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Questions and Answers
What is the main characteristic of leukemia when compared to other types of cancer?
What is the role of genes that are mutated in cancer development?
Which of the following is an example of a chemical carcinogen?
What is the result of retroviruses transforming bcl-2 into an oncogene?
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What is the definition of a neoplasm or tumor?
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What is the reason behind higher distribution of highly water-soluble drugs in premature neonates?
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Why do neonates have a higher risk of CNS adverse effects from phenytoin?
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What is the consequence of reduced CYP2D6 activity in children with ADHD treated with atomoxetine?
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Why is the weight-based dose of gentamicin often higher in premature neonates than in adults?
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What is the reason behind the increased risk of kernicterus and jaundice in neonates?
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What is the characteristic of CYP1A2 activity in fetal liver tissue and newborns not exposed to caffeine in utero?
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Why do antibiotics have improved distribution into the CNS in premature neonates?
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What is the consequence of lower CYP3A4 activity in premature neonates?
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Why do infants require larger doses of anti-epileptic medications like midazolam?
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What is the characteristic of GABA receptors in early infancy?
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What is the reason for reduced clearance of aminoglycosides like gentamicin in newborns?
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Why do newborns exposed to caffeine during gestation have a shorter caffeine half-life?
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What is the effect of dopamine on heart rate in premature neonates?
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What is the reason for the concomitant use of dexamethasone and indomethacin altering the normal progress of renal maturation in the neonate?
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What is the effect of glucuronidation on the elimination of certain drugs in newborns?
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Why do newborns require more frequent dosing of caffeine compared to older infants?
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What is a disadvantage of intramuscular drug administration in neonates?
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Why is subcutaneous drug absorption delayed in neonates?
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What is a characteristic of transdermal drug absorption in neonates?
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What is a risk associated with using iodine as a topical disinfectant before surgery in neonates?
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What is a characteristic of rectal drug absorption in neonates?
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Why is rectal acetaminophen suppository rapidly absorbed in neonates?
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What is a characteristic of blood flow in neonates?
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Why is diazepam gel rapidly absorbed in neonates?
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Study Notes
Cancer Definition and Types
- Cancer is a defect in mechanisms controlling cell survival, proliferation, and death.
Neoplasms (Tumors)
- Abnormal mass of tissue due to abnormal cell growth.
Leukemia
- A blood cancer that doesn't form a tumor.
- Widely spread in the bloodstream and bone marrow.
Causes of Cancer
-
Environmental Factors
- Ionizing radiation
- Chemical carcinogens (e.g., tobacco smoke, alcohols, and asbestos)
-
Chronic Infections (Viruses)
- Hepatitis B and C are associated with Hepatocellular Carcinoma (HCC)
- HIV is associated with certain types of lymphomas
- Retroviruses (e.g., HIV) can transform bcl-2 → oncogene → uncontrolled cell growth and inhibition of cell apoptosis
-
Genetic Factors
- Mutation in tumor suppressor genes
- Genes that suppress malignant cell growth (e.g., p53 gene mutation associated with various solid tumors)
-
Lifestyle Factors
- Unbalanced diet
- Hormones
Pharmacology in Neonates
- Newborns exposed to caffeine during gestation have higher levels of CYP1A2 activity at birth, resulting in a shorter caffeine half-life of 4-5 hours, necessitating more frequent dosing.
Drug Metabolism
- Phase II: Lower UDP-glucuronosyl transferase (UGT) activity affects the metabolism of morphine, chloramphenicol, and acetaminophen.
- Phase I: Lower CYP3A4 activity leads to a slower rate of erythromycin metabolism, increasing the risk of adverse effects.
- Phase I: Genetic polymorphisms of CYP2D6 result in lower activity, affecting the metabolism of atomoxetine, leading to increased heart rate, blood pressure, and impaired weight gain in children with ADHD.
- Phase I: CYP1A2 activity is negligible in fetal liver tissue and in newborns not exposed to caffeine in utero.
Drug Elimination
- Kidneys are not fully developed at birth, resulting in lower GFR, immature tubular secretion, and decreased clearance of aminoglycosides and digoxin.
- Concomitant use of dexamethasone and indomethacin may alter the normal progress of renal maturation in neonates.
Pharmacodynamic Changes
- Reduction in adrenergic receptor density or downregulation of receptors in the myocardium of premature neonates, making them resistant to the effects of β-adrenergic agonists.
- GABA receptors are abnormal in infancy and develop with age, explaining why infants require relatively larger doses of anti-epileptic medications.
Drug Distribution
- Functionally immature blood-brain barrier, resulting in higher drug distribution into the CNS, making antibiotic therapy for sepsis and meningitis more effective.
- Higher total body water, leading to greater distribution of highly water-soluble drugs like linezolid and gentamicin.
- Plasma protein binding is reduced in neonates due to decreased circulating levels of albumin and decreased binding affinity, affecting the distribution of phenytoin and sulfonamides.
Drug Absorption
- Intramuscular & Subcutaneous Absorption:
- Reduced muscle size, weaker muscle contractions, immature vasculature, and reduced skeletal muscle blood flow, leading to reduced absorption of I.M administered drugs in neonates.
- Lower percentage of body fat in neonates, delaying subcutaneous drug absorption (e.g., insulin).
- Transdermal Absorption:
- Greater skin to body surface area ratio, thinner epidermis, better hydration, and greater perfusion, enhancing skin absorption and increasing the risk of significant toxicity.
- Rectal Absorption:
- High contractions in the rectum causing premature expulsion of solid rectal drug formulations (suppositories).
- Rapid absorption of rectal solutions of drugs like diazepam gel.
- Rapid absorption of rectal acetaminophen suppositories.
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Test your knowledge of cancer definition, types, and causes, including environmental factors and chronic infections.
