Pharmaceutical Considerations in Treating Very Young and Geriatric Patients

Very young – The placenta is a site of metabolism for many drugs.

• Drug absorption – The placental barrier is similar to the BBB. Warfarin is teratogenic; heparin is not. In neonates, the gut has higher pH and less bacteria, the skin is more absorbent, and IM injections are variable.

• Drug distribution and metabolism – Theophylline levels are much higher due to less blood protein available for binding (higher amount of free drug available). Theophylline will actually be metabolized to caffeine in the neonatal liver. Chloramphenicol will have decreased conjugation, leading to longer half-life and gray baby syndrome.

• Drug elimination and pharmacodynamics – Many antibiotics are excreted unmetabolized by the kidney so renal status affects blood levels. Digoxin is excreted in its active form in the neonate (much longer half-life – 60-70 hrs), and the neonatal heart is much less sensitive to the effects of digoxin (combats increased half-life).

• Other issues – Accuracy of dosing, caretaker compliance, dosage is calculated by surface area rather than weight.

Geriatrics­ – Problems due to decreasing organ function (homeostenosis) and polypharmacy.

• Pharmacokinetics – Stomach pH increased, leading to less metabolism of levodopa (good thing). Decreased blood flow to organs leads to decreased liver metabolism and decreased renal excretion. Increased body causes storage of lipophilic drugs like diazepam, lidocaine. Decreased albumin, leading to increased free levels of warfarin, phenyotin, narcotics. Increased alpha-glycoprotein, leading to decreased free levels of basic drugs. Decreased body water causes increased concentration of water-soluble drugs such as procainamide, acetaminophen, ethanol. Liver metabolic enzymes decrease (phase 1 mixed function oxidase reactions before phase 2), so drugs with a high first-pass effect (propanolol, diazepam) have longer half-lives (warfarin, ethanol, and digitoxin are NOT affected). Decreased kidney function (decreases 1%/yr after age 50, decreased creatinine clearance) leads to increased half-lives of drugs like digoxin, which are not metabolized in the liver.

• Pharmacodynamics – Sensitivity can increase (opiate, benzodiazepines, antipsychotics) or decrease (beta-adrenergics).

• Other issues – Compliance, fear, comorbidities, polypharmacy.

Category: Pharmacology Notes