Pharmacokinetics and Pharmacodynamics (complete) Flashcards
What is pharmacology?
the science of looking at composition, effects, and uses of drugs
Drug classifications: classified by effects on…
- particular body system
- therapeutic use
- chemical characteristics
- can fall into multiple categories
What is a prototype?
- usually the first medication in a class
- standard in which other drugs are compared to in the class: better or the same?
– morphine
– fluoxetine (Prozac)
– captopril
What is the generic name?
- official name of the medication
- never changes
- must meet same FDA standards
- helps indicate what class a drug falls into (“pril”, “olol’, “statin”
designated by lowercase letter
What is a trade or brand name?
- decided and parented by the manufacturer
- can be several different names
- have FDA approven
Example:
- Prinivil and Zestril (lisinopril)
- Advil (ibuprofen)
What is pharmacodynamics?
Interaction between the living system (person) and the foreign chemicals
How a drug affects the body:
- replaces or acts as a substitute for missing chemicals (ex: insulin)
- increase or stimulate certain cellular activities (ex. beta agonists)
- depress or slow down certain activities (ex. beta blockers)
- interfere with the functioning of foreign cells like microorganisms or neoplasms (ex. antibiotics or chemo)
What are receptor sites?
- receptor site reacts with specific chemicals to cause an effect on the cell
- drugs act on specific areas on cell membrane proteins that each perform a specific function
– lock and key - effect can be to increase or decrease cellular activity
What are agonists?
Occupy and activate receptors
Types:
- full agonist
- partial agonist
What is a full agonist?
Does not need all the sites to produce the desired effect
- can be as little as 10%
Example: morphine, albuterol
What is a partial agonist?
Fall in between - turn on some action, but not completely
- only stimulate some of the receptors (intrinsic activity)
- can act as both agonist and antagonist
– beta blockers with ISA do not lower HR as low as pure antagonists
What are antagonists?
- occupy receptors, but do not stimulate them
- keep the agonist from occupying the same spot and producing a response
Examples
- beta blocker
- charcoal
- naloxone
What is an agonist/antagonist?
Only stimulate some of the receptors and others are blocked
Example: suboxone
What is acute therapy?
usually the patient is very ill and needs immediate therapy
What is empiric therapy?
Medications given because of practical experience and known data
Example: antibiotics for a UTI because most UTI are either E. coli or staph saprophyticus
What is maintenance therapy?
maintains steady dose for chronic conditions that do not resolve
like hypertension
What is supportive therapy
Does not cure but maintains other function until the patient improves
What is palliative therapy
Used for end stage or terminal diseases to make person comfortable
- can be pain medication but also can be meds like chemotherapy
What is critical concentration
The amount of a drug that is needed to cause a therapeutic effect
What is loading dose?
- some medications take a long time to reach a critical concentration
- if the drug effect is needed quickly, a loading dose is given to reach the critical concentration
- it is a higher dose than usually used for treatment
What is the onset of a drug
time it takes to reach a minimum effective concentration
What is the peak of a drug
Occurs when drug reaches its highest blood or plasma concentration
What is the duration of a drug
the length of time the drug has a pharmacologic effect
What is therapeutic drug monitoring
Defined as the use of assay procedures (labs) to determine drug concentration in the blood
- assesses toxic levels
Therapeutic index: margin of safety of drug
- low: narrow margin of safety
- high: less danger
Variation can occur based on pharmacokinetics, disease states, and possible drug interactions
What is the therapeutic range?
Drug concentration from minimum effective concentration to the minimum toxic concentration
refers to the range of blood concentrations representing the lower and upper boundaries of “desirable” blood concentrations of a drug
- lower limit is established so that enough drug is administered to attain therapeutic effect
- upper limit established to avoid or minimize toxicity
should serve as a guide
- not all patients respond the same
- want to treat the patient, not the lab value
What is the trough drug level
- rate of elimination
- typically drawn right before the dose is administered
- lowest point of concentration
What is peak drug level
- rate of absorption
- usually several hours after taking; depends on the med
- about an hour to peak according to professor but is determined by drug
What is pharmacokinetics and what are its 4 stages?
The study of how the body processes a drug; how it works and how it is processes
Four stages:
- absorption
- distribution
- metabolism
- excretion
What is dynamic equilibrium?
The actual concentration that makes it to the body
What does dynamic equilibrium depend on?
- absorption form site of entry
- distribution to the active site
- biotransformation (metabolism in the liver)
- excretion from the body
What is absorption
Defined as what happens to the drug from the time it is introduced to the body until it reaches body fluids and tissues and can be used
- the rate of medication absorption determines how soon the medication will take effect
- the route of administration affects the rate and amount of absorption
- completeness of absorption can differ
What are some barriers to first pass?
All oral medications go through first pass
Barriers:
- presence of food or drugs and how much
– certain foods can increase acidity: milk, alcohol, and proteins can increase breakdown of med
- acidity of stomach:
– food in the stomach increases the acidity and stomach empties slower so drug exposed to acid longer
- blood flow to the GI tract
- length of time in the stomach
– the longer the drug is in the stomach, the longer the absorption
What are some factors affecting absorption?
- intestinal interference
- more blood = better absorption; quicker onset of activity
– IM injection: blood flows faster in the deltoid than the gluteal muscle but gluteal can handle more volume - pain and stress response
– decreased blood flow to GI tract
– autonomic nervous system response - heavy high fat meals
Routes of administration, their barriers, and their absorption pattern
Routes of administration
- oral
- IV
– full absorption into the bloodstream
– most dangerous - IM and SubQ
- Sublinigual/Buccal
– can swallow before it is absorbed
– allows the gastric acid to inactivate the med
– absorbed quickly because mucous membranes are vascular - Rectal/vaginal
– stool will interfere with absorption
– increased vaginal secretions - Inhalation
– inspiratory efforts are essential
– typically rapid absorption through the alveolar capillaries - Transdermal Patches
- Nose/Eye drops
What is distribution?
Describes the process of dissemination of drug throughout the fluids and tissues of the body
What factors can affect distribution?
- drug’s lipid solubility (fat-soluble vs water-soluble)
– water soluble preferred - many drugs cannot cross the blood-brain barrier
- perfusion: if unable to reach the tissues, then systemic administration may not be effective
- temperature
- vasoconstriction vs vasodilation
– vasodilation increasing blood flow
What are protein bound drugs
Some drugs circulate in the bloodstream bound to a protein; others are unbound in the plasma
- Drugs that are protein bound are inactive as the protein-drug complex is too big to enter the tissue
- the free drug is small enough to pass through the capillary wall into the tissue fluid to exert its effect on the cell
Many drugs bind with albumin
- if albumin is low, there are fewer protein binding sites
- drug doses need to be decreases
highly-bound drugs increase risk for drug-drug interactions
What are levels of protein binding
The part of the drug which is bound is unavailable for use; the rest is free drug
Highly protein-bound drug: 85-90% bound
– part that is bound is inactive
Not highly bound drug: 35-45% bound
Some released slowly; others bind more rapidly (loose bind)
What are examples of highly protein-bound medications?
- diazepam
- furosemide
- ibuprofen
- valproic acid
- warfarin
What is the blood-brain barrier
- tightly controls substances that enter and leave the brain
- keeps toxins and many medications away from the CNS; helps maintain homeostasis
-
high lipid soluble are more likely to get across the BBB and reach the CNS while non-lipid soluble drugs can NOT cross BBB
— water soluble tend to not cross - very few antibiotics are lipid soluble: BBB altered by the infection so meds can get through
- adverse effects are more indirect than direct on CNS tissue
Placenta and breast milk and drugs
- many drugs pass through the placenta (primarily by passive diffusion) and can affect the developing fetus
- essentially, all drugs a mother takes have an effect on the fetus
- breastfeeding can expose the baby to medications and possible adverse events
- need to check if medication is safe if breastfeeding
Old Pregnancy Categories
New Pregnancy-Risk Categories (PLLR)
Aim:
- provide patients and healthcare providers with relevant information that allows for informed clinical interpretation and medical management
- all prescription drug labels must be updated as information on medication becomes outdated
Risk categories:
- pregnancy (including labor and delivery)
- lactation
- females and males of reproductive age
Newer FDA pregnancy system has written out information on safety
What is metabolism (biotransformation)?
Liver is the primary site of drug metabolism
- drugs that become biotransformed; usually into a compound that is more water-soluble
- drug excreted into the bile with or without biotransformation
Kidney: drug eliminated into the urine for excretion
Concerns when patient has renal or hepatic impairment
– other factors include age and comorbidities
Metabolism - Hepatic Enzyme System
Is a microsomal system
Phase 1: cytochrome P450 system
– inducers: increase metabolism (process more quickly)
– inhibitors: decrease metabolism (process more slowly)
Phase 2: readies the drug for the kidney
What is the first pass effect?
When a drug is administered orally, it is metabolized by the liver
- a drug that is absorbed from the intestines is carried by blood flow to the liver
- during the drug’s first pass through liver, a large amount is metabolized
- once circulated through rest of body, about 30% is circulated through the liver again
intravenous and sublingual routes bypass the first pass effect
What is the hepatic enzyme system?
- accounts for metabolism of 70-80% of medications
- are many hepatic enzymes responsible for metabolism: CYP450 enzymes
- oxidizes (combine or become combined chemically with oxygen) medications
- everyone’s CYP450 is different, based on genetics:
– can alter function
– increase or decrease plasma concentrations of medications
Inhibitors (slow):
- drug inhibits or slows the activity of the CYP enzyme often leading to HIGH DRUG LEVELS
- drug is slowly metabolized; hangs around
- example: grapefruit juice
- may need to lower dose
Inducers (fast):
- when a drug is able to increase the function of the CYP enzyme often causing SUB-THERAPEUTIC EFFECTS
- drug is metabolized too fast
- may need to increase dose
What is pharmacogenetics?
The study of how a person’s unique genetic makeup (genome) influences his or her response to medications
- identification of genetic variants help to select most appropriate meds and limit adverse effects and maximize beneficial effects
- more than 200 drugs have label info regarding biomarkers; some measurable or identifiable info that can be used to individualize use of drugs
What are liver function tests
simple blood draw
many meds require monitoring of liver function to ensure medication can be properly metabolized
What is elimination
Kidneys are the major organ involved in drug excretion
- drugs are made water soluble in liver so they can be excreted
Other meds need active transport and will exchange an acid/HCO3 to do so (affects acid-base of urine)
Glomerular filtration
Can also occur via:
- skin
- lungs
- feces
- saliva
- bile
Factors influencing drug effect
- gender (muscle mass, pregnancy, weight differences)
- physiological factors (diurnal rhythm, acid-base, hydration, electrolyte balance)
- pathological factors (GI disease, vascular disease, hypotension, renal disease)
- genetics (metabolism, mutations, genomind)
- immunological (allergies)
- psychological (attitude, placebo, trust, control of life)
- environment (sedation/pain, temperature)
- weight (most based on 150lb adult)
- age (children and older adults: less absorption, fewer plasma proteins, less tissue perfusion, metabolism, kidney excretion, polypharmacy)
- drug tolerance (resistance)
- accumulation (too frequently, poor elimination, pt education)
- interactions (adverse events, food)
- additive effect: two meds given that do same thing at lower dose than one med at higher dose (decreases side effects)
- potentiation (one drug makes another more potent)
What is the additive effect
two meds given that do the same thing at a lower dose than one med at a higher dose
decreases side effects
What is potentiation of a drug effect
One drug makes another more potent
What is half-life?
- time it takes for the concentration or amount of a drug to decrease by one-half of the peak level
– when the drug is given on a regular schedule - takes about 5 half lives for the medication to be considered eliminated
– short half-life: out quickly
– long half-life: in body for long time
What are variables that can impact half life?
- age
- circulation
- diet
- hydration status
- gender
- renal and hepatic function
- smoking
- genetics
- comorbidities
What is the steady state?
- the amount of drug being absorbed EQUAL to the amount of drug being eliminated with continuous and/or repeated doses
- rule of thumb is that steady state will be achieved after 5 half lives NOT 5 doses
- does not always mean a person is at or in therapeutic range
What are adverse effects?
undesired effects of meds
- effects other than therapeutic effects
- increased sensitivity
- action undesired effects
- too much or too little
What is overdose?
adverse effect; too much effect
- anticoagulants
- pain medications
- blood pressure
What is the secondary effect?
balance between the desired effect and the adverse effects
- change time to avoid side effects
What is hypersensitivity
adverse effect - allergy, intolerance
What is Steven Johnson Syndrome?
- rare but severe skin reaction triggered by medications; adverse effect
- commonly begins with fever and flulike symptoms
- within few days, skin begins to blister and peel
- typically seen on face and chest before spreading to other parts of body
- also damages mucous membranes, urinary tract, eyes and genitals
- considered to be life-threatening disease
What is stomatitis?
inflammation of the mucous membranes; adverse effect
- common in chemo
- immune modulators
What are superinfections?
adverse effect; bacteria protect us from other bacteria
- normal flora
- vaginal
- GI
- immunocompromised
(this slide didn’t seem very clear)
What are anticholinergic effects?
- block parasympathetic nervous system directly/indirectly
- block cholinergic receptors
symptoms include: dry mouth (xerostomia), dizzy, taste change, paralytic ileus, urinary hesitancy/retention, blurred vision, headache, nasal congestion, dry skin
Examples: spiriva, antihistamines, antipsychotics, atropine, cold remedies
What is Parkinson-like syndrome?
- dopamine levels are affected directly or indirectly
Examples: antipsychotics, neuroleptics, lithium, HTN meds (calcium channel blockers)
Symptoms: akinesia, dyskinesia, muscle tremors, drooling, change in gait, rigidity, restlessness
Relationship between pharmacokinetics and pharmacodynamics (photo)
