Pharmacokinetics answers the question “What does the body do to the drug?” by studying how drugs are absorbed, distributed, metabolized, and excreted. Pharmacodynamics, on the other hand, focuses on “What does the drug do to the body?” by examining how drugs produce their effects through interactions with receptors, enzymes, and other biological targets. 

The journey of a drug through the body can be divided into four stages: 

• Absorption – a drug enters the bloodstream from its site of administration. Most drugs are absorbed through passive diffusion across cell membranes, which requires the drug to be lipid-soluble and non-ionized. The rate and extent of absorption depend on factors such as the drug’s formulation, route of administration, and the pH of the surrounding environment. For example, oral drugs must pass through the gastrointestinal tract and may be subjected to the first-pass effect, where the liver metabolizes a portion of the drug before it reaches systemic circulation.

• Distribution – the drug is distributed throughout the body via the bloodstream. The extent of distribution depends on factors such as blood flow to tissues, the drug’s lipid solubility, and its binding to plasma proteins like albumin. Highly lipophilic drugs, for instance, can cross the blood-brain barrier and accumulate in the central nervous system. The volume of distribution (Vd) is a key parameter that describes how extensively a drug spreads into body tissues relative to the plasma.

• Metabolism – the chemical modification of the drug, primarily in the liver, to facilitate its elimination. Drug interactions often arise at this stage due to competition or inhibition of cytochrome P450 enzymes. For example, inhibitors like grapefruit juice can slow the metabolism of certain drugs, increasing their plasma concentration and risk of toxicity. Metabolism occurs in two phases: 

• • Phase I: Functionalization reactions (e.g., oxidation, reduction, hydrolysis), often carried out by the cytochrome P450 enzyme system, convert the drug into a more polar metabolite.

• • Phase II: Conjugation reactions attach water-soluble groups (e.g., glucuronide, sulfate) to the drug to enhance its excretion.

• Excretion – the removal of the drug and its metabolites from the body, primarily via the kidneys (urine) or the gastrointestinal tract (feces). Drugs eliminated by the kidneys undergo filtration, reabsorption, and secretion in the nephron. Factors like pH can influence the excretion of weak acids or bases, as ionized drugs are less likely to be reabsorbed and more likely to be excreted.

Bioavailability refers to the fraction of an administered dose of a drug that reaches systemic circulation in its active form. Drugs administered intravenously have 100% bioavailability, whereas orally administered drugs often have reduced bioavailability due to the first-pass effect, where the liver metabolizes the drug before it enters systemic circulation. For example, drugs like nitroglycerin are administered sublingually to bypass the first-pass effect and achieve rapid absorption.

The cytochrome P450 enzyme system plays a crucial role in drug metabolism. Certain drugs can act as inducers or inhibitors of these enzymes, leading to significant drug interactions. For example:

Inducers (e.g., rifampin, carbamazepine) increase the activity of P450 enzymes, accelerating drug metabolism and reducing the efficacy of co-administered drugs. Inhibitors (e.g., cimetidine, ketoconazole) decrease enzyme activity, slowing drug metabolism and increasing the risk of drug toxicity.

Drugs can act as:

• Agonists: Molecules that bind to a receptor and activate it, mimicking the action of a natural ligand (e.g., morphine is an opioid receptor agonist).

• Antagonists: Molecules that bind to a receptor but do not activate it, blocking the action of agonists (e.g., naloxone is an opioid receptor antagonist).

• Partial Agonists: Molecules that activate a receptor but produce a submaximal response compared to a full agonist.

• Inverse Agonists: Molecules that reduce the basal activity of a receptor, producing the opposite effect of an agonist.

Dose-response curves illustrate the relationship between the dose of a drug and its pharmacological effect. Two key parameters are derived from these curves:

• Efficacy – the maximum effect a drug can produce, regardless of dose. Drugs with higher efficacy are more effective at achieving the desired therapeutic response.

• Potency – the dose required to produce a given effect. A drug with higher potency requires a lower dose to achieve the same effect as a less potent drug.

For example, morphine and codeine are both opioid analgesics, but morphine is more potent because it produces the same level of pain relief at a lower dose.

The therapeutic index (TI) is a measure of a drug’s safety, calculated as the ratio between the toxic dose (TD50) and the effective dose (ED50). A larger therapeutic index indicates a safer drug. For example, penicillin has a high therapeutic index, making it relatively safe, while drugs like warfarin have a narrow therapeutic index, requiring close monitoring to avoid toxicity. Drugs with a narrow therapeutic index (e.g., digoxin, lithium) have a small margin between therapeutic and toxic doses, increasing the risk of adverse effects if dosing is not carefully managed.