Cell Membrane Transport and Diffusion Mechanisms

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Questions and Answers

What is the primary purpose of a drug's chemical name?

To indicate the drug's effects

To provide a marketing name

To denote its price

To describe the substance chemically (correct)

Which type of drug name is recognized by competent scientific bodies?

Brand name

Common name

Chemical name

Non-proprietary (generic) name (correct)

Which pharmacokinetic process is necessary for a drug to have its effects?

Accumulation in blood plasma

Distribution solely in the liver

Presence in appropriate concentration at the site of action (correct)

Excretion from the body

What is a characteristic of the vascular endothelium?

It filters molecules based on size using a loose matrix. Signup and view all the answers

What major consequence do tight junctions in certain organs have on drug distribution?

They prevent harmful molecules from leaking into organs. Signup and view all the answers

Who is considered the first to attempt a theoretical background of pharmacology?

Galen Signup and view all the answers

What was Paracelsus known for rejecting?

Traditional concoctions Signup and view all the answers

What philosophical stance did Galen take regarding the sources of pharmacological knowledge?

Experience and theory both contribute Signup and view all the answers

Which of the following statements reflects Wepfer's sentiments on poisons?

All substances can be poisons in the right doses. Signup and view all the answers

What is the primary basis of traditional medicine according to the history of pharmacology?

Empirical information Signup and view all the answers

What was a significant advancement made by Johann Jakob Wepfer in pharmacology?

Conducting animal experiments to verify pharmacological actions Signup and view all the answers

Why is the historical aspect of pharmacology important?

It highlights the development of scientific experimentation. Signup and view all the answers

Which approach did early pharmacologists primarily rely on before scientific methods were established?

Empirical observations Signup and view all the answers

What facilitates the transfer of hormones or other molecules in endocrine glands?

Fenestrated endothelium Signup and view all the answers

Which mechanism is the major pathway for drug absorption?

Passive diffusion Signup and view all the answers

Fick's first law of diffusion states that drug molecules move from areas of:

Higher concentration to lower concentration Signup and view all the answers

What primarily influences the absorption of weak acids?

Their pKa and the pH of the surrounding environment Signup and view all the answers

Which type of drugs are poorly absorbed in the gastrointestinal tract?

Stronger bases with pKa > 11 Signup and view all the answers

Which factor is NOT part of the pH partition hypothesis affecting absorption?

The molecular structure of the drug Signup and view all the answers

Why do very weak bases with pKa < 5 have rapid absorption?

They remain unionized across all pH values Signup and view all the answers

How does the pKa of a weak acid influence its absorption in the stomach?

It dictates whether it will be absorbed better in alkaline or acidic conditions Signup and view all the answers

What primarily influences the rate of loss of gases during pulmonary excretion?

Rate of respiration and pulmonary blood flow Signup and view all the answers

What factor influences the quantity of a drug excreted into sweat?

pKa of the drug and pH of secretions Signup and view all the answers

Which statement about drug excretion in milk is true?

Basic drugs are more concentrated in milk due to its acidity. Signup and view all the answers

Which factor does NOT influence the route of drug administration?

Concentration of the drug in the bloodstream Signup and view all the answers

What is a characteristic of oral ingestion as a route of drug administration?

It results in immediate systemic effects. Signup and view all the answers

What is a characteristic of carrier mediated transport?

It can transport molecules against an electrochemical gradient. Signup and view all the answers

Which process involves the movement of drugs along a concentration gradient at an accelerated rate?

Facilitated diffusion Signup and view all the answers

Which factor does NOT modify drug absorption?

Body temperature Signup and view all the answers

What type of substances cannot permeate membranes by passive diffusion?

Hydrophilic substances Signup and view all the answers

Which mechanism primarily governs drug absorption in the gastrointestinal tract?

Passive diffusion (lipid diffusion) Signup and view all the answers

What is the primary function of drug distribution?

To transport drugs from the administration site to various tissues. Signup and view all the answers

Which condition favors the filtration or pore transport mechanism?

Hydrodynamic flow of water Signup and view all the answers

Which factor does NOT affect the solubility of a drug at the site of absorption?

Time of day Signup and view all the answers

Study Notes

Fenestrated Endothelium

Found in endocrine glands
Facilitates transfer of hormones and other molecules through pores in the endothelium

Movement of Small Molecules Across Cell Membranes

Four main ways:
- Diffusion through lipids
- Diffusion through aqueous pores
- Transmembrane carrier proteins
- Endocytosis

Passive Diffusion

Major mechanism for drug absorption
Driven by concentration or electrochemical gradient
Follows Fick's first law of diffusion: molecules diffuse from a region of higher concentration to lower concentration until equilibrium is reached.

Influence of pH on Passive Diffusion

Governed by:
- Dissociation constant (pKa) of the drug
- Lipid solubility of the unionized drug
- pH of the absorption site
Most drugs are weak acids or bases that exist in both ionized and non-ionized forms, with non-ionized molecules being more lipid soluble and diffusing more easily.
Transmembrane distribution of a weak electrolyte is determined by its pKa and the pH gradient across the membrane.

Weak Acids, Bases and Absorption

Weak acids:
- Very weak acids (pKa > 8) are mostly unionized at all pH values, leading to rapid absorption independent of GI pH.
- Acids with pKa between 2.5 and 7.5 are best absorbed in acidic conditions of the stomach (pH < pKa) where they are predominantly unionized.
- Stronger acids with pKa < 2.5 are ionized across the entire GIT pH range and are poorly absorbed.
Weak bases:
- Very weak bases (pKa < 5) are mostly unionized at all pH values, leading to rapid absorption independent of pH.
- Bases with pKa between 5 and 11 are best absorbed in the more alkaline conditions of the intestine (where they are predominantly unionized).
- Stronger bases with pKa > 11 are ionized across the entire GIT pH range and are poorly absorbed.

Brief History of Pharmacology

Medicaments have been used for treating diseases for a long time.
Traditional knowledge, empirical information, formed the basis of early medicine.
Claudius Galen (AD 129–200): First attempted to consider the theoretical background of pharmacology.
Theophrastus von Hohenheim (1493–1541), aka Paracelsus: Rejected irrational concoctions and mixtures of medieval medicine.
Johann Jakob Wepfer (1620–1695): First to verify pharmacological and toxicological actions through animal testing.

Drug Nomenclature

Drugs have three categories of names:
- Chemical name: describes the substance chemically
- Non-proprietary (generic) name: name accepted by a scientific body
- Proprietary (Brand) name: name assigned by the manufacturer

Pharmacokinetics

Deals with absorption, distribution, metabolism, and excretion of drugs.
Drug concentration at the site of action depends on all these processes.
All pharmacokinetic processes involve drug passage across membranes.

Movement of Drug Molecules Across Cell Barriers

Cell membranes act as barriers between the body's aqueous compartments.
For drugs to pass from one side of a cell to the other, they need to cross at least two cell membranes.
Vascular endothelium: Gaps between cells are packed with proteins that act as filters.
Some organs (e.g. CNS, placenta) have tight junctions between cells, preventing harmful molecules from entering.
Other organs (e.g. liver, spleen) have discontinuous endothelium, allowing free passage between cells.

Carrier Mediated Transport

Involves binding of the drug to specific receptors on the membrane for translocation into the cytoplasm.
Characteristics:
- Selectivity
- Competitive inhibition by chemical congeners
- Requires energy
- Saturability
- Movement against electrochemical gradient
Active transport: movement against the concentration gradient
Facilitated diffusion: movement along the concentration gradient but at a faster rate than simple diffusion

Filtration or Pore Transport

Passage through the water-filled pores in membranes.
Accelerated by the hydrodynamic flow of water under hydrostatic or osmotic pressure gradient.
Requires water solubility and a smaller molecular size than the pore diameter.

Drug Absorption

Rate at which a drug leaves its administration site and the extent to which this occurs.
Bioavailability: extent to which a drug reaches its site of action or a biological fluid from which the drug has access to its site of action.
Absorption occurs through one or a combination of the processes described earlier.

Factors That Modify Absorption

Drug solubility at the site of absorption
Dosage form
Local conditions at the site of action
Drug concentration at the site of absorption
Circulation to the site of absorption
Area of the absorbing surface
Route of administration

Drug Distribution

Process by which absorbed drug or drug directly introduced into the circulation is carried to various interstitial and cellular fluids.

Pulmonary Excretion

Any volatile material can be excreted through the lungs, regardless of the route of administration.
Rate of excretion depends on respiration rate, pulmonary blood flow, and gas solubility in blood.

Sweat and Saliva Excretion

Depends on diffusion of un-ionized lipid-soluble forms across gland epithelial cells.
Quantity excreted is determined by the drug's pKa and the pH of the secretions.
Excretion in sweat can cause skin reactions.
Substances excreted in saliva are usually swallowed.

Excretion in Milk

Concentration of drugs in milk depends on:
- Amount of drug in maternal blood
- Lipid solubility of the drug
- Drug's degree of ionization
- Extent of its active excretion
Milk is more acidic (pH 6.5) than plasma, meaning basic drugs are more concentrated in this fluid.

Clinical Significance of Drug Excretion

Excretion determines how long a drug remains in the body, influencing its duration of action.

Routes of Drug Administration

Drugs are administered for local or systemic effects.
The choice of route depends on:
- Target tissue
- Physico-chemical properties of the drug
- Disease state

Systemic Routes of Administration

Oral ingestion: Administration of drugs through the mouth, mostly for systemic effects.

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Description

This quiz covers the mechanisms of movement of small molecules across cell membranes, focusing on passive diffusion and its dependence on factors like pH and drug characteristics. You will explore the role of fenestrated endothelium in hormone transfer and the principles governing drug absorption through diffusion. Test your understanding of these essential concepts in cellular physiology.