effect; Too high: Side effect

What does the acronym ADME stand for in pharmacokinetics?

Absorption, Distribution, Metabolism, Excretion

What are the three physicochemical properties of a drug that affect pharmacodynamics?

Affinity, Efficacy, Potency

According to the notes, what is the formula for the diffusion coefficient in relation to molecular weight ($MW$)?

$$\frac{1}{\sqrt{MW}}$$

Which types of molecules dissolve freely in lipids and penetrate cell membranes freely?

Non-polar (uncharged) molecules

What is identified as one of the most important determinants of the pharmacokinetic characteristics of a small molecule drug?

Lipid solubility

What is the Henderson-Hasselbach Equation as provided in the transcript?

$$pKa = pH + \log_{10}\left(\frac{HA}{A^-}\right)$$

What happens to weak acids at low pH according to the Henderson-Hasselbach principle?

They will be in un-ionized form

What is the specific $pKa$ value of Aspirin provided in the lecture?

$$3.5$$

Why do weak acids become 'trapped' in basic compartments like renal tubules?

Basic environments (ie. $pH > 7$) favour dissociation of acids

How does urinary acidification affect the excretion of weak acids?

Urinary acidification retards excretion of weak acids

What effect does increasing plasma pH with sodium bicarbonate have on weakly acidic drugs in the CNS?

It causes them to be extracted from CNS into plasma where they get ‘trapped’

How is bioavailability defined?

The fraction of ingested dose that gains access to circulation

Why must peptide drugs like Insulin be injected rather than taken orally?

They would be digested

Where does the portal system transport molecules taken via the oral route?

From the gut straight to the liver

What is the route of administration where a drug is injected into the spine, such as during labour?

Intrathecal

What are the two types of carrier-mediated transporters mentioned in the text?

Solute carrier (SLC) transporters and ATP-binding cassette (ABC) transporters

What term is used for foreign chemicals, including drugs, that may be transported by human genes?

Xenobiotics

Which transporter gene polymorphism is associated with less effective glucose regulation in patients taking Metformin?

Organic cation transporter 1 (OCT1)

How many main fluid compartments does a drug distribute between in the body?

$$4$$

What are the four factors that determine the concentration of a drug in each fluid compartment at equilibrium?

1. Permeability across tissue barriers, 2. Protein Binding within compartments, 3. pH partition, 4. Fat:water partition

Which cells line the blood vessels in the CNS to form tight junctions for the Blood-Brain Barrier?

Endothelial cells

Which plasma protein mainly binds acidic drugs?

Albumin

In which type of environment will weak bases accumulate?

Compartments with Low pH