Antibiotics Mechanisms and Effects

Pharmacology and Toxicology

• This is a course on the study of drugs and their effects on living organisms. It also covers the harmful and adverse effects of chemicals, substances, and physical agents on organisms and the environment.

Principles of Pharmacology I

• Pharmacology: The scientific study of the effects of drugs and chemicals on living organisms.
• Drug: A natural or synthetic chemical substance that affects a biological system.

Importance of Pharmacology

• Understanding the biochemical and physiological aspects of drug effects is crucial.
• Determining the effectiveness and safety of medicines helps in diagnosis, prevention, and treatment of diseases.

Toxicology

• The field of science that studies the harmful and adverse effects of chemicals, substances, and physical agents on living organisms and the environment.

Drug-Receptor Interactions

• The ability of a drug to affect a given receptor is important.
• Probability or strength of drug occupying a receptor – Drug's affinity is considered.
• Degree of a drug or ligand activating the receptors - Intrinsic efficacy.

Effect of a Drug Depends on

• Disease states affect drug pharmacology.
• Pharmacokinetics study how the body processes drugs.
• Differentiated receptors mediate biological responses.
• Drug dosage increases until receptor saturation.
• Drug potency/affinity – More potent drug binds faster and releases slower.
• Drug efficacy - ability to block or activate receptors

Dose-Response Relationship

• The dose-response relationship is the most important concept in pharmacodynamics.
• It describes the effect of a drug in relation to its concentration at the receptor.
• Pharmacodynamics describes the course of action of drugs leading to physiological effect at a specific site in the body.

Four Main Pharmacokinetic Processes

• Absorption, distribution, metabolism, and excretion (ADME) are the four main pharmacokinetic processes.
• These processes explain the characteristics of different drugs in the body.
• Patient factors (sex, age, genetics, and diseases) and drug properties (protein binding, molecule size, and chemical characteristics) can influence these processes.

Mechanisms of Absorption from the Gastrointestinal Tract

• Passive diffusion is the most common mechanism for drug absorption.
• It moves drugs from an area of high concentration to one with lower concentration across a membrane.
• Passive diffusion does not involve a carrier.
• Other mechanisms include facilitated diffusion (specialized transmembrane carrier proteins).

Bioavailability

• Bioavailability is the rate and extent that an administered drug reaches the systemic circulation.
• Determining bioavailability is vital for calculating medication dosages for non-intravenous routes.

Drug Distribution - Volume of Distribution

• Acid-base characteristics, lipophilicity of drugs affect volume of distribution.
• Drugs with higher affinity for albumin tend to have lower Vd.
• Lipophilic molecules are more likely to leave bloodstream to areas with high lipid density (like adipose tissue) creating a higher Vd.
• Hydrophilic molecules are less likely to cross lipid bilayers and stay within the bloodstream creating a lower Vd.

Different Routes of Drug Administration

• Enteral route: Rectal route of medication. Rapid and effective absorption of medications. Medications undergo passive diffusion, in part by-passing the liver.
• Parenteral route: Intravenous injection. Most common parental route of administration; bypasses liver's first-pass metabolism. Intramuscular and subcutaneous injection are also part of the parenteral route.

Drug Calculations

• Ratio and proportion method, Desired Over Have or Formula method, and Dimensional analysis method are used to calculate the dosage of medications.

What is Lorazepam?

• Used to treat anxiety and insomnia.
• Classified as a benzodiazepine.
• Commonly used to treat alcohol withdrawal.
• Available in tablet and liquid forms.

Dimensional Analysis Method

• A series of conversion factors are used without memorizing specific formulas, that allow unwanted units to cancel out, leaving just the correct unit.

Step-3: Clinical Research Studies

• Phase 3 studies involve 300 to 3,000 participants for an average period of 1 to 4 years.
• These studies focus on efficacy, and to look for adverse reactions for a specific population.

FDA IND Review Team

• The team consists of specialists with various areas of expertise. Each member evaluates different aspects of the medical trials that are intended for the public.

Principles of Neuropharmacology

• Drugs that alter axonal conduction - Local anesthetics. Stop the nerves' signal transmission to the brain.
• Common drugs used in local anesthetics include amino amides and amino esters.

Monoamines Neurotransmitters

• Serotonin - Calming chemical regulating mood, anxiety, sleep, patterns, appetite, sexuality and pain.
• Dopamine - Act as a "pleasure chemical" released when receiving a reward; relating to food and drugs. Also associated with feelings and mood affecting conditions such as Parkinson's.
• Other relevant conditions such as attention-deficit hyperactivity disorder (ADHD) are relevant to neurotransmitters' effects on behavior.

Central Nervous System Pharmacology

• Sub-classifications and relevant examples are given.

• Narcotic analgesics act on sigma and mu receptors and reduce pain perception.

• Non-narcotic agents decrease prostaglandin synthesis to reduce inflammation.

• Anticonvulsant medications affect GABA, sodium and or acetylcholine levels.

• Side effects of some of the drugs relevant to the Central Nervous System are discussed, like constipation and headache.

Common Causes of Peptic Ulcer Disease

• Infection with Helicobacter pylori is a significant factor
• Non-steroidal anti-inflammatory drugs (NSAIDs)
• Tobacco smoking
• Stress due to other health conditions

Factors Increasing the Risk of Developing Peptic Ulcers

• Alcohol consumption, smoking, uncontrolled stress and undesirable eating habits increase the risk.

Drugs for Gastrointestinal Disease – Nonprescription Medicines

• Antacids neutralize stomach acid (e.g., Mylanta).
• Proton pump inhibitors block acid production (e.g., lansoprazole, omeprazole, esomeprazole)
• H2 blockers also block acid production and allow for healing of the affected area.

General Side Effects of H2 Blockers

• H2 blockers are generally safe but some complications such as changes in the effectiveness of pain medications may occur in some.
• May affect absorption of vitamin D, and other nutrients.

How Do Antiemetic Medications Work?

• Block signals in the brain responsible for nausea and vomiting.
• Block the related chemical messengers.
• Some examples include histamine, dopamine, serotonin, and neurokinins

Different Antiemetic Drugs

• Antagonists of different NTs can work in different ways to prevent nausea and vomiting.

Adsorbents used in Treatment of Diarrhea

• Bind and inactivate bacterial toxins and other substances that cause diarrhea.
• May also adsorb digestive enzymes, nutrients, or drugs.

Gas with Loose Stools

• May be due to conditions like diverticulitis, or increased bacteria in the small intestine.
• May also be related to low fiber diet, lack of physical activity, and obesity.

Bristol Stool Chart

• Different types of stool are categorized in the chart that help indicate constipation.

How Do Different Laxatives Work?

• Bulk-forming laxatives increase stool bulk to stimulate the bowel.
• Emollient stool softeners lubricate the stool for easier passing.
• Osmotic laxatives draw water into the bowel and soften stools for easier passage.
• Stimulant laxatives promote intestinal contractions to facilitate movement of stools.

How About Mineral Oil Enema for Constipation?

• Mineral oil enema coats the fecal contents, preventing water absorption.
• Lubricates stool for easier passage.
• Can aid with some specific conditions (e.g. hemorrhoids).

Principles of Antimicrobial Pharmacology

• Antimicrobials are a broad group of agents that aim to reduce the possibility of infection and sepsis.
• Antibiotics are a subgroup of antimicrobials that are derived from molds or synthetically made to kill bacteria (bactericidal) or prevent their growth (bacteriostatic).
• The mechanism of action for various antibiotics is to interfere with bacterial cell wall synthesis, plasma membrane integrity, nucleic acid synthesis, ribosomal function and metabolic pathways (e.g., folate synthesis).

Drugs for Treating Asthma

• Asthma inhalers contain different types of medication, including relievers (short-acting bronchodilators) and preventers (steroid inhalers).
• Long-acting bronchodilators are another type of medication.
• Steroid inhalers help reduce inflammation in the airways, prevent airways from narrowing when they are triggered.

Chronic Obstructive Pulmonary Disease (COPD) – Risk Factors

• Risk factors for COPD include smoking (and secondhand smoke), family history with an AATD gene and/or other genetic factors, history of respiratory infections, lung irritants (like chemical fumes) and obesity.

Steroid Inhalers for COPD

• For patients with symptoms of breathlessness or escalating flare-ups, steroid inhalers reduce inflammation in the airways and help prevent worsening disease.

Steroid Tablets for COPD

• A short course of steroid tablets is prescribed for worsening COPD to reduce inflammation, but the side effects (such as weight gain, mood swings, and osteoporosis) should be considered. These oral medications should only be used when necessary, as part of an overall treatment plan.

Antibiotics for Adults Aged 18 Years and Over

• First choice – Doxycycline, 200 mg on first day, followed by 100 mg daily for 4 days.
• Alternative options – Amoxicillin, Clarithromycin, and Erythromycin. A dosing regimen is listed.

How to Test for Theophylline?

• The theophylline test monitors blood theophylline levels.
• The test is usually requested as a trough level, taken just before the next dose.

Method of Analysis of Theophylline

• High performance Liquid Chromatography (HPLC) can precisely detect and quantify theophylline in plasma samples.

Principles of Gastrointestinal Pharmacology

• Motility of Gastrointestinal (GI) Tract: The muscular contractions of the GI tract are responsible for moving food through the gut. Circular and longitudinal muscles produce peristaltic waves, moving food from mouth to anus.
• Pathologies of Gastrointestinal (GI) Tract: Impairment of digestive functions like absorption, secretion, and motility may occur due to malfunctions, conditions like IBS, Dyspepsia, peptic ulcers, GERD, or IBD.
• Difference between Functional and Organic GI Disorders: Functional disorders have changes in function but not in measurable changes in tissues, organs, or body systems, whereas organic disorders involve measurable changes in the related tissues or organs.
• Common Causes of Peptic Ulcer Disease: Infection with Helicobacter pylori and use of non-steroidal anti-inflammatory drugs (NSAIDs) are common causes. Less common causes include tobacco smoking and stress due to other health conditions.
• Factors Increasing the Risk of Developing Peptic Ulcers: Alcohol consumption, smoking, uncontrolled stress, and undesirable eating habits.
• Drugs for Gastrointestinal Disease – Nonprescription Medicines: Antacids, proton pump inhibitors, and H2 blockers are discussed for treatment of conditions.

Principles of Endocrine Pharmacology

• Difference between Endocrine and Exocrine Glands: Endocrine glands secrete hormones directly into the bloodstream, while exocrine glands secrete products via ducts to epithelial surfaces.
• Overactive Thyroid (Hyperthyroidism) and Underactive Thyroid (Hypothyroidism): Symptoms and effects of these thyroid conditions are covered.
• Medications for treating Hyperthyroidism and Hypothyroidism: Methimazole and Propylthiouracil are used for hyperthyroidism, and levothyroxine, liothyronine, or liotrix are used for hypothyroidism.
• Other Relevant Considerations: Medications for treating diabetes such as insulin and insulin pumps are also discussed, along with different methods of administration methods such as insulin injections and medication delivered through an insulin pump.
• Other Relevant Considerations: Progestins, and estrogen receptor modulators. These drugs are related to hormone levels with respect to different illnesses.
• Other Relevant Considerations: Other different types of medications and conditions are mentioned for the treatment of some disorders (e.g. the male reproductive system).

Principles of Inflammation and Immune Pharmacology

• What is the Immune System? The immune system includes a network of cells, organs, and tissues involved in fighting infections and diseases and the related white blood cells are studied.
• Barrier Defenses: The protective systems (e.g., oral cavity, skin, stomach) are significant to preventing pathogens from entering the body.
• What is Inflammation: Inflammation is the body's response to harmful stimuli, and it plays a crucial role in the repair process and supporting overall health.
• Antirheumatoid Drugs: These drugs are used to treat inflammatory arthritis by targeting the immune system.
• Diagnosis of Rheumatoid Arthritis: The methods used for diagnosing this conditions (e.g., medical history, physical examination, blood tests, X-ray, ultrasound, and MRI) are part of the discussion to help aid in identifying the disease, and are important aspects of healthcare treatment.
• Drugs for Treatment of Rheumatoid Arthritis: NSAIDs, corticosteroids, and other disease modifying antirheumatic drugs (DMARDs) are types of drugs used to treat conditions for this type of arthritis.
• Systemic Lupus Erythematosus (SLE): A chronic autoimmune disease affecting multiple body systems.
• Drugs for Treatment of SLE: Treatments like NSAIDs and antimalarial drugs are studied when the disease affects the body.
• Multiple Sclerosis (MS): A chronic autoimmune disorder affecting the central nervous system. The symptoms and possible causes are discussed such as: autoimmune diseases, environmental and infectious agents, and genetics related. How these affect different people in different ways is also covered.

This quiz covers key aspects of various antibiotics, including how daptomycin inhibits bacterial growth, the classification of fluoroquinolones, and the specific infections treated by rifamycin. Test your knowledge on common side effects and the mechanisms of action related to these crucial medications.