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List four principles of pharmacology that the oral health professional must understand in order to provide information on drug effects
- how it works (mechanism of action)
- potential adverse or side effects (ADEs)
- oral health education info related to drug effects
- risks of taking a drug
the science of molecular interactions between drugs and body constituents, it relates to the biochemical and physiologic actions of a drug
The absorption, distribution, metabolism, and excretion of a drug
Describe the steps a drug follows after being delivered to body cells.
- it initiates a drug-induced effect - formation of a bond
- then a molecular event called the drug's mechanism of action
List seven features of receptors.
- cellular macromolecules
- location is on the cell surface or within the cell
- hundreds of different receptors on a single cell
- complementary fit between drug and receptor
- electrochemical charge
- hydrophilic or hydrophobic
- only one drug molecule can occupy a receptor at one time
Describe the features of the four types of chemical bonds between a drug molecule and the complementary receptor. Which type is the most common in drug-receptor complexes?
- ionic bonds - atom with an excess of electrons has a negative charge which causes an attraction to an atom with a deficiency of electrons; a positivelly charged drug molecule is attracted to a negatively charged receptor site. The bonds are weak
- Hydrogen bond - when bound to nitrogen or oxygen, hydrogen atoms are positively polarized and bind to negatively polarized atoms. weaker than ionic bonds
- covalent bonds - strongest type; a drug and receptor share electrons by two atoms; tetracycline and dentin
- van der Waals force - mutual attraction between organic molecules throug shifting electron density in or around a molecule that results in positive or negative charge
- most common is ionic bond
Define the roles of affinity and intrinsic activity in drug action. Which is related to potency?
- affinity - when a drug moves so close to its receptor that the attractive force between them becomes great enough to overcome the random motion of the drug, and it binds to the receptor
- intrinsic activity - the ability of an agonist to interact with a receptor and intiate a response
- affinity is related to potency
What is the difference in the effect of a weak agonist when compared to a partial agonist? Identify both in a log dose curve illustration.
a weak agonist must be bound to many more receptors to produce the same effect; a partial agonist has low intrinsic activity, so will never produce the same effect as a strong or weak agonist
Describe the relationship of efficacy and the ceiling dose concept.
efficacy is the maximum response produced by a drug, a state of optimal receptor occupancy by drug molecules; the ceiling dose is when no additional doses on top of efficacy would benefit the effect
Define ED50 and LD50
- ED50 - the dose of the drug required to produce a desired response in 50% of individuals (median effective dose)
- LD50 - If death is the measured end point, for the response in 50% of individuals (median lethal dose)
What is the therapeutic index? How is it used? What is the formula to determine TI, and what is the significance of a high number?
- margin of safety of a drug
- it is used in evaluating potential therapeutic agents, and it is a dose - response curve, if the slope is steep there is a narrow range between dosages that produce safe and toxic effects etc
- TI is the ratio LD50/ED50
- the higher the value, the safer the drug
Describe the stages a drug goes through from the time of administration to the elimination of the drug
- absorption into the body
- distribution in the body including the site of action
- metabolsim to prepare the drug for removal
- excretion from the body, and the effect is terminated
Compare the features of ionized molecules with those of nonionized forms as the molecule moves through tissues to cause an effect.
- nonionized molecules (acidic drug in acid environment) are lipid soluble and pass through the biologic membranes easily
- Ionized drugs (a basic drug in an acid environment) are water soluble, and must pass through water pores of membranes, or be transported through special transport mechanisms
What is the role of a specialized transport mechanism in moving a drug molecule across the membrane? Give an example of a specialized transport vehicle.
- to help large, ionized, water-soluble drug molecules cross the biologic membrane
- facilitated diffusion
- active transport
Identify 3 factors that affect the absorption of a drug.
- degree of ionization
- formulation (liquid or solid)
- circulation to area
- area of absorptive surfaces
- route of administration
From where in the GI tract are most drugs absorbed?
upper small intestine
Describe how taking a drug that alters the pH of the stomach can affect the absorption of a drug.
If a drug is basic and mixes with the acid of the stomach it will ionize some of the acids requiring specialized transport mechanisms
Describe two means to alter a drugs absorption through modifying the formulation.
- enteric coating
- combining intraoral topical agents with an insoluble agent so it doesn't dissolve in the saliva
Identify features of enteral and parenteral ROAs.
- enteric - placed directly into GI tract by oral or rectal administration - must pass through liver before distribution
- parenteric - bypass the GI tract and include injection, inhalation, and topical routes, including direct application to mucosa or sublingual routes
Describe how the first-pass effect influences the onset of drug action
It affects how much of the drug gets into the circulation; if the drug is attached to albumin, it will be protected from metabolism in the liver, if not, it will undergo the first-pass effect
List parenteral routes, and identify the route used in most emergency situations
- IV is most often used in emergency situations; it is the most predicatble ROA
What is the most predictable ROA?
What are the precautions to follow when using topical agents?
- limiting the area of application in order to reduce absorption
- aviod placement of an occlusive dressing
- aviod application over abraded areas or where skin is not intact
- consider allergic potential
Describe features of distribution that affect a drug molecule reaching the receptor.
- The organs it is being distributed to
- molecular weight
- concentration in plasma
- lipid solubility
- if they are bound to plasma proteins and can't bind to therapeutic receptors
What is the role of albumin in blood?
It binds drug molecules to them and carries them throughout the vasculature
Identify the organ responsible for most drug metabolism.
Describe the 4 ways that drugs are altered during biotransformation.
- active drug to inactive drug
- active drug to active or toxic metabolite
- inactive drug to active drug
- unexcretable drug to excretable drug
What are the differences between phase I reactions and Phase II reactions in biotransformations?
- Phase I - chemical structure is modified through oxidation, reduction, or hydorolysis, require little energy, throughCYP450
- Phase II - chemical structure is modified by conjugation to a large polar endogenous molecule; all phase II metabolites are pharmacologically inactive
Which enzyme system is the primary pathway for drug metabolism?
In which organ are most drugs excreted? What is the primary area where this occurs?
- renal excretion, in the glomeruli
Describe the process of drug excretion.
blood flows to the kidneys, drugs are brought into the glomeruli, the drug is filtered there, and is either reabsorbed into the tubular lumen and back to the circulation, or excreted in the urine
Define a drug's half life.
the time required for the plasma concentration of a drug to decrease by 50%
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