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Class notes Philosophy 1010
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Lecture notes of 8 pages for the course Philosophy 1010 at Saint Louis University (notes)
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MODULE 4│PHARM 4BIOPHARMACEUTICS
BIOPHARMACEUTICS Biopharmaceutics involves factors that influence:
• Bio – life 1. The design of the drug product.
• Pharmaceutics – General area of study concerned with the 2. Stability of the drug within the drug product.
formulation, manufacture, stability and effectiveness of 3. The manufacture of the drug product.
pharmaceutical dosage forms. 4. The release of the drug from the product.
• Examines the interrelationship of the physical/ chemical 5. The rate of dissolution/ release of the drug at the absorption
properties of the drug, the dosage form (drug product) in site.
which the drug is given, and the route of administration on 6. Delivery of drug to the site of action which may involve
the rate and extent of systemic drug absorption. targeting a localized area for action or systemic absorption of
drug.
INTRODUCTION
PHARMACODYNAMICS
DRUGS
• Refers to the relationship between the drug concentration at
• These are substances intended for use in the diagnosis, the site of action (receptor) and pharmacologic response,
cure, mitigation, treatment or prevention of disease. including biochemical and physiologic effects that influence
• Drugs are given in a variety of dosage forms or drug the interaction of drug with the receptor.
products such as solids (tablets, capsules), semisolid, • What the drug does to the body
liquids, suspensions, emulsion, etc., for systemic or local
activity. Toxicokinetic
• Drug product can be considered to be drug delivery systems • Application of pharmacokinetic principles to the design,
that release and deliver drug to the site of action that they conduct and interpretation of drug safety evaluation studies
produce the desired therapeutic effect and are also designed and in validating dose-related exposure in animals.
specifically to meet the patient’s needs including palatability,
convenience and safety. Clinical Toxicology
• The study of adverse effects of drugs and toxic substances
Drug Product Performance (poisons) in the body.
• The release of drug substance from the drug product either
for local drug action or for drug absorption into the plasma for PHARMACOKINETICS
systemic therapeutic activity.
• The release of the drug substance from the drug product • Is the science of the kinetics of drug absorption, distribution
leading to bioavailability of the drug substance and and elimination (metabolism and excretion)
eventually leading to one or more pharmacologic effect.
PRINCIPLES OF PHARMACODYNAMICS
BIOAVAILABILITY
Pharmacodynamics – “What the drug does to the body”
• Refers to the measurement of the rate and extent of active • Study of the biochemical and physiologic effects of drugs in
drug that reaches the systemic circulation. biological systems,
• means access to the bloodstream • Study of the mechanism by which these effects are produced
→ Mechanism of Drug Action (MOA)
Sequence of events
A. PHARMACODYNAMICS: MECHANISM OF DRUG ACTION
Absorption
1. Receptor-mediated
• Receptor – cellular macromolecule, or an assembly of
Drug release and Drug in systemic
Dissolution circulation
Drug in tissues macromolecules, that is concerned directly and specifically in
chemical signaling between and within cells
2. Non-Receptor-mediated
• Examples:
Elimination
• Direct chemical interaction – acid neutralizers
(antacids), chelating agents (drugs that coat and coat
bind to heavy metals that are present in excessive
Excretion and Pharmacologic
amount in the body)
Metabolism clinical effect
• Colligative mechanism (dependent on the particles of
Critical Manufacturing Variables the drug in solution)/ mass effect – osmotic diuretics
• The most important steps in manufacturing process. • Counterfeit incorporation – purine-pyrimidine analogues
Biopharmaceutical Consideration in Drug Product Design RECEPTOR LOCATIONS
• Cell membrane
Items Considerations
• Cytoplasm
Therapeutic Drug is intended for rapid relief of symptoms,
• Nucleus
Objectives slow extended action given per day (weeks or
longer), or chronic; is the drug for local action
or systemic action
Drug (API) Physical chemical properties of API, including
solubility, polymorphic form, particle size
Route of Oral, topical, Parenteral, transdermal,
Administration inhalation, etc.
Drug Dosage and Large or small drug dose, frequency of doses,
dosage regimen patient acceptance of drug product, patient
compliance
Type of Drug product Orally disintegrating tablets, immediate release
tablets, transdermal, parenteral, implant, etc.
Method of Variables in manufacturing process, including
Manufacture weighing, blending, release testing, sterility
Module 4 – Biopharmaceutics Page 1 of 8 RJAV 2022
, • Cell membrane • Voltage-gated Na+ channel – blocked by Class I
• GPCRs antiarrhythmics, local anesthetic, tetrodotoxin, saxitoxin
• Ion Channels • Voltage-gated K+ channel – blocked by Class III
• Kinases antiarrhythmics such as Amiodarone and Sotalol
• Catalytic receptors • Voltage-gated Ca2+ channels – blocked by CCBs such as
• Enzymes Verapamil, Diltiazem, Amlodipine.
• Transporters
• Structural protein and other molecules b. Ligand-gated
• Cytoplasm and Nucleus
• Structural protein and other molecules
• Thyroid hormone receptor
• Steroid receptors
*Gating mechanism is controlled by a certain binding site, particularly a ligand
RECEPTORS may be able to interact. So, if a ligand interacts at the binding site, it will cause
a change in configuration of the gate causing the gate to open and that will
1. GPCR (G protein-coupled receptor) now allow the movement of certain molecules or ions
• 7-transmembrane spanning receptor • Nicotinic receptor (Na+) Channel) – blocked by
• Metabotropic – effects due to metabolites (or 2nd neuromuscular blockers derived from tubocurarine
messengers) • GABAA receptors (Cl- channel) – stimulated by BZDs,
• Involved in signal transduction Barbs
• Most common receptor
3. Kinases and Catalytic Receptors
* The cell membrane and the GPCR consist of molecule that reverses the
entire span of the cell membrane 7 times so that’s the reason we call it 7-
transmembrane spanning receptor. Now intracellularly, this receptor is
associated with the G-Protein it is called G-Protein because this protein is
intimately link to GDP. When a Drug or a Ligand bind to receptor the GDP is
replaced by GTP and once this happens it will lead to production of 2nd
messengers. If on the other hand the G-protein is not activated meaning the
GDP is not replaced by GTP then what we expect would be a decrease in the
2nd messengers. This process where a drug binding to receptor that is found at *Are characterized by receptors that exist as monomers. What happens with
the cell membrane which leads to stimulation of intracellular protein like the G- the monomers is that when the ligand interacts with the monomers, they
protein is what we refer to as a Signal transduction process. dimerize and this dimerization of receptors will lead to the activation of the
receptors. There are several types of Kinases and Catalytic Receptors, and
this type will depend on whether the kinase is an integral component or part of
Types of GPCR: the entire receptor molecule or is a separate molecule from the receptor
molecule.
Gs
• Activation of AC (Adenylyl cyclase)
✓ Increase in cAMP
✓ Ex: Beta-receptors
*It will activate the enzyme called Adenylyl cyclase this
enzyme coverts ATP to the active cAMP intracellularly.
cAMP inside the cell is metabolized by the enzyme
Phosphodiesterase III which converts it to the inactive AMP.
Gi
• Inhibition of AC (Adenylyl cyclase)
✓ Decrease in cAMP → inhibitory
4. Enzymes
✓ Ex: alpha 2 presynaptic receptors
• ACE (Angiotensin Converting Enzyme) or Kininase II –
Gq
responsible for converting Angiotensin I to the more active
• Activates PLC (Phospholipase C) – acts in triglycerides Angiotensin II (responsible for vasoconstricting effect and drug such
✓ Splits PIP2 → IP3 + DAG (2nd messengers; primarily as: Captopril, Enalapril, Lisinopril can inhibit the activity of
involved in smooth muscles activities, so they increase Angiotensin Converting Enzyme this class of drugs are called ACEi)
intracellular calcium level in smooth muscles and are involved in • COX (Cyclooxygenase): inhibit by NSAIDS
the phosphorylation and activation of the myosin light chain
• MAO: inhibited by MAO-Is
kinase)
• Non-specific: Tranylcypromine, Isocarboxazid,
✓ Ex: alpha postsynaptic receptors
Phenelzine
✓ Location: smooth muscles → contraction
• MAOA: Moclobemide (RIMA)
• MAOB: Selegiline, Rasagiline, Safinamide
2. Ion channels
5. Transporters
a. Voltage-gated
*Cell membrane and examples of Ion channel at the end, you see a gating
mechanism that prevents ions from moving in or out through the channel. A
voltage-gated ion channel is primarily governed by a change in the membrane The characteristics of a transporter or carrier molecule, is that it brings ions
potential. So, at resting state we know that the inside of the membrane is more into or out of the cell by changing its confirmation or configuration. In the case
negative than the outside if there is a change however in the membrane of Na+-K+ ATPase it brings out 3 Sodium ions as it brings in 2 Potassium ions,
potential such as the inside becomes less negative or even positive there will the movement of this carrier requires energy or ATP.
now be a change in configuration of the gate which prevents the movement of
ions through the channel and may lead to opening of the gate.
Module 4 – Biopharmaceutics Page 2 of 8 RJAV 2022
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