Drugs and Diseases Module II Fall 2024 PDF

2024-09-09 Dr. Usama Elbayoumi 1 PHAR18629 1 2 PHAR18629 2 1  2024-09-09 What is Pharmacology? Pharmacology is the branch of medi...

2024-09-09 Dr. Usama Elbayoumi 1 PHAR18629 1 2 PHAR18629 2 1  2024-09-09 What is Pharmacology? Pharmacology is the branch of medicine and biology that studies the interactions between drugs and living organisms. It involves understanding how the body affects the drug (pharmacokinetics) and how the drug affects the body (pharmacokinetics) 3 PHAR18629 3 What is “Drug” A substance used in the diagnosis, treatment, mitigation, or prevention of a disease or condition, or to affect the structure or function of the body. 4 PHAR18629 4 2  2024-09-09 Drugs – What we need to know Development Strengths Names Classification Dosage Sources Forms Mission Location 5 PHAR18629 5 6 PHAR18629 6 3  2024-09-09 Target identification (disease research) 7 PHAR18629 7 Target Validation (will we really get the effect?) 8 PHAR18629 8 4  2024-09-09 Lead Compound Identification by screening a library of molecules 9 PHAR18629 9 Lead Optimization (improve safety, selectivity, absorption, metabolism, etc.) 10 PHAR18629 10 5  2024-09-09 In-Vitro Testing (cell-based testing for toxicity and mechanism of action) 11 PHAR18629 11 In-Vivo Pre-clinical Testing (animal models – Test toxicity, dynamics, and kinetics) 12 PHAR18629 12 6  2024-09-09 Formulation Development 13 PHAR18629 13 Clinical Trials Phase Description 20-100 healthy volunteers use the drug for one-few months Phase I General impression about the effect, adverse effects, toxicity, acceptable dose, kinetics, dynamics and interactions 200-300 patients use the drug for several months to 2 years Phase II Learn more about safety and efficacy and determine the most effective dose and regimen Hundreds to thousands of patients The duration depend on the diseases Phase III Learn more about the drug and compare safety and efficacy to other therapies and test the effect on different levels of severity Thousands of patients (including patients with other diseases) Phase IV Ongoing monitoring/ comparison of the drug efficacy and (Post safety, identify new indications, test the drug on new Marketing) populations, and identify rare adverse reactions. It may result in drug withdrawal or restrictions. 14 PHAR18629 14 7  2024-09-09 https://app.biorender.com/biorender-templates/t-6369333ba24cc6457e749d87 15 PHAR18629 15 16 PHAR18629 16 8  2024-09-09 Drug Names Each Drug Has 3 Names Chemical Name Generic Name Brand Name(s) 17 PHAR18629 17 Drug Names Chemical Name Describes the chemical make up of the drug Difficult and not commonly used N-(4-hydroxyphenyl)acetamide, N-(4-hydroxyphenyl)ethanamide 18 PHAR18629 18 9  2024-09-09 Drug Names Generic Name Non-proprietary name. Assigned to chemicals by WHO (International Non-proprietary Names (INN) system – internationally recognized) and United States Adopted Names (USAN) Council. They usually match with few exceptions. Names should be easy to pronounce, not confusing with other names, and consistent (e.g., statin) 19 PHAR18629 19 Drug Names Brand Name Proprietary name or trade name Assigned to the drug by the manufacturer and approved by authorities. Protected by trademark laws. 20 PHAR18629 20 10  2024-09-09 21 PHAR18629 21 22 PHAR18629 22 11  2024-09-09 Sources of Drugs Natural Synthetic Biotechnology 23 PHAR18629 23 Sources of Drugs – Natural Plants https://jk-ingredients.en. https://pfaf.org Digoxin Sennosides (Digitalis Lanata) (Senna Alexandria) 24 PHAR18629 24 12  2024-09-09 Sources of Drugs – Natural Animals 25 PHAR18629 25 Sources of Drugs – Natural Microorganisms https://en.wikipedia.org/wiki/P https://www.sciencesource.com enicillium_chrysogenum Penicillin Streptomycin (Penicillium chrysogenum) (Streptomyces griseus) 26 PHAR18629 26 13  2024-09-09 Sources of Drugs – Natural Marine Sources https://www.flickr.com https://inaturalist.ca Trabectedin Ziconotide (Sea squirt Ecteinascidia (Venom of cone snail turbinata) Conus magus) 27 PHAR18629 27 Sources of Drugs – Natural Mineral Sources https://www.britannica.com/s https://en.wikipedia.org/wiki/ cience/calcium-carbonate Magnesium_sulfate Calcium Carbonate Magnesium Sulfate 28 PHAR18629 28 14  2024-09-09 Sources of Drugs – Synthetic Acetaminophen Diazepam Ramipril Atorvastatin 29 PHAR18629 29 Sources of Drugs – Biotechnology Adalimumab Human Insulin Erythropoietin Interferon https://www.sciencedirect.com/topics/phar macology-toxicology-and-pharmaceutical- science/recombinant-human-insulin 30 PHAR18629 30 15  2024-09-09 31 PHAR18629 31 Expression of Drug Strength Expression Examples Quantity of the drug g (gram), mg (milligram), mcg (microgram), mEq (milliequivalent), mmol (millimole) Proportion of the % drug per unit Ratio 1:10,000 Measure of Units biological effect 32 PHAR18629 32 16  2024-09-09 Expression of Drug Strength 33 PHAR18629 33 34 PHAR18629 34 17  2024-09-09 Drug Classification Legal Classification Dispensing requirements: prescription drugs and non-prescription drugs. Drug schedule: narcotics, controlled, targeted substances, and prescription drugs list. 35 PHAR18629 35 Drug Classification Pharmacological/Therapeutic Effect Vasodilators Antacids Analgesics Antihypertensive drugs Anticoagulant drugs Antidepressants 36 PHAR18629 36 18  2024-09-09 Drug Classification Chemical Structure Beta lactams Opioids Steroids Benzodiazepines 37 PHAR18629 37 Drug Classification Mechanism of Action SSRI (Selective Serotonin Reuptake Inhibitor) CCB (Calcium Channel Blockers) ACEI (Angiotensin Converting Enzyme Inhibitors) 38 PHAR18629 38 19  2024-09-09 Drug Classification Route of Administration Oral Sublingual Rectal Vaginal Topical Parenteral Inhalers Transdermal 39 PHAR18629 39 Drug Classification Dosage Form Solid: tablets, capsules, powders, etc. Liquids: solutions, suspensions, emulsions, etc. Semisolid: creams, ointments, etc. Gaseous 40 PHAR18629 40 20  2024-09-09 Drug Classification Sterility Sterile drugs Non-sterile drugs 41 PHAR18629 41 Drug Classification WHO ATC System Classify the drugs based on the anatomical (A), therapeutic (T) and chemical (C) base. Each drug has an alpha-numeric code that describes the drug classification 42 PHAR18629 42 21  2024-09-09 Drug Classification WHO ATC System Level Example 1- Anatomical Indicates the main anatomical group (e.g., (C) for Cardiovascular system). 2- Therapeutic Indicates therapeutic subgroup (e.g., 03 for Diuretics) 3- Pharmacological Refers to the pharmacological subgroup (e.g., (C) for loop diuretics). 4- Chemical Further refines the classification (e.g., (A) for Sulfonamides). 5- Substance Specifies the actual drug (e.g., (01) for Furosemide). 43 PHAR18629 43 Drug Classification WHO ATC System C03CA01 Cardiovascular 44 PHAR18629 44 22  2024-09-09 Drug Classification WHO ATC System C03CA01Diuretic 45 PHAR18629 45 Drug Classification WHO ATC System C03CA01 Loop 46 PHAR18629 46 23  2024-09-09 Drug Classification WHO ATC System C03CA01 Sulfonamide 47 PHAR18629 47 Drug Classification WHO ATC System C03CA01 Furosemide 48 PHAR18629 48 24  2024-09-09 Drug Classification AHFS (American Hospital Formulary Service) Widely used in north America. Each drug has a 2,4, or 6-digit code with three level of hierarchal information. 49 PHAR18629 49 https://www.ocpinfo.com/wp-content/uploads/2022/12/AHFS- american-hospital-formulary-service-rise-online-training.pdf 50 PHAR18629 50 25  2024-09-09 51 PHAR18629 51 Drugs Dosage Forms Solids Liquids Drugs Dosage Semisolids Forms Gaseous Others 52 PHAR18629 52 26  2024-09-09 Drugs Dosage Forms Solid Liquids Drugs Dosage Semisolid Forms Gaseous Others 53 PHAR18629 53 Solid Dosage Forms Tablets Capsules Powder/Granules Suppositories Lozenges 54 PHAR18629 54 27  2024-09-09 Tablets Prepared by the compression of the active ingredients along with other additives. Can be administered by many routes: oral, sublingual, buccal, chewable, vaginal, and implantable tablets. 55 PHAR18629 55 Tablets 56 PHAR18629 56 28  2024-09-09 Tablets Additive Purpose Diluents Make the tablets bulky to ease swallowing and handling Binders Promote adhesiveness of ingredients, give tablets strength, and intactness Disintegrants Ensure tablets breakdown into small particles in body fluids Lubricants Prevent the sticking of the powder to equipment Glidants Improve the flow of the powder mixture during manufacturing 57 PHAR18629 57 Tablets Additive Purpose Coating Agents Protective, decorative, or controlling drug release Coloring Agents Improve appearance and identification Sweeteners Used in chewable and dispersible tablets Wetting Agents Enhance the solubility of poorly soluble drugs Preservatives Enhance stability and shelf-life of the moisture-sensitive, and sugar-containing formulations. 58 PHAR18629 58 29  2024-09-09 Types of Tablets Conventional (Compressed) Tablets Prepared by the compression of the active ingredients Intended for immediate release 59 PHAR18629 59 Types of Tablets Coated Tablets Enteric coated Sugar coated: mask taste, improve appearance, ease swallowing, and protect from air Film coated: a layer of thin polymer that mask taste, and improve appearance, and stability 60 PHAR18629 60 30  2024-09-09 Types of Tablets Coated Tablets Targeted Coating: dissolve at certain location within the GIT. Delayed release coating: Release the drug after certain time of administration 61 PHAR18629 61 Types of Tablets Multilayered Tablets Used to promote sequential release or mix incompatible drugs https://www.ptk-gb.com/about/news/latest- news/multi-layer-tablets/ 62 PHAR18629 62 31  2024-09-09 Types of Tablets Matrix Tablets The drug is dispersed within a polymer or hydrophobic matrix which controls the rate of drug release. https://www.researchgate.net/figure/Mechanism-of-drug-release-from-matrix-tablets_fig4_334957997 63 PHAR18629 63 Tablets Advantages of Tablets Convenience Accurate Dosing Stability: longer shelf-life compared to liquid Cost-Effectiveness: suitable for large scale production, making them affordable. 64 PHAR18629 64 32  2024-09-09 Tablets Advantages of Tablets Versatility: coated, controlled release, chewable, etc. Ease of distribution: packaging, storage, transportation, etc. Identifiable 65 PHAR18629 65 Tablets Disadvantages of Tablets Formulation limitations: poor compressibility, poor wettability, instability, or sensitivity to heat and moisture during manufacturing Delayed onset: not ideal for very fast effect due to the need for disintegration, dissolution, absorption, etc. 66 PHAR18629 66 33  2024-09-09 Tablets Disadvantages of Tablets Oral tablets: Swallowing difficulty (e.g., elderly and children) Objectionable taste/odor 67 PHAR18629 67 Capsules A dosage form in which one or more substance are enclosed within a gelatin or polymer shell which may be soft or hard. Intended to be swallowed whole but occasionally, it can be opened, sprinkled, and ingested (e.g., lansoprazole capsules) 68 PHAR18629 68 34  2024-09-09 Types of Capsules Hard Gelatin Capsule Composed of two rigid shells (body and cap) that fit together to enclose the drug. They are typically filled with powders, granules, pellets, or small tablets https://blog.capscanada.com/gelatin- capsules-everything-you-need-to-know 69 PHAR18629 69 Types of Capsules Soft Gelatin Capsule (Softgels) Made from a flexible, gelatin-based shell that is often plasticized with glycerin or sorbitol Typically contain drug liquid, oil-based formulations, or suspensions 70 PHAR18629 70 35  2024-09-09 Capsules Advantages of Capsules Ease of swallowing. Capsules can be opened (restrictions apply). Taste and odor masking Flexible formulation: contain powder, liquid, granules, pellets, etc. Hard gelatin capsules dissolve and release the drug rapidly in the stomach compared to tablets Protect the drug from light, moisture, and oxygen 71 PHAR18629 71 Capsules Disadvantages of Capsules Higher production cost Moisture sensitive (low = brittle, high = soft) Temperature sensitive Not suitable for hygroscopic substance Risk of cross-linking Liquid-filled capsules may leak Not suitable for vegetarian/vegan (hydroxypropyl methyl cellulose are available) 72 PHAR18629 72 36  2024-09-09 Suppositories Intended for insertion into body orifices where they melt, or dissolve, and release the drugs Made of drug mixed with a base Variable sizes and shapes Used for local or systemic effect Can be rectal, vaginal (Pessaries), and urethral suppositories (Bougies) 73 PHAR18629 73 Suppositories Advantages of Suppositories See rectal route of administration 74 PHAR18629 74 37  2024-09-09 Suppositories Disadvantages of Suppositories May require special storage Less convenient for frequent administration 75 PHAR18629 75 Powder A mixture of finely divided drugs or chemicals in dry form Can be used internally (e.g., polyethylene glycol) or externally (talcum powder) 76 PHAR18629 76 38  2024-09-09 Powder Advantages of Powder Can be mixed with food or liquids, making them easier to administer Rapid onset of action because of fast dissolution and absorption Flexible dosing More stable, compared to liquids Less expensive to manufacture and package 77 PHAR18629 77 Powder Disadvantages of Powder Less palatable (taste and texture) Dosing inaccuracy if not pre-packaged Handling can be messy Hygroscopic powders may clump or disintegrate Measuring out the dose can be inconvenient and time consuming Not suitable for all drugs (e.g., drugs with poor solubility, or the need for controlled release) 78 PHAR18629 78 39  2024-09-09 Drugs Dosage Forms Solid Liquids Drugs Dosage Semisolid Forms Gaseous Others 79 PHAR18629 79 Liquid Formulations Solution Suspension Elixir Emulsion 80 PHAR18629 80 40  2024-09-09 Liquid Formulations Advantages of Liquid Formulations Rapid absorption (particularly solutions) Easier to swallow Flexible dosing Multiple Routes of administration Customizable flavor (if used orally) 81 PHAR18629 81 Liquid Formulations Disadvantages of liquid Formulations Liquid formulations (especially solutions) are generally less stable than solid forms Taste and texture Bulkier, heavier, and less convenient to transport Spillage Measurement issues Susceptible to microbial contamination 82 PHAR18629 82 41  2024-09-09 Solutions A homogenous mixture composed of one or more solute dissolved in solvent Advantages of Solutions Sam advantages for liquids plus Rapid onset of action Uniform distribution allows consistent dosing 83 PHAR18629 83 Solutions Solutions are used for many routes of administration. In the next few slides, we will focus oral solutions 84 PHAR18629 84 42  2024-09-09 Oral Solutions Solute(s) dissolved in water or cosolvent/water mixture and may contain flavoring agents Types: solutions in water, syrup, and elixir https://aplmed.com 85 PHAR18629 85 Oral Solutions Oral Syrup Oral solutions that contain high concentration of sugar “Syrup” is a term used to describe liquid dosage prepared in a sweet viscous vehicle. Syrup NF is a concentrated or nearly saturated aq. solution of sugar (85% w/v) 86 PHAR18629 86 43  2024-09-09 Oral Solutions Oral Syrup Advantages: self-preserved (with sugar concentration of 65 – 70%) Disadvantages: Low solvent capacity for water soluble drugs If diluted becomes media for bacterial growth Temperature changes may cause crystallization 87 PHAR18629 87 Oral Solutions Oral Elixir Oral solutions that contain alcohol as cosolvent (alcohol conc.= 5 – 40 %). It used to dissolve drugs with little solubility Less susceptible to microbial contamination https://odanlab.com/product/newdex amethasone-elixir/#iLightbox[]/0 88 PHAR18629 88 44  2024-09-09 Oral Solutions Oral Elixir Disadvantages Alcohol contents is unsuitable for certain cultures Possible drug-alcohol interaction Potential abuse 89 PHAR18629 89 Suspensions A heterogeneous mixture composed of finely divided powder of insoluble drug dispersed in water. https://www.castanet.net/news/West- Kelowna/401545/Pharmacies-ready-to- help-find-Plan-B-to-amoxicillin 90 PHAR18629 90 45  2024-09-09 Suspensions Contain suspending agent such as Acacia, Tragacanth, or Methylcellulose Some unstable drugs are supplied in dry powder and water is added to form suspension at the time of dispensing https://images.app.goo.gl/i993JuSPqvCj7hG36 91 PHAR18629 91 Suspensions Problems with Suspensions Sedimentation, flocculation, and floating https://www.viscotec.de/en/suspensions-and-their-filling/ 92 PHAR18629 92 46  2024-09-09 Suspensions Problems with Suspensions Sedimentation More dense particles settle at the bottom of the container Result in uneven drug distribution Prolonged semination can https://www.researchgate.net/figure/Repres entative-example-of-the-sedimentation-and- redispersion-of-the- cause caking diazoxide_fig2_309023827 93 PHAR18629 93 Suspensions Problems with Suspensions Floating Less dense particles float on the surface Result in uneven drug distribution 94 PHAR18629 94 47  2024-09-09 Suspensions Problems with Suspensions Flocculation Individual drug particles aggregate into loose clusters or flocs. The particles are easily redispersed It is desirable because it prevents caking 95 PHAR18629 95 Suspensions Advantages of Suspensions Suitable for drugs unstable in solution Suitable for drugs insoluble in water Better taste masking by converting soluble drug to insoluble form The particle size can be adjusted for slow drug release 96 PHAR18629 96 48  2024-09-09 Suspensions Disadvantages of Suspensions Sedimentation, caking, and floating Risk of inaccurate dosing Texture Complex formulation: particle size, viscosity, suspending agents, etc. 97 PHAR18629 97 Emulsions A dosage form in which the drug is dispersed (dispersed phase) as fine droplets in an immiscible liquid (continuous phase) The drug can be oil suspended in water (o/w) or aqueous drug suspended in oil (w/o) 98 PHAR18629 98 49  2024-09-09 Emulsions Require an emulsifying agent (e.g., acacia, tragacanth, soaps, 1% benzalkonium chloride, spans, tweens) to prevent separation and promote re-distribution 99 PHAR18629 99 Emulsions https://www.mdpi.com/2073-4441/15/17/3093 Droplets form a concentrated layer at the top or the bottom of the emulsion. Results from difference in density It is reversible 100 PHAR18629 100 50  2024-09-09 Emulsions Droplets of the dispersed phase merge https://www.mdpi.com/2073-4441/15/17/3093 Results from weakened/rupture film around the droplets Less reversible than creaming and can lead to breaking 101 PHAR18629 101 Emulsions https://www.mdpi.com/2073-4441/15/17/3093 Breaking (cracking) is when the dispersed phase separate from the continuous phase. Results from failure of the emulsifying system due to heat, pH change, extreme coalescence Irreversible 102 PHAR18629 102 51  2024-09-09 Emulsions Advantages of Emulsions Enhanced solubility for poorly soluble drugs Enhanced stability for drugs unstable in water Controlled drug release Improved taste masking 103 PHAR18629 103 Emulsions Disadvantages of Emulsions Subject to coalescence and breaking Complex formulation Risk of inaccurate dosing 104 PHAR18629 104 52  2024-09-09 Drugs Dosage Forms Solid Liquids Drugs Dosage Semisolid Forms Gaseous Others 105 PHAR18629 105 Semisolid Dosage Forms Creams Ointments Gels Lotions Pastes 106 PHAR18629 106 53  2024-09-09 Creams Creams contain one or more active ingredients dispersed or dissolved in a hydrophilic base Commonly used topically but may have systemic effect 107 PHAR18629 107 Creams Advantages of Creams Easy to apply and spread Cosmetically accepted – non-greasy Washable Rapid absorption and fast effect Moisturizing effect because of emollient property 108 PHAR18629 108 54  2024-09-09 Creams Disadvantages of Creams Short action – frequent application Potential for skin irritation especially if applied to inflamed area or if it contains preservative or fragrance Limited occlusive effect – less effective in preventing evaporation of moisture from the skin 109 PHAR18629 109 Ointments Ointments contain one or more active ingredients dispersed of dissolved in an oleaginous base Commonly used topically but may have systemic https://www.britannica.com/science/petroleum-jelly effect 110 PHAR18629 110 55  2024-09-09 Ointments Advantages of Ointments Effective occlusion Enhanced drug penetration: oily base penetrate deeper skin Long-lasting effect because of the residual effect Less irritation compared to creams (no preservative, additives, etc.) – eye/ sensitive skin 111 PHAR18629 111 Ointments Disadvantages of Ointments Greasy/ sticky texture Not washable Less cosmetically acceptable Slow absorption = slow effect Not suitable for hairy areas – scalp Pore blockage leading to folliculitis or acne https://www.aucklandskinclinic.co.nz/folliculitis/ 112 PHAR18629 112 56  2024-09-09 Gels Semisolid formulation that typically contain alcohol Alcohol serves a gelling agent, solvent, penetration enhancer, preservative, and cooling agent Gels are typically clear or translucent Self-drying 113 PHAR18629 113 Gels Advantages of Gels Ease of application Cooling effect Cosmetically acceptable Rapid absorption Suitable for hairs areas 114 PHAR18629 114 57  2024-09-09 Gels Disadvantages of Gels Skin dryness (most drying among all) Skin irritation 115 PHAR18629 115 Lotions Semisolid formulation that consist of o/w emulsion or w/o emulsion Spread easily Suitable for hairy areas https://www.bwitchingbathco.com/Golden-Oats- Shea-Butter-Hand-and-Body-Lotion-p/bl55go.htm 116 PHAR18629 116 58  2024-09-09 Pastes A dosage form that is thicker and stiffer than other semisolids and it contains a high concentration (20- 50%) of finely dispersed solid particles within a base Do not spread easily and stick well to skin, so form protective layer The high concentration has high absorbing effect make them useful for weeping skin 117 PHAR18629 117 Drugs Dosage Forms Solid Liquids Drugs Dosage Semisolid Forms Gaseous Others 118 PHAR18629 118 59  2024-09-09 Gaseous Dosage Forms Refer to medicinal products that are administered in a gaseous state, usually through inhalation. Anesthetics (e.g., https://www.medicaldevice- halothane, chloroform), network.com/features/anaesthetic-gas-recycling/ and oxygen 119 PHAR18629 119 Gaseous Dosage Forms Inert gases can be used as propellent in inhalers Gaseous drugs have a fast action and provide dose control They have short action, may cause lung irritation, and effect depends on technique https://en.m.wikipedia.org/wiki/File: Salbutamol2.JPG 120 PHAR18629 120 60  2024-09-09 Drugs Dosage Forms Solid Liquids Drugs Dosage Semisolid Forms Gaseous Others 121 PHAR18629 121 Other Dosage Forms Patches A drug delivery system used to deliver the drug to/via the skin Intended for systemic or local https://www.deltamodtech.com/blog/transdermal- use patches-how-to-choose-the-right-materials/ There are different types 122 PHAR18629 122 61  2024-09-09 Patches Advantages of Patches Long action Bypass the liver Improve adherence Provide constant drug release 123 PHAR18629 123 Patches Disadvantages of Patches Skin irritation Adhesion issues Variable absorption Not suitable for all drugs 124 PHAR18629 124 62  2024-09-09 https://www.osmosis.org/learn/Aspects_of_Safe_Medication_Administration 125 PHAR18629 125 Routes of Administration Oral Sublingual Buccal Parenteral (IV, IM, SC, and intradermal) Inhalation Intranasal Rectal Vaginal Topical (dermal, otic, ophthalmic) Transdermal Urethral Implants 126 PHAR18629 126 63  2024-09-09 Oral Route (PO) Dosage forms: tablets, capsules, powders, liquids, and gels Intended effect: systemic (common) or local GIT effect (uncommon) Some drugs are used orally as orally disintegrating tablets 127 PHAR18629 127 Oral Route (PO) Advantages Convenience and compliance Oral medications are often less expensive Variety of dosage forms can be administered orally Orally disintegrating tablets work fast and suitable for patients who cannot swallow 128 PHAR18629 128 64  2024-09-09 Oral Route (PO) Disadvantages Drug taste can be a problem First-pass metabolism Delayed onset of action Gastrointestinal adverse reactions May not be suitable for all patients Absorption concerns: interactions (drugs/food), pH, gastric emptying and motility 129 PHAR18629 129 Sublingual Route (SL) The medication is placed under the tongue to dissolve and be absorbed Dosage forms: tablets, https://snacksafely.com/2019/11/sublingual- and solutions (spray) epinephrine-tablet-awaiting-clinical-trials-would- replace-the-need-for-auto-injectors-and-syringes/ Intended effect: systemic Drug absorption site: sublingual mucosa http://nitrolingual.com/how-to-use 130 PHAR18629 130 65  2024-09-09 Sublingual Route (SL) Advantages Rapid onset of action Bypass first pass metabolism Suitable for patients who cannot swallow Suitable for drugs that cannot be taken orally due to drug characteristics 131 PHAR18629 131 Sublingual Route (SL) Disadvantages Not for all drugs (must be fat soluble and potent) Unpleasant taste Limited absorption site (only small amount is absorbed) Saliva, pH, the presence of foods or drinks, and variations in mucosal permeability can affect absorption 132 PHAR18629 132 66  2024-09-09 Buccal Route The medication is placed between the tongue and inner cheek Dosage forms: tablets, and lozenges Drug absorption site: https://www.embrace-the-elements.com/2024/07/ems- buccal mucosa medication-administration-buccal.html 133 PHAR18629 133 Buccal Route Advantages Bypass first pass metabolism Rapid onset of action Suitable for drugs that cannot be taken orally due to drug characteristics Suitable for patients who cannot swallow 134 PHAR18629 134 67  2024-09-09 Buccal Route Disadvantages Not for all drugs (must be a potent drug) Unpleasant taste Saliva, pH, the presence of food or drink, and variations in mucosal permeability can affect absorption Limited absorption site (only small amount is absorbed) 135 PHAR18629 135 Parenteral Route Dosage forms: solutions, suspensions, and emulsions Drugs can be injected IM, SC, IV, ID, intrathecally, intra- articular Deltoid, gluteal and thigh Fat layer under the skin https://www.biorender.com/template/parenteral-route-of-drug-administration 136 PHAR18629 136 68  2024-09-09 Parenteral Route Advantages Rapid onset of action (especially IV) Bypass the GIT: suitable for poorly absorbed, acid-sensitive drugs, unconscious patients, patients who cannot swallow, etc. Bypass first pass metabolism Targeted delivery: Intra-articular and intrathecal https://www.macmillan.org.uk/cancer-information-and-support/treatments-and- drugs/intrathecal-chemotherapy 137 PHAR18629 137 Parenteral Route Disadvantages Pain and anxiety Improper technique can cause infection, phlebitis, tissue damage, etc. The drug must be sterile (high cost and strict preparation) Require training Once administered, the drug cannot be removed 138 PHAR18629 138 69  2024-09-09 Parenteral Route Route Advantages Immediate onset 100% bioavailability IV Precise control over drug delivery Suitable for large volume Rapid absorption than SC IM Suitable for depot effect Can inject larger volume than SC Suitable for self-administration SC Slow and sustained absorption 139 PHAR18629 139 Parenteral Route Route Disadvantages Higher risk of complications IV Require skilled personnel Can be painful IM Risk of hitting a nerve Variable absorption based on muscle mass and blood flow Slow absorption (but longer duration) compared to IV and IM Limited to small volumes (2 ml) SC Variable absorption due to variation in blood flow and fatty tissues 140 PHAR18629 140 70  2024-09-09 Inhalation Route The drug is delivered directly into the lungs using devices such as inhalers, nebulizers, or dry powder inhalers. Dosage forms: gaseous, dry powder, or mist Absorption site: lung vasculature Intended effect: local and systemic effect 141 PHAR18629 141 Inhalation Route Advantages Rapid onset of action Drug used for local effect have minimal absorption Bypass first pass metabolism Self-administration Afreeza 142 PHAR18629 142 71  2024-09-09 Inhalation Route Disadvantages Dependence on proper technique Variable drug deposition Device maintenance Some devices can be expensive Drugs must be formulated into inhalable forms – limited use 143 PHAR18629 143 Intranasal Route The drug is administered through the nasal passage. Dosage forms: gaseous, solutions, and suspensions Absorption site: nasal mucosa Intended effect: local and systemic effect https://www.ctvnews.ca/health/flu-shot-or-nasal-spray- conflicting-studies-lead-to-confusion-1.3633892 144 PHAR18629 144 72  2024-09-09 Intranasal Route Advantages Rapid onset of action Bypass first pass metabolism Suitable for self administration Drugs used for local effect have minimal systemic absorption 145 PHAR18629 145 Intranasal Route Disadvantages Not suitable for all drugs Variable absorption due to congestion, mucous, polyps, etc. Limited volume of administration (usually < 1 ml) 146 PHAR18629 146 73  2024-09-09 Rectal Route The drug is administered into the rectum Dosage forms: suppositories, ointments, solutions (enemas), creams, gels, and foams Absorption site: rectal https://myhealth.alberta.ca/Health/Pages/conditi ons.aspx?hwid=ug2974&lang=en-ca mucosa Intended effect: local and systemic effect http://www.squarepharma.com.bd/prod uct-details.php?pid=434 147 PHAR18629 147 Rectal Route Advantages Partially bypass first-pass metabolism Alternative when oral route is not suitable: swallowing difficulty, children, unconscious patients, and drugs that cause upset the stomach or vomiting Bypassing the GIT: reduce degradation 148 PHAR18629 148 74  2024-09-09 Rectal Route Disadvantages Discomfort and acceptance Variability in absorption: contents, base melting, depth of insertion, fecal matter, and variable blood flow Not suitable for all drugs Difficulty in administration Expulsion Subject to first pass metabolism 149 PHAR18629 149 Vaginal Route The drug is administered into the vagina Dosage forms: suppositories, tablets, creams, gels, films, and others Absorption site: vaginal mucosa https://www.medicalnewst Intended effect: local oday.com/articles/323008 and systemic effect 150 PHAR18629 150 75  2024-09-09 Vaginal Route Advantages Bypass first-pass metabolism Alternative route in patients who cannot take the drugs orally Versatile dosage forms https://www.washingtonpost.com/national/health-science/magazine-reports-on-alleged-dangersof-vaginal- ring-contraceptive/2013/12/20/02ae498c-669c-11e3-ae56-22de072140a2_story.html 151 PHAR18629 151 Vaginal Route Disadvantages Gender-specific Variable absorption due to vaginal secretions, menstrual cycle, vaginal pH Messy Interference with sexual activities 152 PHAR18629 152 76  2024-09-09 Topical Routes Route Advantages The drug is applied onto the skin Dosage forms: semisolid, liquids, and powder Dermal Can be messy and the drug effect depends on the skin condition such as thickness, and hydration The drug is applied into the eye Dosage forms: ointments, solutions, and suspensions The drug must be sterile Ophthalmic It has quick onset, but self-administration can be difficult, require proper technique to minimize absorption, and is used for small volume (1-2 drops) The drug is applied into the ears Dosage form: solutions and suspensions Otic Self-administration can be difficult, require proper technique, to avoid complications, and used for small volume 153 PHAR18629 153 Transdermal Route The drug is administered onto the skin for systemic effect Dosage forms: creams, ointments, gels, and patches Absorption site: the skin blood vessels Nitrodur Product Monograph Intended effect: systemic effect 154 PHAR18629 154 77  2024-09-09 Transdermal Route Advantages Sustained release Bypass of first-pass metabolism Stable plasma drug levels 155 PHAR18629 155 Transdermal Route Disadvantages The drug must be potent (limited skin absorption capacity), oil soluble, and have a small molecule Absorption is affected by skin thickness, sweating, hydration, temperature, and the site of application Patch adhesion problems 156 PHAR18629 156 78  2024-09-09 157 PHAR18629 157 Pharmacokinetics The branch of pharmacology that deals with the study of how the BODY AFFECTS THE DRUG during the DRUG JOURNEY from the site of administration until it is eliminated from the body 158 PHAR18629 158 79  2024-09-09 Pharmacokinetics A (absorption) D (distribution) M (metabolism) E (elimination) https://genomind.com/providers/introduction-to-pharmacokinetics-four-steps-in-a-drugs-journey-through-the-body/ 159 PHAR18629 159 Pharmacokinetics A (absorption) D (distribution) M (metabolism) E (elimination) https://genomind.com/providers/introduction-to-pharmacokinetics-four-steps-in-a-drugs-journey-through-the-body/ 160 PHAR18629 160 80  2024-09-09 Drug Absorption Drug absorption refers to the process by which a drug moves, after administration, across cell membranes, into the bloodstream. 161 PHAR18629 161 Drug Absorption Drug Factors Affecting Absorption Solubility: Drugs must dissolve in bodily fluids Dosage form Drug formulation (e.g., sustained release, too much binder, etc.) Molecular Size Drug chemistry: Lipophilic or hydrophilic Drug stability (e.g., degradation by acid) Drug interaction: IV incompatibility and interactions in the stomach 162 PHAR18629 162 81  2024-09-09 Drug Absorption https://www.verywellhealth.com/und erstanding-intestinal-villi-562555 Route of Administration Factors The route of administration Surface area for absorption Condition of absorption site (e.g., cracked skin) First pass metabolism Blood flow at the absorption site (e.g., IM versus IV) https://www.teethtalkgirl.com/d ental-health/caviar-tongue/ 163 PHAR18629 163 Drug Absorption The Membrane 164 PHAR18629 164 82  2024-09-09 Drug Absorption The Membrane The cell membrane is composed mainly of lipid and protein. The framework consists of a double layer of phospholipids. https://blog.cambridgecoaching.com/what-is-the- phospholipid-bilayer-and-what-determines-its-fluidity 165 PHAR18629 165 Drug Absorption The Membrane Molecules are embedded in the bilayer Cholesterol: strengthen the membrane and make it more water impermeable https://old-ib.bioninja.com.au/standard-level/topic-1-cell-biology/13-membrane-structure/cholesterol.html 166 PHAR18629 166 83  2024-09-09 Drug Absorption The Membrane Molecules are embedded in the bilayer Proteins: act as receptors, carriers (channels), form glycoproteins which are important for cell identification, and as adhesion molecules https://socratic.org/questions/what-do-proteins-do-in-the-cell-membrane 167 PHAR18629 167 Drug Absorption How Drugs Cross the Cell Membrane 168 PHAR18629 168 84  2024-09-09 Drug Absorption Membrane Factors Affecting Absorption Membrane permeability Lipophilic drugs pass through membranes Small hydrophilic drugs can pass through the pores Drugs move across the membrane by carriers Presence of efflux pumps Blood supply across the membrane 169 PHAR18629 169 Drug Absorption Physiological Factors Affecting Absorption Age: decreased GI fluids and absorption surface area Factors affect contact time: delayed gastric emptying, diarrhea, sweating, GI diseases (e.g., Crohn’s disease), etc. 170 PHAR18629 170 85  2024-09-09 Drug Distribution The process of drug transportation into the bloodstream to various tissues and organs 171 PHAR18629 171 Drug Distribution Drug Factors Affecting Distribution Lipophilic drugs penetrate more tissue while water soluble drugs remain in the bloodstream Molecular size Binding to plasma proteins (e.g., albumin) versus free drug 172 PHAR18629 172 86  2024-09-09 Drug Distribution Drug Factors Affecting Distribution Drugs competition for the binding site (e.g., warfarin) Drug affinity to tissues (e.g., tetracycline and bone or anesthetics and fat tissue) 173 PHAR18629 173 Drug Distribution Tissue Factors Affecting Distribution Blood flow to tissues: tissues with higher blood flow (e.g., liver, kidneys, heart) versus low blood flow (e.g., fat, bone) 174 PHAR18629 174 87  2024-09-09 Drug Distribution Tissue Factors Affecting Distribution Capillary permeability: capillaries in the liver have pores while the blood-brain barrier (BBB) has tight junctions (only highly lipid soluble can cross BBB) https://neupsykey.com/the-blood-brain-barrier- choroid-plexus-and-cerebrospinal-fluid/ 175 PHAR18629 175 Drug Distribution Physiological Factors Affecting Distribution Age: less albumin, and body fluids, and more fat Pregnancy: more fluids and change in albumin Liver diseases: less albumin Heart diseases: less circulation Renal failure: less albumin Inflammation: increases permeability of blood vessels 176 PHAR18629 176 88  2024-09-09 Drug Metabolism Chemical alteration of the drug to water soluble metabolites that can be removed by the kidney Metabolites can be inactive, less active, or more active than the drug What is a prodrug? 177 PHAR18629 177 Drug Metabolism The liver is the primary site for metabolism. Other sites are the intestines, lungs, kidneys, and blood. https://stock.adobe.com/search /images?k=liver+cartoon 178 PHAR18629 178 89  2024-09-09 Drug Metabolism Pathways of Drug Metabolism Phase I: Oxidation (most important – catalyzed by cytochrome P450 enzymes = CYP450), reduction, or hydrolysis Phase II: Conjugation with water soluble compound (e.g., glucuronidation = glucuronic acid) 179 PHAR18629 179 Drug Metabolism Cytochrome P-450 Enzymes (CYP450) A family of enzymes Catalyze drug oxidation reactions – metabolize many drugs and even endogenous substances (e.g., steroids) or toxins (ex. tobacco smoke or char-broiled meat). These enzymes play major role in drug interactions. 180 PHAR18629 180 90  2024-09-09 Drug Metabolism Cytochrome P-450 Enzymes (CYP450) CYP450 inducers: drugs that INCREASE the effect of CYP450  INCREASE the metabolism of other drugs or their own metabolism  REDUCE the drug effects Examples of enzyme inducers: tobacco smoke, phenobarbital, carbamazepine, and phenytoin 181 PHAR18629 181 Drug Metabolism Cytochrome P-450 Enzymes (CYP450) CYP450 inhibitors: drugs that DECREASE the effect of CYP450  DECREASE the metabolism of other drugs or their own metabolism  INCREASE the drug effects and adverse reactions Examples of enzyme inhibitors: azoles antifungals (e.g., fluconazole), macrolides antibiotics (e.g., clarithromycin and erythromycin), and St. Johns wart 182 PHAR18629 182 91  2024-09-09 Drug Metabolism Factors Affecting Metabolism Variation in the gene encoding the CYP450 enzymes: slow metabolizers, fast metabolizers, and ultrafast metabolizers Age: slow metabolism in neonates and elderly = higher chance of toxicity Gender: may result in some variation 183 PHAR18629 183 Drug Metabolism Factors Affecting Metabolism Liver diseases Alcohol use induces some CYP450 members Enzyme induction and inhibition by drugs Drugs may fight for the metabolizing enzymes Metabolizing Enzymes 184 PHAR18629 184 92  2024-09-09 Drug Elimination The processes by which drugs and their metabolites are removed from the body. 185 PHAR18629 185 Drug Elimination Elimination Mode First order: a constant fraction (e.g., 10%) of the drug is eliminated per unit of time (most drugs) Zero-order: a fixed amount (e.g., 10mg) of the drug is eliminated per unit of time (ex. alcohol) 186 PHAR18629 186 93  2024-09-09 Drug Elimination Elimination Pathways Renal elimination: filtration, secretion, reabsorption, and excretion https://www.medicineslearningportal.org/2015/07/kidney-and- liver-clearance.html 187 PHAR18629 187 Drug Elimination Elimination Pathways Hepatic elimination: via bile (e.g., digoxin) Pulmonary elimination: gases (e.g., halothane), are excreted through the lungs. Gastrointestinal (GI) excretion: via stool (e.g., iron and fibers) Breast milk Minor routes: sweat (e.g., caffeine and amphetamines) and saliva (e.g., phenytoin) 188 PHAR18629 188 94  2024-09-09 Drug Elimination Drugs Factors Affecting Elimination Drug Characteristics: water soluble drugs are easier to eliminate. Lipid soluble drugs are reabsorbed Protein binding reduces renal elimination Drug competition for renal elimination (e.g., aspirin and methotrexate) 189 PHAR18629 189 Drug Elimination Physiological Factors Affecting Elimination Age: Elderly and neonates Disease states: renal diseases, liver diseases (affect bile formation), and heart failure pH of the urine: basic urine eliminates acidic drugs and vide versa Blood flow to organs involved in elimination 190 PHAR18629 190 95  2024-09-09 Pharmacokinetics Kinetic Parameters 191 PHAR18629 191 Pharmacokinetics Kinetic Parameters Cmax : The highest level (the PEAK) the drug reaches in the blood after a specific dose. Area Under the Curve (AUC): The amount of the drug AUC available to the target tissue (bioavailability) Tmax : The time it takes to Trough : The lowest level the reach Cmax drug reaches in the blood 192 after aPHAR18629 specific dose. 192 96  2024-09-09 Pharmacokinetics Important Definitions Drug dose: The mount of drug administered at one time. Factors affect the dose include age, weight, gender, race, nutritional state, disease states, pregnancy, and interacting drugs. 193 PHAR18629 193 Pharmacokinetics Important Definitions Clearance rate: The rate at which a drug is eliminated from a specific volume of blood per unit of time Half-life (written as t ½): The time the body takes to eliminate half of the drug in the body at any time 194 PHAR18629 194 97  2024-09-09 195 PHAR18629 195 Pharmacodynamics The branch of pharmacology that deals with the study of HOW THE DRUG AFFECTS THE BODY during the DRUG JOURNEY from the site of administration until it is eliminated from the body 196 PHAR18629 196 98  2024-09-09 Pharmacodynamics Mechanism of Action The drug must reach the target tissue After reaching the tissue, the drug must interact with the tissue to produce the desired effect The mechanism of action describes the way by which the drug alters the physiological processes, leading to the desired therapeutic effect. 197 PHAR18629 197 Pharmacodynamics Mechanism of Action There are two major categories of mechanisms of action Receptor-medicated mechanism Non-receptor-mediated mechanism 198 PHAR18629 198 99  2024-09-09 Pharmacodynamics Receptor-Mediated Mechanism of Action What is a receptor? A special protein ON the surface of a cell (extracellular) or IN the cell (intracellular) https://slideplayer.com/slide/4663463/ 199 PHAR18629 199 Pharmacodynamics Receptor-Mediated Mechanism of Action The drug must bind firmly to its receptor in a lock-and-key fashion. This property is known as selectivity https://adhdrollercoaster.org/adhd-genetic-testing/genes-affect-best-adhd-medication/ 200 PHAR18629 200 100  2024-09-09 Pharmacodynamics Receptor-Mediated Mechanism of Action The binding of the drug must be easy and strong enough (not easily removed) – this is known as affinity 201 PHAR18629 201 Pharmacodynamics Receptor-Mediated Mechanism of Action The drug can bind to: the active site of the receptor a different site of the receptor, called the allosteric site, that affects alters active site. 202 PHAR18629 202 101  2024-09-09 Pharmacodynamics Drug Active Site Endogenous Compound Allosteric Site Active Site Allosteric Site Active Site Allosteric Site Drug 203 PHAR18629 203 Pharmacodynamics Receptor-Mediated Mechanism of Action After the drug binds to the receptor, there are three effects: Effect Description The drug activates the receptor and produce a full Agonist response similar to endogenous substance (e.g., salbutamol and beta-2 receptors) The drug activates the receptor but produces a weaker Partial response than full agonists (e.g., aripiprazole and D2 Agonist receptors) The drug does NOT activate the receptor and blocks the Antagonist effect of the endogenous substances (e.g., metoprolol and beta-1 receptors) 204 PHAR18629 204 102  2024-09-09 Pharmacodynamics Receptor-Mediated Mechanism of Action Types of Antagonist Competitive Antagonist: competes with endogenous substance for the same binding site on the receptor. The effect is reversible by increasing the concentration 205 PHAR18629 205 Pharmacodynamics Receptor-Mediated Mechanism of Action Types of Antagonist Non-Competitive Antagonist: binds to a different site on the receptor (allosteric site) and change the active site shape and thus prevent the endogenous substance from binding to its receptor. The effect is irreversible 206 PHAR18629 206 103  2024-09-09 Pharmacodynamics Receptor-Mediated Mechanism of Action Important Issues with Receptors Receptor Occupancy Theory: the magnitude of a drug’s effect is directly proportional to the number of receptors occupied by the drug 207 PHAR18629 207 Pharmacodynamics Receptor-Mediated Mechanism of Action Important Issues with Receptors Prolonged exposure to certain drugs may be associated with less response due to 2 phenomena Desensitization (Tachyphylaxis) Downregulation 208 PHAR18629 208 104  2024-09-09 Pharmacodynamics Receptor-Mediated Mechanism of Action Important Issues with Receptors Desensitization (Tachyphylaxis) The receptor becomes less responsive Occurs rapidly Reversible Examples: Salbutamol and nitroglycerin 209 PHAR18629 209 Pharmacodynamics Receptor-Mediated Mechanism of Action Important Issues with Receptors Downregulation The number of the receptors decreases (removal or destruction) Occurs over long time Difficult to reverse Examples: opioids 210 PHAR18629 210 105  2024-09-09 Pharmacodynamics Receptor-Mediated Mechanism of Action Important Issues with Receptors Significance of desensitization and downregulation: The patient needs a large dose for the same effect – TOLERANCE The drug should be used as needed The patient may need a drug holiday 211 PHAR18629 211 Pharmacodynamics Non-Receptor-Mediated Mechanism Simple chemical interaction. (e.g., antacids) CaCO3 + 2HCl = CaCl2 + H2O + CO2 212 PHAR18629 212 106  2024-09-09 Pharmacodynamics Non-Receptor-Mediated Mechanism Direct effect on the cell (e.g., osmotic effect of Mannitol) https://tmedweb.tulane.edu/pharm wiki/doku.php/mannitol 213 PHAR18629 213 Pharmacodynamics What is Osmosis? Osmosis is the diffusion of water across the cell membrane from an area of greater water concentration (low osmotic pressure) to an area of lower water concentration (greater osmotic pressure) https://quizlet.com/439194251/isotonic- hypertonic-hypotonic-solutions-diagram/ 214 PHAR18629 214 107  2024-09-09 Pharmacodynamics Non-Receptor-Mediated Mechanism Interaction with lipid membrane (e.g., volatile anesthetic) Inhibiting or stimulating enzymes (what is enzyme?) 215 PHAR18629 215 Pharmacodynamics What is Enzyme? Enzymes are complex proteins that serve as catalysts of biological reactions What does enzyme do? It lowers the activation energy (the energy required to start the reaction)  the reaction proceeds rapidly 216 PHAR18629 216 108  2024-09-09 Pharmacodynamics What is Enzyme? Characteristics of enzymes Very small amount is needed (very potent) Enzymes are not consumed in the reaction Many enzyme-catalyzed reactions are reversible In some cases, the enzyme catalyzes the reaction and its reverse 217 PHAR18629 217 Pharmacodynamics What is Enzyme? How Enzymes Work Substrate(s) bind selectively to the enzyme’s active site forming a complex The binding causes changes in the substrate molecule(s) that reduce the energy required for the substrate(s) to interact 218 PHAR18629 218 109  2024-09-09 Pharmacodynamics 219 PHAR18629 219 Pharmacodynamics Regulation of Enzymes Feedback and feedforward regulation Proteolytic cleavage https://old-ib.bioninja.com.au/higher-level/topic-7-nucleic-acids/73-translation/protein-modification.html 220 PHAR18629 220 110  2024-09-09 Pharmacodynamics Regulation of Enzymes Feedback and feedforward regulation Proteolytic cleavage Enzyme stimulants 221 PHAR18629 221 Pharmacodynamics Regulation of Enzymes Enzyme inhibitors: competitive (bind to the active site) or non-competitive (bind to allosteric site) 222 PHAR18629 222 111  2024-09-09 Pharmacodynamics Non-Receptor-Mediated Mechanism Interaction with carrier protein 223 PHAR18629 223 Pharmacodynamics Non-Receptor- Mediated Mechanism Blocking the reuptake certain chemicals (e.g., serotonin reuptake inhibitors) Image from Hole’s Essentials of Human Anatomy and Physiology, 10th edition, page 220 224 PHAR18629 224 112  2024-09-09 Pharmacodynamics Non-Receptor-Mediated Mechanism Incorporation into cellular components leading to interference with normal cell function (e.g., 5- flurouracil) https://molpharm.aspetjournal s.org/content/99/6/412 225 PHAR18629 225 Pharmacodynamics Drug Effect After the drug reaches the tissues and interact with the site of action it will produce an “EFFECT” The drug effect can be: Desired Effect Undesired Effect 226 PHAR18629 226 113  2024-09-09 Pharmacodynamics Desired Therapeutic Effect The desired drug effect (the effect for which the drug is administered) is known as “THERAPEUTIC EFFECT” The therapeutic effect can be a Local Effect: an effect that is confined to a specific part of the body Systemic Effect: a generalized effect on the entire body 227 PHAR18629 227 Pharmacodynamics Desired Therapeutic Effect Types of Therapeutic Effect Curing a disease (e.g., antibacterial drugs) Controlling the disease – no cure (e.g., salbutamol) Slowing the disease progression (e.g., dementia) Preventing a disease or symptoms (e.g., vaccines) Replacing a missing natural chemicals (e.g., insulin) Supplementation (e.g., vitamin D). Diagnosing a disease (e.g., radioactive dye) 228 PHAR18629 228 114  2024-09-09 Pharmacodynamics Desired Therapeutic Effect Dose-Response Curve In many cases increasing the drug dose increases the drug effect until it reaches the Ceiling Effect which is defined as a point at which no more clinical response occurs with increased dose. 229 PHAR18629 229 Pharmacodynamics Desired Therapeutic Effect Dose-Response Curve https://toxedfoundation.org/basics-of-dose-response/ 230 PHAR18629 230 115  2024-09-09 Pharmacodynamics Desired Therapeutic Effect Minimum effective concentration (MEC): The minimum drug level in the blood at which most patients will experience the therapeutic effect. Minimum toxic concentration (MTC): The minimum drug level in the blood at which most patients will experience side effects or toxicity. Therapeutic range/window: The difference between MEC and MTC. 231 PHAR18629 231 Pharmacodynamics https://ditki.com/course/pharmacology/glossary/pharmacology/therapeutic-index-therapeutic-window 232 PHAR18629 232 116  2024-09-09 Pharmacodynamics Desired Therapeutic Effect Onset of drug effect: The time it takes for a drug to reach its therapeutic effect (or the minimum effective concentration) Duration of drug effect: The time the drug concentration remains effective (remains at or above the minimum effective concentration) 233 PHAR18629 233 Pharmacokinetics Kinetic Parameters Onset of action: The length of time it takes for a drug to reach its therapeutic effect (or MEC). Duration of action: The length of time the drug remains at/above the MEC and remains AUC effective 234 PHAR18629 234 117  2024-09-09 Pharmacodynamics Desired Therapeutic Effect Potency versus Efficacy Efficacy: the maximum effect the drug can produce, regardless of dose. A more effective drug produces a higher effect compared to less effective drugs 235 PHAR18629 235 Pharmacodynamics Which drug is more effective, (A) or (B)? https://psychedelicreview.com/finding-the-psychedelic-sweet-spot/ 236 PHAR18629 236 118  2024-09-09 Pharmacodynamics Desired Therapeutic Effect Potency versus Efficacy Potency