Pharmacokinetics Flashcards
What are the four pharmacokinetic properties that determine the speed of onset of drug action, the intensity of the drug’s effect, and the duration of drug action?
Absorption
Distribution
Metabolism
Elimination
Absorption, distribution, metabolism, and elimination determine what?
The speed of onset of drug action, the intensity of the drug’s effect, and the duration of drug action.
Which route of administration is safest and most common?
Enteral (mouth, sublingual, buccal).
What does enteric coating accomplish, and what is an example of a drug that is commonly coated so?
It resists the chemical actions of the stomach but dissolves readily in the upper intestine. Aspirin is one such drug.
What is an example of an extended release drug?
Morphine.
Why are parenteral drugs sometimes preferable to other types?
If a drug (such as heparin) is poorly absorbed or is unstable in the GI tract (such as insulin), this route allows the drug to bypass these obstacles.
What are some disadvantages of parenteral drugs?
They are irreversible, can lead to infections and local tissue damage, and can cause fear and pain in the patient.
Name two examples of drugs delivered by oral inhalation.
Albuterol (bronchodilator), fluticasone (corticosteroid).
Name three examples of drugs delivered by nasal inhalation.
Oxymetazoline (nasal decongestant), calcitonin (treatment for osteoporosis), desmopressin (treatment for diabetes insipidus).
Name one drug delivered by intrathecal/intraventricular routes.
Amphotericin B (treatment for cryptococcal meningitis).
When would a topical drug be desired?
For local effect of a drug.
Name one drug delivered topically.
Clotrimazole (treatment for dermatophytosis).
When would a transdermal drug be desired?
For sustained delivery of a drug.
Name three drugs delivered transdermally.
Nitroglycerin (treatment for ischemic heart disease caused by angina pectoris), scopolamine (for motion sickness), nicotine (smoking cessation).
What is the definition of bioavailability?
The percentage of drug that gets into the bloodstream.
What are the different methods of drug absorption from the GI tract?
Passive diffusion, facilitated diffusion, active transport, and endocytosis/exocytosis.
Which method of drug absorption is most common?
Passive diffusion.
What four ideas describe passive diffusion?
1: Drug moves from area of high concentration to area of low concentration.
2: Does not involve a carrier.
3: Is not saturable.
4: Shows low structural specificity.
How would you describe facilitated diffusion?
Drug enters cell through specialized transmembrane proteins that undergo conformational changes to allow their passage into the cell, moving them down their concentration gradient. It does not require energy, can be saturated, and may be inhibited by compounds that compete for the carrier.
How would you describe active transport?
Drugs that closely resemble naturally occurring metabolites may use these carrier proteins. This form of transport requires energy. Drugs may be moved against the concentration gradient. These systems can be saturated, and may be competitively inhibited by other substances.
Name one molecule taken up by endocytosis.
Vitamin B12, across the gut wall.
Name one molecule released by exocytosis.
Norepinephrine, from membrane-bound vesicles in the nerve terminal.
For a weakly acidic drugs and weakly basic drugs, which forms can permeate through membranes?
For weak acids (HA↔H+ + A-), the protonated form HA permeates.
For weak bases (BH+↔ B + H+), the uncharged form B permeates.
What does pKa represent?
It measures the strength of the interaction of a compound with a proton. Lower pKa is more acidic, higher pKa is more basic.
How do pH and pKa relate in terms of acidic and basic drug permeability?
If the environmental pH is less than the drug’s pKa, the drug will trend toward its protonated forms (HA or BH+). If the environmental pH is greater than the drug’s pKa, the drug will trend toward its deprotonated forms (A- or B).
Does low pH environment favor acidic or basic drugs?
Low pH favors acidic drugs (depending on the individual drug’s pKa) since the protonated form HA is not charged, thereby allowing it to cross the membrane.
Does high pH environment favor acidic or basic drugs?
High pH favors basic drugs (depending on the individual drug’s pKa) since the deprotonated form B is not charged, thereby allowing it to cross the membrane.
What are some factors (apart from pH) affecting absorption?
Blood flow to site, total surface area, contact time at the surface, and expression of P-glycoprotein.
What is the purpose of P-glycoprotein?
It is a multidrug transmembrane transporter protein that transports many kinds of molecules across cell membranes (out of the cell). In the liver, it transports drugs into bile for elimination; in the kidneys, it pumps drugs into urine for excretion; in brain capillaries, it pumps drugs back into blood, limiting their access to the brain.
What is meant by the term “first-pass metabolism”?
When a drug enters portal circulation (such as when taken orally) and as such is exposed to the liver and/or gut first. If the drug is rapidly metabolized there, the amount of drug that enters systemic circulation unchanged is severely limited.
How does a drug’s solubility affect its absorption?
Drugs that are very hydrophilic are poorly absorbed due to their inability to cross the cell membrane. Drugs that are very hydrophobic are also poorly absorbed since they are insoluble in body fluids and therefore cannot gain access to the surface of cells. Drugs must be mostly hydrophobic with some solubility in aqueous solutions. (This is why many drugs are either weak acids or weak bases.)
What is bioequivalence?
It is a term used to describe two drugs if they show comparable bioavailability and similar times to achieve peak blood concentration.
What is therapeutic equivalence?
When two drugs are pharmaceutically equivalent with similar clinical and safety profiles.
What are some factors that can influence drug distribution?
Cardiac output and regional blood flow, capillary permeability, tissue volume, degree of binding of drug to plasma and tissue proteins, and relative hydrophobicity of drug.
