Pharmacokinetics and Pharmacodynamics: How Drugs Move and Work

What Pharmacokinetics Means for EMS

Every drug you give a patient travels through the body along a predictable path. Pharmacokinetics describes what the body does to the drug: how it is absorbed, moved to tissues, chemically changed, and finally removed. Pharmacodynamics describes what the drug does to the body: how it binds to receptors and produces an effect. As an EMT or paramedic, understanding both concepts helps you anticipate when a drug will start working, how strong the effect will be, and why two patients given the same dose can respond very differently.

Absorption

Absorption is the movement of a drug from the site of administration into the bloodstream. The route of administration is the single biggest factor controlling how fast this happens.

• Intravenous (IV): Drug enters the bloodstream directly — absorption is essentially instantaneous. Onset of action is fastest.
• Intramuscular (IM): Drug must cross muscle tissue and capillary walls. Onset is slower than IV but faster than oral, and is affected by local blood flow. Poor perfusion (shock, hypothermia) slows IM absorption significantly.
• Subcutaneous (SQ): Slower than IM because subcutaneous tissue is less vascular.
• Oral (PO): Drug is absorbed through the gastrointestinal tract and passes through the liver before reaching systemic circulation — this is the first-pass effect, which can substantially reduce the amount of active drug that reaches the target tissues.
• Sublingual / intranasal / inhaled: Bypass the first-pass effect and allow relatively rapid absorption.

Distribution

Once a drug is in the bloodstream, it is distributed to tissues. Two important concepts govern how widely a drug spreads:

Protein binding: Many drugs attach to plasma proteins (mainly albumin) while in the blood. Bound drug is pharmacologically inactive — only free (unbound) drug can act at receptor sites. Patients with low albumin (common in malnutrition, liver disease, or the elderly) have less protein to bind a drug, meaning more free drug is available and the effect is amplified at standard doses.

Volume of distribution (Vd): A mathematical expression of how widely a drug is distributed into body tissues versus remaining in the plasma. A high Vd means the drug distributes extensively into tissues (e.g., fat, muscle) and plasma concentrations are relatively low. Body composition matters: obese patients have more adipose tissue, which can serve as a reservoir for fat-soluble drugs and prolong their duration of action.

Metabolism

Metabolism (biotransformation) is the chemical alteration of a drug, primarily in the liver, into metabolites that are usually less active and easier to excrete. Liver enzymes, especially the cytochrome P450 system, carry out most of this work.

Factors that reduce hepatic metabolism lead to higher, more prolonged drug concentrations:

• Liver disease (cirrhosis, hepatitis)
• Advanced age — liver mass and blood flow decline with age
• Drug-drug interactions — one drug can inhibit or induce enzymes that metabolize another

Polypharmacy — the use of multiple medications simultaneously — multiplies interaction risks. In the geriatric patient, five or more medications is common, and the chance of a clinically significant interaction rises sharply with each added drug.

Excretion

Most drug metabolites are eliminated by the kidneys in urine. Some drugs are excreted through bile, breath, or sweat. Renal function is measured clinically by creatinine clearance or estimated glomerular filtration rate (eGFR). When renal function is reduced — as in chronic kidney disease or in elderly patients whose kidney mass normally decreases with age — drugs and their active metabolites accumulate, raising the risk of toxicity at standard doses.

Onset, Peak, and Duration

Three time-based concepts describe a drug's clinical behavior:

• Onset of action: Time from administration until the drug reaches a concentration sufficient to produce an effect.
• Time to peak (Tmax): The point at which plasma concentration (and usually effect) is greatest.
• Duration of action: How long the drug maintains a therapeutic effect, largely controlled by its half-life — the time required for the plasma concentration to fall by half. After approximately four to five half-lives, the drug is considered essentially eliminated.

The therapeutic window is the range of plasma concentrations between the minimum effective concentration and the toxic concentration. A narrow therapeutic window means that small changes in dose or pharmacokinetics can tip a patient into toxicity.

Patient Factors That Alter Drug Response

| Factor | Mechanism | Clinical implication |

|---|---|---|

| Advanced age | Reduced liver and kidney function, lower albumin, altered body composition | Lower doses often needed; prolonged effect |

| Low body weight | Less volume of distribution for some drugs | Standard weight-based dosing may require adjustment |

| Obesity | Larger Vd for fat-soluble drugs | Duration of action may be extended |

| Liver disease | Impaired metabolism, low albumin | Higher free-drug levels; longer duration |

| Renal disease | Reduced excretion | Drug and metabolite accumulation; toxicity risk |

| Polypharmacy | Enzyme competition, protein-binding competition | Unpredictable altered effects |

Safety Considerations

Always reassess the patient after drug administration. Even a drug you give frequently can behave differently in a patient with altered physiology. When in doubt about dose or expected response in a high-risk patient, contact medical direction. Document the route, dose, time, and patient response for every medication. Recognizing that a drug is taking longer than expected to work — or is working too strongly — is as important as giving the right dose in the first place.