SURGICAL DENTISTRY AND TREATMENT PRESCRIPTIONS AND DRUG INTERACTIONS IN THE ELDERLY
PLAN
Introduction
- Reminder of pharmacokinetic and pharmacodynamic aspects
- Pharmacokinetic aspect
- Routes of administration
- Absorption and bioavailability
- Transport and distribution
- Biotransformation
- Excretion
- Pharmacodynamic aspect
- Impact of senescence on pharmacokinetics
- Absorption
- Transport and distribution
- Biotransformation
- The elimination
- Impact of senescence on pharmacodynamics
- Drug interactions and iatrogenesis with commonly prescribed drugs in oral medicine
- Definition of a drug interaction
- Definition of drug-induced iatrogenesis
- Most prescribed drugs in the elderly
- Most frequently prescribed drugs in oral medicine
- Main drug interactions and Odontostomatology
- Prescription rules for the elderly
- Patient related
- Linked to the prescribed molecule
Conclusion
Introduction :
Elderly people are not only victims of physiological aging but often also of multiple pathologies.
This combination will modify the pharmacokinetics and pharmacodynamics of the drugs, with increased risks of toxicity, adverse effects, and interactions.
To better understand the problem of prescriptions for geriatric patients, it seems essential to us to clearly define the concept of an elderly person. In other words, what are the criteria taken into account to qualify a subject as an “elderly person”?
- Reminder of the pharmacokinetic and pharmacodynamic aspects:
A good understanding of the different pharmacokinetic stages as well as the main pharmacodynamic mechanisms of drugs is an essential prerequisite to better assimilate the effects of senescence on these different stages as well as the consequences in the prescription and choice of molecules in our daily practice.
- Pharmacokinetic aspect:
Pharmacokinetics can be defined as the fate of a drug in the body from the site of administration to the site of excretion. This fate goes through the following steps: routes of administration, absorption and bioavailability, transport and distribution, biotransformation and excretion.
- Routes of administration:
There are many of them. We will distinguish:
– Systemic pathways; these are those in which the active ingredient first passes through the bloodstream before reaching the target. These include:
*Enteral routes: per os, sublingual and rectal;
*Parenteral routes: intravenous, intramuscular, subcutaneous, pulmonary.
– Topical or local routes : the active ingredient acts at the site of administration. We will distinguish: the cutaneous, vaginal, oropharyngeal and conjunctival routes.
- Absorption and bioavailability:
– The site of absorption depends on the route of administration. During this absorption, the systemic circulation is affected. Among these barriers, we can note: the digestive mucosa, the alveolocapillary barrier.
– Bioavailability is the quantity of the active ingredient that reaches the systemic circulation. It depends essentially on the quality of absorption, the first hepatic, enterocyte and pulmonary passages.
1.1.3. Transportation and distribution:
This distribution depends on the one hand on the physicochemical properties (liposolubility, hydrosolubility) of the active ingredient and on the other hand on the composition of the different tissues (presence of receptors, transporters, water, lipid and protein content).
1.1.4. Biotransformation:
This is the transformation of the active ingredient. This takes place mainly in the liver but also the lungs and kidneys. It remains closely linked to the proper functioning of these different organs.
- Excretion:
It is the elimination of the active ingredient from the body. This takes place mainly in the liver (bile ducts) and the kidneys. It remains closely linked to hepatic and renal clearance.
- Pharmacodynamic aspect:
It is the study of the mechanisms of action of the active principle or its metabolites at the level of the target cell allowing the desired pharmacological effect to be obtained.
At the level of target cells (body cells or pathogens such as bacteria, viruses, fungi.
- Impact of senescence on pharmacokinetics:
- Absorption:
Senescence is responsible for the following changes: decreased gastrointestinal motility, increased gastric pH, decreased concentration of proteins responsible for active transport, decreased absorption surface. All these changes lead to the following pharmacokinetic consequences:
– Modification of the degree of ionization of weak acids and weak bases;
– A slowdown in gastric emptying;
– Decreased absorption by active transport.
- Transport and distribution:
Aging causes a decrease in serum albumin and a modification of the different compartments in the body, including an increase in fat mass and a decrease in protein mass and body water volume.
TABLE – MODIFICATION OF THE DIFFERENT COMPARTMENTS OF THE ORGANISM DUE TO SENESCENCE
- Biotransformation:
Essentially hepatic, biotransformation is therefore subject to hepatic modifications due to senescence. Among these modifications, we note: a decrease in hepatic mass, a decrease in the number of functional hepatocytes, a decrease in enzymatic activity with a decrease in oxidation and a decrease in hepatic blood flow. As an ultimate consequence, a decrease in hepatic clearance of drugs with a high hepatic extraction coefficient. Therefore an increased risk of toxicity.
- Elimination:
Drug elimination is mainly via the kidney. Functional changes due to renal senescence are: decreased renal blood flow, decreased glomerular filtration, decreased glomerular secretion. Pharmacokinetic consequences are: decreased elimination of drugs or their metabolites and accumulation of drugs with tubular elimination. These drugs require dosage adjustment based on renal clearance.
- Impact of senescence on pharmacodynamics:
Senescence can lead to a modification of the different cellular targets (in particular receptors or intracellular targets) of the active principle. This leads either to an increase in sensitivity to certain drugs with the appearance of more adverse effects or to the ineffectiveness of the drug.
This impact on pharmacodynamics is all the more important when there is polymedication. Hence the interest in assessing the geriatric risk before each prescription in those over 65 years of age.
- Drug interactions and iatrogenesis with commonly prescribed drugs in oral medicine:
4.1. Definition of a drug interaction:
Drug interaction is when two drugs A and B, administered simultaneously to a patient, drug A (called precipitant) interferes with the pharmacokinetics and/or pharmacodynamics of drug B (called object) thus leading to a modification of the clinical effects of the drug.
These clinical changes include:
– An increase in clinical efficacy;
– A decrease in clinical effect;
– An increase in known side effects;
– The appearance of new side effects.
These interactions are classified into 5 categories of decreasing severity
SURGICAL DENTISTRY AND TREATMENT PRESCRIPTIONS AND DRUG INTERACTIONS IN THE ELDERLY
TABLE -ORCA CLASSIFICATION (OPERATIONAL CLASSIFICATION OF DRUG INTERACTION)
4.2. Definition of drug-induced iatrogenesis:
As for drug-related iatrogenesis, it is the set of negative consequences on the state of health of a patient caused by drug prescriptions even in the absence of a prescription error.
Particularly in the elderly (over 65 years old), it is often the consequence of three main factors:
– The existence of a drug interaction not taken into account when prescribing. (This is the most frequent due to polymedication).
– Failure to adapt dosages to the various physiological changes due to senescence. Failure to take medications not recommended for elderly people.
– Failure to take into account the existence of a pathological condition (comorbidity)
– The existence of hypersensitivity.
4.3. Most prescribed drugs in the elderly (all specialties combined):
According to the 2000 ESP survey carried out by the HAS, the most frequently prescribed drug classes (all specialties combined) in subjects over 65 years of age are:
– Cardiovascular drugs: anticoagulants, antihypertensives, hypolipidemics, antiarrhythmics, nitrate vasodilators;
– Central nervous system and psychotropic drugs: mood stabilizers, antidepressants, serotonergic or adrenergic drugs;
– Digestive system medications: laxatives, muscle relaxants;
Locomotor system drugs: analgesics, nonsteroidal anti-inflammatory drugs, glucocorticoids;
– Painkillers: all levels.
It is therefore essential for any practitioner to be familiar with the interactions between commonly prescribed drugs in odontostomatology and the different drug classes.
4.4. Most frequently prescribed drugs in oral medicine:
SURGICAL DENTISTRY AND TREATMENT PRESCRIPTIONS AND DRUG INTERACTIONS IN THE ELDERLY
TABLE – MOST COMMONLY PRESCRIBED DRUGS IN ORAL MEDICINE
4.5. Main drug interactions and Odontostomatology:
SURGICAL DENTISTRY AND TREATMENT PRESCRIPTIONS AND DRUG INTERACTIONS IN THE ELDERLY
- Prescription rules for the elderly:
A good prescription in elderly subjects must aim at therapeutic efficacy and non-harmfulness. For this, it is essential to analyze a certain number of parameters before any prescription.
- . Patient related:
These different parameters are collected during a complete and thorough clinical examination followed by biological and radiological analyses if necessary.
– Precise and concise diagnosis: Any prescription must be justified. This is the very basis for choosing a therapeutic class.
– The patient’s hydration status. Any dehydration leads to a risk of renal and hepatic toxicity and overdose.
– The patient’s nutritional status: Nutrition has a direct impact on plasma proteins (mainly albumin) involved in the transport of molecules and therefore on the free fraction. Malnutrition can lead to an increase in the free fraction of the drug and therefore an increased risk of overdose and toxicity.
– Renal function: Assessed by creatinine clearance, it is essential in the case of choosing a molecule with renal extraction or a narrow therapeutic margin. It may require a specific dosage adjustment.
– Liver function: Assessed by measuring liver enzymes, it allows the dosage of molecules with high metabolism or hepatic extraction to be adapted.
– All current treatments: Polymedication is very common in elderly subjects with an increased risk of drug iatrogenesis. It is therefore more than necessary to carefully list all the molecules taken (including self-medication) before any addition of molecules in order to prevent drug interactions and therefore iatrogenesis.
– Associated pathologies: It is obvious that the existence of a pathological terrain in addition to the phenomena of senescence leads to specific prescription methods. This involves looking for long-term conditions (IRC, HTA, Diabetes, etc.).
– Cognitive abilities: Necessary for compliance, management and understanding of treatment instructions.
- Related to the prescribed molecule:
– The predominant elimination route: If renal elimination, adjust the dosage according to creatinine clearance. However, if hepatic metabolism and excretion, the dosage will depend on the liver function test and the possible intake of hepatic inhibitors or inducers.
– The duration of action of the drug: It is important to know the half-life of each molecule prescribed because it allows you to determine the number of doses per day. In the elderly, it is advisable to use molecules with a short half-life.
– The hydrophilic or lipophilic nature of the molecule: Indeed, in the elderly, fat mass increases to the detriment of the fluid compartment, thus leading to a risk of overdose for lipophilic drugs. It is therefore essential to reduce the dose of lipophilic drugs.
– The therapeutic margin of the molecule: (difference between the effective dose and the toxicity threshold). Be careful with molecules with a low therapeutic margin because of the increased risk of toxicity.
– Adverse, pharmacological (known) effects as well as contraindications: Always take these characteristics into consideration when choosing the molecule best suited to the patient.
– The medical service rendered: It takes into consideration the benefit/risk ratio, the seriousness of the condition treated and the place of the molecules in the therapeutic strategy.
SURGICAL DENTISTRY AND TREATMENT PRESCRIPTIONS AND DRUG INTERACTIONS IN THE ELDERLY
Drug treatment of the elderly according to the benefit-risk balance
– The galenic form: The oral form should always be preferred except in cases of severe swallowing disorders.
– The appropriateness or otherwise of the molecule: Certain molecules are not recommended for elderly patients because the risks far outweigh the benefits.
Once these different parameters have been analyzed, the most suitable molecule will be prescribed in accordance with the recommendations and clinical and/or biological monitoring will be put in place until the drug is stopped.
Conclusion :
The medication is an opportunity for the elderly patient. Prescribing well requires knowing the patient to be treated well. The prescriber must coordinate the prescription with his or her treating colleagues. Increased vigilance by the prescriber regarding the iatrogenic risk, and better education of the elderly patient can certainly reduce the iatrogenic risk and avoid interactions and adverse effects.
SURGICAL DENTISTRY AND TREATMENT PRESCRIPTIONS AND DRUG INTERACTIONS IN THE ELDERLY
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