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At the end of the lecture, the student should be able to: List ways in which drug absorption, distribution, metabolism and excretion are altered by age and the consequent effects of drug action. Describe pediatric dosage considerations Describe the pharmacological properties that influence drug transfer both across the placenta and into the breast milk Describe factors that determine the teratogenic potential of drugs once they enter the embryonic/foetal circulation.
Learning outcomes
Describe altered physiology and polypharmacy in the
elderly. Identify common herbal and traditional medicines. List potential interactions between herbal and conventional medicene.
Key terms
Polypharmacy,
Pediatric dosage, Carrier mediated transport, teratogens, Mutagens, `carcinogens, Transdermal drug administration, Non compliance, `passive diffusion, Herbal medicines, conventional medicines.
very young and the elderly. Infants and the very elderly tend to be the most sensitive to the effects of the drugs. Common problem is the slowed peristalsis and the gastric emptying time. Activity and concentrations of digestive secretions are lower in newborns . Infants and elderly require special considerations for medication administration.
intramuscularly may be affected by the differences in muscle mass, blood flow to the muscles, and muscle inactivity of patients who are bedridden. though the outer layer of the skin (stratum corneum) is not fully developed. The reason being that the skin at this stage would be fully hydrated and thus the water soluble drugs are absorbed more easily. susceptible to skin absorption because plastic acts as an occlusive dressing that increases hydration of the skin. nappy rash)
Transdermal administration in elderly is always unpredictable. Dermal thickness usually decreases with aging which may enhance absorption but there can be some factors which diminish absorption. Example, drying of skin,wrinkles,and a decrease in hair follicles. With aging there will be decreased cardiac output and diminished tissue perfusion. This may affect transdermal drug absorption.
for the infants and elderly to swallow. The medication needs to be crushed and mixed with water. Taste becomes a factor when administering liquid medications because liquid medications comes in contact with the taste buds. However, time release tablets, enteric coated tablets and sublingual tablets should not be crushed because of the effect of the absorption rate and potential for the toxicity.
Elderly patients usually have reduced salivary flow and this makes chewing and swallowing more difficult.
Gastrointestinal absorption of medicines is often influenced by a variety of factors. E.g.-gastric pH,gastric emptying time, motility of GI tract, enzymatic activity, blood flow of the mucous lining of the stomach and intestines, permeability and maturation of the mucosal membrane and the concurrent disease processes.(discuss in pairs)
water soluble drugs and may require higher doses in milligram per kilogram than the elderly.
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Drugs that are insoluble are transported in the circulation by being bound to plasma proteins (albumin and globulin) Protein binding is reduced in preterm infants because of: Decreased plasma protein concentration Lower binding capacity of protein Decreased affinity of proteins for drug binding
binding sites. Some drugs can displace bilirubin from the protein binding sites and allow the bilirubin to pass into the brain causing Kernicterus( is the degeneration of brain nerve cells caused by binding of bilirubin to the cells).
medicines. It is controlled by factors such as genes,diet,age,and maturity of enzyme systems in liver. All enzyme systems are present at birth but they mature at different rates. The weight of the liver, the number of functioning hepatic cells, and hepatic blood flow decrease with age. This results in slow metabolism of drugs in elderly.
Renal function reaches to an adult level at 1 year of age As body matures, important physiologic changes take
place in the kidneys, including decreased renal blood flow caused by arthrosclerosis and reduced cardiac output, a loss of glomeruli,and decreased tubular function.
clearance of drugs. The action of the drugs may be prolonged in this case and may accumulate to toxic levels if no adjustment of dosages is considered
Muscle mass in children is lower but the body water percentage is higher.
These factors affect absorption, distribution,
metabolism and excretion of drugs. The physiological differences between adults and children suggest that pharmacokinetic behavior of some drugs vary according to the age. A dose administered to an adult is never equivalent to the pediatrics.
pediatric dosage.
pediatrics to prevent toxicities. Therfore,it is equally important to obtain accurate height and weight measurements on a regular basis.
administer medications to pediatric patients. Oral and parenteral medications available in powder form should be diluted properly according to the manufacturers directions to allow accurate measurements of solution being administered
Pregnancy
During pregnancy any chemical or drug substances consumed and absorbed may reach the fetus by way of the maternal circulation and cross the placenta or
be transferred to the baby and newborn via breast milk. Drugs cross the placenta and induce adverse fetal effects. This depends on the pharmacological properties of the drugs e.g. the type of drug, the drug concentration and fetal age. Transfer of drugs across the placenta depends on the physicochemical properties of the drug, protein binding and lipid solubility.
Pregnancy
Transfer of drugs primarily involves simple diffusion. In pregnancy, low molecular weight drugs which are
lipophilic,ionized and non-protein bounded are able to cross the placenta, while drugs of high molecular weight cross very poorly.
transferred to the colostrums and breast milk. Drugs are handled by different pathways in the infant and the fetus, so the impact of maternal medications on the infant is probably less as the drug is diluted in the maternal circulation and the amount of milk taken by the infant is often small.
on the relationship of several factors: - dosing and route of administration - drugs distribution - its protein binding - maternal metabolism and excretion
are higher degree of ionization, low molecular weight of the drugs, greater fat solubility and higher concentration of drugs. Transfer of drugs into milk occurs by both passive diffusion and carrier mediated transport.
vulnerable to the teratogenic effects of various drugs and chemicals. Drugs can exert a beneficial effect in the fetus, cause adverse effects or act as teratogens,mutagens or carcinogens. 3-12 weeks of pregnancy is when the extremities(arms,legs, and toes), central nervous system (CNS) ,muscle and organs are developing most rapidlyteratogens can cause birth defects characterized by the absence or malformation of arms and legs.
fetal hypoxia, premature delivery, and congenital abnormalities ( skull defect, cardiac abnormality), cerebral infarction or stroke.
Polypharmacy- refers to use of multiple medications by a patient. The elderly use more drugs because illness is more common in older persons.e.g. Cardiovascular Diseases,Arthritis,Gastrointestinal Disorders, and Bladder Dysfunction. Altered drug effects are common in elderly patients but can often be avoided. We should be aware of age related changes in drug absorption,distribution,metabolismand elimination. Doctors may need to adjust drug dose, frequency, or the choice of drug altogether as they consider the physiologic changes of aging.
Group Activity
1. Identify common herbal and traditional medicine
(brain storm) Debate: 2. We believe that herbal medicine is better than conventional medicine /disagree (1 from each group)
used for skin applications, burns, used in many shampoos and conditioners. Garlic-member of the onion family. Consuming large amounts of garlic prevent heart disease. Ginger-used as an antiemetic in nausea associated with travel or pregnancy.
References
Porth, C.M. (2004). Essentials of
Path physiology: Concepts of Altered States. Philadelphia; Lippincott Williams & Wilkins.