Drug movement- absorption and distribution

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What are the processes that take place when a drug enters the human body?

Absorption- drug is absorbed from site of administration, entry into the plasma
Distribution- drug leaves bloodstream and is distributed into interstitial and intracellular fluids
Metabolism- drug transformation by metabolism - liver and other tissues
Excretion- drug and/drug metabolites excreted in urine, faeces or bile

What are the outcomes of administering a drug with increasing plasma concentrations?

If the right dosage of a drug is administered through an appropriate route, it should give the required therapeutic effects. If it is lower in dose or through a different route, it may offer subpar benefits. However, a dosage too high may also make us susceptible to the toxic effects of the drug.

What is a membrane barrier?

The cell membranes are barriers between the aqueous compartments of the body. The plasma membrane separates the extracellular 'compartment' from the intracellular 'compartment'

What are the methods in which smaller molecules would cross the cell membranes?

<ol> <li>Passive diffusion</li> <li>Facilitated diffusion</li> <li>Active transport</li> <li>Endocytosis</li> </ol> Signup and view all the answers

What is passive diffusion?

Small molecules move directly through the lipid or through aqueous pores formed by aquaporins that transverse the lipid bilayer. Many lipid soluble drugs cross cell membranes in this way. Signup and view all the answers

What is facilitated diffusion?

Small molecules move via specialised carrier proteins that bind the drug on one side of the bind molecule on one side of the membrane then change conformation and release on the other side. It does not require energy, but it does require a concentration gradient. Signup and view all the answers

What is active transport?

Small molecules move via specialised carrier proteins. It requires energy and can move the drug molecules across the concentration gradient. Signup and view all the answers

What is endocytosis?

Endocytosis through pinocytosis is a process in which there is an invagination of a part of the membrane. The drug is encased in a small vesicle then 'released' inside the cell. Signup and view all the answers

How does lipid solubility affect the rates of diffusion?

Nonpolar or lipid-soluble materials pass through plasma membranes more easily than polar materials, allowing a faster rate of diffusion. Signup and view all the answers

What are the principal sites of carrier mediated drug transport?

Carrier mediated drug transport including facilitated diffusion and active transport has principle sites of action:- <ol> <li>Blood brain barrier</li> <li>Gastrointestinal tract</li> <li>Placenta</li> <li>Renal tubule</li> <li>Biliary tract</li> </ol> Signup and view all the answers

Why is carrier mediated transport important?

Carrier mediated transport is important for some drugs that are chemically related to endogenous substances such as neurotransmitters. Signup and view all the answers

What is pKa in drug absorption?

pKa is the pH at which 50% of the drug is ionised and 50% is un-ionised. Signup and view all the answers

What does the proportion of ionisation of a drug depend upon?

It depends on both the pKa of the drug and the local pH Signup and view all the answers

Which acids and bases are more well absorbed?

Weak acids and weak bases are well absorbed but strong acids (pKa<3) and strong bases (pKa>10) are poorly absorbed. Signup and view all the answers

What is the relationship between the pH of the environment and the drugs?

Acidic drugs become less ionised in an acid environment. Basic drugs become less ionised in a basic environment. Signup and view all the answers

How can we determine if a drug is acidic or basic?

Lower the pKa, the more acidic it becomes. And, higher the pKa, the more basic it is. Signup and view all the answers

What is the relationship between ionisation of drugs and diffusion?

The more the drug is in its un-ionized form, the more likely it is to be lipid-soluble and transferred by passive diffusion through the membrane. Signup and view all the answers

What happens to weak bases in compartments with low pH and weak acids in compartments with high pH?

Accumulation Signup and view all the answers

What happens to weak acids in low pH environments and weak bases in high pH environments?

Good absorption Signup and view all the answers

What is the apparent volume of distribution?

The apparent volume of distribution (Vd) describes the extent to which a drug partitions between the plasma and tissue compartments. For a drug with equal potency, a drug with high Vd will require a higher dosage than a drug with low Vd. Signup and view all the answers

What is the relationship between Vd and the hydrophilic or lipophilic nature of the drug?

The hydrophilic or ionised drugs have a lower Vd while lipophilic or unionised drugs have a higher Vd Signup and view all the answers

What is the effect of plasma protein binding for drugs?

<ol> <li>Plasma protein binding reduces the availability of the drug for diffusion to the drug target organ.</li> <li>It may reduce the transport of the drug to the non vascular compartments</li> <li>High protein binding can slow drug elimination by preventing metabolism in the liver and glomerular filtration.</li> </ol> Signup and view all the answers

What is the relationship between availability of the drug in the vascular space, plasma protein binding and Vd?

Drug that does not exhibit high plasma protein binding easily diffuses across the membrane making it easier for the target organ to associate with the drug. This decreases the drug's plasma concentration but increases Vd. And vice versa. Signup and view all the answers