Dr AZZA ELSHERBINY Assistant professor of pharmacology

By the end of this lecture the student should be able to describe: 1-The changes in physiological functions in elderly 2-The changes in pharmacokinetics in elderly 3-Pharmacodynamics changes in elderly 4-Drug interactions in elderly 5-Changes in drug effects in elderly 6-Adverse drug reactions in the elderly 7-Practical aspects of geriatric pharmacology

GENERAL CONSIDRATIONS 1-An increasing number of adults ≥65 years are living with multiple health problems 2-There are more women than men among older population. 3-Among all persons ≥65 years of age, the five leading causes of death are heart diseases, cancer, stroke, chronic obstructive pulmonary diseases, influenza and diabetes 4-There is high incidence of adverse effects in elderly due to polypharmacy, reduced drug elimination, multiple disease states and ↑ drug sensitivity 5-Other problems in elderly are patient compliance, memory changes, hear loss and ↓ vision

PHARMACOKINETIC CHANGES IN THE ELDERLY -Physiological changes associated with aging, diseases and pharmacological factors can affect pharmacokinetic parameters. These changes can alter drug response

Absorption: Can be affected due to physiological changes:- 1-Delayed gastric emptying rate 2- ↑ Gastric pH 3- ↓ splanchnic blood flow 4- ↓ absorptive surface 5-Impaired intestinal motility

Disease states:- e.g. 1-Achlorhydria 2-Diarrhea 3-Gastrectomy 4-Malabsorptive syndromes 5-Pancreatitis

Pharmacological factors:- e.g. 1-Drug interactions 2-Antacids 3-Anticholinergics 4-Cholstyramine 5-Food

Distribution Physiological changes What is the effect of the changes in serum albumin and in body fats on drug distribution? 1- ↓ cardiac output 2- ↓ total body water 3- ↓ Lean body mass 4- ↓ Serum albumin 5- ↑ α1-acid glycoprotein 6- ↑ body fat QUIZE:- What is the effect of the changes in serum albumin on drug distribution?

Disease states 1-CHf 2-Dehydration 3-Edema 4-Ascites 5-Hepatic failure 6-Malnutrition 7-Renal failure

Pharmacological Factors 1-Drug-drug interactions 2-Protein binding(displacement) can you provide examples?

Metabolism 1- ↓ Hepatic mass 2- ↓ Enzyme activity 3- ↓ Hepatic blood flow Explain the following, ↓ enzyme activity at old age?

Disease states 1-CHF 2-Hepatic failure 3-Malignancy 4-Malnutrition 5-Thyroid disease 6-Viral infection

Pharmacological Factors 1-Alcohol 2-Smoking 3-Induction of metabolism 4-Inhibition of metabolism Explain the effects of both enzyme induction and inhibition on drug response?

Excretion Physiological changes 1- ↓ Renal blood flow 2- ↓ GFR 3- ↓ Tubular secretion 4- ↓ Renal mass ↓ renal elimination ↑ adverse effects of drugs (drugs eliminated by kidney) Drugs highly dependent on renal function for elimination (Aminoglycosides, acetazolamide, allopurinol, amantadine, amiloride, atenolo, cephalosporines, Clonidine, fluconazole, H2 antagonists, enalapril……………………………etc…)

PHARMACODYNAMICS CHANGES IN THE ELDERLY These changes due to inefficient homeostatic adjustments or receptors sensitivity

Homeostasis Orthostatic or postural hypotension occurs as a result of impaired baroreceptor function And a failure of cerebral blood flow auto regulation. Can be aggravated by 1-Sympatholytics 2-Volume-depleting drugs and vasodilating agents These can contribute to falls in blood pressure. Most common drugs which are used and produce interfere with homeostasis 1-TCAS:- hypotension,and has other side effects such as tremors, cardiac arrhythmias, sedation 2-Antihypertensive;- most of them causes postural hypotension

Impaired in coordination in old age -Benzodiazepines and sedative hypnotics:- sedation, weakness, ↓ coordination, confusion -Narcotic analgesics:- sedation, ↓ coordination, confusion -Antipsychotics:- sedation, extra pyramidal effects

Receptor sensitivity changes can lead to exaggerated response (e.g. nitrazepam, heparin, warfarin) 1-A decline in the dopamine system ↑ sensitivity to dopamine blocking agents(e.g. neuroleptics, metoclopramide) 2-Cholinergic deficits in the central nervous can ↑ susceptibility to confusion caused by ant-cholinergic Agents What are the drugs that can induce confusion in older patients?

ADVERSE DRUG REACTIONS IN THE ELDERLY 1-Studies have shown that the percentage of patients with adverse reactions ↑ from about 10% When a single drug is being taken nearly 100% when ten drugs are taken 2-What are the other reasons for high incidence of errors in prescribed drugs?.

DRUG-DRUG INTERACTIONS -Enzyme inhibitors:-e.g. Cimetidine(H2 blocker) inhibits the hepatic metabolism of many drugs including phenytion Mention other drugs are affected by liver enzyme activity? -Enzyme inducers What are the enzyme inducers, explain their effect on other drugs?

PRACTICAL ASPECTS OF GERIATRIC PHARMACOLOGY Drug therapy has considerable potential for both helpful and harmful effects in elderly This balance may be tipped in the right direction by adherence to a few principles 1-Take a careful drug history, why? (Drug-drug interaction, drug induce disease, drug Treating disease) 2-Prescribe only for a specific indication and real need of the drugs

PRACTICAL ASPECTS OF GERIATRIC PHARMACOLOGY 3-Define the goal of drug therapy, start small dose and increase gradually Wait at least 3 half-lives of the drug, until reach the expected response (why), If no improvement ↑ dose if no response shift to a different drug 4-Maintain a high index of suspicion regarding drug reactions and interactions in elderly 5-Simplify the regimen as much as possible ( ↓ number of drugs being taken, Collect the drugs that can be taken at same time of the day)