GUIDLINES TO CONSIDER WHEN PRESCRIPNING ANALGESICS AND ANTIBIOTICS FOR ELDERLY IN DENTAL PRACTICE

1. ‫’’“بسم ال الرحمن الرحيم‬
‫غافر‬

2. Clinical PK consideration in
elderly
By
Dr. Ahmed Shaker
Ali
Dept of pharmacology
Faculty of medicine
Ahmedshaker21@ yahoo.
com
Bl 7. G751 Ex. 22330
5th yr dental 11 -2-1434

3. An elderly with renal impairment , what the appropriate
regimen of Augmentin ?
Leaflet of the drug mentioned
Patients with impaired renal function do not generally require a reduction in
dose unless the impairment is severe. Severely impaired patients with a
glomerular filtration rate of <30 mL/min. should not receive the 875-mg
tablet. Patients with a glomerular filtration rate of 10 to 30 mL/min. should
receive 500 mg or 250 mg every 12 hours, depending on the severity of the
infection. Patients with a less than 10 mL/min. glomerular filtration rate
should receive 500 mg or 250 mg every 24 hours, depending on severity of
the infection.
Hemodialysis patients should receive 500 mg or 250 mg every 24 hours,
depending on severity of the infection. They should receive an additional
dose both during and at the end of dialysis.

4. How about Voltaren ?
Special Populations
Hepatic Insufficiency: Hepatic metabolism accounts for almost 100%
of Voltaren elimination, so patients with hepatic disease may require
reduced doses of Voltaren compared to patients with normal hepatic
function.
Renal Insufficiency: Diclofenac pharmacokinetics has been
investigated in subjects with renal insufficiency. No differences in the
pharmacokinetics of diclofenac have been detected in studies of
patients with renal impairment. In patients with renal impairment
(inulin clearance 60-90, 30-60, and < 30 mL/min; N=6 in each group),
AUC values and elimination rate were comparable to those in healthy
subjects.
BUT elderly are more predisposed for ADE specially renal impairment

5. OBJECTIVES
– To optimize use of drugs in elderly
TOPICS
– Introduction
– Reduced renal function with aging
– Assessment of renal function
– Dose adjustment in renal impairment
– Liver disease
– Other PK variables

6. Elderly may suffer one or more chronic disease
Multiple Diseases – ASHD
– CHF – Diabetes Mellitus
– COPD – Osteoporosis
– CRF
– DJD
– Chronic liver disease
– Dementia – Others

7. Aging is associated with normal
changes
Relative increased in fat ?
Decreased bone density
Decreased muscle
Decreased water content
– Ref: Cefalu CA. Clinical Pharamcology. In: Burke MM &
Laramie JA. Primary Care of the Older Adult. 2000, p. 90.

8. Normal Physiological Changes of the
Organ Systems
Liver- decreased blood flow;
Decreased Phase I Metabolism
Kidney- decreased creatinine clearance with
advanced age
CNS-increased risk of confusional states primarily
secondary to anti-cholinergic agents
Intestinal tract-- malabsorption-- not clinically significant
in absence of disease

9. Normal Changes of Aging-Hepatic
Phase I Metabolism-rate of metabolism
slows (oxidation, reduction, hydroxylation)
Phase II Metabolism-rate stays the same
(conjugation with glucronic acid, sulfation
methylation, acetylation)
– Examples-benzodiazepines
» Short acting-Phase II only-appropriate
» Long acting-Phase I and II-inappropriate, long half-lives
Reference: Beers MH. Medication Use in the Elderly. In: Calkins ,
Ford & Katz, 1992, p. 40.

10. Normal Changes of Aging :-Renal
Age-related reduction in renal blood
flow and creatinine clearance in the
face of a normal BUN and serum
creatinine:
Implications-
– Adjust dose of renally excreted drugs
with age according to creatinine
clearances (Clcr ) for certain drugs

11. Degree of renal impairments
for prescribing purposes
GFR : Ml/min renal impairment
20-50 mild
10-20 moderate
< 10 severe

12. Nephrotoxic drugs
1) Pre-renal
NSAIDs even short courses– renal
under- perfusion
ACE inhibitors ( angiotensin converting
enzyme ) in patient with compromised renal
perfusion

13. Nephrotoxic drugs cont
2) Intrarenal damage :
Glomerunephritis : Captopril, antibiotics
including pencillins , sulphonamides and
Rifampicin
Interstitial nephritis : Penicillin,
cephalosporines, NSAIDs and Rifampicin
Direct toxicity to renal tubules : aminoglycosides,
amphotercin, Cyclosporine A

14. Nephrotoxicity Cont
3-Biochemical changes :
Excessive vit D replacement : hypercalcemia –
precipitates or exacerbate renal impairment
Other : Cefixime rare cases
NSADs ; Analgesic
Analgesics :
nephropathy
Analgesic nephropathy have been most
commonly seen with combination analgesics that
contain aspirin and or Paracetamol

15. GFR & CKD
GFR is a direct measurement of kidney
function and reduced before the onset of
symptoms of kidney failure.
A decrease in GFR correlates with the
pathogenic severity of kidney disease.
Replacement therapy with dialysis or
transplantation becomes necessary when
the GFR decrease below 15mL/min/1.73m2.

16. (GFR tests).
Serum Creatinine : (Scr)
 Simple.
Χ Misleading .
Χ Scr may remain constant although GFR decline
specially in elderly.
Χ Several variables : age, diet ,muscle mass etc

17. (GFR tests).
Urine collection (24h)
[Urine Cr] X Volume (ml)
24Cr Cl=
[Serum Cr] X Time 1440 min?

18. Disadvantages of 24 hr urine
collection
ΧTime consuming
ΧErrors in collection time / volume
ΧTroublesome to both patients & Lab
ΧMay over estimate GFR by 10-30 %
ΧEffect of drugs ??

19. Estimating creatinine clearance
Cockcroft & Gault equation
(modified )
Men: CrCl = 1.23 x (140 – Age) x Wt
SrCr
Women: CrCl = 1.04 x (140 – Age) x Wt x
SrCr
CrCl = Creatinine clearance (ml/min)
Age (Years)
Wt = Weight (kg)
SrCr = Serum creatinine (micromole/L l)
Ref: Ref: Cefalu CA. Clinical Pharmacology. In: Burke MM & Laramie JA.
Primary Care of the Older Adult. 2000, p. 92.

20. Adjust Dose: GFR < 50 ml/min*
Antimicrobials Cardiovascular
Acyclovir Methyldopa
Amantidine Most ACE Inhibitors*
Aminoglycosides Atenolol, Nadolol, Sotalol
Amphotericin Digoxin
Aztreonam Procainamide*
Cephalosporins (many) Others
Imipenem
Lithium
Penicillins (most)
Meperidine*
Quinolones (most)
Acetaminophen**
Sulbactans
H2 Blockers (most)
Sulfonamides
Albuterol
Tetracycline**
Glyburide
Vancomycin Insulin *Refer to
Methotrexate detailed
protocols

21. Clinical significance of renal
impairment
Prolonged half life (T1/2) is common
T1/2 = 0.693 x Vd
Cl
Longer dosing interval should be considered for
drugs which depends mainly on renal
elimination
Longer time is required to
1. Attain steady state
2. Or until body is drug-free in case of toxcicity

22. Methods of dose adjustment in renal impairment
If mild , drug has wide therapeutic range
usually no need to adjust the dose
• If moderate or severe , or the drug has
narrow therapeutic range , appropriate
adjustment is essential
• A- reduce the dose keep dosing interval as
normal
• B- normal dose but Longer dosing interval

23. Factors affecting drug metabolism
Main site of drug metabolism = LIVER
 Drug metabolism can be affected by:
1. First pass effect
2. Hepatic blood flow
3. Liver disease
4. Drugs which alter liver enzymes

24. Factors affecting drug metabolism
I. Genetic factors
e.g acetylation status
I. Other drugs
o hepatic enzyme inducers
o hepatic enzyme inhibitors
I. Age
Impaired hepatic enzyme activity
o Elderly
o Children < 6 months (especially premature babies)

25. Enzyme Inducing Drugs
Phenytoin
Phenobarbitone
Carbamazepine
Rifampicin
Griseofulvin
Chronic alcohol intake
Smoking

26. Enzyme Inhibiting Drugs
Inhibit the enzymes which break down
drugs
Decreased rate of drug breakdown
Smaller dose of affected drug needed to
produce the same clinical effect

27. Enzyme Inhibitors
Erythromycin Oral contraceptives
Ciprofloxacin Sodium valproate
Metronidazole Cimetidine
Chloramphenicol Omeprazole
Sulphonamides Calcium channel blockers
Acute alcohol Amiodarone
Allopurinol Dextropropoxyphene
Phenylbutazone Fluconazole
Isoniazid

28. Drugs subjected to Hepatic Metabolism
NSAIDs; Aspirin Ca channel blockers
Acetaminophen Alpha blockers
Erythromycin Statins
Ketoconazole Dilantin
Tetracyclines Valproic acid
Lidocaine Carbamazepine
Metoprolol Tricyclic Antidepres
SSRIs Neuroleptics

29. Pharmaceutical Agents That Require
Hepatic Metabolism
Benzodiazepines
Cimetidine
Ranitidine
Famotidine
Terfenadine
Proton pump inhibitors
Schwartz JB. Clinical Pharmacology. In:
Hazzard WR et al. Principles of Geriatric
Medicine and Gerontology, 4th Ed., 2000, p. 309-
319.

30. The Cytochrome System
CYP1A2
CYP2C
CYP2D6
CYP3A
– Involves Model Compounds, Drug Substrates,
Inducers, and Inhibitors
– Ref: Schwartz JB. Clinical Pharmacology. In:
Hazzard WR et al. Principles of Geriatric Medicine
and Gerontology, 4th Ed., 2000, p. 308.

31. Particular Agents of Concern in the
Elderly-highly bound to protein
Phenytoin
Carbamazepine
Barbiturates
Warfarin
Malnutrition or hypoproteinemia is associated with
increased free fraction of drug and increased toxicity
Ref: Physicians Desk Reference, Medical Economics-
Thomson Healthcare,55th Edition, 2001, p. 2427.

32. Physiological changes of the GI Tract
Stomach- little change in gastric acidity with aging. In
presence of dsyphagia and H2 blocker therapy, may
increase risk of morbidity and mortality from pneumonia
(bacteria more viable after aspiration due to reduced
acidity)
Decreased GI motility and blood flow-- increased
frequency of constipation
– Ref: In: Hall KE, Wiley JW. Age-Associated Change in
Gastrointestinal Function. In: Hazzard WR et al. Principles of
Geriatric Medicine and Gerontology, 4th Ed., 2000, p. 835-842.
–

33. NSAIDs*:
Can Worsen HBP- removal of NSAID can affect mean
blood pressure control
Fluid retention
Worsen CHF
Cause confusion
GI bleeding
Newer Cox-2 agents, gastric sparring
Less risk of Alzheimer's and cognitive decline
*In high doses or used chronically
Ref: Carson JL & Strom BL. Use of Nonsteroidal Anti-Inflammatory Drugs.
In: Hazzard WR et al. Principles of Geriatric Medicine and Gerontology, 4 th
Ed., 2000, p. 1113-1119; Stewart WF et al. Risk of Alzheimer’s disease and
duration of NSAID use. Neurology, 48, 1997, p. 626-632.

34. “Tips” for Safe Traditional
NSAID Use
Substitute acetaminophen when possible instead
of NSAID
Guide the patient to avoid misuse of
acetaminophen.
Use PRN when possible
Use lowest dose possible
Use for acute flare for 7-10 days then d/c
When necessary for chronic use, insist on routine
q 3 month. RFT &LFT & and CBC
Consider institutional changes to allow relatively
safe analgesics

35. ‫.‬ ‫المقامة اليمانية لصفات الصادقين‬
‫ال صا دق في إيمانه‬
‫ّ ِ‬
‫يؤمن بالله وملئكته وكتبه ورسله واليوم الخر والقدر خيره‬
‫وشره‬
‫يحب الرسول ويطيعه فيما أمر ويحب أصحاب رسول ا جميعا‬
‫وكذلك أمهات المؤمنين وأهل بيته أجمعين . يعتقد أنهم خير‬
‫القرون ويعرض عما يروجه أهل الضلل من شبهات وظنون .‬
‫عقيدته التباع وترك البتداع . يؤمن بان ا أتم نوره وأكمل‬
‫دينه ورضي السلم دينا‬
‫وان القوانين الوضعية منبوذة وضيعه وانه ل يصح إيمان من‬
‫عادى أو عطل الشريعة .‬
‫يوقن إن الشرك أعظم الظلم وان ا ل يغفر أن يشرك به‬
‫ويغفر ما دونه من الذنوب .‬
‫ل يدعو مع ا أحدا ول يستعن بسواه ول يسال غيره قضاء‬
‫الحوائج وتفريج الكروب .‬
‫يحب في ا المؤمنين ويبغض في ا الكفار والمنافقين .‬
‫يكثر من النوافل ويحافظ على الفرائض - يشهد الجماعات -‬
‫ويسارع في الخيرات .‬
‫يعظم القرءان ف يتعلم ه ويعلمه – ويتدبره ويعمل بمحكمه‬

36. ‫.‬‫المقامة اليمانية لصفات الصادقين‬
‫نظره اعتبار وصمته فكر وكلمه خير وذكر -ل ينشغل بما ل‬
‫يعنيه ول يطلب فوق ما يكفيه .‬
‫أ ذا ابتلى صبر و إذا أعطي شكر و إذا س ئ ل بذل و إذا عز تواضع‬
‫َِ‬ ‫ُِ َ‬ ‫َِ‬ ‫َِ‬ ‫َ‬
‫و إذا تولى أمرا رفق .‬
‫َِ‬
‫موقر للكبير رحيم بالصغير – يوف بالعهد أمين – ويسعى على‬
‫اليتيم والمسكين‬
‫تراه دوما حليما وإذا مر باللغو مر كريما .‬
‫يحرص على هدى وسنة محمد صلى ا عليه وسلم خير النام –‬
‫ويصل الرحام ويفشى السلم – ويطعم الطعام ويصلى والناس‬
‫نيام .‬
‫– يأمر بالمعروف وينهى عن المنكر ويجاهد بماله ونفسه في‬
‫سبيل ا متبعا للشريعة - ول يسب أهل الكفر والضلل‬
‫والجاهلين سدا للزر يعه .‬
‫علم أن صلح القلب هو أصل صلح الجسد - فلم يحمل في‬
‫قلبه حقدا ول حسد –‬
‫و علم إن العمال بالنيات - فتحرى الخلص وداوم على‬
‫سؤال ا العون على الثبات .‬
‫لم تغره زخارف دار ا لغ رور عن أحوال القبور و أهوال ي وم‬
‫َ ْ‬ ‫َ‬ ‫ْ ُ‬ ‫َ‬