Geriatrics

Dr. Bereket Molla Tigabu

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Pharmacokinetic changes
• All four components of pharmacokinetics are affected by aging
• the most clinically important and consistent is the reduction of renal elimination of
drugs
❑ Absorption
• Peristalsis is weaker and gastric emptying delayed
• Relative achlorhydria can decrease the absorption of nutrients such as
vitamin B12, calcium, and iron
• Aging facilitates atrophy of the epidermis and dermis along with a
reduction in barrier function of the skin.
• Tissue blood perfusion is reduced, leading to decreased or variable rates of
transdermal, subcutaneous, and intramuscular drug absorption

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Distribution (1)
❖ Lean body mass can decrease by 12% to 19% through loss of skeletal
muscle in older adults.
• blood levels of drugs primarily distributed in muscle increase (eg, digoxin),
presenting a risk for overdose
❖ Adipose tissue can increase with aging by 18% to 36% in men and 33% to
45% in women.
• Fat-soluble drugs (eg, diazepam, amitriptyline, amiodarone, valproic acid, and
verapamil) have increased volume of distribution (Vd ), leading to higher tissue
concentrations and prolonged duration of action
Greater Vd leads to increased half-life and time required to reach steady-state
serum concentration

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Distribution (3)
❖ Total body water decreases by 10% to 15% by age 80.
• lowers Vd of hydrophilic drugs (eg, aspirin, digoxin, morphine, lithium, and
ethanol) leading to higher plasma drug concentrations than in younger adults when
equal doses are used
❖ Plasma albumin concentration decreases by 10% to 20%, although disease
and malnutrition contribute more to this decrease than age alone
• warfarin, phenytoin, and diazepam

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Metabolism (1)
• Drug metabolism is affected by age, acute and chronic diseases, and
drug–drug interactions
❖ Liver mass is reduced by 20% to 30% with advancing age, and hepatic
blood flow is decreased by as much as 50%
• Metabolic clearance of some drugs is decreased by 20% to 40% (eg, amiodarone,
amitriptyline, warfarin, and verapamil)
• the effect of morphine is increased due to a decrease in clearance by
around 33%.
• increases in bioavailability can be seen with propranolol, levodopa,
calcium channel blockers, tricyclic antidepressants, and statins.

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Metabolism (2)
• Aging does not affect drugs that undergo phase II hepatic metabolism,
known as conjugation or glucuronidation, but conjugation is reduced with
frailty
Temazepam and lorazepam are examples of drugs that undergo phase II
metabolism

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Elimination
•

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Pharmacodynamic Changes (1)

❖ Cardiovascular System
• Decrease in arterial compliance and baroreceptor reflex response increase
susceptibility to orthostatic hypotension when taking drugs that affect the
cardiovascular system and lower the arterial blood pressure.
• tricyclic antidepressants, antipsychotics, loop diuretics, direct vasodilators, and
opioids.
• Older patients have a decreased β-adrenergic receptor function
• less sensitive to β-agonist and β-adrenergic antagonist effects in the cardiovascular
system and possibly in the lungs, but their response to α-agonists and antagonists is
unchanged

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Pharmacodynamic Changes (2)

❖ Central Nervous System
❑ The blood–brain barrier becomes more permeable as people age
• geriatric patients exhibit a greater sensitivity to the effects of drugs that
gain access to the CNS, especially anticholinergic medications
• lower doses result in adequate response, and higher incidence of adverse effects
may be seen with standard and high doses.
• For example, lower doses of opioids provide sufficient pain relief for older
patients, whereas conventional doses can cause over sedation and respiratory
depression
• Examples of problematic medications include benzodiazepines, antidepressants,
antipsychotics, neuroleptics, and antihistamines

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Pharmacodynamic Changes (3)

❑ a decrease in the number of cholinergic neurons as well as nicotinic and
muscarinic receptors, decreased choline uptake from the periphery, and
increased acetylcholinesterase.
Older adults have a decreased ability to compensate for these imbalances of the
neurotransmitters, which can lead to movement and memory disorders.
❑ Older adults have an increased number of dopamine type 2 receptors
making them more susceptible to delirium from anticholinergic and dopaminergic
medications
❑ Reduced number of dopamine and dopaminergic neurons in the substantia
nigra of the brain
higher incidence of extrapyramidal symptoms from antidopaminergic medications
(eg, antipsychotics)

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Pharmacodynamic Changes (4)

❖ Fluids and Electrolytes
• Fluid and electrolyte homeostatic mechanism is decreased in the older
adult population.
• The multitude of factors involved include decreased thirst and
cardiovascular reflexes, decreased fluid intake, decreased ability of the
kidneys to concentrate urine, increased atrial natriuretic peptide, decreased
aldosterone response to hyperkalemia, and decreased response to
antidiuretic hormone
• The result is an increased incidence of hyponatremia, hyperkalemia, and
prerenal azotemia, especially when the older patient is taking a diuretic
(eg, hydrochlorothiazide, furosemide)

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Pharmacodynamic Changes (5)

❖ Glucose Metabolism
• An inverse relationship between glucose tolerance and age has been
reported
• Due to an impaired autonomic nervous system, older patients may not
distinguish symptoms of hypoglycemia such as sweating, palpitations, or
tremors

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Drug-related problems
❑ Polypharmacy medication reconciliation
❑ Inappropriate prescribing Beers criteria
Benzodiazepines, 1st generation antihistamines, Tricyclic antidepressants,
NSAIDs
❑ Undertreatment
❑ Adverse Drug Reaction
• increase with polypharmacy use, and are the most frequently occurring
drug-related problem among older nursing home residents
❑ Non-adherence

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Case-1
• S.E., an 85-year-old woman, 5’ 2’’ and 102 pounds, with a serum
creatinine of 1.6 mg/dL, is admitted for chest pain and shortness of breath,
and to rule out myocardial infarction (MI). Her physician is concerned
about over sedation with narcotics and prescribes ketorolac 30 mg every 6
hours IV. She has a history of severe HF and angina for which she takes
lisinopril 10 mg daily, furosemide 40 mg daily, aspirin 81 mg daily, and
isosorbide mononitrate 30 mg daily. The lisinopril dosage is increased to
20 mg daily, and the furosemide dosage is also increased to 40 mg twice
daily. Her blood pressure (BP) is 110/66 mm Hg, and her urine output has
been 20 to 30 mL/hour for 4 hours since ketorolac was initiated. What risk
factors are present in S.E. for drug-induced renal problems?

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Therapeutic consideration during pregnancy

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pregnancy

Introduction (1)
• Human chorionic gonadotropin (hCG) can be detected in maternal urine 8
or 9 days after ovulation
• By day 10 post-fertilization, the blastocyst is implanted under the
endometrial surface and receives nutrition from maternal blood.
• Embryonic period (week 2-week 8)
• Week 8-until term ( 40 weeks) fetus
• Gravidity is the number of times that a woman has been pregnant.
• A multiple birth is counted as a single pregnancy.
• Parity refers to the number of pregnancies exceeding 20 weeks of
gestation and relates information regarding the outcome of each
pregnancy.

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pregnancy

Introduction (2)
• For example, in a woman who has been pregnant four times; has
experienced two term deliveries, one premature delivery, and one
spontaneous abortion would be designated G4P3
• Pregnancy lasts approximately 280 days (about 40 weeks or 9 months)
• Gestational age refers to the age of the embryo or fetus beginning with the
first day of the last menstrual period, which is about 2 weeks prior to
fertilization.
• When calculating the estimated due date, add 7 days to the first day of the
last menstrual period then subtract 3 months.
• Pregnancy is divided into three periods of 3 calendar months, each called a
trimester

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pregnancy

Pharmacokinetic Changes During

Pregnancy
• Maternal plasma volume, cardiac output, and glomerular filtration increase
by 30% to 50% or higher, potentially lowering the concentration of renally
cleared drugs
• Plasma albumin concentration decreases, which increases the volume of
distribution of drugs that are highly protein bound
• Hepatic perfusion also increases
• Activity of cytochrome P450 3A4, 2C9, and 2D6 is increased while that of
1A2 is decreased
• Nausea and vomiting, delayed gastric emptying, variable HCl secretion,
increased gastrin production alter absorption

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pregnancy

Transplacental Drug Transfer

• Affected by lipid solubility, electrical charge, molecular weight, and
degree of protein binding of medications
• Drugs with molecular weight greater than 1,000 Da, such as insulin and
heparin, do not cross the placenta in significant amounts.
• Lipophilic drugs, such as opioids and antibiotics, cross the placenta more
easily than do water-soluble drugs
• Maternal plasma albumin progressively decreases, while fetal albumin
increases
• Fetal pH is slightly more acidic than maternal pH, permitting weak bases
to more easily cross the placenta

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pregnancy

DRUG SELECTION DURING

PREGNANCY (1)
• Medication exposure is estimated to account for less than 1% of all birth
defects
• Birth defect affected by the stage of pregnancy during exposure,
medication route of administration, and dose
• first 2 weeks following conception, exposure to a teratogen may result in an
“all-or-none” phenomenon
• embryonic period exposure structural anomalies
• For the remainder of the pregnancy, exposure to teratogens may result in growth
retardation, central nervous system (CNS) abnormalities, or death

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pregnancy

DRUG SELECTION DURING

PREGNANCY (2)
• Examples of medications associated with teratogenic effects in the period
of organogenesis include
• chemotherapy drugs (eg, methotrexate and cyclophosphamide),
• sex hormones (eg, androgens and progestational drugs),
• lithium,
• retinoids,
• thalidomide,
• certain antiepileptic drugs, and
• coumarin derivatives
• Product labeling pregnancy subsection and lactation subsection
• Pregnancy category (A, B, C, D and X) should be removed except for
OTC medicines

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pregnancy

Preconception planning (1)

• to ensure optimal health and improve pregnancy outcomes
❑ Use of known teratogens
• Antiepileptic use the lowest possible dose
• Isotretinoin discontinue at least 1 month before attempting
• Oral anticoagulants switch to non-teratogenic anticoagulant (LMW heparin)

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pregnancy

Preconception planning (2)

❑ Life style factors
• Alcohol fetal alcohol syndrome
• Obesity neural tube defect, preterm delivery, DM, hypertension
• Tobacco use preterm delivery, spontaneous abortion, low birth weight, maternal
prenatal mortality

❑ Vitamins and Minerals Supplementation

• To meet proper nutritional requirements during critical periods of organogenesis
and fetal growth.

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pregnancy

Preconception planning (3)

❑ IRON REQUIREMENTS
• A woman needs about 18 to 21 mg of iron/day during pregnancy
• Prenatal vitamins usually contain 30 to 60 mg of elemental iron.
• Women with iron deficiency anemia should be given 60 to 120 mg of elemental
iron daily
❑ FOLATE REQUIREMENTS
• The most common major congenital abnormalities are neural tube defects (NTDs),
cleft palate and lip, and cardiac anomalies
• Folic acid supplementation of women substantially reduces the incidence of NTDs

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pregnancy

Preconception planning (3)

• Folic acid supplementation between 0.4 and 0.9 mg daily is recommended
throughout a woman’s reproductive years, since many pregnancies are unplanned
and may not be recognized until after the first month

• Women with previous NTD-affected pregnancies who plan another pregnancy

should take 4 mg/day of folic acid at least 1 month before conception and through
the first 3 months of pregnancy

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 Case-2
• S.C. is a 29-year-old, G1, P1 woman who is interested in becoming
pregnant. Her past medical history is significant for hypothyroidism. She
currently is taking levothyroxine 88 mcg by mouth daily. Provide
appropriate counseling to S.C. with regard to preconceptional care.

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