Chapter 1 Flashcards
Pharmacokinestics
What the body does to a drug
Pharmacodynamics
What the drug does to the body
4 Pharmacokinetic properties that determine onset, intensity, and duration of drug action
- Absorption
- Distribution
- Metabolism
- Elimination
Enteral adminitration
administering a drug by mouth; most common
Can be oral or sublingual/buccal
Two types of oral preparations
- Enteric-coated preparations (ex. omeprazole, aspirin)
2. Extended-release preparations (ER or XR) (ex. morphine)
Half life of morphine
2 to 4 hours; therefore, must be administered 6x per day to provide continuous pain relief
Parenteral administration
drugs introduced directly in to the systemic circulation (ex. heparin poorly absorbed in GI tract; insulin unstable in GI tract)
3 Major Parenteral Routes
- Intravenous (IV) - Ex. Rocuronium, a NM blocker
- Intramuscular (IM) - Ex. haloperidol, medroxyprogesterone
- Subcutaneous (SC) - Insulin and heparin
Types of Administration Routes
Enteral (Oral, Sublingual/buccal) Parenteral (IV, IM, SC) Oral/Nasal inhalation Intrathecal/Intraventricular Topical Transdermal Rectal
Desmopressin
Administered intranasally in the treatment of diabetes insipidus
Oral Absorption Pattern
Variable; affected by many factors
Intravenous Absorption Pattern
Absorption not required
Subcutaneous Absorption Pattern
Depends on drug diluents:
- Aqueous solution: prompt
- Depot preparations: slow and sustained
Transdermal (patch) Absorption Pattern
Slow and sustained
Rectal Absorption Pattern
Erratic and Variable
Inhalation Absorption Pattern
Systemic absorption may occur; this is not always desirable
Sublingual Absorption Pattern
Depends on the drug:
Few drugs (ex. nitro) have rapid direct systemic absorption
Most drugs erratically or incompletely absorbed
Oral Pros and Cons
+ Safest and most common; convenient, and economical route of administration
- Limited absorption of some drugs; food may affect absorption, patient compliance is necessary, drugs may be metabolized before systemic absorption
Intravenous Pros and Cons
+ immediate effects, ideal if dosed in large volumes, suitable for irritating substances and complex mixtures; valuable in emergencies, dose titration possible, ideal for high molecular weight proteins and peptide drugs
- unsuitable for oily substances, bolus injection may result in adverse effects; most substances must be slowly injected, strict aseptic techniques needed
Subcutaneous Pros and Cons
+ Suitable for slow-release drugs, ideal for some poorly soluble suspensions
- pain or necrosis if drug is irritating, unsuitable for drugs administered in large volumes
Intramuscular Pros and Cons
+ suitable if drug volume is moderate, suitable for oily vehicles and certain irritating substances, preferable to intravenous if patient must self-administer
- affects certain lab tests (creatine kinase); can be painful, can cause IM hemorrhage (precluded during anticoagulation therapy)
Transdermal (patch) Pros and Cons
+Bypasses the first-pass effect; convenient and painless, ideal for drugs that are lipophilic and have poor oral bioavailability, ideal for drugs that are quickly eliminated from the body
-some patients are allergic to patches, which can cause irritation; drug must be highly lipophilic, may cause delayed delivery of drug to pharmacological site of action, limited to drugs that can be taken in small daily doses
Rectal Pros and Cons
+ partially bypasses first-pass effect, bypasses destruction by stomach acid, ideal fi drug causes vomiting, ideal in patients who are vomiting, or comatose
- drugs may irritation the rectal mucosa, not a well-accepted route
Inhalation Pros and Cons
+ Absorption is rapid; can have immediate effects, ideal for gases, effective for patients with respiratory problems, dose can be titrated, localized effect to target lungs: lower doses used compared to that with oral or parenteral administration; fewer systemic side effects
- most addictive route (drug can enter the brain quickly); patient may have difficulty regulating dose; some patients may have difficulty using inhalers
Sublingual Pros and Cons
+ Bypasses first-pass effect; bypasses destruction by stomach acid, drug stability maintained because the pH of saliva relatively neutral; may cause immediate pharmacological effects
- limited to certain types of drugs, limited to drugs that can be taken in small doses; may lose part of the drug dose if swallowed
Mechanisms of Absorption of Drugs from the GI tract
- Passive Diffusion
- Facilitated Diffusion
- Active transport
- Endocytosis and Exocytosis
Factors influencing Absorption
- Effect of PH
- Blood flow to absorption site
- Total surface area available for absorption
- Contact time at the absorption surface
- Expression of P-glycoprotein
pKa
Ionization constant; ratio between charged and uncharged forms determined by the pH at the site of absorption and by the strength of the weak acid or the weak base
pKa relationship to acidicty
Lower pKa = more acidic
Higher pKa= more basic
Distribution Equilibrium
permeable form of a drug achieves an equal concentration in all body water spaces
Why do the intestines have more absorption than the stomach?
1000- fold surface area
Receives more blood flow
When pH < pKa, what forms predominate?
Protonated forms of HA and BH+ predominate
When pH> pKa, what forms predominate?
Deprotonated forms A- and B predominate
P -glycoprotein
Transmembrane transporter protein responsible for transporting various mmolecules, including drugs, across cell membranes; transports drugs from tissues to blood (pumps drugs out of cells); multidrug resistance
Where is P-glycoprotein expressed?
Tissues throughout the body including liver, kidneys, placenta, intestines, and brain capillaries
Areas of high expression of P-glycoprotein ___________ drug absorption.
reduces
Bioavailability
Rate and extent to which an administered drug reaches the systemic circulation; important for calculating drug dosages for nonintravenous routes of administration
IV administration confers ______ % bioavailability.
100%
Factors that Influence Bioavailability
- First-Pass Hepatic Metabolism
- Solubility of the drug
- Chemical Instability of the drug
- Nature of the drug formulation
Bioequivalence
Two drugs formations are bioequivalent if they show comparable bioavailability and similar times to achieve peak blood concentrations.
Therapeutic Equivalence
Two drug formulations show therapeutic equivalence if they are pharmaceutically equivalent (same dosage, same active ingredient, same route of administration) with similar clinical and safety profiles.
What does clinical effectiveness depend on?
Both the max serum drug concentration and the time required (after administration) to reach peak concentration
Drug Distribution
process by which a drug reversibly leaves the bloodstream and enters the interstitium (Extracellular fluid) and the tissues
Distribution of the drug from the plasma to the intersititium depends on….
CO & Local Blood Flow Capillary Permeability Tissue volume Degree of binding of the drug to plasma and tissue proteins Relative lipophilicity of the drug
Volume of Distribution (Vd)
fluid volume that is required to contain the entire drug in the body at the same concentration measured in the plasma
Vd = (Amount of drug in body) / (plasma concentration at time zero)
Drugs with high molecular weight or is extensively protein bound gets trapped where?
Plasma Compartment (Ex. Heparin)
Low Vd that approximates plasma volume
Drug has low molecular weight but is hydrophilic ends up where?
Extracellular Fluid (Ex. Aminoglycoside antibiotics)
It can pass through endothelial slit junctions of capillaries into interstitial fluid; hydrophilic drugs cannot move across lipid membranes into intracellular fluid
Drug has low molecular weight but is lipophilic ends up where?
Total body water (ex. ethanol)
It can move into interstitium through slit junctions and also pass through cell membrane into intracellular fluid. 60% of body weight.
An increase in Vd ______ the half-life and ________ the duration of action of hte drug.
Increases, extends
