Pharmacokinetics: Drug Administration Routes, Transport, and Absorption Factors

Flashcards covering routes of drug administration, cellular transport mechanisms (passive, active, facilitated diffusion, and vesicular transport), acid-base ionization principles with the Henderson-Hasselbalch equation, and physical determinants of drug absorption.

What is inhalation as a route of drug administration?

The administration of a drug through the respiratory tract, where it is absorbed across the respiratory mucosa and pulmonary epithelium.

Why is the inhalation route particularly rapid and effective for drug delivery?

The lungs possess a very large surface area and a rich blood supply, enabling rapid absorption (almost as quick as IV administration) while acting directly on the lungs to reduce systemic side effects.

What are the three examples of inhaled drugs and their clinical uses mentioned in the lecture?

Albuterol (salbutamol) to relieve bronchospasm in asthma, fluticasone to reduce airway inflammation, and inhaled anesthetic gases used during anesthesia.

What is the intranasal route of administration, and what is its primary advantage?

Delivering a drug directly into the nasal cavity (typically as drops or a spray), which allows for local action or systemic absorption.

What are three examples of drugs administered intranasally and their indications?

Mometasone for nasal inflammation (such as allergic rhinitis), desmopressin for diabetes insipidus, and salmon calcitonin in selected cases of osteoporosis.

What is the anatomical difference between intrathecal and intraventricular drug administration?

Intrathecal administration introduces a drug into the cerebrospinal fluid (CSF), usually in the subarachnoid space, whereas intraventricular administration introduces a drug directly into the cerebral ventricles containing CSF.

Why are intrathecal and intraventricular routes necessary, and what is an example drug given intrathecally?

They are required because the blood–brain barrier restricts drug entry from the bloodstream into the brain and CSF; an example is amphotericin B administered for selected cases of severe fungal meningitis.

What is topical drug administration, and what type of effect does it generally produce?

Applying a drug to a body surface (such as the skin, eye, or mucous membrane) generally aimed at producing a local effect.

What are three examples of topical medications mentioned in the lecture?

Clotrimazole cream (to treat fungal skin infections), tropicamide eye drops (to dilate the pupil), and cyclopentolate eye drops (to dilate the pupil and temporarily paralyze accommodation).

What is the primary difference in therapeutic goal between topical and transdermal drug delivery?

Topical administration usually aims for a local effect, whereas transdermal administration delivers a drug through the skin into the systemic circulation to produce a systemic effect.

What are the advantages of transdermal administration, and what are three examples of transdermal patches?

Advantages include sustained controlled drug delivery, avoiding the GI tract, bypassing first-pass metabolism, and reducing dosing frequency; examples include nitroglycerin (angina), scopolamine (motion sickness), and combined hormonal contraceptive patches.

Why does rectal administration only partially bypass hepatic first-pass metabolism?

The upper rectum drains mainly into the portal circulation leading to the liver, whereas the middle and lower rectum drain partly into systemic circulation, resulting in approximately $50\%$ of rectal drainage bypassing the portal circulation.

What are the key disadvantages of rectal administration?

Absorption can be erratic and incomplete, some drugs cause mucosal irritation, and administration can be inconvenient.

What is passive diffusion, and what is its role in drug absorption?

The movement of a drug down its concentration gradient without energy expenditure; it is the most common mechanism by which drugs cross biological membranes.

How do lipid-soluble versus water-soluble drugs cross biological membranes during passive diffusion?

Lipid-soluble drugs pass directly through the lipid bilayer, whereas water-soluble drugs cross through aqueous channels or pores if they are sufficiently small.

What is facilitated diffusion, and how does it differ from simple diffusion?

It is carrier-mediated transport down a concentration gradient that does not require energy; unlike simple diffusion, it requires a specific carrier protein and can therefore be saturated and inhibited.

What is active transport, and what are its key transport characteristics?

An energy-dependent carrier-mediated process (often using ATP hydrolysis) that can move substances against a concentration gradient and is subject to saturation and inhibition.

How do endocytosis and exocytosis differ in their transport mechanisms?

Endocytosis brings substances into the cell by forming vesicles from the cell membrane, whereas exocytosis releases substances outside the cell by vesicle fusion with the cell membrane.

What are two physiological examples of vesicular transport mentioned in the lecture?

Intestinal uptake of the vitamin B12–intrinsic factor complex via receptor-mediated endocytosis, and release of norepinephrine from nerve terminal storage vesicles via exocytosis.

Why does the non-ionized form of a drug cross lipid membranes more readily than the ionized form?

The non-ionized form is uncharged and dissolves better in the lipid bilayer, whereas the ionized form is electrically charged and interacts more readily with water.

What happens to the ionization state of a weak acid ($HA \rightleftharpoons H^+ + A^-$) at low versus high pH?

In an acidic environment (low pH), a weak acid remains predominantly non-ionized ($HA$); in an alkaline environment (high pH), it loses a proton and becomes predominantly ionized ($A^-$).

What happens to the ionization state of a weak base ($BH^+ \rightleftharpoons B + H^+$) at low versus high pH?

In an acidic environment (low pH), a weak base retains or accepts a proton and becomes predominantly ionized ($BH^+$); in an alkaline environment (high pH), it loses a proton and becomes predominantly non-ionized ($B$).

What is $pKa$, and what does a lower versus higher value indicate?

A property related to the tendency of a drug to donate or retain a proton; a lower $pKa$ indicates a stronger acid, whereas a higher $pKa$ indicates a weaker acid (or more basic character).

What is the ratio of ionized to non-ionized drug when environmental pH equals the drug's $pKa$?

The protonated and deprotonated forms are equal ($[HA] = [A^-]$ or $[BH^+] = [B]$), meaning the drug is $50\%$ ionized and $50\%$ non-ionized.

What is the Henderson–Hasselbalch equation for a weak acid?

$$pH = pKa + \log\left(\frac{[A^-]}{[HA]}\right)$$

What is the Henderson–Hasselbalch equation for a weak base?

$$pH = pKa + \log\left(\frac{[B]}{[BH^+]}\right)$$

What is distribution equilibrium?

The state reached when the concentration of the permeable, non-ionized form of a drug becomes equal across the relevant compartments.

What are the three major physical factors that influence drug absorption?

Blood flow to the absorption site, total surface area available for absorption, and contact time at the absorption surface.

How does blood flow maintain drug absorption, and what clinical state reduces it?

Adequate blood flow carries absorbed drug away to maintain the concentration gradient; clinical shock decreases peripheral blood flow and reduces subcutaneous drug absorption.

How does the absorptive surface area of the small intestine compare to that of the stomach?

The small intestine has an absorptive surface area approximately $1{,}000$ times that of the stomach due to its extensive folds, villi, and microvilli.

How do severe diarrhea and delayed gastric emptying influence drug absorption?

Severe diarrhea accelerates transit and reduces contact time, decreasing total absorption; delayed gastric emptying slows the drug's arrival into the small intestine, delaying the onset of absorption.