Intro 2 Pharmacokinetics Flashcards
Define Pharmacology
study of interactions of chemicals within living systems
Define Medical pharmacology
science of substances used to prevent, diagnose, and treat disease
Define Drug
any substance that brings about a change in biologic function through its chemical actions
Define Receptor
the molecular components of the body with which a drug interacts to bring about its effects
a) What are the 3 types of receptor bonds and b) name an example of each?
- Covalent, Electrostsatic, and Other
- Covalent bonds: very strong, usually irreversible
- Electrostatic bonds: weaker bonds
- Other bonds (very weak): hydrogen bonding, etc.
Define Pharmacokinetics
Actions of the body on a drug
What are the 4 actions of the body on a drug?
Absorption, Distribution, Metabolism, and Elimination
Define Pharmacodynamics
Actions of the body on a drug
what reaction specific drugs have on the body
What are the major routes of administration for medications and describe each.
Parenteral, Enteral, and Other
- Parenteral: Doesn’t utalize GI
- Enteral: Utalizes GI
- Other
Name the 3 major Parenteral routes
IV, IM, and SC
What are the advantages of Parenteral administration (IV, IM, SC)?
- Rapid onset of action
- avoidance of harsh GI envt
- can be utilized in unconscious
What are the disadvantages of Parenteral administration (IV, IM, SC)
- Overdoses can’t be as readily treated
- pain/fear associated w/ administration
- higher infection risk
What are the risks associated with IV injection?
- Infections through contamination at injection site
- Hemolysis
- Pain/injection site reaction
Describe the absorption of IM administration
- Requires absorption from site of administration by avoids GI tract & 1st pass
- Drugs in aqueous solutions–> rapid absorption
- Depot formulations (non-aqueous)–> slow absorption/sustained release
Describe SQ administration
- requires absorption from administration site
- slower than IV
- minimizes some risks associated with IV administration
What are the advantages of Oral (PO) administration?
- Easy to administer
- Minimizes risk of systemic infections
- Overdoses can potentially be treated
What are the disadvantages of PO administration?
- Complicated drug absorption pathways with 1st pass effect
- Acidic GI envirnoment
- Absorption is influenced by food intake or other drugs
Describe Sublingual (SL) administration
Placement of drug under tongue, which allows for direct diffusion into systemic circulation
What are the advantages of SL administration?
- Convenient administration -rapid absorption
- low risk of infection
- Avoidance of harsh GI environment & 1st pass effect
What are the advantages of Rectal (PR) administration?
- Prevents destruction of drugs by harsh GI
- Lower rates of biotransformation from the liver than PO
- Useful in emesis (vomiting)
- Useful in unconsciousness or actively seizing pts.
What are the disadvantages of PR administration
- Discomfort
- Drugs can cause irritation/inflammation of rectal mucosa
- Absorption greatly varies
Describe inhalation administration
- Effective for respiratory conditions due to direct delivery to the site of action
- delivery to large surface
- used for gases
- minimization of systemic side effects
Describe intranasal administration
Absorbed for local effects or systemic effects
Describe intrathecala administration (space under membrane of brain or sc)
- Direct administration into CSF
- Useful in treating meningitis
Describe topical administration
- Mostly reserved for local effects of drugs
- Applied to skin, eyes, etc.
Describe transdermal administration (ex patch)
- Systemic effect by application of drug to the skin
- Varying rate of absorption based on skin condition at the site of application
- used for sustained delivery of drugs
Define absorption
The transfer of a drug from its site of administration to the blood stream
Name the factors that affect absorption
Solubility Concentration Blood flow Surface area Contact time pH
Name the mechanisms of absorption
Passive diffusion, Facilitated diffusion, active transport, and endocytosis
Describe how concentration affects absorption
High concentrations of a drug lead to more absorption than low concentrations of a drug
Describe how blood flow affects absorption
Greater blood flow leads to higher rates of absorption
Describe how surface area affects absorption
More surface area for absorption leads to more rapid absorption (ie. lungs, intestine)
Describe how contact time affects absorption
The greater the contact time, the greater the absorption
Describe how pH affects absorption
pH directly determines the amount of ionized vs. unionized (which affects solubility)
-only ionized (no charge) forms can cross cell membranes
What donates a proton to form anions?
Weak acids
What accepts a proton to form cations?
Weak bases
What is the Henderson-Hasselbalch used to determine?
The ratio of ionized to unionized
How is a pka value linked to an acid?
The lower the pKavalue, the stronger the acid
Define Bioavaliability (F)
Fraction of unchanged drug reaching the systemic circulation following administration
What is the bioavaliability (f) of an IV injection?
100%
What does the bioavaliability of an PO medication depend on?
Absorption (rate/extent) and Metabolism (1st pass effect)
Describe the 1st pass effect
- After absorption, portal blood takes the drug to the liver before entering the circulation
- When passing through the liver, the drug may be metabolized/inactivated, or excreted into bile–> less active drug makes it to systemic circulation
What formula is used to determine bioavaliability?
F = f x (1-ER)
(f)=extent of absorption (ER)=extraction ratio .
Define distribution
Delivery of a drug from the systemic circulation to target tissues
What are the major determinants of drug distribution?
- Blood flow
- Capillary permeability & Blood brain barrier
- Drug structure,properties/ characteristics
- Protein binding
How does blood flow affect distribution?
Greater blood flow leads to faster distribution of drug
Name high flow and low flow areas of distribution in the body
(high flow) brain, liver, kidney
(low flow) adipose tissue
Define capillary permeability
Capacity for drug molecules to pass through capillary walls
What type of capillary permeability does the Brain have?
continuous capillary structure (does not allow drugs through)
Describe the mechanisms of the BBB
(Lipid soluble)
-Dissolve in membrane of endothelial cells
(Specific transporters)
-Carry the drug through the membrane of endothelial cells
Left off on distribution factors slide 33; also revisit question 7: Describe transport mechanisms of a drug from the site of administration to the site of action.
go back
Define volume of distribution (Vd)
Distribution of drug within the fluid compartments of the body
(tells how much blood is in the body as opposed to the blood)
*How much body water is located intracellularly?
2/3
*How much body water is located extracellularly?
1/3
*How much body water is located intravascular (IV)?
1/4
*How much body water is located interstitial (IS)?
3/4
What percentage of the body is composed of water?
60%
- What formula is used to calculate volume of distribution?
Vd = D/ C
- D: total amount of drug in body
- C: plasma concentration of drug
*What does a small Vd indicate?
The drug is primarily in the plasma
*What does a high Vd indicate?
A high concentration of a drug in the extravascular space (in tissues)
- What formula would you use to approximate how much drug is needed to achieve the appropriate concentration level based on current plasma level?
(Vd) (C2-C1)
- C1 = Current plasma concentration
- C2 = Desired plasma concentration
What occurs when a protein binds to a drug?
The protein renders the bound drug inactive
- What type of protein binding is reversible?
Binding to albumin
- What occurs in protein binding competition?
2 different drugs have a high affinity for abumin and they compete for the binding site
- You have a patient who is currently taking a drug (D1) that is protein bound. Another protein-bound drug is added (D2). What will occur?
- D1 will be displaced from binding sites by D2
- Toxicity may occur with D1 since the displaced drug (D1) has become activitated
- Toxicity may occur with D2 since there is a higher fraction of free drug and no available binding sites
*You have a patient who is taking D1 and D2 (both protein bound). What will happen if D1 is discontinued?
- Once D1 is eliminated, D2 will have more avaliable protein binding sites
- D2 will become protein bound, and thus inactive
- Sub-therapeutic levels of D2 may occur
What occurs during distribution?
The drug may initially be distributed to one area and then redistributed to another
How might inflamed meninges alter distribution?
They may increase the distribution of drugs in the CSF with meningitis
What affect might inflammation/infection have on distribution?
- A layer of WBC and fluid from edema may lead to decreased drug distribution to infected area
- inflammation may increase blood flow due to inflammatory response and increased distribution to the affected tissues
*Which route of administration typically has the quickest onset of action (effect)?
Intravenous
*What route of administration is LEAST desirable for a drug that is not stable in an acidic environment?
Oral
*What mechanism of absorption is capable of moving drugs against a concentration gradient?
Active Transport
*A patient taking two highly protein-bound drugs abruptly stops taking one of them. The therapeutic effect of the continued drug would be expected to
Decrease (because the drug is now available for binding to a protein; if the drug binds to a protein it would become inactive and decrease the therapeutic effects)
*Estimate the oral bioavailability of a drug that is 100% absorbed and has an extraction ratio of 0.25
F =f x (1-ER) = 100 x (1-25)=
75%
