Routes of Administration Flashcards
Most desirable RoA is what?
At the drug’s site of action if this is possible
Decrease side effects, decrease dose, decrease cost, immediate action, maximum bioavailability
What do we need to consider for patient-specific RoA?
Age and physical condition
What do we need to consider for specific drugs’ routes of administration?
First pass effect, solubility, stability, absorption, dose (IV for large doses)
What do we need to consider with regards to diseases for routes of administration?
Systemic or local effects
Time of action
Sublingual dosage form, DoA, and onset
Tablets and drops
1-3 minute onset
30 minute DoA
Ointment dosage forms, DoA, and onset
Dosage forms = transdermal patch (40-60 minute onset, 18-24 hour DoA)
Dosage form = ointment (20-60 minute onset, 4-8 hour DoA)
IV infusion onset, and DoA
Parenteral solution
Immediate onset
DoA = several minutes
Buccal dosage forms, onset, and DoA
Extended release tablets
2-3 minute onset
DoA = 5 hours
Translingual dosage forms, onset, and DoA
Dissolving tablets (Onset = 2-4 min, DoA = 30-60 minutes) Extended release tablets (Onset = 20-45 min, DoA = 8-12 hours)
Advantages of oral route of administration
Systemic/local effect
Safe
Comfortable
Different release rates
Disadvantages of oral route of administration
First pass effect - lower bioavailability
Unpredictable absorption
If a drug is given in soluble form or it dissolves rapidly, what is the rate limiting step for its absorption?
Membrane transport
If rate of dissolution is slow, what might happen to the drug?
The drug may not be absorbed to a sufficient extent
What are the two factors that affect drug dissolution and release in the oral route of administration
Formulation and intrinsic dissolution
Rank these dosage forms in terms of dissolution: Tablets, solutions, suspensions, capsules
Solutions > Suspensions > Capsules > Tablets
What does intrinsic dissolution refer to?
The ability of the drug (not the formulation) to dissolve
What factors affect intrinsic dissolution? How do they affect it?
Increase in temperature (can increase or decrease saturated solubility, increases diffusion coefficient)
Viscosity of medium (decreases diffusion coefficient - dissolution will decrease if viscosity increases)
Agitation (decreases thickness of diffusion layer therefore increasing dissolution rate)
Change in pH (Changes saturated solubility)
Reduction of size (surface area for dissolution)
What factors affect solubility?
Polymorphism (forming complexes with ions - can increase duration of action)
Hydrated vs. anhydrous form
Salt form (usually more solubility, but some have less solubility - like penicillins)
What are the four major mechanisms of drug entry into cells?
- Diffusion (high concentration to low concentration - ONLY unionized drugs can pass membrane via diffusion because positive drugs will be trapped by membrane and negative charged drugs will be repelled)
- Facilitated diffusion (high concentration to low concentration using carrier or channel proteins)
- Active transport (uses ATP - low concentration to high concentration for water soluble or large molecules)
- Exocytosis or endocytosis (slow and inefficient, minor route for drug absorption)
What are ABC efflux proteins?
“Gatekeepers” - limit amount of drug entering cell
Works against drug absorption
In terms of membrane permeability, what are other factors that affect drug absorption from the oral route?
Age (increases or decreases permeability/absorption)
Disease of GI tract
Lipophilicity of drug
Surface area (particle size)
In terms of residence time, what are other factors that affect drug absorption from the oral route?
Food (fasting - drug will leave quicker than with a full stomach)
Other drugs (e.g., anti-cholinergic vs. laxative)
Diseases (neuropathy diabetes will slow absorption)
Age (decrease in gastric acidity, number of absorptive cells, intestinal blood flow, rate of gastric emptying, intestinal mobility)
What are some of the actions that metabolites can have?
Equal activity to the drug
No/reduced activity
Increased activity (prodrugs)
Toxic properties not seen with parent drug
What are the four major mechanisms of drug metabolism?
Oxidation (oxidases bound to ER of liver cells)
Reduction (reductase in liver and gut)
Hydrolysis (esterase in liver)
Conjugation (glucoronide conjugation, methylation, acylation)
What is bioavailability? How do you determine bioavailability?
The rate and extent of drug absorption
Bioavailability = AUC oral / AUC IV
IV administration has no absorption phase so its initial concentration is 100%
What is data for bioavailability used to determine?
Amount/proportion of drug being absorbed
Rate at which drug was absorbed
Duration of drug’s presence
What is bioequivalence?
Compares bioavailability of different drugs (e.g., brand vs. generic)
What is the difference between buccal and sublingual routes of administration? What is one of the major advantages of using this route?
Buccal is in the cheek and has less blood flow, therefore it has a slower onset and a longer duration of action
Sublingual is under the tongue and has high blood flow, therefore it has a fast onset
Using either of these routes bypasses first pass metabolism
What are the different dosage forms and volumes for parenteral solutions?
IV = 1-1000mL; solutions, emulsions; nearly all drug classes IM = 0.5-4mL; solutions, emulsions, oils, suspensions; nearly all drug classes SC = 0.5-2mL; isotonic formulation; insulin, vaccine Intradermal = 0.05mL; isotonic; diagnostic agents
What are some advantages of using parenteral solutions?
Increased absorption
Emergency use
Rapid absorption
Treat patients who cannot/will not take drugs orally
Administer smaller/larger doses
Administer high molecular weight drugs (e.g., insulin)
Reliable and more controlled release
What are some disadvantages of parenteral solutions?
Discomfort
Possibility for infection/tissue damage
Toxicity (accidental overdose)
Sterility and cost
What increase absorption of parenteral solutions?
Warmth, exercise will increase blood flow and absorption
Physicochemical properties of the drug (solubility, polarity, ionization, molecular size)
Of the parenteral solutions, which one can have a very long duration of action (without continuous administration)?
IM injections (depot)
What is the basis for freezing at the dentist?
A delay in absorption using epinephrine mixed with lidocaine - this narrows blood vessels and delays absorption of drug
What are topical and transdermal routes of administration?
Topical = skin surface (ointments, creams, pastes, powders, aerosols, lotions) Transdermal = skin (transdermal patches, discs, solutions)
What layer of skin must the drug reach to enter systemic circulation? What are the three layers of skin?
The dermis (second layer of (alive) skin)
Epidermis is outermost layer, followed by dermis, then subcutaneous (fatty) layer that provides insulation and energy supply
What is the dermis composed of?
Microvasculature, lymphatic system, nerves, mast cells, fibroblasts
What is the basal lamina in the skin?
Network of filamentous glycoproteins with anchoring fibrils extended into the dermis
Attach epidermis to dermis
Supply mechanical support
Semi-permeable membrane
What is the epidermis composed of?
Keratinocytes (basal, prickle, granular)
Langerhans cells
Melanocytes
What is the stratum corneum? What is it composed of? Most importantly, what is the main protein?
Protein rich cells separated from each other by thin layer of intercellular lipids
Inside crystalline and dense structure
Roughly hexagonal and flat
Closely fitted structures
The extracellular space is filled with lipid lamellae
Protein - mainly keratin (40%)
Water (40%)
Lipids, triglycerides, free fatty acids, cholesterols, ceramides (20%)
What is the site of action for topical drugs such as sunscreen, bugspray, anti-acne meds, anti-perspirants, anti-infective medications?
Skin surface
Site of action for antihistamines and anaesthetics?
Epidermal/dermal layers
Site of action for nitroglycerin patches, scopolamine, nicotine?
Systemic circulation
Three types of absorption from the skin?
Transcellular (travels through cells)
Paracellular (travels between cells)
Absorption through hair follicles (rare)
What are six factors that affect drug absorption from the skin?
Hydration of skin (increases absorption) Solubility of drugs in stratum corneum Formulation components pH Binding of drugs to skin Drug metabolism in skin
For rectal administration, which veins are found high in the rectum and low in the rectum?
High in rectum = superior rectal vein (carries drugs to liver)
Low in rectum = inferior and middle rectal vein
What dosage forms are used for conjunctival administration?
Contact lens inserts, ointments
Dosage forms for intraocular administration?
Solutions, suspensions
Dosage forms for intraaural administration?
Solutions and suspensions
Dosage forms for intranasal administration?
Solutions, sprays, inhalations, ointments
What are the three barriers for delivery to the eye?
Cornea (has three layers - epithelial, lipid, endothelial)
High capacity of cornea for drug metabolism
Existence of tears
What is unique about the nasal route of administration? What are some drugs administered by nasal sprays?
Only part of body with direct connection to the CNS and atmosphere
Anti-diuretic hormone, gonadotropin-releasing hormone, calcitonin, insulin
What is the dosage form for intrarespiratory drugs? What are the effects of drug absorption in the lungs?
Aerosols for intrarespiratory drugs
Local and systemic effects (0.5-1um drugs stay in the lungs)
Lungs have large SA for drug delivery and fast absorption (with alveoli)
Examples of local and systemic effect drugs
Local effect (glucocorticoids and bronchodilators) Systemic effect (anesthesia, migraine, diabetes)
