Basic Principles of Pharmacotherapy Flashcards
What are the 5 routes of administering medications
- IV
- Subcutaneous
- Intramuscular
- Oral
- Rectal
What term describes the absorption, distribution, metabolism (biotransformation) and elimination of drugs?
pharmacokinetics
What is the name for the effects drugs have on the body?
pharmacodynamics
What is the name for the effect the body has on a medication?
pharmacokinetics (absorption, distribution, metabolism, elimination)
Lack of full absorption of a drug and first-pass metabolism will reduce what?
bioavailability.
ex. IV 100% bioavailable (absorption circumvented)
What limitation or precaution comes with intravenous route?
increased risk of adverse effects
What is the bioavailability via the subcutaneous route?
75-100%
What is the bioavailability via the intramuscular route?
75-100%
What is the bioavailability of oral route?
5-100%
What are two limitations or precautions of the intramuscular route?
- Can’t use if on anticoagulant (Warfarin)
2. May interfere with interpretation of certain diagnostic tests (creatine kinase)
Is buccal or sublingual administration subject to first-pass metabolism?
No, it is absorbed directly into the venous circulation
Is trandermal route fast or slow? Systemic or local effect?
Transdermal route is slow, systemic, and first-pass effect is avoided.
IM drug absorption is impossible to predict in which population?
pediatric
What needs to be considered for premature infants receiving medication orally?
gastric pH is elevated because of immature acid secretion
What 3 things impact oral absorption in pregnant patients?
- Nausea and vomiting
- Delayed gastric emptying
- Increase in gastric pH may affect the absorption of weak acids and bases
In geriatric patients, most drugs are absorbed via what?
passive diffusion
Because nutrients like vitamin B12, iron and calcium are absorbed via ______ they may have impaired absorption in geriatric population.
active transport
Concentration of a drug is greatly reduced before it reaches the systemic circulation is known as?
First-pass effect
liver and gut wall
Time required for serum concentrations to decrease by one-half after absorption and distribution are complete/
Half-life
Paracellular transport and diffusion are examples of what type of drug movement?
Passive transport
Facilitated diffusion and drug transporters are which type of transport?
Active transport
relates amount of drug in the body to the serum concentration
Volume of distribution (Vd)
Pediatric patients have higher or lower binding of drugs to plasma proteins?
Decreased binding of drugs, so more free drug
Is plasma albumin concentration higher or lower in pregnant patients?
Plasma albumin concentration decreases in pregnant patients (so, increased volume of distribution of drugs that are highly protein bound)
Drugs bind to and activate the receptor in some fashion, which directly or indirectly brings about the effect
Agonist
Specific molecules in a biologic system with which drugs interact to produce changes in the function of the system.
Receptors
compete with and prevent binding by other molecules
antagonist
drugs bind to the same receptor molecule but do not prevent binding of the agonist
Allosteric
Name 3 sites of drug metabolism
- Liver
- Kidney
- Tissues like intestinal wall or blood
What drug metabolism reaction converts the parent drug to a more polar (water-soluble) or more reactive product by unmasking or inserting a polar functional group (-OH, -SH, -NH2)
Phase I Reactions
Generic name for the group of enzymes that are responsible for most drug metabolism oxidation reactions
Cytochrome P450
Increases water solubility by conjugation of the drug molecule with a polar moiety such as glucuronate, acetate, or sulfate
Phase II Reactions
ATP-dependent transport molecule found in many epithelial and cancer cells. The transporter expels drug molecules from the cytoplasm into the extracellular space. In epithelial cells, expulsion is via the external or luminal face
P-glycoprotein, MDR-1
Are polar metabolites generally harder or easier to excrete?
Polar metabolites are generally more easily excreted
Drug which can increase the activity of CYP450?
Inducer (so less therapeutic effect)
Drug which can decrease the activity of a CYP450 enzyme?
Inhibitor (so, less drug metabolized and greater therapeutic effect/toxic effect)
Drug which is metabolized by one of the CYP450 enzymes
Substrate
Ex. Acetaminophen is metabolized by CYP1A2
- Often subsequent to Phase I
- Highly polar conjugate is formed
Phase II reaction
Verapamil, and furanocoumarin components of grapefruit juice (highest in zest) are examples of what?
inhibitors of intestinal P-glycoprotein
Which pathway is well developed in infants?
Sulfation
Which pathway is undeveloped in infants?
Glucuronidation pathway
Efficiency of renal excreation is determined by what 3 things
- Glomerular filtration
- Tubular secretion
- Tubular reabsorption
Is drug metabolism faster or slower in infants compared to older children and adults?
Infant drug metabolism substantially slower
In what situation does hepatic perfusion increase (and extraction of drugs)?
Pregnancy
True or False: Phase I (oxidation, reduction, hydrolysis) metabolism increases in geriatric patients
False
Condition in which the average total amount of drug in the body does not change over multiple dosing cycles
steady state
ie, rate of drug elimination = rate of administration
How many half-lives lives to get to steady state?
4-5 half-lives
Steady-state serum drug concentrations change proportionally with long-term daily dosing in _____________
linear pharmacokinetics
What determines the time required to reach steady state and the dosage interval?
Half-life
What is the most important pharmacokinetic parameter?
Clearance
What determines clearance?
blood flow to the organ that metabolizes or eliminates the drug
Rate of elimination (units per hour) is proportional to concentration is what type of elimination?
First-order elimination: rate of elimination proportional to concentration
*more common
Rate of elimination of a drug is constant, independent of concentration
Zero-order elimination
Can GFR be measured directly?
NO (variables: gender, age, weight, race)
Maternal plasma volume, cardiac output, and glomerular filtration increase/decrease?
increase by 30-50%
What trait of pregnancy effects excretion of drugs?
Higher levels of estrogen and progesterone alter liver enzyme activity
Which equation is the standard for drug dosing?
Cockroft-Gault Equation
Name of equation that is more accurate and used to make eGFR?
Modification of Diet in Renal Disease (MDRD)
Greatest effect an agonist can produce if the dose is taken to the highest tolerated level
Efficacy
