18.1 Pharmacology Foundations: Classification, Pharmacokinetics & Pharmacodynamics

18.1 Pharmacology Foundations: Classification, Pharmacokinetics & Pharmacodynamics

CPCF Appendix A foundational knowledge #5 is one of the largest single items in the framework. It requires the Primary Care Paramedic to understand the paramedic's role in medication therapy, medication sources and drug classifications, naming conventions, mechanisms of entry and elimination, factors affecting absorption and distribution, dosage calculation, drug interactions, indications and contraindications, side effects, reference data, overdose recognition, the rights of administration, routes and injection sites, patient and supply preparation, and the procedures that follow a medication error.

This section covers the science. Section 18.2 covers safe administration and calculation, and Section 18.3 covers the routes named in skill #32.

The Paramedic's Role in Medication Therapy

A PCP administers medication under a medical directive or delegated authority, within the regulator-defined scope of practice for the designation (indicator A3.2 and competency H1), and within their own competence. Three implications are examinable:

1. Knowing a drug does not authorize giving it. Scope, authorization, and personal competence are independent gates (Section 4.3).
2. The paramedic administering is accountable for the decision and the act (indicator A2.3), even when the order came from someone else. "I was told to" is not a defence for administering a drug with an obvious contraindication.
3. Indicator H3.2 requires you to apply knowledge of the indications, contraindications, methods, and potential complications of every therapy you use. If you cannot state all four for a drug, you are not ready to give it.

Drug Names and Sources

Always communicate in generic names. Trade names vary between manufacturers and between countries, and a single generic drug may have a dozen brand names. Patients, however, know their medications by brand — so take the history in whatever name they use and convert it for the record and the handover.

Sources: plant (digoxin, atropine, morphine), animal (some insulins historically), mineral (magnesium sulfate), synthetic (most modern agents), and biotechnological (recombinant insulin, monoclonal antibodies).

Pharmacokinetics: What the Body Does to the Drug

Four processes, in order — ADME.

Absorption

Movement from the site of administration into the systemic circulation. Intravenous administration bypasses absorption entirely and is therefore 100% bioavailable and fastest.

Factors that change absorption:

• Route — see Section 18.3 for the onset ordering
• Perfusion at the site — this is the single most important prehospital factor. A shocked, vasoconstricted patient absorbs subcutaneous and intramuscular drugs slowly and unpredictably, which is why the intravenous or intraosseous route is preferred in shock, and why the well-perfused vastus lateralis is chosen for intramuscular epinephrine in anaphylaxis
• Lipid solubility and molecular size
• Gastric contents, pH, and motility for oral drugs
• First-pass metabolism — oral drugs are absorbed into the portal circulation and pass through the liver before reaching the systemic circulation, where a large fraction may be inactivated. Sublingual, buccal, rectal, inhaled, and parenteral routes bypass first pass, which is why sublingual nitroglycerin works and swallowed nitroglycerin does not

Distribution

Movement from blood into tissue, determined by perfusion, protein binding, and barriers.

• Protein binding: only the unbound (free) fraction is active. Hypoalbuminaemia — malnutrition, liver disease, critical illness — raises the free fraction and the effect of a standard dose. Competition for binding sites is a major interaction mechanism.
• Barriers: the blood-brain barrier admits lipid-soluble drugs; the placenta admits most drugs, so any drug given to a pregnant patient should be assumed to reach the fetus.
• Volume of distribution explains why water-soluble drugs are dosed on lean body weight and lipid-soluble drugs distribute extensively into adipose tissue.

Metabolism (Biotransformation)

Predominantly hepatic, mostly via the cytochrome P450 enzyme system. Metabolism usually inactivates a drug, but sometimes activates a prodrug.

• Enzyme inducers (carbamazepine, rifampin, chronic alcohol) speed metabolism and reduce drug effect.
• Enzyme inhibitors (many antifungals, macrolide antibiotics, grapefruit juice) slow metabolism and increase drug effect, sometimes to toxicity.
• Liver disease reduces metabolism — standard doses of sedatives, opioids, and benzodiazepines behave as relative overdoses.

Excretion

Mostly renal, with biliary, pulmonary (volatile agents), and minor routes in sweat, saliva, and breast milk. Renal impairment causes accumulation of renally cleared drugs, and the older adult has reduced clearance even with a normal creatinine.

Half-life is the time for the plasma concentration to fall by half; roughly four to five half-lives are needed to eliminate a drug, and the same to reach steady state on repeated dosing. This is the concept behind renarcotization: naloxone has a half-life of roughly 30 to 90 minutes while many opioids last far longer, so the patient can re-sedate after naloxone wears off.

Pharmacodynamics: What the Drug Does to the Body

Most drugs act on receptors:

Other core concepts: potency (dose required for an effect) is not the same as efficacy (the maximal effect achievable); the therapeutic index is the margin between an effective and a toxic dose, and drugs with a narrow index — digoxin, lithium, warfarin, phenytoin, theophylline — are the ones that cause prehospital toxicity; tolerance requires increasing doses for the same effect; tachyphylaxis is rapid tolerance after repeated doses over a short interval, as seen with repeated salbutamol.

Interactions

CPCF #5 names three interaction types explicitly:

• Drug–drug: nitroglycerin with a PDE-5 inhibitor (catastrophic hypotension); an opioid with a benzodiazepine (respiratory depression); an anticoagulant with an antiplatelet (bleeding); a beta blocker blunting the response to epinephrine in anaphylaxis.
• Drug–food: grapefruit juice inhibiting cytochrome P450; vitamin K-rich foods opposing warfarin; tyramine-containing foods with monoamine oxidase inhibitors.
• Drug–condition: a beta blocker in asthma (bronchospasm); an NSAID in renal impairment or gastrointestinal bleeding; ASA in a child with a viral illness (Reye syndrome).

Interactions can be additive, synergistic (greater than additive — the opioid and benzodiazepine combination), or antagonistic.

Adverse Effects and the Special Populations

• Side effect: a predictable, dose-related, non-therapeutic effect — salbutamol causing tremor and tachycardia.
• Adverse drug reaction: a harmful, unintended response at normal doses.
• Allergic reaction: immune-mediated, and not dose-related. Distinguish it from intolerance. A patient who reports that morphine makes them nauseated has an intolerance, not an allergy, and recording it as an allergy may deny them appropriate analgesia for life.
• Idiosyncratic reaction: unexpected and unpredictable.
• Iatrogenic: caused by the treatment itself.

Special populations: neonates and infants have immature hepatic and renal clearance; children are dosed by weight, with a maximum that must not exceed the adult dose; older adults have reduced clearance, more drugs, and more interactions (Section 16.2); pregnancy alters volume of distribution and protein binding, and every drug should be assumed to cross the placenta; renal and hepatic impairment both cause accumulation.

[!IMPORTANT] Polypharmacy is a clinical finding, not background information. A medication list is a compressed medical history and a risk assessment. Beta blockers explain an absent tachycardia in shock; anticoagulants convert a minor fall into a major head injury; diuretics and ACE inhibitors explain electrolyte disturbance; anticholinergics explain hyperthermia and confusion. Read the list, and read what is missing from it — the insulin that has run out, the diuretic that was stopped last week.