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CONTINUING MEDICAL CONTINUING

EDUCATION
CONTINUINGMEDICAL
MEDICALEDUCATION
EDUCATION

Akreditasi IDI – 3 SKP

Principles of Drug Use in the Elderly
Arini Setiawati
Dept. of Pharmacology and Therapeutics, Faculty of Medicine,
University of Indonesia, Jakarta, Indonesia

ABSTRACT
There is a multitude of problems in prescribing drugs for elderly (> 60 years) patients caused by pharmacokinetic changes, pharmacodynamic
changes, and drug-disease interactions. Special precautions should be given, particularly to several commonly prescribed drugs among
elderly.

Key words: pharmacodynamic changes, pharmacokinetic changes, drug-disease interactions

ABSTRAK
Terdapat beberapa masalah yang harus diperhatikan pada penggunaan obat di kalangan lanjut usia mengingat telah terjadinya perubahan
farmakokinetik, farmakodinamik, dan interaksi obat-penyakit. Beberapa hal perlu diperhatikan secara khusus, terutama untuk obat-obat yang
sering digunakan oleh para lanjut usia. Arini Setiawati. Prinsip-Prinsip Penggunaan Obat di Kalangan Lanjut Usia.

Kata kunci: perubahan farmakokinetik, perubahan farmakodinamik, interaksi obat-penyakit

INTRODUCTION 1. Oral absorption 4. Drug distribution
There is a multitude of problems in prescrib- In the elderly, gastric acid secretion decreases, There are several factors involved in drug dis-
ing drugs for elderly (> 60 years) patients. the resulting increase in gastric pH causes de- tribution changes in the elderly:
crease in dissolution and absorption of several • The elderly tends to have less total body
1. In normal aging, physiologic functions de- substances (i.e: ketoconazole, itraconazole, water, causing less volume of distribution of
crease, causing a decline in the homeostatic and iron). Other changes are lower intestinal some water soluble drugs (e.g. ethanol, ci-
reserve. Changes in physiologic function also absorption area (around 20-30%), lower gas- metidine, gentamicin), leading to increase in
alter pharmacokinetic and pharmacodynamic trointestinal blood flow (estimated 40%) and plasma concentration.
profiles of certain drugs, while lowered ho- lower gastrointestinal motility. Lower active • Less lean body mass leads to lower vol-
meostatic reserve alters drug response. Both transport causes lower absorption of several ume of distribution of digoxin from 25% up
changes in pharmacologic profile and drug substrates that need active transport mecha- to 50%, causing higher plasma concentration,
response will cause an increase in adverse nism such as calcium, iron, vitamin B1, vitamin and thus loading dose needs to be lowered.
drug events in the elderly. B12, I-dopa. • Increasing total body fat (18%-36% for
2. Elderly patients have multiple diseases, male, 33%-45% for female) may affect volume
requiring multiple medications, which cause 2. Transdermal absorption of distribution of some fat soluble drugs (such
a lot more drug-drug interactions. In the elderly, hydration and lipid content of as thiopental, diazepam, chlordiazepoxide,
3. Atypical disease presentation in elderly stratum corneum become less, causing lower and clobazam). These changes lead to longer
patients causes wrong diagnosis, leading to percutaneous absorption and lowering the elimination half life.
wrong medication. bioavalibility of relatively hydrophilic com-
4. Adverse drug events in the elderly may be pounds e.g. hydrocortisone, aspirin, caffeine, 5. Plasma protein binding
misinterpreted as a new medical problem, for and benzoic acid. • The elderly have less (6-20%) plasma alb
which another drug is given, this may cause umin. It will decrease protein binding of acidic
additional adverse event, requiring another 3. First pass metabolism drugs with high protein binding e.g. phenylb-
drug, and a prescribing cascade is developed. Hepatic blood flow decreases, thus it may utazone, salicylate, phenytoin, warfarin, valp-
increase the bioavailibility of certain drugs roic acid, naproxen), leading to increase in free
PHARMACOKINETIC CHANGES with high HE (hepatic extraction) such as (active) drug concentration (> 50 – 100%).
There are several pharmacokinetic changes labetalol, metoprolol, propranolol, CCBs, and • While plasma albumin becomes less,
that occur in the elderly: morphine. plasma α1-acid glycoprotein in the elderly in-

Alamat korespondensi email: makhyan.jibril@gmail.com

CDK-211/ vol. 40 no. 12, th. 2013 887

cimetidine. HCT. acting CCBs have been shown to be more acting benzodiazepines for elderly. the elderly are drugs in the elderly patients. furosemide. kidney physiological changes: low renal mass increase adverse reactions of anticholinergics: also cardiovascular reflexes decreased in the (decreases by 25%-30%). CYP2C19. Hepatic metabolism lead to pharmacodynamic changes of certain • Along with aging process. reduced. clonazepam. therefore close monitoring For ClCr < 25 mL/min: if the calculated dose 2. 40 no. and elderly. is uncommon. it is recom- (1%/year decline after 40 years old). Cardiovascular drugs less sensitive to induction of these enzymes: • Decrease in β-receptor response. urinary retention.g. (e. elderly patients may undergo 3 • High sensitivity to anticholinergics may ACEIs leads to higher plasma concentrations. CONTINUING MEDICAL EDUCATION creases. This formula is for rough estimation only. No activity. CCBs. 2013 . and ministration may be more appropriate. analgesic effect in. Anticoagulants of antiarrhythmic concentration is needed. also decreases. causing lower clearance meperidine in the elderly. The clearance decreases. No change in short-acting nifedipine. lithium. Long quinidine). 3. Renal excretion pertensive effect of verapamil and diltiazem. No change in heparin sensitivity in the elderly centration. creases. maintenance dose of digoxin may need Use of NSAIDs may increase risk of hyper. Titrate the dose to therapeutic ef- There are several physiologic changes which fect. Long- nitidine. therefore close monitoring is needed Elderly tend to have low clearance and low in NSAIDs administration. cisplatin. there- as digoxin. mon problem in the administration of cardio- ClCr = 0. therefore titrate to the lower doses. and use short ticoagulant effect of warfarin. farin. including postural hypotension. it must be followed by close increases the free concentration of warfarin. Analgesics & NSAIDs ter to reduce initial dose of α-blockers. and cause decrease in free (active) drug con. CYP3A3/4. atenolol). ra. lead. aminoglycosides. since its usage may acting benzodiazepines instead. dosage which will decrease the adverse drug re- tabolizing enzymes. These 3 changes will affect certain drugs There are some commonly prescribed drugs • α-blockers which are eliminated by renal excretion (such in the elderly: To avoid risk of first dose hypotension. therapeutic index of antiarrhythmics. duced hypotension risk and more convenient rate. 10-15%). plasma concentrations of CCBs half life of these drugs (e. • Low baroreceptor activity may increase actions. it is bet- as ACEIs. alfentanyl. risk of first dose hypotension. effective in the elderly. temazepam. and decreases in the amount of drug • Low diuretic response decreases diuresis • β-blockers metabolized by liver enzymes. rate. therefore titrate the dose based on INR. PHARMACODYNAMIC CHANGES is reported. In the elderly. Studies • Diuretics CYP1A2. heparin sensitivity was reported. Avoid • Low liver blood flow (decreases by 35%) risk of postural hypotension in response to using diuretics in patients with hypokalemia leads to lower liver perfusion (decreases by antihypertensive agents. may be higher. • Antiarrhythmics may be used: orrhage. Elderly may have lower Vd of digoxin. therefore smaller dose ad- theophylline. therefore diuretics can be used in low leads to decrease in total amount of drug me. th. showed that these changes lead to less tachy. 12. In the elderly. es analgesic effect of fentanyl. • ACEIs 7. vascular drugs to the elderly. for the patient. monitoring of serum drug concentration. digoxin. warfarin. but dosage adjustment fore loading dose of digoxin may need to be bleomycin. metformin. • Digoxin For drugs with narrow therapeutic index such Hepatic metabolism of acetaminophen is re. II) with high and low hepatic extraction. It is estimated 888 CDK-211/ vol.g. which in- crease the toxicity. increase risk of CV mortality.8 x → Subtherapeutic dose tidine increases plasma concentration of war. CYP2C9. barbiturates. lidocaine. due to the • High sensitivity to warfarin increases an. Cockcroft & Gault equation kalemia. low renal blood flow dementia. Due to the low glomerular filtration ment (DM) based on ClCr is needed. and prolonged elimination half life. For po. Avoid using barbiturates and long morphine. Due to the low clearance of morphine and acting α-blockers have 2 known benefits: re- lithium. and low faster heart rate. and death from GI hem. Postural hypotension is one of the most com- For ClCr > 100 mL/min: if the calculated dose While concomitant use of warfarin with cime. propranalol. renal failure. Diuretics are most effective in patients with low • Low liver mass (liver weight decreases by cardia in response to isoproterenol and less renin hypertension. but the response • Decreased liver enzymes will affect drugs • High sensitivity to benzodiazepine in. Based on these factors. thus adjust the dose based on metabolized by liver enzymes (phase I & phase creases sedation effect of certain drugs such BP and heart rate. and • CCBs (Calcium Channel Blockers) ing to lower clearance and longer elimination nitrazepam. aminoglycosides. This will lead to higher protein bind. 6. as diazepam. change in α-receptor response was observed. and imipramine). effect of furosemide. duced in the elderly. • High brain sensitivity to narcotics increas. • High sensitivity to CCBs increases antihy.2 x → Toxic dose Anticoagulant effects of warfarin increase in the elderly. constipation. and melphalan. benzodiazepines. (its prevalence increases in the elderly). but avoid the use of prolonged duration of action. decreased renal clearance of In general. to be reduced too. concomitant use with phenylbutazone ing of basic drugs with high protein binding tentially toxic drug. ClCr = 2. 1. To estimate ClCr.5 – 0. mended to lower initial dose of ACEIs to avoid glomerular filtration rate (decreases by 35%). The elderly have low renin 20-50% and liver volume decreases by 25%) bradycardia in response to propranolol. dosage adjust.

antidepressants.321(5):303-9. lidocaine. 5. antiarrhythmics. Wait at least 3 half-life before increas- elderly due to their prolonged duration of ac. Many drugs commonly prescribed for drugs. 6. nifedipine. other than undergo physiological cluding OTC drugs). Int J Clin Pharmacol Ther Toxicol. patient with advanced cancer: patients with age of these drugs. and the interactions with existing dis- Hypnotics use is recommended only for few leading to increased concentration of drugs ease and drug. increasing the oral bioavailibility associated with less cardiovascular and anti. know the patients’ medical history completely Choices of antihypertensive agent for the el. once or twice daily). Vestal RE. lorazepam) perience respiratory depression. Management of drug therapy in the elderly.33(4):302-12. Mayo Clin Proc. since cacy correlates with age). Therefore it is very important to (such as anticholinergics. act with drug administration. Fleming KC. Provide falls and trauma. I-dopa. Drug prescribing for elderly patients. 2. caffeine. it is recommended to give low fects may change with aging process. be cautious ulcer. There are many other diseases that may inter- tural hypotension are α-blockers. Kinirons MT. but have higher CNS sensitivity. such as peptic adrenergic neuron blockers. LOW) • Patients with benign prostate hyperplasia 6. • Antidepressants changes. then titrate upward. For example. Vestal RE. Geriatric pharmacology. drug-induced disease). In: Melmon KL. nitrates. tively safer than TCADs. Other than drugs mentioned above. sion (sedation & confusion) which may lead to nary disease (COPD) who received β-blockers 8. of drug-disease interactions: 4. Gurwitz JH. and because the el. g. Be alert to the possibility of drug reactions triazolam. 40 no. and if they receive ing dose (GO SLOW). Titrate drug dosage to therapeutic re- Barbiturates are not recommended for the who receive anticholinergics will experience sponse. Record a complete history of drug use (in- dose at bedtime. Tsujimoto G. Simplify the therapeutic regimen (reduce lower urinary flow. • Elderly with dementia who receive one of drugs. indomethacine) may lism. Be familiar with the pharmacological of plicated than other antideppressants. • Chronic heart failure or chronic liver dys. Montamat SC. antihypertensives [β-blockers. New York: McGraw-Hill. 1989. CDK-211/ vol. sertraline seems to tration. g. each day. there are 10 principles of drug leads to higher risk of adverse effects of these therapy in the elderly: drugs. oxazepam. In summary. use smaller initial doses (START rebound may occur. these drugs have central anticholinergic effects. Clinical pharmacokinetic considerations in the elderly: An update. 4. Regularly review treatment plan. initial dose. espe.g. other antipsychotics. Psychotropic drugs elderly. Other than drug-disease interaction. Morrelli HF. CONTINUING MEDICAL EDUCATION that 20% of persons > 65 years and 30% of that elderly may have low clearance of drugs. decongestants (α-agonists). the drug prescribed. phenothiazines. in case of felodipine). digitalis. derly are diuretics (low renin) and CCBs (effi. Pharmacokinetic and pharmacodynamic principles of drug therapy in old age. less than 66 years old tend to have higher risk • TCADs of oversedation. and dis- • Other things that need to be known are opiates. Clin Pharmacokinet. 2013 889 . Elderly. higher urinary retention. steroids. Pattern of drug side ef. with low initial dose and titrate up slowly. phenothiazines and before prescribing any medication. 1997. take at the same time of Benzodiazepines cause excessive CNS depres. persons > 75 years experience postural hy. tion will lead to higher risk of adverse events. th. antihistamines H1. N Engl J Med. 4th ed. charcoal grilled meat and • Antipsychotics the elderly (e. tions. 5. then it should be tapered off because with high hepatic extraction (e. when giving drugs with anticholinergic activity hypertension. 2000. Nierenberg DW.70:685-93. cyclosporin. Hoffman BB. imi. P3A4 substrates (e. Hoffman BB. g. which may interact with drug adminis. 1995. Haloperidol is cially for CNS side effects. they receive narcotic analgesics they will ex. weeks. and if suitable preparation and container. Chapter 21. ACEIs. and interactions with disease states and other are best because causing less adverse events. Other example is naringin (in grapefruit derly are vulnerable to adverse effects of this also cause depression. opiate analgesics). Evans JM. juice) that may block the metabolism of CY- class of drug. pramine). benzodiazepines. chronic renal insufficiency. 3.80:1302-10. but patients older than 66 years SUMMARY TCADs metabolism is lower in the elderly. Cusack BJ. editors. and medium-acting benzodiazepines (e. 1997. Some cases below are few examples 3. cholinergic adverse effects. Encourage treatment adherence. there are which will cause cognitive impairment in the several food that may interact with certain 4. Known iatrogenic causes of pos. In general. • Elderly with chronic obstructive pulmo. benzodiazepines. Make an accurate diagnosis (beware of Antidepressants for the elderly: SSRIs are rela. and paracetamol metabo- give variable responses. Short. old may have higher risk of delirium. cruciferous vegetables may increase theo- Antipsychotics usage in the elderly tends to reserpine]. 10. will suffer from bronchoconstriction. Vestal RE. REFERENCES 1. number of drugs. Hashimoto K. Crome P. 1989. 9. including hip fracture. Melmon and Morrelli’s clinical pharmacology: Basic principles in therapeu- tics. from delirium. temazepam. TCADs. ARBs. and antipsychotics. It is recommended to give lower initial DRUG-DISEASE INTERACTIONS 1. therefore start potension.g. aging. may also develop diseases related to 2. Aging and pharmacology. Evaluate the need for drug therapy be the better choice because it is least com. Cancer. phylline. For example. diabetes. Mikkelson KG.27(1):3-26. habits and diet. these drugs: anticholinergics. the age related altera- • Hypnotics function will decrease hepatic blood flow. levodopa will suffer continue drugs that are no longer needed. they will have 7. resulting in increased drug toxicity. Chutka DS. e. TCADs. 12. diuretics.