Pharmacology: Drug Reactions & Therapy in Elderly

• The document provides an overview of pharmacology, focusing on adverse drug reactions, drug therapy in the elderly, and drug interactions.

Undesired Drug Reactions

• Undesired Drug Reactions (UDRs) can be beneficial, but should be anticipated in medicinal treatment.
• The Bundesinstitut für Arzneimittel und Medizinprodukte (BfArM) defines UDRs as detrimental and undesired reactions to a medication designed for humans.
• Frequency of UDRs include: Very frequent (>10%), Frequent (1-10%), Occasional (0.1-1%), Rare (0.01-0.1%), Very rare (<0.01%).
• Health practitioners and patients should report drug reaction concerns to BfArM and pharmaceutical companies.

Drug-Specific, Dosage-Dependent Side Effects

• Individual tolerance can vary substantially even if these effects are generally predictable based on a drug's pharmacodynamic effects..
• These vary genetically, epigenetically, or through environmental variables affecting the absorption, distribution, metabolism, and excretion of the drug.
• The forms of side effects vary depending on the medication, and can range from central nervous system difficulties, gastrointestinal trouble, and liver and renal parenchymal damage to blood count abnormalities, reproductive disorders, and carcinogenic effects.

Drug-Induced Diseases and Secondary Undesired Drug Reactions

• Drug-induced diseases are medical conditions caused by pharmaceuticals that persist even after the medication is stopped.
• Secondary undesired drug reactions result from a medicine's main action, such as broad-spectrum antibiotics hurting the bacterial flora.

Drug Allergies

• 15-20% of all observed UDRs are drug allergies, affecting the skin.
• Maculopapular exanthema, urticaria, and angioedema are possible.
• Allergic reactions to drugs are dose-independent and not unique to the drug, involving immunologic mechanisms that require previous exposure.
• Genetic predisposition and application form influence the reaction to the drug.
• The reaction of the antibody with the medicine's determinant group causes group antigenicity, where similar drugs cause allergic reactions if they contain the same determinant.
• There are two types of hypersensitivity reactions:
  • Antibody-mediated.
  • T-lymphocyte-mediated.
  • These cause excessive reactions that are harmful to the organism.

Antibody- and T-Lymphocyte-Mediated Hypersensitivity Reaction

• Antibody-mediated hypersensitivity reactions are divided into:
  • Type-I (anaphylactic).
  • Type-II (cytotoxic).
  • Type-III (immune complex-mediated).
• Type-I reactions are mediated by IgE antibodies on mast cells and basophilic granulocytes, typically occurring within minutes to an hour after application known as immediate-type reactions.
• Type-II reactions are triggered by antibodies binding to cellular antigens on blood cells triggered by penicillins and sulfonamides, developing hours after medicine intake.
• Type-III reactions are caused by immune complex formation and deposition in tissues such as glomeruli, serous membranes, joints, and vascular endothelium.
• T-Lymphozyten-mediated hypersensitivity reaction Type IV (late type):
• Cellular hypersensitivity relies on a T-lymphocyte-caused immune response.
• The drug or it's metabolites react forming a complex with a protein of the body, the allergie takes days or weeks to reach the high point.

Pseudo-Allergic Adverse Reactions

• Pseudo-allergic reactions occur directly from the medicine, not from immunological response.
• The reaction does not require sensitization and can occur upon first use.
• Pseudo-allergic reactions consist of analgesic-asthma (after acetylsalicylic acid) and anaphylactoid responses (after radiocontrast media administration).

Hematological Disorders Caused by Drugs

• Uncommon, they have high morbidity and mortality, especially in older patients which include aplastic and hemolytic anemia, agranulocytosis, and thrombocytopenia.
• They are caused by direct toxic or immunological effects of a medicine or its metabolites.

Impairment of Driving Ability

• 25% of vehicular accidents in Germany are related to medication use.
• Many medications and alcohol impair reaction time.
• After outpatient operations involving anesthetics, driving ability is severely limited for 48 hours post-application.
• Vision issues may impair driving, even without concurrent reaction time impairment.
• Over-the-counter painkillers for the flu hinder driving and reaction time, this can also be escalated by pseudoephedrine.
• Doctors and pharmacists should advise patients, especially first-time users.

Adverse Effects in the Embryonic, Fetal, Postnatal, and Lactation Period

• Medicines used in pregnancy need compelling indication and caution due to harm to the fruit.
• No substance is 100% safe, harms can occur during blastogenesis, embryogenesis, and fetogenesis.
• Benefit-risk evaluations should be done.
• Risk assessed need to consider:
  • Timing of medicine use.
  • Placental transfer.
  • Teratogenicity of the medicine.
• Certain medications will affect the fetus, only having a negative impact if the medicate passes the placenta.
• There is a lack of clinical studies, there is application monitoring and experience.
• Schaefer's "Drug Prescribing in Pregnancy and Lactation" is a useful guide.
• Untreated diseases and conditions can be dangerous to the mother and the baby.
• Risk-benefit analysis is important for pregnant people.

Drug Dependency

• Psychological and physical dependence with increased doses is a sign of drug addiction, posing health risks.
• Potentially addictive substances should be avoided.
• Misused medications are used to increase performance, push down problems, or relax/sleep.
• 10% of medicines have abuse and dependency potential and lead to addiction through misuse, including opioid, psychostimulants, laxatives, pain relievers, decongestants, hypnotics, and tranquilizers like Zopiclone and Zolpidem.

Drug Therapy in Old Age

• About 29% of Germans are 60+ yet this group is neglected in research.
• Pharmacological trials exclude the elderly and lack representative studies.
• Pharmacology in old age is only briefly in standard pharmacological textbooks.
• Elderly have medication adverse effects and these affect malnutrition.
• Older people experience chronic basic conditions frequently, with people over 70 having 5 conditions.
• Identifying UDRs in elderly is harder due to basic existing complaints.
• A typical side effect is attributed to an underlying disease.
• Multiple drugs are a risk factor for drug interactions.
• Older people do not get malnutrition taken seriously, with weight loss regarded as a normative symptom.
• However, that weight loss makes the malnutrition worse and is hard to build back up.

Nutritional Status in Old Age

• Psychological and social factors of old people are important:
  • Poor mental health (dementia).
  • Depression, isolation, sadness.
  • Addiction.
  • Poor life quality.
• Reduced financial options, difficult routes and food prep are hindrances to adequate nutrition
• They lower appetite, food drive, and decrease energy intake.

Physical Changes in Old Age

• The most changes are from functional reserves of organs, and can lead to appetite loss.
• Diminished sensory perceptions affect appetite -- taste, smell, and failing eyesight.
• Common in older people, it decreases food amounts, which then decreases the enjoyment.
• Appetite changes also come from illness, medicine, dementia, or emotional problems.
• Hormone changes affect appetite, the Leptin, Insulin, and gastrointestinal hormone concentrations increase, and enhance satiety.
• Hunger-boosting Ghrelin levels decrease.
• The central drive that is controlled in the hypothalmus is decreased.
• Most internal organs get less weight and less flow.
• Reduced cell restoration rates of the mucous membrane reduce digestive enzymes and hydrochloric acid secretion.
• Higher pH values in stomach and proximal small intestine cause bacterial overgrowth, reducing bioavailability of iron, calcium, and B12.
• This will cause diarrhea.
• Body composition changes with age:
  • Body fat rises.
  • Hormonal and inactivity changes causes heart problems, insulin resistance, and diabetes.
• Muscle decreases, along with cell materials and bone mass, at the expense of the fats.
• Serious diseases impact nutrition due to forgetting to eat or doing too much body activity.
• Stroke patients have motor impairments and swallowing issues, restricting nourishment.
• Illness results in raised energy needs, need to monitor.
• Examples of the illnesses:
• Acute infections.
• Hyperthyroidism.
• Morbus Parkinson.
• Diabetes Mellitus.
• Inflammatory bowel diseases.
• Chronic obstructive pulmonary diseases.
• Cardiac cachexia.
• Tumors/cancers.
• Decubitus.

Adequate Drug-Therapy in Old Age

• There are few clinical drug studies involving old people and drug interations are poorly understood.
• The US Beers list is a drug list that old people should avoid, along with the needed doses.
• This was made by 6 US medical experts and in 2012 came with the help of the American Geriatrics Society.
• For the drug treatment the PRISCUS List was made, made using scientific releases on interaction topic.
• It is a list of inadquate medicines and the right doses of those medicines.
• In Germany, they have come up with Fit fOR The Aged (FORTA) and the "Multimedikation."

Drug Interactions

• Drug interactions are qualitative or quantitative changing of a drug in the presence of another.
• There are pharmakokinetic and pharmakodynamic interactions that can lead to an increase or decrease in effect.
• About two in ten UDRs come from drug interactions.
• Pharmakodynamic interactions hit the drug's first result.
• They are also a desired increase or unwanted increases.
• Pharmakokinetic can affect resorption distribution biotransformation and elimination between medicines.
• Effects are affected by physiological reasons.
• There are genetic components making up the amount of interactions.
• Multi-morbidity and Poly-Pharmazie almost always come up with drug interaction.
• Often, you do not only have one issue, this is known as multimorbidität.
• Patients with more than one medicate going on will have poly-pharmazie which requires a medicine.
• There is no definition so it takes 5 drugs or more.
• Older people take more medicines.
• It makes the interaction risk exponential.
• Also, they have liver function, increasing plasma levels.
• Medicine issues need evaluation.
• They produce many reactions and can make you desenitized.
• Hard to rate danger of interactions.
• Working with the database of interactions is like driving with the Navi.
• It can be done in combination.
• Every medicine needs analysis.

Interactions Between Medicines and Micronutrients

• Selective removal of a pathological health state by a medicine requires manipulation.
• The side effects are known if a substance happens to go on a certain circuit.
• This includes medicine and important nutrients.
• Various ingredients need to be considered here, with specific being chem structure.
• Dosage and width should be known.
• Micronutrient aspects need to be looked over.
• Physiological effects will occur.