Exam 2 - Pharmacokinetics Flashcards
What is bioavailability?
The amount of active drug available after it is metabolised in the liver.
What happens to lipophilic medications during distribution?
Lipophilic medications tend to accumulate in fat and poorly vascularized tissues, like bone.
What role does the blood-brain barrier play in medication distribution?
The blood-brain barrier blocks most medications from entering brain tissues, except for fat-soluble and low-polarity medications.
How does the lipid composition of cell membranes affect medication distribution?
Fat-soluble molecules cross cell membranes faster due to the lipophilic nature and phospholipid composition of the membrane.
How does body fat percentage affect medication distribution?
Fat deposits retain lipid-soluble medications and release them over time, leading to prolonged pharmacological effects in obese patients.
How do factors like disease and injury affect medication distribution?
Inflammation, disease, and injuries like burns can increase capillary permeability, altering protein binding and allowing more free medication to reach tissues.
Where does drug metabolism mainly take place?
In the liver.
Where does drug excretion mainly take place?
In the kidneys.
How quickly do drugs reach general circulation when injected?
Drugs reach general circulation quickly and have an immediate effect.
What is the first-pass effect?
The metabolism of a drug by the liver before it enters general circulation.
Which vein carries orally administered drugs to the liver?
The hepatic portal vein.
What is the role of hepatic microsomal enzymes, such as p450, in drug metabolism?
They convert lipophilic drugs into hydrophilic compounds for excretion.
What is enzyme induction in drug metabolism?
The process where repeated use of certain drugs increases the amount of metabolic enzymes, thereby increasing drug metabolism.
What is enzyme inhibition in drug metabolism?
When certain drugs compete to bind to metabolic enzymes, decreasing drug metabolism.
How does an increased metabolic rate affect a drug’s duration and intensity of effect?
It decreases the drug’s duration and intensity by facilitating excretion.
How does a decreased metabolic rate affect a drug’s duration and intensity of effect?
It increases the drug’s duration and intensity.
What are some other routes of drug excretion besides the kidneys?
Excretion through breast milk (in lactating women), exhalation through the lungs, release into bile, and elimination through saliva and sweat.
what is Pharmacotherapy?
use of drugs to prevent or treat diseases
2 types of drug classifications
Therapeutic
pharmacologic
Therapeutic Classification
overall treatment category
Antibiotics, antidiabetics, antihypertensive
Pharmacologic classification
how is treats at site of action
calcium channel blocker, ACE inhibitor, beta-blocker
What is Pharmacology?
the study or science of drugs
What is Pharmaceutics?
- preparing and dispensing drugs
- includes dosage form design
— form determines rate of drug dissolution and absorption
— Example: liquid absorbed faster than tablets
Abbreviations indicating prolonged TE
CR: controlled release
SA: sustained action
XL: extended length
XT: extra time
CD: controlled delivery
TR: time release
ER: Extended release
LA: long acting
Considerations for extended release drugs
- release of drug molecules over a prolonged period
- prolongs drug absorption 8-24 hours
- requires fewer doses, improved compliance
- cannot be crushed or chewed → possible toxicity
— Long dose delivered all at once
Types of oral drug preparations from fastest to slowest
- Buccal (side of cheek) & sublingual {SL)
- Liquids & syrups
- Capsules
- Tablets
- Enteric Coated tablets
Where do enteric coated tablets dissolve?
Dissolve in small intestine d/t alkaline environment
What is Pharmacokinetics?
- “kinetics” = movement
- study of the drug movement throughout the body
- 4 processes (ADME)
— Absorption: how does it get in?
— Distribution: where will it go?
— Metabolism: how is it broken down?
— Excretion: how does it leave?
ADME: Absorption
- rate affected by route
- oral medications undergo first-pass effect
- Enteric absorption can occur in stomach and/or small intestine
What affects absorption?
Absorption affected by
- acidity
- food (presence or absence)
- age
- others
- Gastrectomy = reduced surface area
Routes of administration
- Enteral
- Parenteral
- Topical
What are first pass enteral routes?
– oral, GI tract (mouth to rectum)
– first pass metabolism
– less than 100% available
What are non-first pass enteral routes?
- orally disintegrating tablets (ODTs)
- oral soluble films
- Sublingual & buccal (transmucosal)
How do non-first pass enteral drugs get absorbed?
- oral cavity highly vascularized
- do not undergo first-pass effects: direct to bloodstream
Ex: zofran
Saliva doesn’t count
First Pass Routes
- Oral
- Rectal
Non-First Pass Routes
- Inhaled
- IV
- Sublingual
- Intranasal
- IM
- Subcutaneous
- Transdermal patches
How are rectal drugs distributed?
- used for both local and systemic delivery
- may be considered enteral or topical
- mixed first-pass and non-first-pass absorption and metabolism
ex: Rectal acetaminophen
— Reduces fever = systemic
ex: Rectal dulcolax
— Stimulates BM = local
What is Parenteral route?
– IM, IV, subcutaneous
– avoid first pass
– IV is only 100% available option
What is Topical route?
– ointments, gels, patches, drops, inhalers
– some avoid first pass
ADME: Distribution
transport of drug from bloodstream to
- Most metabolically active organs first = more blood flow
- heart
- liver
- kidneys
- brain - Less metabolically active second
- muscle
- skin
- fat
- once in the bloodstream, elimination starts
— primarily liver and kidneys
What happens to unbound drug molecules?
- unbound drugs free to distribute and reach site
- Pass through membrane to target tissue
- More unbound = greater rate of elimination
How does protein binding affect distribution?
- drugs bound to plasma proteins are pharmacologically inactive
- Cannot get through membrane to reach target tissue
- binding reduces onset time
- extends duration & elimination
ex: Warfarin needs to be bound to proteins
- 99% bound to albumin
- 1% free
Onset 36-72 hours
Elimination (duration) 2-5 days
What are Factors that may affect protein binding?
- How much protein is in your system
- Nutrition, age, liver failure
— Liver produces proteins - Other drugs using up protein for their binding = competing for binding sites
— High affinity gets first pick. Bound proteins will be displaced.
What happens when a drug can’t bind its protein?
- Drugs that can’t bind when they should = toxicity
ADME: Metabolism
- Liver is mostly responsible for drug metabolism (enzyme activity)
- Most common liver enzyme = P450
— Lipid → water solubility
— Goal is water solubility so that kidney can filter out inactive metabolite
Biotransformation
- chemical alteration of drugs –> more easily excreted from the body.
- occur primarily in the liver
1. reduces number of active drug molecules /or/
2. activates drug
— (prodrug) Designed to be activated in the liver
— Think prohormone
Consequence of slow metabolism
- TE lasts longer
- Onset and duration prolonged
- Working slower, staying longer
- Toxicity is concern
How does age affect metabolism?
- Low HCl-
- Less muscle = slower metabolism
- Higher fat
- Less liver enzymes
ADME: Excretion
- kidneys primarily responsible
- small fraction excreted in original compound
- Some excretion through stool
What could affect excretion?
- Kidney disease/failure
- Higher risk of toxicity b/c drug in system longer
- Dialysis = possible intervention
Why is knowing about first-pass effect and bioavailability important?
- First pass reduces therapeutic effect
— slows the action time.
— If pt needs action immediately, med should go directly to the blood - The first-pass effect can significantly reduce the oral bioavailability
- can also cause high inter-patient variability
— variation in the expression and activity levels of metabolizing enzymes
Transdermal Patches Distribution
Fentanyl
- Location doesn’t matter.
- Systemic effect
- Slow onset → long duration
OTC pain patch
- Place on painful area
- Local anesthetic
Onset of action
time for drug to start physiologic response
Peak effect
Time required for drug to reach max therapeutic response
Duration of action
length of time drug concentration is sufficient to elicit therapeutic response
Half-life
- time required for 50% of drug to be removed by the body
Ex: 100mg with 12 hr half life
100 mg → 12 hr = 50 mg → 12 hr = 25 mg → 12 hr = 12.5 mg…
Steady State
(reach steady state): 50% in blood, 50% eliminated
- Should wake patients to administer meds to keep up with elimination, maintains steady state of TE
- It takes four to five doses of a regularly scheduled drug to reach a steady state, depending on the drug’s half life.
- This is important because the steady state concentration of a drug is necessary for adequate symptom management
Pharmacodynamics
drug-induced physiological changes
Mechanism of action
- effect based on characteristics of cells/tissue targeted by the drug
- Drugs exert action via receptors, enzymes, and non-selective interactions
Affinity
Physiologic response based on “fit” to receptor
Receptor site bonding types
Drugs act by forming chemical bonds with specific receptor sites
- Agonist: best fit = best response (TE)
- Antagonist = block receptors
— Ex: narcan blocks receptor for morphine binding
— Also displaces bound morphine
Partial agonist: diminished response
Leafy green veg interaction with warfarin
Leafy green veggies (K) → warfarin
↑ intake of leafy green veggies may ↓ anticoagulant effect
K stim clotting
Grapefruit juice interaction with drugs
- Grapefruit juice → cardiac medications, anti-seizure, anti-cholesterol, anti-anxiety
- Cause problems with liver enzymes and transporters
- Too much or little drug
Valerian root interaction with drugs
Valerian root → CNS depressants
- Can increase drowsiness and sedation
- Stim sleep
Polypharmacy
- “many drugs”
- Rx and OTC (ie., dietary supplements)
- longer lifespans and aging baby boomers
— longevity ↑ need for medications - greater the possibility of experiencing AEs and drug interactions
— Ex: diuretic with beta blocker → risk of hypOtension
Aging Effects On Pharmacokinetics
CV, GI, Hepatic, Renal all affect excretion → toxicity risk
Age and CV
Reduced output = reduced absorption and distribution
Age and GI
Increased pH → alkaline secretions = altered absorption
Reduced peristalsis → delayed gastric emptying
Age and Hepatic
Less enzyme production = less metabolism
Less blood flow = less metabolism
Age and renal
Low blood flow = low excretion
Low function = low excretion
Low GFR = low excretion
Dosing Variations For The Elderly
- ½ to ⅔ of standard adult dose
- Dose is range: “Start low and go slow”
- Increase dose based on response
- Look at geriatric dosing recommendations in drug guide before administering
Ethnic & Cultural Factors Influence On Pharmacotherapy
- Medication beliefs
- Question need for medications
- Beliefs about disease and self-management approach
- Influences by culture, family experiences, and individual preferences
- Mistrust of HCP –> lower medication adherence
Ethnic & Cultural Factors Influence On Pharmacotherapy
Medication beliefs
- Language barriers to adherence
- Limited English proficiency
- HCP may spend less time if interpreters not available
- Miscommunication issues and poor follow-through
Ethnic & Cultural Factors Influence On Pharmacotherapy
- Complementary and Alternative Medications (CAM)
- Used with prescribed medication or as an alternative
- Use of natural products
- Mind and body practices: yoga, meditation, prayer…
- More economical than prescribed medications
