Pharm 1 Lecture Flashcards
Pharmacology
the study of drugs and their action on a critter’s body
Drugs
substances which can affect a critter
Pharmacodynamics
the branch of pharmacology dealing with reactions between drugs and living systems
what a drug does to a critter
Pharmacokinetics
mathematical description of the processes through which a drug is handled once introduced into the body
what the critter does to the drug
toxicology
the study of how drugs poison cells, critters and/or ecosystems
LADME
liberation, absorption, distribution, metabolism, elimination
Liberation
process of the drug being “liberated” from its carrier tablet, capsule, etc.
aka disintegration
Absorption
the nature and characteristics of how a drug moves from its site(s) of administration into the critter’s plasma (usually)
What variables affect absorption past a membrane?
Size of drug molecule (small ones go through)
Ionization of drug (nonionized go through)
Lipid solubility (lipophilic go through)
pH
Administration route
Dosage form
Drug solubility
Distribution
dissemination of a drug throughout the “compartments” of a critter’s body, such as plasma, tissues, or organs
Where are IV drugs preferentially absorbed on bypass?
Muscle or brain; won’t be disseminated equally; depends how easily it moves into the membrane
What is the major vehicle for distribution of drug?
Bloodstream
What can affect distribution of a drug?
blood flow, fat, or water solubility
protein binding
Metabolism
the biotransformation of a drug into other (secondary) compounds (which can also be drugs). Frequently a task performed by the critter’s liver (kidney, skin, lungs too)
After the drug has been absorbed and distributed, what happens?
The body work to break it down via metabolism into metabolites
What is the major organ for metabolism?
Liver
How does the liver metabolize?
Via drug oxidation by the Cytochrome P-450 enzyme system
Cytochrome P-450 enzyme system
enzymes induce (increase) or inhibit (decrease) metabolic activity.
Why do people who frequently drink alcohol become more tolerant to it?
enzyme induction by the cytochrome P-450 enzyme system
What kind of metabolism capability does the fetal liver have?
Fetal liver has 1/3 the drug metabolism capacity as the adult liver therefore metabolism is reduced at birth
Aging accounts for what percent reduction of liver mass?
20-30% of liver mass
Elimination/Excretion
process that removes a drug from an organism in urine, feces, etc. IF a drug isn’t removed fast enough it bio-accumulates in the critter
How can drugs be excreted?
Urine, Feces, pulmonary system, skin and hair
What affects metabolism?
Liver function and enzymes
What is the main route of elimination of drugs?
Renal system
What affects elimination?
Renal blood flow and kidney function
2 Categories of drug administration
Enteral
Parenteral
First pass effect
For each drug a certain % is converted from the original “mother” compound into some intermediate metabolite
What form is the drug passed on as after first pass effect?
Either the chemically intact drug or as a metabolite
Parental Routes of Administration
IV Intra-arterial Intramuscular Subcutaneous Inhalation Topical Intraosseus transdermal Intrathecal/intraventricular (brain) (Rectal?)
IV Absorption: Continuous Infusion
Ex. IV drip; gives a regulated, consisted dose over time, causing a steady state in drug concentration
IV Absorption: Intermittent Dose
Ex. Injection; has peaks and troughs in drug concentration
Off-Label Use
use of pharmaceuticals or medical devices for an (FDA) unapproved age group, unapproved dosages, unapproved form of administration, or unapproved indication
What percent of hospitalized patients experience ADR’s? (mild to severe)
A least 5%
Additive Interactions
1+1 = 2
The summation of the effects of two (or more) drugs given together is equal to each of them given separately but at the same time.
Synergistic Interactons
1+1 = 3
The summation of each individual drug’s activity exceeds the sum of the two individual drugs
Potentiation
1+0 =3 One drug (which has no direct effect) increases the response of the other drug, which normally has a lesser effect
Passive Diffusion
Doesn’t require energy
Drug moves from area of high concentration to low concentration
Facilitated Diffusion
Doesn’t require energy
Used for “large” molecules
can be “saturated”
Active Transport
Required energy (ATP)
Can move drugs against a concentration gradient
can be saturated
Endocytosis/Exocytosis
Engulfment of large drugs by a cell in a membrane-lined vessicle
Requires energy and cells
Types of Passive Diffusion
Aqueous Diffusion
Lipid Diffusion
What type of diffusion does the Fick Equation represent?
Aqueous diffusion
What is the Fick Equation?
(Area of diffusion surface x difference in concentration)/(Thickness of diffusion interface surface)
How can we “trap” acidic or basic drugs in the renal tubules for increase excretion?
Make them more polar
How do acid drugs get trapped?
Trapped as anions in alkaline urine
How do basic drugs get trapped?
Trapped as cations in acidic urine
pH Equation
pH = -log [H+]
“Acidic” drugs have a ________ pk <7.00
lower; ex. warfarin
“Basic” drugs have a ________ pk >7.00
higher; ex. phenylephrine
Drug selectivity
the extent to which a drug acts at one specific receptor site
Receptor
A macromolecule or the component of a cell or organism that interacts with a drug and initiates the chain of biochemical events leading to the drugs observed effects
3 Things May Happen when a drug binds to a receptor
- Ion channel can be opened or closed (calcium channel blockers)
- Biochemical messengers activated (ex. beta-adrenergics causing increased cyclic 3, 5 AMP)
- Normal cellular function turned off or on (ex. antibiotics destroy cell wall)
Racemic Mixtures
contain two different isomers; isomers have exact same elemental components but the molecular arrangement is different; each isomer can have different pharmacologic activity
Adrenal medulla produces what kind of epinephrine? Which has _______x the vasopressor effect as the opposed form
Left-handed, 15 x
Vasopressor
Raises blood pressure
What form of epinephrine is long-acting and more stable?
“Right-handed” form
What form of epinephrine do pharmacological preparations make?
50/50 mixtures of left and right-handed forms
4 Tenants of Law of Mass Action
- Pharmacological effects are reversible bc drug-receptor complex is reversible.
- Pharmacological effects are proportional to the number of receptors occupied.
- Pharmacological effects plateau because they are limited by the total number of receptors
- Drug effects are proportional to the dose
Agonists
Bind to and activate a receptor which directly or indirectly brings about an effect
Activates receptor
Antagonists
bind to a receptor and prevent binding of other molecules or drugs; often has little or no inherent response
Partial Agonists
produce a lower response than full agonists; effects of both but less of an effect
Agonist/Antagonists
have properties of both an agonist and an antagonist; has effect of one and blocks the effect with the other
Intrinsic Activity
measure of drugs effectiveness of causing a response (efficacy)
What intrinsic activity does an antagonistic drug have?
0, meaning it would bind but have no response
What instrinsic activity would a full agonist have?
1
What intrinsic activity would a partial agonist have?
0.5 (or somewhere between 0 and 1)
Spare Receptor Concept
- Maximal response can be achieved by an agonist even if only a fraction of the receptors are occupied
- Sensitivity of the cell to an agonist concentration depends on affinity of receptors for the drug and total receptor concentration
Concentration- Time Curves
describe drug kinetics such as elimination rates, half-lives, clearance, volume of distribution, etc.
Effect- Concentration Curves
“Dose-response Curves”
Chemical Antagonism
Ex. heparin/protamin
Actually interact
Physiologic Antagonism
Ex. Dexamethasone/insulin
Lisinopril/epinephrine
4 Types of Receptors
- Regulatory Proteins (neurotransmitters/hormones)
- Enzymes
- Transport proteins (Na/K ATPase)
- Structural proteins (tubulin-receptor for colchicine)
3 Aspects of Drug Receptor Function
- Receptors determine the nature and characteristics of “Drug Concentration-Effect Curve”
- Receptors function as regulatory proteins and part of chemical signaling mechanisms that provides targets for drugs
- Receptors determine the therapeutic and toxic effects of drugs on a critter
4 Transmembrane Signaling Mechanisms
- Ligand Gated Ion Channels (Cholinergic nicotinic receptors)
- G protein-coupled receptors (a and b adrenoceptors)
- Enzyme linked receptors (insulin)
- Intracellular receptors (steroid receptors)
Signal Amplification
One drug molecule interacts with many receptors
The activated receptors can persist for longer than the original drug ligand/receptor complex existed
Tolerance
Increased amount of a drug is needed to produce the same effect
Desensitization
Long-term exposure of a drug to cells or tissues makes those tissues less responsive over time
Down-Regulation
Occurs over a longer period than desensitization (hours to days to weeks)
Receptors are internalization and eliminated
Consequently, the effects of down-regulation are longer-lasting
Potency
The amount of drug necessary to produce an effect of a given magnitude; differences can be overcome by simply giving more drug
How are potencies compared?
By the amount of drug required to produce 50% of the maximal effect (EC50)
Efficacy
The ability of a drug to elicit a response when it interacts with a receptor
Therapeutic Index
Ratio of the drug doses that produces a specified toxic effect in 50% of the population vs the dose that produces a specified therapeutic effect in 50% of the population
TD50/ED50
What is considered a narrow therapeutic index?
Anything less than 2
What has a small therapeutic index?
Warfarin; ecmo/vads
What has a large therapeutic index?
Penicillin
