Introduction to Pharmaceutics.pdf

Introduction to Pharmacology Lyndsey Garde, PharmD, BCACP, CDOE Manager, Specialty Pharmacy Clinical Services Director, PGY-1 Community Based Pharmacy Residency Program Rhode Island Hospital (Lifespan)...

Introduction to Pharmacology Lyndsey Garde, PharmD, BCACP, CDOE Manager, Specialty Pharmacy Clinical Services Director, PGY-1 Community Based Pharmacy Residency Program Rhode Island Hospital (Lifespan) 1 Objectives 1 2 3 4 5 Define the terms used Describe the Select a dosage form Differentiate an Define the terms to describe various advantages and and route of agonist, partial related to the routes of disadvantages of administration based agonist, and an regulation of receptor administration different routes of on patient-specific antagonist function administration information 2 3 Sub-Disciplines of Pharmacology Pharmacodynamics: effects and mechanisms of drug action Drug-receptor interactions Dose-response relationships Signal transduction Pharmacokinetics: movement of drug throughout the body including: Absorption Distribution Metabolism Excretion Pharmacogenetics: genetic factors play a role in the following: Rate of drug metabolism Drug-induced toxicity Drug-induced allergies 4 Drug Administration Drug treatment requires getting a drug to its specific target site or sites in tissues where the drug has its action. Drug is introduced into the body (the process of administration), sometimes far from this target site. Drug must move into the bloodstream (the process of absorption) and be transported to the target sites where the drug is needed (the process of distribution). Some drugs are chemically altered (the process of metabolism) by the body before they take effect, others are metabolized afterward, and still others are not metabolized at all. The final step is the removal of the drug and its metabolites (byproducts) from the body (the process of elimination). 5 With respect to dosage forms, the following aspects are important: What they are Why we need them What goes into them (ingredients) How they are made How they are tested What effect they have on the body (biological system) How the body affects them Their stability The advantages and disadvantages of each type How to choose from the different types of dosage forms, of the same drug, for a particular patient 6 7 Need for Dosage Forms Dosage forms are the physical unit or form in which drugs, or active pharmaceutical ingredients (API), are supplied to the patient. Contains inactive ingredients, or excipients, which help to create the dosage form, or confer specialized attributes to the dosage form. Older dosage forms cease to be popular and are discontinued. New or novel dosage forms are the subject of research and development. 8 Routes of Drug Administration with the Corresponding Dosage Forms Route Dosage Forms Route Dosage Forms Oral Syrups Rectal Creams Elixirs Ointments Emulsions Gels Tablets Suppositories Oral disintegrating tablets Aerosol foams Sustained-release tablets Enemas Enteric-coated tablets Vaginal Creams Capsules Ointments Softgels Gels Oral Mucosal Tablets Suppositories Solutions Softgels Thin Films Topical Creams Gels Ointments Creams Gels Ointments Transdermal patches Pastes Lotions Colonic Rectal foams 9 Routes of Drug Administration with the Corresponding Dosage Forms Route Dosage Forms Route Dosage Forms Otic Aqueous drops Ocular Drops Oily drops Suspensions Gels Nasal Creams Topical devices Ointments Inserts Gels Intraocular injections Drops Sprays Intravenous Aqueous solutions Metered-dose sprays Intramuscular Aqueous solutions Pulmonary Metered-dose inhalers Oily solutions Dry powder inhalers Suspensions Capsules for dry powder inhalation Nebulized solutions Subcutaneous Aqueous solutions Aqueous suspensions 10 The goal of the preparation of dosage forms is to provide an accurate amount, or dose, of the drug in a physical entity or unit that is convenient to administer, that provides stability to the drug, and in which the entity, itself, is stable. 11 The Ideal Therapy Administer to a patient a single drug which has only one effect. Desired to treat the disease and there would be no unwanted or side effects. The drug would pass directly to the site of action, which is normally, but not always, a drug receptor in an organ, or part of an organ, where the effect is required. The desired response, such as the relief of pain, it is brought about in that part of the body only, without affecting other organs. 12 A “Package Deal” The remaining, intact, drug passes into the Dosage form is general circulation and Pharmaceutical scientists, clinicians, swallowed. carried to the site of and the patient population must action. contend with drugs with multiple effects, including many undesirable effects. Passes into the The blood carries the drug to the liver where stomach and releases The drug’s beneficial effects and its its drug content. a portion is metabolized side effects are a “package deal”: it is to an inactive form. not possible to have one without the other at the present time. The “route of drug administration” Drug then passes into Upon absorption, the means the passage or path by which drug passes into the the small intestine. bloodstream. the drug is introduced into the body 13 Which Route of Drug Administration to Utilize? Often there is a choice. What are the properties of the drug under consideration? The choice will depend on factors such as Us a systemic effect, or a localized effect, desired? The nature of the drug The therapeutic need What is the metabolic profile of the drug and in which locations is it metabolized? The stability of the drug in biological fluids What is the stability of the drug? The permeability of different tissues The condition of the patient Is the typical patient ambulatory or hospitalized? 14 Oral or Enteral Route Pros Safe Convenient May be less expensive Cons First pass effect Slower onset of action Drug-food interactions 15 16 Some Potential Problems Patients with difficulty in swallowing The taste of the drug may dissuade patients from taking the medication The drug may cause nausea or irritation The highly-acidic environment in the stomach may promote drug degradation. Enzymes in the gastrointestinal tract may degrade the drug Absorption may be limited 17 Liquid vs. Solid Oral Dosage Forms Pros Accurate dose Less bulky Longer beyond use date More palatable Special release characteristics Cons More specific dosing Easier to swallow Faster onset of action 18 Controlled Release Dosage Forms Pros Cons Less fluctuation in drug blood levels Loss of flexibility in adjusting the dose Frequency reduction in dosing Inability to manipulate administration Enhanced convenience and compliance Reduction in adverse side effects 19 Buccal and Sublingual Delivery Pros Avoid first pass effect Rapid onset of action Cons Avoid in patients with oral cavity injury Avoid eating/drinking until medication dissolves completely 20 Rectal Delivery Pros Cons Lower first pass effect than oral Irregular and unpredictable administration absorption Alternate oral route if patient is Embarrassment or discomfort for unable to take by mouth patient or caregiver Avoid in patients with immunosuppression or increased risk of bleeding 21 Transdermal Only a small part of the skin needs to be utilized Delivery Can be applied to different areas of the body at each Allows skin to recover dosing interval Epidermis of the skin contains densely packed cells which contain keratin (a wax-like substance), and the epidermal layer is a barrier to drug absorption Provides slow permeation Provides long duration of resulting in consistent drug action levels for extended periods 22 Pulmonary Delivery Used mostly for local delivery of drugs (e.g. bronchodilators and anti-inflammatory steroids for asthma and chronic obstructive pulmonary disease) The following attributes of the lungs make this route advantageous: The surface area is large It is well supplied with blood vessels The drug passes directly into the bloodstream and the effect is, therefore, very rapid The route avoids hepatic first-pass. The size of particles administered by means of inhalation influences the part of the lung which they reach Large particles, for example, do not go down far enough into the lung where the drug is needed 23 Intramuscular Injection Pros Sustained effects Suspension allows a slow release Solution allows a rapid release Cons Inadvertent subcutaneous administration Pain/patient anxiety Risk of nerve injury Avoid in patients with increased bleeding tendency 24 Subcutaneous Injection 25 Intravenous Administration Pros Can administer drugs destroyed or inactivated in GI tract or with poor bioavailability Rapid onset of action Cons Removal after inadvertent overdose is more difficult More expensive Administered by trained professional Infection risk 26 Summary Dosage forms are necessary for several primary reasons including: to provide accurate dosing, convenience of administration, and protect the drug. Dosage forms may also control the rate of drug release, mask the taste of the drug, separate incompatible ingredients, etc. The oral route of drug administration is well known but several alternative routes are used to confer specific advantage, or used when specific drugs cannot be administered via the oral route. Innovative, novel drug delivery systems can supply drugs to an organ that is difficult to reach by conventional routes, without causing systemic toxicity. 27  What are the body Where is the function changes caused molecular site of action? by a drug (pharmacodynamics)? Pharmacology What is the relationship and the between the Dose vs. Effect? How does a drug produce its effect? Pharmacist What is the interplay What is the fate of the between genetic drug once it enters the makeup and drug body (pharmacokinetics)? response? 28 Drug-Receptor Interactions Receptors: protein molecules including enzymes, transporters and ion channels where a ligand (specific endogenous neurotransmitter/hormone or an external pharmacological agent (drug)) binds to, resulting in a cellular response. Orphan Receptors are receptors for which the ligand remains unknown. Ligand is an ion or molecule that forms a complex with a biomolecule to serve a specific biological purpose 29 Endogenous Ligands Neurotransmitters[NT]: chemical messengers signaling across a synaptic cleft Acetylcholine [Ach] Epinephrine [EPI] Norepinephrine [NE] 30 Endogenous Ligands Hormones (peptide): secreted from neuroendocrine cells into the blood to signal at distant cells and tissues. Aldosterone Insulin Nerve growth factor [NGF] Thyroid hormone [TH] 31  DRUG: A chemical agent that selectively interacts with specific target molecules (i.e. receptors) to alter their specific physiological functions. Agonist: drug that activates Pharmacodynamics receptors to result in either stimulation or inhibition of the function of various types of cells and organs. Antagonist: drug that prevents receptor activation by agonists. 32 Factors Contributing to Drug Effect 1. Drug dosage: effect of drug increases with increased amount of drug up to the POINT OF RECEPTOR SATURATION 2. Number of Receptors: receptors may be differentially expressed in one tissue to the next and, therefore, mediate different levels of biological responses. 3. Disease states: disease states can effect drug pharmacology 4. Drug Efficacy/Intrinsic activity: ability to activate or block a receptor: maximum effect a drug can produce regardless of the dose 5. Drug Potency/Affinity: rate of drug-receptor binding and drug-receptor release: amount of drug needed to produce a particular effect: drug affinity for receptor: 33 Summary Depending on their effect on receptors in the body, drugs can be grouped into receptor agonists, partial agonists, and antagonists. An agonist is a drug that binds to a receptor and activates it, mimicking the effects of the body's natural ligands. It can have a full or high efficacy on the receptor. A partial agonist also binds to a receptor but only partially activates it. It has lower efficacy than a full agonist. An antagonist binds to a receptor but does not activate it. Instead, it blocks or interferes with the action of other ligands and drugs. 34 References "Dosage Forms and Routes of Drug Administration." Pharmaceutics for Pharmacy Students Ed. Indiran Pather. McGraw Hill, 2024, https://accesspharmacy.mhmedical.com/content.aspx?bookid=3459&sectionid=285254048. Goodman & Gilman's: The Pharmacological Basis of Therapeutics, 13e Eds. Laurence L. Brunton, et al. McGraw-Hill Education, 2017, https://accessmedicine.mhmedical.com/content.aspx?bookid=2189&sectionid=165936845. 35 Thank you Lyndsey Garde, PharmD, BCACP, CDOE [email protected]