Week 2 Flashcards
Onset of action
The first sign of therapeutic effect on the drug concentration curve.
Peak level
Highest concentration of a drug in the system. Make sure the therapeutic level is reached without being toxic.
Trough level
The lowest concentration of a drug in the system before another dose is given. Important when trying to keep a dose in therapeutic range.
Blood-brain barrier
Has a protective function. Made up of a single layer of epithelial cells, tight junction if epithelial cells. Astrocytes surround capillaries to prevent unwanted molecules from getting from the capillaries into the CSF. to enter the CAF, molecules have to be small, lipid-soluble, lower iconic charge, same pH as CHF.
Fetal placental barrier
Delivers nutrients but protects from pathogens, drugs, and the mother’s immune system. Barrier. Between maternal and fetal blood flow. Has few intercellular. Bridges (cell junctions) which prevents things from passing the barrier. Sugars, fats, I2, antibodies, idea, and CO2 can still pass the barrier.
Renal insufficiency
Can cause a buildup of renally-excreted drugs.
Off-label prescribing
Use of FDA-approved drug in a dose or route for which it was not approved or for a clinical condition other than the FDA-approved use.
Pediatric absorption
Gastric ph does not reach adult level until 1. If an acidic environment is needed for absorption, less will be absorbed by infants.
Greater BSA. Greater absorption of topical meds
Infant skin more permeable. More absorption of topical meds.
Immature peripheral circulation. Prevents absorption of IM or SQ meds.
Pediatric distribution
Differences in body water and fat.
Immature liver function. 0-6 mo less albumin and fewer plasma proteins. Fewer binding sites, so higher concentrations of 2 or more drugs or less affinity for one of them.
Immature blood-brain barrier- not developed at birth, leading to greater risk of CNS toxicity.
Phase 1 Metabolism in pediatrics
CYP3A7:
cytochrome P450. The earliest isoenzyme to show activity. Present in utero and rapidly decreases after birth. Then CYP3A4 and 5 increase after 6 mo.
Pediatric excretion
Neonate or preterm infant has immature kidneys.
Monitor drug doses and therapeutic blood levels to prevent toxicity.
Reduced GFR and decreased tubular secretion and reabsorption during the first 6 months leads to extended 1/2 life.
3 months: kidneys concentrate urine at the adult level, but urinary excretion is low until approximately 30 mo.
FDA pregnancy categories
A: controlled studies in prefers and no risk.
B: animal studies show no risk. No pregnant human studies.
C: animal studies show no risk. No human studies. Benefits might outweigh risks.
D: risk; benefit might outweigh risk in serious situation.
X: demonstrated fetal abnormalities; risk outweighs benefit; should not be used.
Absorption in pregnancy
Progesterone decreases gastric tone and mobility. Prolonged stomach emptying time. Alters pharmacokinetics of oral meds.
Progesterone promotes respiratory changes. Increased tidal volumes, increased pulm vasodilation, inhaled drug absorption increased.
Distribution and metabolism in pregnancy
HR increases 10-15 bpm
50% inc in blood vol causes hemodilution of albumin to potentiate drug distribution.
Plasma lipid levels increase altering drug transport and distribution.
Drugs compete for receptor sites occupied by hormones resulting in more unbound free drug.
Drugs that are not lipophilic enter fetal circulation
Drug metabolism is not affected by pregnancy or lactation.
Distribution during lactation
Drugs with increased lipid solubility and low protein binding such as CNS agents pass easily into breast milk.
Drugs of low molecular weight pass into milk
Low pH produce high concentrations
Drug therapy and the geriatric patient
Polypharmacy: taking multiple meds with multiple interaction and ADRs at the same time.
Multiple prescribers= multiple drugs
Physical body changes: inc proportion of body fat, inc cardiovascular effects, reduces renal function, inc effect of drugs on the CNS.
Absorption in the geriatric population
Decrease gastric acid: drugs requiring an acidic environment to dissolve with take longer to be absorbed. Decreases systemic availability
Reduced blood flow to organs decreasing drug absorption
Decreases blood flow, so dec absorption at IM or SQ site.
Overall slowed drug absorption related to decreases gastric acidity, GI motility, and reduced blood flow.
Drug distribution in the elderly
Decreases drug distribution: decreased body mass, reduced albumin, less effective blood-brain barrier, dec cardiac output, changes in body weight, poor nutrition, dehydration, inactivity, bedrest
Drug metabolism in the elderly
Liver size declines and there is a decrease in hepatocytes.
The liver’s capacity to remove metabolic byproducts is reduced.
Aging effects the efficacy of Phase 1 end phase metabolism. Slowed metabolism, reduced oxidation, increased drug blood levels, extended 1/2 lives.
Drugs requiring oxidation for metabolism
Phenobarbital
Phenytoin
Methylxanthines
Drug excretion in geriatric patients
Can have decreases renal function, GFR, and renal tubular excretion.
Car levels may remain normal despite decreased GFR levels.
Less Cr levels in general because of less body mass.
Ginger
High doses may interfere with cardiac, antidiabetic, or anticoagulant therapy.
Ginseng
Increase effect of MAO inhibitors, antihypertensives, and hypoglycemics.
Interferes with action of steroids.
Red ginseng may increase CNS stimulant effects of coffee or tea.
Garlic
Interferes with hypoglycemic therapy
May potentiate antithrombotic therapy
May increase bleeding and clotting times with antiplatelet or anticoagulant therapy
Allergic reactions
Hypersensitivity responses.
Small drugs are not immunogens.
Drugs act as happens (bind covalently with a protein to trigger an immune response)
Four types of hypersensitivity responses.
Type 1 hypersensitivity response
Results from production of IgE after exposure to an antigen.
Urticaria, wheezing, rhinitis, anaphylaxis.
Type II hypersensitivity response
Occurs when drug binds to cells (RBCs) and is recognized by an antibody, usually IgG.
Complement and cytotoxic T cells are activated
This response is rare
Type III hypersensitivity response
Occur when antibodies (IgG and IgM) are formed against soluble agents. This antigen-antibody complexes are deposited in tissues such as joints and lungs.
Causes serum sickness. Example: Ceclor
Type IV hypersensitivity response (delayed-type hypersensitivity)
Cytotoxic T cells are activated.
Poison ivy and poison oak. Contact dermatitis. With repeated exposure to drugs, a cytokines storm can be triggered.
Preclinical trials
First step in the discovery of a potential new drug molecule. Prior to phase I trial. Designed to provide basic safety, bioavailability, pharmacokinetic, and initial efficacy data about the drug.
Development of suitable formulations for clinical use.
Reproduction tox.
Long-term cardiogenic testing.
Phase I of clinical trial
First administration of new med product to humans. Healthy volunteers.
Purpose: eval safety; tolerability; pharmacodynamic effect (HR, BP, etc); absorption, distribution, metabolism, and excretion.
Will be stopped if 1/2 life too short or long, poor bioavailability, ECG changes, severe ADRs.
Phase II of drug trials
Testing efficacy and safety on target population.
Proof of concept. Tested on 13-100 pts
Drug efficacy compared to competitors, safety profiles, probability of success,
Phase IIb tests different doses
Phase III of drug trials
Minimum of 2. Several thousand patients. Confirms clinical doses, frequency, and timing. Tests the hypothesis. ADRs collected to assess benefit-risk potential.
Morbidity and mortality end points, timely completion, monitor drop-out rate.
Phase IV of clinical trials
Data submitted to regulatory agencies
New drug application takes 15 mo. Expedited for HIV and onc drugs
Harmful effects can lead to withdrawal of drug.
Orphan Drug
Drugs for rare diseases. Fast tracks review process and market exclusivity for 7 years.
