Pharmacology: mechanisms, maintenance, and inventory

• Unit 3 covers Pharmacology

Enabling Learning Objectives

• Differentiate drugs on the IDMT formulary by class, mechanism of action, common side effects, and which drugs can/should be used based on patient presentation.
• Apply medication bioavailability to different patient scenarios.
• Describe how drug receptor interactions occur.
• Comprehend the effects drugs have on the autonomic nervous system.
• Identify the effects drugs have on different receptor times in the body.
• Differentiate between different bacteria types.
• Draw conclusions regarding the accountability, maintenance, and inventory of medications.
• Demonstrate how to properly maintain an AF 579.
• Draw conclusions regarding the dispensing & prescribing criteria for medications.
• Apply medication routes and bioavailability to different patient scenarios.

Overview

• Pharmacologic principles
• Commonly used medications
• Accountability and maintenance
• Perform inventory
• Maintain AF 579
• Prescribing criteria
• Dispensing criteria

Pharmacology Basics

• Pharmacology studies substances that interact with living systems through chemical processes.
• These interactions often involve binding to regulatory molecules to activate or inhibit normal body processes.
• Medical pharmacology focuses on substances used to prevent, diagnose, and treat disease.
• Toxicology is a branch of pharmacology that studies the undesirable effects of chemicals on living systems from cells to complex ecosystems.

Important Principles

• All substances, under certain circumstances, can be toxic.
• Chemicals in botanicals (herbs and plant extracts) are no different than chemicals in manufactured drugs, except for the proportion of impurities.
• Any substance can be harmful if taken in the wrong dosage.
• “The dose makes the poison", as asserted by Paracelsus (1493-1541).
• A drug is any substance that brings about a change in biologic function through its chemical actions and it can act as activators or inhibitors.
• Drugs bind to target biologic molecules termed receptors.

Drug Actions

• A drug agonist activates a receptor. Can be a full agonist, partial agonist, or inverse agonist.
• A drug antagonist inhibits a receptor by binding to it and preventing binding by other molecules, and can be competitive and reversible or irreversible
• Receptors control pharmacologic events leading to the drug's observed effects.
• Most receptors are proteins, including regulatory proteins, enzymes, transport proteins, and structural proteins.

Drug-Receptor Interaction

• For a drug to bind to a receptor, the receptor site must be selective for a particular drug like a lock and key.
• A drug must have the appropriate size, electrical charge, shape, and atomic composition to interact chemically with a receptor.
• The receptor must change its function in such a way that the function of the biologic system (cell, tissue) is altered upon binding.
• Termination of drug action can occur via dissociation of the drug from the receptor over time due to weak bonds.
• Strong, irreversible bonds necessitate the destruction of the drug-receptor complex through metabolism, exemplified by aspirin.

Drug Absorption

• A drug must be absorbed into the blood from the administration site and distributed to its site of action, crossing intestinal walls, capillary walls, and the blood-brain barrier.
• Bioavailability is the amount of drug that reaches the systemic circulation .
• Bioavailability depends on the extent of absorption from intestinal walls and first-pass elimination.
• First-pass elimination lowers bioavailability, where the drug enters the bloodstream of the liver and gets partially metabolized after absorption from the gut.
• IV administration equals 100% bioavailability with the most rapid onset.
• IM or SC administration yields 75 to 100% bioavailability.
• Oral administration yields 5 to 100% bioavailability with significant first-pass effect.
• Rectal administration yields 30 to 100% bioavailability with less first-pass effect.
• Transdermal administration yields 80 to 100% bioavailability with very slow absorption, with no first-pass effect and prolonged duration of action.
• Inhalation administration includes 5 to 100% bioavailability with rapid onset.

Drug Elimination

• Drug elimination occurs through two major routes:
• Via the liver, through biotransformation of the parent drug to one or more metabolites
• Via the kidneys, that clear the unchanged drug.
• Half-life is defined as the time required to change the amount of drug in the body by one-half during elimination.

Autonomic Nervous System Review

• The autonomic nervous system controls functions performed without conscious thought such as cardiac output, blood flow, and digestion.
• It is composed of two divisions: parasympathetic (rest and digest) and sympathetic (fight or flight).
• The parasympathetic nervous system inhibits, promotes the resting state, and is associated with acetylcholine (ACh) via cholinergic fibers and receptors.
• Cholinergic effects includes constricting the pupils and bronchioles, defecation, urination, bradycardia, salivation, sweating, and lacrimation.
• The sympathetic nervous system stimulates, promotes the fight or flight response, and neurotransmitters are norepinephrine and epinephrine.
• Adrenergic nerve fiber and receptor types, where the receptor includes adrenergic neurons alpha1, alpha2, beta1, and beta2.
• Adrenergic effects includes dilating pupils and bronchioles, constricting blood vessels, accelerating the heart, and increasing sweating, salivation and strength.

Alpha Receptors

• Alpha-1 (α₁) receptors cause arterial and venous vasoconstriction.
• Alpha-2 (α₂) receptors inhibit sympathetic tone on vasculature, relaxing arteries and veins.

Beta Receptors

• Beta-1 (β₁) receptors in the heart increase heart rate and contractility, while those in the kidney increase renin production.
• Beta-2 (β₂) receptors work on smooth muscle and cardiac muscle, increasing heart rate and contractility.

Commonly Used Medications

• CNS stands for central nervous system.
• CV stands for cardiovascular.
• EENT stands for ears, eyes, nose, throat.
• GI stands for gastrointestinal.
• GU stands for genitourinary.
• Resp stands for respiratory.
• MSK stands for musculoskeletal.
• Heme stands for hematology.
• Some medications will contain the eye, skin, renal, metabolic, and other generic (Trade) names.

Antihistamines

• Histamine is a neurotransmitter and mediator of allergic reactions that is active in inflammatory and immune responses.
• Histamine stimulates sensory nerve endings in the CNS, increases heart rate, acts as a vasodilator, raises capillary permeability in the CV system, smooth muscle bronchoconstriction in the respiratory system, and smooth muscle contraction and stimulates gastric acid in the GI system.
• Histamine receptors (H₁) are found in the endothelium, smooth muscle cells and nerve endings.
• Histamine receptors (H₂) are found in gastric parietal cells.
• First generation antihistamine examples include diphenhydramine, promethazine, and meclizine.
• Second-generation antihistamine examples include loratadine, cetirizine, and fexofenadine.
• Clinical applications for allergic reactions include motion sickness.
• Mechanism of action blocks H₁ receptors.

First and Second Generation Anti-histamines

• First-generation antihistamines have strong sedative effects and more likely to block autonomic receptors.
• Allergic reactions and motion sickness can be treated with diphenhydramine. Motion sickness can also be treated with promethazine and meclizine.
• Second generation antihistamines have less distribution to the CNS and are less sedating. Allergic reactions can be addressed using loratadine, cetirizine, and fexofenadine.
• Adverse effects of antihistamines includes excessive sedation and anticholinergic effects in the CNS.
• The clinical effectiveness of a second-generation antihistamine may diminish over time.
• Switching to a drug in the same class may restore clinical effectiveness.
• An example antihistamine is azelastine, which is used for seasonal allergic rhinitis, allergic conjunctivitis, and vasomotor rhinitis. H₁-receptor inhibits histamine actions of nasal mucosa.
• Some adverse effects of azelastine includes headaches and somnolence in the CNS as well as a bitter taste in the GI.
• An example antihistamine is olopatadine, which is clinically applied to allergic red eye symptoms. H₁-receptor antagonist inhibits histamine actions of conjunctival epithelial cells.
• The adverse effects include headache in the CNS, stinging/burning/foreign body sensation/dry eyes and pharyngitis in the respiratory system.

Gastrointestinal Drugs

• Ranitidine and cimetidine are used for gastroesophageal reflux disease and peptic ulcer disease.
• Such drugs block H₂ receptors on gastric parietal cell and suppress basal and meal-stimulated acid secretion of hydrochloric acid. It inhibits about 60-70 percent of acid secretion in a 24 hours period.
• Adverse effects are very rare though can include malaise and vertigo in the CNS.
• Hemolytic adverse effects include pancytopenia and angioedema.
• Other adverse affects include anaphylaxis.
• Omeprazole and esomeprazole are used for gastroesophageal reflux disease and peptic ulcer disease and blocks the final common pathway of acid secretion gastric parietal cell, which is the proton pump H+, K+-ATPase.

GI Medications

• Bismuth subsalicylate is used in the nonspecific treatment of dyspepsia and acute diarrhea. It acts as a mucosal protective agent, coating ulcers and erosions, creating a protective layer against acid and pepsin. It also provides antimicrobial effects and binds exotoxins.
• The major adverse reaction is GI with harmless temporary blackening of the tongue and stool.
• Bulk forming laxatives like psyllium and methylcellulose are used with indigestible, hydrophilic colloids that absorb water, forming a thick gel that distends the colon and promotes peristalsis.
• Osmotic laxatives like polyethylene glycol, PEG will balance the isotonic solution that contains an inert, nonabsorbable sugar PEG causing increased stool liquidity.
• Stimulant laxatives like bisacodyl induce bowel movements through a poorly understood mechanism, possibly acting through enteric nervous system stimulation.
• GI adverse effects include cramps, boating, flatulence, gas, nausea, metabolic side effects include electrolyte abnormalities.
• Loperamide is used in mild to moderate acute diarrhea.

Vomiting and Nausea

• The brainstem "vomiting center" is a loosely organized neuronal region within the lateral medullary reticular formation.
• Neural receptors involved are adrenergic, histamine H₁, serotonin 5-HT₃, neurokinin 1 (NK₁).
• Ondansetron is used to treat emesis attributable to vagal stimulation and chemotherapy. It blocks peripheral 5-HT3 receptors on intestinal and spinal nerves, and the adverse effects include headache, dizziness, fatigue, and malaise in the CNS, constipation and diarrhea, and MSK pain.
• Promethazine is used to treat nausea and vomiting and its mechanisms of action is the inhibition of dopamine, adrenergic, and H₁ receptors.
• Adverse effects includes sedation, drowsiness, and dizziness in the CNS.

NSAIDs

• Immune response occurs when immunologically competent cells are activated in response to foreign organisms/substances..
• Variety of effect on blood vessels, nerve endings and on inflammatory cells. COX-1 •Constituitive (homeostatic) COX-2 •Induced with inflammation Prostaglandins •Gastroprotection/ Platelet aggregation •Renal function

NSAIDs •Examples: nonselective COX inhibitors include ibuprofen, diclofenac, indomethacin, naproxen, piroxicam and ketorolac: COX-2 selective inhibitors includes celecoxib,meloxicam.

MOA: NSAIDs also have antipyretic and analgesic effects but are used mainly for their anti-inflammatory properties; anti-inflammatory activity is mediated chiefly through inhibition of prostaglandin biosynthesis; final elimination is by renal excretion. COX-1 •Found in many tissues •Important for a variety of physiologic responses •(GI tract, kidneys, platelets) COX-2 •Found primarily in inflammatory cells •Selective COX-2 NSAIDs - same efficacy with less GI side effects •Only coxib available in the US --> celecoxib (10-20x more selective for COX-2) •NSAIDs with greater selectivity and preference for COX-2 --> meloxicam

Adverse Effects: CNS: headaches, tinnitus, dizziness CV: hypertension, edema, rarely MI/CHF PULM: vasoconstriction GI: pain, nausea, vomiting, ulcers or bleeding

Selective COX-2 NSAIDs and Traditional NSAIDS

• 25-50% of Pt on clinical trials with NSAIDS have gastritis, 10-20% have peptic ulcers at endoscopy.
• Coxibs select for COx-2 enzyme decrease peptic ulcers by 75% and ulcer induced complications by 50%. Additional Adverse Effects: Renal: renal insufficiency, renal failure, hyperkalemia, proteinuria Hepatic: abnormal LFTs Heme: rare thrombocytopenia, neutropenia, easy bleeding or bruising Skin: rashes, pruritus IDMTs are limited to prescribing 2400mg ibuprofen daily

Prostaglandins and Platelets

•The original NSAID": aspirin rarely used as an antiprostaglandin synthesis inflammatory at smaller doses (81-325mg) it possess antiplatelet effects Decreases incidence of cardiovascular events IRREVERSIBLY inhibits platelets, effects last for 8-10 (the lifespan of a platelet) Adverse reactions: Easy bleeding, bruising, tinnitus Avoid high doses in patients with G6PD, as easier bleeding may potentially occur

Skeletal Muscle Relaxants

• Use cyclobenzaprine, methocarbamol and tizanidine for short-term relief: Acute muscle spasms.
• Spasmolytic Drugs are helpful against the following: Spasticity: Increase in tonic stretch reflexes Flexor muscle spasms with muscle weakness
• tizanidine: alpha-2 agonist
• cyclobenzaprine, methocarbamol: centrally acting, (poorly understood inhibition of muscle stretch reflex) AE: tizanidine:
• CNS; drowsiness, dizziness, asthenia
• EENT: dry mouth Heme: hepatotoxicity cyclobenzaprine, methocarbamol: CNS: antiadrenergic effects
• sedation, confusion, transient visual hallucinations

Analgesics & Pain

Important to know MOA for Analgesics that are being dispensed! 1)Acetaminophen •Treatment of mildmoderate pain

• Inhibit prostaglandin synthesis +Antipyretic and analgesic agent Lacks any antiinflammatory properties Larger doses: dizziness, excitement, disorientation

• Hepatic: Therapeutic doses: increase in hepatic enzymes Larger doses: severe hepatotoxicity Heme: pancytopenia Metabolic: hypoglycemia Skin: rash IDMTS are limited to prescribing a patient 3000mg acetaminophen daily

Opioid Agonists

Morphine:

• prototypical opioid agonist discovered in 1803 from opium obtained by the poppy Papaver somniferum •Examples: morphine, acetaminophen/hydrocodone, fentanyl, codeine

Clinical Applications: Analgesia: severe,constant pain Acute pulmonary edema associated with left ventricular heart failure Suppression of cough Diarrhea MOA: •main opioid receptor u(MU)-opioid receptor

• Agonist bind to receptors located in brain and spinal cord regions involved in transmission and modulation of pain +Main clinical effect: analgesia +concurrent effects: euphoria, sedation respiratory depression IDMTS are limited to prescribing 5 tabs acetaminophen/codeine daily AE: CNS: sedation Resp: repiratory depression GI: nausea, vomiting, constipation Other:
• tolerance: with repeated therapeutic doses there is a gradual loss of effectiveness physical dependence: defined as characteristic withdrawal when a drug is stopped or an antagonist is administered "addiction •Naloxone, Naltrexone +Known or suspected opioid-induced respiratory depression MOA: precise mechanism is unknown, but likely involves competitive antagonism of more than one opioid receptor in the CNS AE: CNS seizures •CV cardiac arrest ventricular fibrillation

Corticosteroids

• Corticosteroids many metabolic effects on the body, but their most important clinical effect is their anti-inflammatory and immunosuppressive effects •Examples: prednisone Clinical Application Examples: •Allergic reactions: asthma, contact dermatitis, drug reactions, allergic rhinitis, urticaria Systemic inflammation and infections: sepsis Inflammatory conditions of bones/joints: bursitis

MOA:

• *Anti-Inflammatory Effects:

• Suppressive effects on several mediators of inflammation

• inflammatory pathway: Inhibits phospholipase A2 and reduces expression of COX-2
• *When Directly Applied Topically To Skin: Vasoconstriction Decreased Capillary Permeability By Reducing Amount Histamine Released By Immune Cells
• *Medication administration: For oral or topical formulations: dosage should be as low as possible, short terms and intermittent administration should be used, when possible
• *Contraindications & Cautions: Peptic ulcer Certain infectious illnesses (VARICELLA & TB) Hypertension Psychoses Diabetes Osteoporosis Glaucoma

Corticosteroid and Administration

• Adverse Effects;

+Unusual to see serious side effects when used for LESS THAN 2 WEEKS "When used long-term (more than 2 weeks); +Metabolic Risk For Iatrogenic Cushing's Syndrome: Exposure to Excess Glucocorticoids May Lead To Rounded Plethoric" Face And Trunk Obesity Muscle Wasting Mental Wasting Mental Disorders Hypertension Osteoporosis Diabetes +Impaired wound healing Peptic ulcers +AdrenalinsuFiciency if used for long term and stopped abruptly

Special Considerations: Oral corticosteriods may be given as a “burst” or “taper”

• *Burst: same dosage daily for 5-7 days
• Example; prednisone 40mg podailly x 5 days
• **Taper: Start at higher dose for 3-5 days and slowly decline Click here for Topical Steroid Potency Table from UpToDate
• **Low potency, hydrocortisone ++High potency: clobetasol
• High potency Clobetasol Topical: Averse Effects: Metaboliç: long-term usage in large amounts may lead to iatrogenic Cushing; skin: Atrophy Rosacea Hypopigmentation

Examples; fluticasone propionate, mometasone. Clinical Application is management of seasonal and perennial allergic and non-allergic rhinitis.

Adverse Effects: headaches, MSK and respiratory function changes (joints & chest).

Cardiac Medications

Blood pressure is sustained through Cardiac output and peripheral vascular resistance by the heart Kidney regulates the volume of intravascular fluid Medications Diurectics Sympathoplegics Direct vasodilators Angiotensin pathways The pressure by relaxing the intravascular smooth muscle dilating restricted vessels and reducing peripheral Thiazides Work in the distal convolute tubule within the kidney Loops MOST EFFICACIOUS work on the LOOP of HENLE within the kidney

• Adverse side effects: GI issues Endocrine GU Polyuria Heme anemia Electrolyte

Angiotensin Pathway

Angiotensin pathway medications: agents that are BLOCK production or of the angiotensin agents therefore reducing peripheral vascular restriction

• Angiotensin is caused by the kidneys releasing Renin "Angiotensin is produced and the Renin affects the the angiotensin to to produce angiotensin Angiotensin 1 is then converted. Angiotensin in the is is converted by ENZYMES in the endothelial and turning into Angiotensin 2 helps maintain high vascular RESISTANCE AND maintains the restriction of Vasoconstriction

ACE inhibitors

• Inhibits conversion +Lisnopril, benazepril, rampiril
• *ARBS(angiotensin receptor binding agents) Block receptors of Angiotensin Losartan, Valsartan are agents +Side effects of these medications-orthostatic hypotension from going prone to standing. Also cough

Beta-Blockers and EENT Meds

• Beta blockers reduce blood pressure by reducing peripheral vas resistance, inhibiting cardiac function and increased venous poling Beta blockers examples include propranalol metoprolol atenolo •Side effects of beta blockers can be dizziness drowsiness and decreased hr

E.E. N. T and Respiratory

• Carbamide: helps facilitate ear wax removal H2O2 softens impacted ear wax Adverse Effects is it can cause skin irritation

Clinical application-Mucinex Increases respiratory action from secretions +Side of effects is headache on large doses dizziness

Nasal Decongestants & Antivirals

"Many preparations for pseudoephedrine or phenephtrine to treat URI nasal complaints Causes vasoconstriction on nasal mucous, causes hypermia swelling leading to decreased nasal congestion

Contra= hypertension & coronary artery issues Adverse reaction anxiety dizziness tremor Oxymetazoline-nasal congestion spray is similar Name it so make can be used cautiously with people as as hyperthyroidism Adverse effects dizziness drowsiness HA CNS-limited trans thermal patch Clinstipation

• Scopolamine helps with motion sickness in GI Amantadine & Ribavirin

Pharmacology of ENT & Skin

• *Name: benzonate (Tessalon Perles)

• Clinical application cough MOA: topical anesthetic respiratory receptors +AE- CNS- headaches

• Other Benzocaine

• Clinical Application sore throat or mouth +Mechanism or nerve block in oral cavity +AE localized itching and rashes montelukast inhibits leukotrienes, which relieves asthma

• Examples include Albueterial levalbuterol

• -- Eye Medications ---