Introduction to Pharmacology

Introduction to Pharmacology

• Pharmacology studies drugs and their interactions with living organisms.
• Drugs or medicines are chemical substances affecting living processes via binding to receptors.
• Drugs alter physiological functions in organisms, producing either beneficial or harmful effects.
• Benefits of medications include improvement of ailments, while side effects and adverse effects can cause harm.
• Side effects refer to a medicine's undesirable effect on the body.
• Adverse effects refer to the harmful impact of medicine on the body.
• Clinical pharmacology or pharmacotherapeutics deals with the therapeutic effects of drugs.
• Clinical pharmacology aims to prevent, diagnose, and cure illnesses or diseases.
• Furthermore it prevents or alters disease processes, modifies cell functions without initiating them, and mimics or interferes with endogenous substances.

Drug Names

• Chemical name describes the chemical structure of a drug.
• Generic name is the nonproprietary or common name.
• Trademark or brand name is proprietary, given by the pharmaceutical company.
• Drug may cause fatigue and sedation.
• Drug interferes negatively with cognitive and motor functions, impairing performance during therapy.
• Drugs may cause loss of muscle strength.
• Sedatives, opioids, and muscle relaxants are examples of drugs that may cause loss of muscle strength.
• Ideal drug treatment schedules include peak analgesic and anti-tremor effects.
• Peak anti-tremor effect is ideal for Parkinson's Disease patients to improve performance during therapy.
• Drug treatment should avoid peak sedation effect.

Drug-Rehab Therapy Interactions

• Heat causes peripheral vasodilation, exacerbating orthostatic hypotension.
• Orthostatic hypotension leads to low blood pressure when rising from sitting or lying.
• Constant movement during therapy may result in syncope.
• Precautions should be in place during whirlpool and heating modalities.
• Adverse Drug Reactions (ADRs) account for 3-7% of hospital admissions in the US.
• ADR’s occur during 10-20% of hospital admissions, with 10-20% fatalities.
• Many ADRs are preventable, requiring vigilance during therapy.
• Overall average incidence of ADRs is 9.52%
• Male patients account for 54.6%, while females account for 45.4% of ADRs.
• Antimicrobials are the most common class of drugs related to ADRs.
• A proactive approach educating patients/caregivers in monitoring the adverse effects is very beneficial.

Divisions of Pharmacotherapeutics

• Pharmacokinetics describes how the body acts upon a drug.
• Pharmacodynamics explains how a drug acts upon the body.
• Pharmacokinetics involves drug transport to the target site and removal or excretion of the drug from the body.
• Stages include drug absorption, distribution, metabolism and excretion.
• Pharmacodynamics describes how the active form of a drug interacts with its site of action, affecting living processes.
• Impact of the drug produces a biological effect, leading to a body's biological response which has a dose-response relationship.

Pharmacokinetics - Absorption

• Absorption is the entry of a drug from the administration site into the circulation.
• The route of administration is a key factor.
• Absorption through the oral route is the most common, convenient, and economical.
• Tablets, capsules, or liquid suspensions are the means of administering drugs through this route.
• Sequence of oral absorption: Mouth Intestines Epithelium Blood Vessels LIVER (first pass metabolism) Systemic Circulation.

Liver First Pass Metabolism

• Liver First Pass/Presystemic Metabolism reduces drug concentration before it reaches systemic circulation.
• Reduces bioavailability of drug.
• Enzymes (gastrointestinal lumen enzymes; gut wall enzymes; bacterial enzymes & hepatic enzymes) metabolize the drug.
• 20% of the drug is metabolized.
• Alternative routes bypass the liver: topical patch, intranasal or intravenous.

Oral Drugs Special Features

• The Fast Oral Disintegrating System dissolves immediately in the oral mucosa for those who have dysphagia or emesis.
• This system is useful in situations where there is water unavailability.
• Medications comes in tablet, wafer, gum or film form.
• Timed release or sustained release means the medication dissolves slowly, uniformly to prolong absorption.
• An Enteric coating resists acid but dissolves in alkaline pH.
• The Enteric coating helps to avoid stomach irritation, dissolve in intestines for absorption, and avoid degradation of drug in acid.
• Mucoadhesive microspheres delay and increase efficiency of absorption.
• Lipid soluble medicines increase the rate of transfer across membranes by simple/passive diffusion.
• Water or Non-lipid solubles have an inability to easily bind with fat cells which delays absorption possible.
• Transfer instead must utilizes proteins which requires more energy than lipid soluble drugs.
• Intravenous administration is the quickest onset but most difficult route for self-administration, which is an aqueous solution form.
• The medicine is directly quick to the bloodstream.
• Intramuscular and subcutaneous administration provides Prolonged absorption and is easier to self administer (Formulation in oil suspensions).
• Injection avoids nerves especially the sciatic nerves.
• Sublingual administration is Fairly rapid absorption & onset of action via venous drainage (Takes about 1-3 minutes to reach superior vena cava).
• The drug put under the tongue dissolves rapidly due to saliva where the systemic effect is exerted through the sublingual mucosa.
• The topical administration has less systemic absorption especially via Skin creams, ointments, lotions, liniments, powder & gels.

Distribution

• Process of distribution into the tissues is dependant on the blood flow.
• Flow moves from More > Less.
• MORE blood flow goes to the Heart, Liver, Kidney, and Brain which are vital for survival.
• LESS blood flow goes to the Muscle, Viscera, Skin, and Adipose Tissue.
• A drug-plasma protein complex retains the drug within the vascular space, and is reversible.
• The complex acts as a "Vehicle" that carries the drug
• The vehicle depends on the drug concentration (law of mass action).
• Lower affinity is kicked out by a higher affinity drug
• The vehicle is also dependent on the affinity to binding sites.
• Readily available storage leads to longer duration of action & slower onset of action.
• Competition for binding sites may occur In Multiple Drug Therapy or POLYPHARMACY so use caution.
• Displacement will cause an increase in "free" or unbound drugs, which may create an adverse reaction.
• Toxicity is possible if a drug is kicked out by a higher affinity drug at an untimely event.

Bioavailability

• Bioavailability refers to the amount of drug that reaches its target of action.
• Initial administration of a drug at a higher dose is the loading dose.
• Loading dose Allows you to see the initial effect of a drug on a person quicker.

Biological Half-Life

• Biological Half-Life refers to time of response, and may be longer in duration of action as compared to plasma levels.
• Therapeutic range is the range of drug concentration in the plasma.
• Below which the desired effect is not seen.
• Above which toxic effects are seen.
• The Blood-Brain Barrier (BBB) prevents easy access to the CNS due to tight junctions between capillary endothelial cells.
• Acts as a selective filter & protective coat.

BBB Issues

• Limits the passage of pathogens or toxins.
• Non-polar & lipid-soluble drugs pass BBB via passive diffusion.
• Other drugs pass through BBB via active/facilitated transport.
• Hypertonic solutions (High concentration of solutes) provide a 30 min. window, as cells are shrunk & junctions opened temporarily.
• The hypertonic solution takes out the water to shrink the drug so it can enter the tight junctions of the BBB.
• Nanotechnology - smaller drugs that can pass the said tight junctions without needing to shrink it.
• Nanoparticles (NPs) - mediated drug delivery is emerging as an effective and noninvasive system to treat cerebral diseases.

Volume of Distribution

• Estimates a drug's distribution within the body.
• The estimate is calculated by the ratio of amount of drug administered to drug plasma concentration.
• Extremely high amounts of H20 in the body reduces drug effectivity due to lower comparative drug-blood concentration.
• Liver failure alters body fluids and plasma-protein binding.
• Dehydration reduces total body fluids

Elimination Half-Life

• Aids in noting when the patient can take the next dose.
• Amount of time required for the drug plasma concentration to be reduced to 1/2 of the original amount. Dependent on:
• Plasma protein binding influences volume of distribution.
• Liver metabolism influences volume of distribution.
• Renal elimination affects drug clearance and elimination.
• Metabolism & Elimination: Drug Liver for Biotransformation into water-soluble products via the liver microsomal enzymes.

Pharmacodynamics

• Similar to Plasma Protein Binding (PPB) - reversible & follows “Law of Mass Action".
• Different from PPB more specific affinity & a cellular reaction is triggered.
• Configuration is important for it to fit.
• A Receptor is a specific protein macromolecule on a cell membrane (or inside), that recognizes a drug by using a 2nd messenger.
• Actions Alter membrane properties, change ionic permeability of membranes, change cellular transport systems, alter enzyme activity, and alter synthesis of cellular products.
• Agonists bind to a receptor and produce action with 100% effect.
• Antagonists (blockers) produces no action but blocks another substance, producing 0% action.
• Partial agonists produce suboptimal action and blocks another agonist from binding, resulting in 50% effect.
• Potency to Produce a certain effect, Efficacy is the Maximum response to a drug. A: Same effect but delays response Non-competitive: Reduction in the effect
• Choosing between the two is dependent on the situation.

Pain and Inflammation: Relevant Definitions

• Pain, according to the World Health Organization (WHO) and International Association for the Study of Pain (IASP), is an unpleasant sensory and emotional experience associated with actual or potential damage, described in terms of such damage.
• The Joint Commission on Accreditation of Healthcare Organization (JCAHO) recognizes Pain as a fifth vital sign, alongside temperature, respiration, pulse, and blood pressure.
• Inflammation is a body's second line of defense against invasion by pathogens.
• Process:
• Damaged tissues release histamines, increasing blood flow to the injury area.
• Histamine makes capillaries leak, releasing phagocytes and clotting factors into the wound.
• Phagocytes engulf bacteria, dead cells, and cellular debris.
• Platelets move to seal the wound.
• Pain types include nociceptive, neuropathic, and mixed pain.
• Nociceptive pain is due to injury to body tissue including musculoskeletal, cutaneous, or visceral areas.

Nociceptive Pain Types

• Originates from inflammation, limb pain after fracture, joint pain in osteoarthritis, or post-operative visceral pain.
• Described as aching, sharp, or throbbing.
• Neuropathic pain stems from a primary lesion or dysfunction in the nervous system.
• Pain is usually peripheral or central nervous system, can include Peripheral and Central conditions.
• Descriptions include burning, tingling, or hypersensitivity to touch or cold.
• Mixed pain includes neuropathic and nociceptive components.
• Nultidisciplinary Strategies for pain treatment include: education & dialogue, physical methods, medication, nerve blocks, joint injections, radiofrequency, pulsed radiofrequency stimulation therapy, procedures and physical medicine.
• Additional strategies: Psychological help, pain management programs and surgery.

Pain Management

• Multimodal or balanced analgesia refers to Use of more than 1 method of controlling pain to achieve either additive beneficial effects / reduce side effects.
• May include drug + non-drug treatment.
• Arachidonic acid and the cyclooxygenase pathway are key in inflammation. They produce prostaglandins and prostacyclin
• Autocrine or paracrine mediators, including prostaglandins.
• Medicine for Pain includes Acetaminophen or Paracetamol inhibit the COX 3 enzyme.
• In treating liver metabolism, metabolism in the liver is important to consider in the treatment.
• Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) most common pain reliever prescribed by physicians. Have Comparable efficacy, but have their Differences in Potency.
• NSAIDs inhibit the cyclooxygenase enzymes to provide pain relief and reduce swelling.