Pharmacokinetics Flashcards
Pharmacokinetics vs. Pharmacodynamics
Pharmacokinetics: how an organism affects a drug
Pharmacodynamics: how the drug affects the organism.
Pharmacokinetics, general
The route of how drug through moves through (kinesis) the body:
Absorption
Distribution
Elimination
Methods of absorption
Presences of food is able to enhance or inhibit absorption of different drugs
Non-oral routes bypass the stomach acid, preventing the rapid breakdown
o Sublingual o nasal o inhalation o rectal o spinal fluid o subcutaneous • injection • skin patch • depot (intradermal or intramuscular injection, gradual release)
Distribution
Depends on how soluble the drug is in fat
* the extent to which a drug can bind with blood proteins
*affects how much can pass through membranes
Absorption Considerations
Sfx affect compliance
o e.g. Prozac many people experience nausea
o vomit, nausea, kids not wanting to swallow pills
• e.g. skin patch for ADHD medication
G.I. tract absorption
o e.g. Paxil – well absorbed
• patients with G.I. issues consider this is a better choice for better absorption
• e.g. Topamax taken rectally
Almost all drugs are metabolized through the liver–Name the 2 important exceptions
- Lithium: excreted in urine unchanged, whole
*Lithium is toxic at high levels
*Routinely measure Li level in urine
*Low blood volume, dehydration = danger
→ as clearance of lithium levels decrease, lithium increases, possibly toxic
- Neurontin (gabapentin)
o pain management, anxiety, and epilepsy
Elimination: Metabolism
Metabolism: all chemical reactions involved in maintaining the living state of the cells and the organism
The liver is the major location for metabolism of drugs
Chemical reactions are organized into metabolic pathways
Sequences of enzymes transform one chemical is through a series of steps into another chemical
Enzymes
Enzymes drive desirable reactions that require energy that will not occur by themselves
Enzymes act as catalysts that allow the reactions to proceed more rapidly.
Cytochrome P450
Extensive system of enzymes involved in RX metabolism
Primarily found in liver cells but are also located in cells throughout the body (there are some P450 enzymes found in the brain)
Drug-drug interactions
If the same enzyme is responsible for metabolizing both drugs →less availability of enzyme, higher concentration / possible imbalance
Adusting dosages can correct for this
“1st Pass Metabolites”
Enzymes in the small intestines metabolize some drugs as soon as they enter the G.I. tract, before they enter the bloodstream
o e.g. Paxil is well absorbed
Portion of drug is converted to weaker metabolites that lasts in system even longer
Elimination through lungs
e.g. Alcohol
Direct connection between lungs and bloodstream
Breathalyzer measure concentration in exhalation
Half-Life
The duration between intake and how long it takes for half of the medication to be eliminated
i.e. how long before until 50% of original dose remains
General rule: 5-6 half-lives to clear drug from body
*Time of ½ life does not accelerate as concentration decreases
“Poor Metabolizers”
Half-life differs from drug to drug
AND
person-to-person
*partly depending on how many enzymes people have
An individual’s P450 system affects the individual way one gets rid of drugs in the body
Poor metabolizers are at a higher risk of toxic levels
Evidence that different ethnicities have different prevalence of “poor metabolizers”
• Causasian 7%
• Asian 1%
Individual Factors affecting Half-life
P450 CYP2D6 doesn’t change with age, but metabolism can change due to individual factors:
Kidney function
Liver function
Disease-related to blood flow
drug-drug interactions
age-related diseases
*It can vary 15 fold person to person
