DRUG THERAPY IN ELDERLY

classification >65 years

65- 75 – young old

Up to 85 – old old

> 85 - very old

Reasons for considering drug therapy in elderly as a specific group

Physiological and pharmacological changes in elderly Elderly consume good portion of health expenditure ADRs more common in elderly Polypharmacy more (multiple diseases): drug interactions

more Increased error in taking medicines Frailty, poor appetite and nutrition, forgetfulness,visual

impairment, lack of self care, lack of supervision, financial problems

Physiological changes Changes in body composition : lean body mass, body size, body water,bone density, albumin AND Increased

body fat & α1 acid glycoprotein

GIT : gastric acidity,Delayed gastric emptying time, in GIT & liver blood flow.

RS : in total vital capacity & bronchial ciliary function CVS : in baroreceptor activity,COP & myocardial sensitivity to

beta agonists/antagonists Renal : GFR,renal blood flow& tubular secretion NS : Cognition defects,Reduction in central NTs, Impaired

cerebral autoregulation

Physiological changes contd…. GU : Prostate hypertrophy in males,Vaginal

atrophy and menopause in females Endocrine : Increased incidence of DM & thyroid

disorders Musculoskeletal : Reduction in muscle mass ,Power &

Joint flexibility.

Pharmacological changes

Pharmaceutical factors Pharmacokinetic changes Pharmacodynamic changes

Pharmaceutical factors Difficult to swallow Tab , Capsules Easy to swallow syrups, suspensions Medicines should be in easily opened containers Labelling in large print , clear

Pharmacokinetic factors Absorption : Drugs absorption from intestine is slow

( decreased motility & decreased blood flow)

Distr ibution : Increase in free acidic drugs (decreased plasma albumin & decrease in free basic drugs (increased α1 acid glycoprotein). Lipid soluble drugs accumulate more (body fat more in elderly)

Metabolism : Enzyme activity in liver decreasedoral bioavailability of drugs with high first pass metabolism increased.

Excretion : Excretion of drugs decreased (renal function reduction). Dose of drugs excreted through kidney has to be reduced.

Excretion Cockcroft-Gault formula Creatinine clearance ml/mt = (140-age)× wt(Kg) 72 X S.Creatinine Females – multiplied by 0.85

Pharmacodynamic factors Reduction in receptors Reduced sensitivity of receptors

ADRs peculiar to elderly

Treatment of HTN often results in postural hypotension, falls, injury (cerebral autoregulation deficient, peripheral autonomic responses sluggish in response to hypotension)

Diuretics lead to hypokalemia & can lead to digitalis toxicity if co-administered.

Brisk diuresis can lead to A/c urinary retension in old men with BPH

Precipitation of gout with diuretics Confusion precipitated with anticholinergis/antihistaminics Use of antipsychotics can lead to parkinsonism for which elderly

are more prone Greater incidence of peptic ulcer with NSAIDs(due to decreased

clearance of NSAIDs)

Constipation precipitated by anticholinergics / opioids / antipsychotics

CNS drugsSedative hypnotics

Prolongation of half life of benzodiazepines, barbiturates (due to decreased metabolism-excretion)

Half l i fe of Lorazepam,Oxazepam less affected. Hence preferred over Diazepam, barbiturates

Side effects like ataxia, motor incoordination to be looked for while prescribing these drugs.

CNS drugsOpioid analgesics

Elderly sensitive to respiratory depression due to decreased respiratory reserve.

Morphine, codeine use justified in chronic painful conditions but with caution

CNS drugsAntipsychotics

Classical antipsychotics associated with EPS & can worsen Parkinsonism if present.Their Anticholinergic effects can worsen BPH, AD if present. Alpha blocking property (CPZ) can cause orthostatic hypotension Atypical antipsychotics (eg :Olanzapine,Aripiprazole) preferred.

Antidepressants Avoid TCA with anticholinergic S/E ( Preferred – Nortriptline, Desipramine)Safe - SSRI

CNS drugs

AntimaniaLi excreted by kidney. Doses in elderly should be adjusted depending on kidney function.Thiazides reduce Li clearance. Li doses should be reduced further in presence of thiazides.

Carbamazepine, Valproic acid preferred over Li

CVSAntihypertensives

Thiazides are 1st step in Rx of HTN. Low doses are used because of higher incidence of arrhythmias, DM, gout in elderly. (hypokalemia, hyperglycemia, hyperuricemia are S/E of thiazides)CCBs are safe & useful if angina is coexistentB blockers less useful unless heart failure present. Can be dangerous in COPD patients. Can cause bradycardia in elderly.ACEI less useful unless DM/heart failure presentCheck for orthostatic hypotension in all elderly receiving antihypertensives

CVSCardiac glycosides

Digoxin - half life increased as Clearance decreased (decreased renal function). Hence digoxin dose to be adjusted according to kidney function.

Elderly more sensitive to digoxin induced arrhythmias & Extra cardiac side effects

cvs

Antiarrhytmics Avoid Disopyramide due to its anticholinergic effects & negative inotropic effects.Reduce dose of Qunidine, Lignocaine (as their excretion through kidney reduced)

Antiinflammatory drugs

NSAID – GI bleeding, renal damage Steroids – Osteoporosis

Antidiabetics

Chlorpropamide, Glibenclamide not used –hypoglcemia highGlipizide, Gliclazide – used Metformin Nateglinide

Antibiotics

Penicillin, Cephalosporin,Nitrofurantoin, FQs, Aminoglycosides --- dose adjusted

Tobramycin Ceftriaxone, Cefperazone

Principles of treatment in elderly Careful drug history Prescribe only for specific & rational indication Define the goal of therapy Start with lowest dose & titrate Avoid Polypharmacy If possible-One drug for two indications Avoid symptomatic treatment without specific diagnosis Choose the right dosage forms Financial problems – prescribe cheaper alternatives rule out non compliance/errors in taking drugs Watch for ADRs & drug interactions

Drug therapy in Pregnancy & lactation

Introduction Most drugs administered to mother can cause placenta and

affect the fetus Teratogenic affects are the important consideration while

prescribing during pregnancy History : Thalidomide disaster

USFDA drug categories in pregnancy

A Adequate studies in pregnant women, show no risk to fetus

Inj MgSo4, thyroxine, fol ic acid

B Adequate human studies lacking but animal studies show no risk to fetus OR adequate studies in pregnant women show no risk to fetus but animal studies have shown an adverse effect on fetus

Penicillin, Amox, erythromycin, paracetamol, lignocaine, cefaclor

C No adequate studies in pregnant women, animal studies are lacking/show adverse effect on fetus, but potential benefit may warrant use of the drug in pregnant woman despite the potential risk (RISK CAN’T BE RULED OUT)

Most drugs (morphine, steroids, adrenaline, bupivacaine, atropine)

D Evidence of fetal risk, but potential benefit may be acceptable despite potential risk (POSITIVE EVIDENCE OF RISK)

Aspirin, antiepileptics

X Studies in humans/animals show fetal risks. Absolutely contraindicated

Isotretinoin, estrogens, cytotoxic drugs

Examples of teratogenic effectsThalidomide Phocomelia

Methotrexate Hydrocephalus, cleft palate

stilboestrol Vaginal adenocarcinoma in teenage offspring

Tetracycline Bone & teeth abnormalities

Warfarin CNS & skeletal defects

Phenytoin Hydantoin syndrome

Carbamazepine NTD

Valproate Spina bifida

ACEI Renal tubular dysgenesis, oligohydramnios

Lithium Fetal goitre, Ebstein’s anomaly

Isotretinoin Craniofacial, CVS defects

Principles of prescribing in pregnancy

Wherever possible, use non drug therapy Prescribe drugs only when definitively needed As far as possible, avoid medication in the first trimester of

pregnancy Use lowest effective dose for shortest period & if possible

give drug intermittently Choose drugs having best safety record over time Avoid newer drugs unless safety is clearly established Discourage patient from self medication & OTC.

Prescribing for common problems during pregnancy

Nausea, vomit ing Reassurance, high carbohydrate diet, antihistaminic-antiemetic (diphenhydramine, doxylamine)

Heartburn Avoid fatty food/alcohol/smoking. Non systemic antacids & Metoclopramide

constipation High fibre diet, plenty of oral fluids, mild laxatives like milk of magnesia, bisacodyl

Safe & unsafe drugs for various disorders in pregnancy

SAFE NOT SAFE

ANTIMICROBIAL THERAPY

B lactam antibiotics, erythromycin base, nitrofurantoin, methenamine, nystatin, miconazole

erythromycin estolate (hepatotoxicity), Aminoglycoside, TC, Chloramphenicol, Co-trimoxazole, Sulfonamides, nalidixic acid, Griseofulvin, Ketoconazole, FQs

ANTITUBERCULAR DRUGS

INH, Ethambutol Rifampicin, Streptomycin

ANTHELMINTHICS

Metronidazole (low doses), Diloxanide, Chloroquine, Quinine, Piperazine, Pyrantel

Primaquine, mefloquine, Mebendazole

ANALGESICS

Paracetamol Aspirin , other NSAIDs

ANTIHYPERTENSIVESAlpha methyl dopa, CCB, labetalol B blockers, ACEI, ARBs

HEART DISEASESimilar treatment as non pregnant with Digoxin ANTICOAGULANTHeparin warfarin ASTHMAInhaled B agonists, inhaled steroids

DIABETES MELLITUS

Diet restriction, insulin if needed OHA

THYROTOXICOSIS

Propylthiouracil> carbimazole Radioactive iodine

EPILEPSY

PB , (Phenytoin) (supplement folic acd &vit K) Valproic acid, Carbamazepine

Other CNS drugs

BZD, Barbiturates, antidepressants,opioids (best avoided near term to avoid neonatal CNS depression)

Lithium

Prescribing during lactation Most drugs administered to lactating mother detected in

breast milk(in lower conc than maternal plasma) Ideally medicines to be taken 30-60 min after nursing or 3-4

hrs before next feed to allow time for many drugs to clear from mother’s blood.

Drugs for which safety during lactation not established should be avoided/breast feeding avoided during their use.Eg : Anticancer drugs, immunomodulators

Drugs excreted in high conc in breast milk & those which can cause adverse effects in infant : Tetracyclines, INH, Sedative-hypnotics, Opioids, Lithium, radioactive iodine

Drugs which are excreted in small amounts in breast milk but can cause adverse effects in fetus: Penicillin (hypersensitivity), sulfonamides(hypersensitivity, kernicterus, hemolysis in G6PD deficient infants)

Drugs that are safe : insulin, adrenaline(destroyed in gut of infant)

warfarin, caffeine, digoxin, propranolol, thiazides, spirinolactone, tolbutamide,

ACEI, Antihistaminics, Carbamazepine, Rifampicin, Pyrazinamide, Ethambutol, Nifedipine, Clavulanic acid (very low conc in milk…hence safe)