Intro to Pharamacology Flashcards
study of substances that interact with living systems through chemical processes, especially by binding to regulatory molecules and activating or inhibiting normal body processes
Pharamacology
- what the BODY does to the DRUG
- great practical importance in the choice and administration of a particular drug for a particular patient e.g. renal function
Phamokinetics
Comes into play with choosing drug
- what the DRUG does to the BODY
- determines the group in which the drug is classified e.g. beta blockers
- Like mechanism of action
Pharmacodynamics
Drug to Body, determins class of drugs
What are the 4 elements of pharmacokinetics?
- Absorbtion
- Distribution
- Metabolism
- Excretion
ADME
Metabolims & Excretion are both elemination
Where do many orally administered medications pass through first after gut?
The liver then into plasma compartment
What part of the drug can enter the free tissues or site of action receptors?
Only the free drug can exit the plasama compartment
Injection of the drug into tissue
Intramuscular administration of drug
Injection of the drug straight into the blood; plasma
Intravenous
WHat are the 3 routes of drug administration?
- Oral
- Intramuscular injection
- Intravenous injection
Explain the time course of drug action
- Take drug, drug gets absorbed absorption phase
- Drug concentration increases to peak
- Drug gets distributed around body distribution
- Drug is excreted & metabolized elimination phase
What are the 4 diffrent ways drugs can cross memebranes?
- Aqueous diffusion
- Lipid Diffusion
- Special carries
- Endo/Exocytosis
What kind of drug permeation?
Drugs may diffuse passively through aqueous channels in the intercellular junctions (eg, tight junctions,
Aqueous Diffusion
What kind of drug permeation
lipid soluble drugs pass through lipid cell membrane
Lipid Diffusion
What kind of cell permeation?
Drugs with the appropriate characteristics may be transported by carriers into or out of cells
Special Carrier Diffusion
What kind of drug permeation
Very impermeant drugs may also bind to cell surface receptors (dark binding sites), be engulfed by the cell membrane ____ , and then released inside the cell or expelled via the membrane-limited vesicles out of the cell into the extracellular space____
Endocytosis & Exocytosis
What 5 thing does the rate and amount of absorbtion of a drug depend on?
- Local blood flow at site of admin (more flow= absorb better)
- Lipid Solubility (more lipid soluble easier to cross membrane)
- Molecular size (smaller passes esier throguh membrane)
- Local pH & Drug ionization (ionized drugs will not cross membrane)
- Total Surface Area of Absorbtion (More SA beter)
Where is the primary site of absorbtion for most oral drugs? why?
The small intestine
* It has vili that increase SA for absorbtion
fraction of unchanged drug reaching the systemic circulation following administration by any route
Bioavailability
Expressed in %
What is the bioavailibility of oral administered drugs? How about IV?
i.e How much will end up in systemic circulation
Oral= 75% bioavailable
IV= 100% always
metabolism of orally administered drug in the liver BEFORE it reaches the systemic circulation
First-Pass Effect
First-Pass Elemination
What is the result of a high first pass effect?
Decreased in bioavailibity
less reaches the systemic circulation
What Route of Admin?
PROS
* Conveinient
* Large surface area for absorbtion
CONS
* Drug metabolims
* Incomplete absorbtion
* First pass effect
* GI upset
Oral (PO)
What route of admin?
PROS
* Direct
* No First pass effect
* Slow infessions of rapid onset of action
* Esier to titrate does
CONS
* Req IV acess
* Hard to remove
* Vascular injury
Intravenous IV
What route of admin?
PROS
* To specific organs; brain & heart
CONS
Intra-arterial
What route of admin?
PROS
* Good for depot storage (if oil based)
* Rapi onset of action
CONS
* Pain at site of infection
Intra-muscular (IM)
What route of admin?
PROS
* Non irritating small volumes
* Even slow absorbtion
* Adrenaline in local anesthetics
CONS
* Paina at site of infection
Subcutaneous (SC)
What route of admin?
PROS
* Conventiant
* Localizied
* Limited systemic absorbtion
CONS
* Effects limited to area of application
Topical
What route of admin?
PROS
* Immediate action in lungs
* Rapid delivery to blood
* Local or systemic action
CONS
* Must be in gas, vapor, or aerosol form
Inhalation
What route of admin?
PROS
* Rapid onset of action
* No first pass effect
CONS
* Must be lipid soluble
Buccal
What route of admini?
PROS
* Direct application
* rapud onset of action
CONS
* Injection at site of application
* Delayed onset of action
Tansdermal
relates the amount of drug in the body to the concentration of drug (C) in blood or plasma
Volume of Distribution
What does a high volume of distribution signify?
Means that most of the drug concentration is enteing the extravascular tissue.
high amount of drug in the body
What affects Vd?
Affected by tissue and plasma binding and to which it binds more strongly too.
What does a low volume od distribution signify?
Most of the drug concentration is in the vascular compartment (blood)
If a drug is highly bound to plasma protien what is trend in VD
Low value of distributuion because it is stuck in the vascular compartment.
What are the ways in which drugs are bound?
- Free
- Bound to plasma protiens (albumin(
Why is it dangerous to administer two drugs are highly bound to plasma protein?
Discplacement of one or the other drug from plasma protiens can **result in toxicitiy. **
monitor pt. more
Only ____ can distribute into tissues and exert its action
free drug
What are some principles of drug protein binding
- Affinity of protien binding site (irreverisble?)
- Saturation of binding site (highly bound + loose= toxicity)
- Decreased albumin concentration (ex. liver faliure)
- Competition for binding sites & substrates
- Drug interactions
Drug will accumulate until the amount of drug administered per unit of time is EQUAL to the amount eliminated per unit of time
Plateu
Steady State Concentration
Plasma concentration are at steady state
At what halft life does steady state normally occur?
At about 4-5 half lifes, plasma concentration reaches Css
90 then 100%
Single large dose of druge used to raise the plasma concentration to a therapeutic level more quickly than would occur through repeated smaller doses—helpful when it takes a long time to reach steady-state
Loading Dose
- Most drug dosing regimens
- maintain a steady state of drug in the body, ie, just enough drug is given in each dose to replace the drug eliminated since the preceding dose
Maintenence Dose
type of elemination
Biotransformation, body making drug more water soluble so it can leave!
**lipophillic to hydrophyllic*
Metabolism
There are two phases in the metabolisms P1 & P2 where do they mainly occur?
The liver 2
What is the first route of metabolims a drug can take after absorbtion?
Straight through phase 1 and then conjucated in phase 2.
What is the second route of metabolims a drug can take after absorbtion?
Enters phase one and splits into
* Drug metabolite with modified activity
* Inactive drug metabolite
They then anter phase 2 and conjugate
What is the third route of metabolims a drug can take after absorbtion?
It can go straight through phase 1 and 2 and striaght to elemination. Excreted unchanged in the urine.
metabolism
What are the 3 elements of Phase 1 and what is the main purpose?
- Oxidation
- Reduction
- Hydrolysis
Increasing water solubility of the drug for excretion
How does phase 1 of metabilims increase water solubility?
By adding or unmasking a polar functional group
OH, −NH2, −SH
Metabolism
What enzymes mediate Phase 1?
Cytopchrome p450 liver enzymes
Metabolism
What is the most common Cytochrom p450 enzyme that mediates phase 1 of metabolism?
CYP3A4
other Isoforms of Cytochrom P450
Metabolism
What reaction occurs in Phase 2?
Conjucation reactions
Metabolism
When an endogenous substrate, combines with newly added functional group to form a highly polar functional group
glucuronic acid, sulfuric acid, acetic acid, or an amino acid
Phase 2 of Metabolism
Further increases water solubility and elimination
Why do we look at all the isoforms of Cytochrom P450?
Use of drugs can induce or inhibit certain isoforms.
Result from?
- Increased synthesis or decreased rate of degradation of p450
- Accelerates metabolism of drug
- Results in decreased effect
- May increase toxicity of drugs that are transformed to reactive metabolites
Induction of the Cytochrome 450
Results from?
- Bind to p450 enzyme (sometimes irreversibly)
- Decreases metabolism of drug or endogenous substances
- Results in increased effect/toxicity
Inhibition of Cytocrhome 450
Amiodarone is an inhibitor of CYP2C9 and CYP3A4 which inhibits the metabolism of Warfarin which does what?
Increases the risk of bleeding caused by elevted levels of Warfarin in the body
Carbamazepine is an inducer of CYP3A4 which induces more metabolims of oral contraceptives which does what?
Increases risk of unplanned pregnancy caused by decreaed levels of the oral contraceptive (metabolized!)
metabolism
what are the 6 phase two reactions?
- Methylation
- Sulfation
- Acetylation
- Glucoronidation
- Glucothionine Conjucation
- Glycine Conjucation
MSA-GGG
Elimiation 2.
What are the 3 main routes of excretion
KIDNEY
1. Glomerular filtration
2. Tubular secretion
3. Passive Excretion
If somthing is not very water soluble where will it most likely be excreted out of?
Biological stool
Why do you have to be cautious when administering drugs to a pregnant newly birthed mother?
Drugs can be excreted through breast milk!
Elemination rate
Estimates in creatine clearence (CrCl)
Cockroft-Gault equation
Depends on renal function
indicates the time required to attain 50% of steady state—or to decay 50% from steady-state conditions.
Half Life
Useful in designing drug dosage regimines
EX. half life is 10 hours.
* How long to reach stead state?
* How long to eliminatr?
- 40-50 hours for both either way
What is the goal of eleminatinon?
goal of metabolism is to de-toxify drugs, and make them either more water soluble (for excretion in the urine) or more fat soluble (for excretion in the bile, and then into the feces).
any substance that brings about a change in biologic function through its chemical actions
Drug
target molecule in the biologic system that plays a regulatory role
Receptor
a compound that binds to a receptor and produces the biologic response by activating the receptor
Agonist
a compound that binds to a receptor but does not activate generation of a signal
Antagonist
Interferes with the agonist ability to activate the receptor, doesnt generate a signal, no effects on its own, simply a stop
Explain a competative antagonist
Maximal effect reached but at higher doses of agonist
The agonist and antagonist compete for site of receptor but the antagonist is not covalantely bound so it comes off and allows for agonist binding.
Explain non-competative agonist
Reduced maximal effect even at high doses of agonist
- Irreverisble
- Allosteric
Explain mechanism of irreversible non-competative inhibitor
The antagonist covalantely bonds to the receptor site blocking agonist and there lowering max effect
Explain mechanism of allosteric non-competative inhibitor
The antagonist binds to site that is not the receptor, changing the shape of receptor site and **preventing binding of agonist. **
Drug Receptor interaction
Much more rapid maximal effect
- Agonist
- Allosteric activator
Drug Receptor interaction
Normal response
Only an Agonist
Drug Receptor interaction
Delayed incresed, but eventually reaches maximal effect (still less)
- Agonist
- Compentative inhibitor
Drug receptor interaction
Drug never reaches the steady state
- Agonist
- Allosteric Inhibitor
produces the biologic response but cannot produce 100% of the response even at high doses
Partial Agonist
Some designed on purpose.
What is an example when you prescribe a partial agonist?
Trying to get some one off opiod addiction, does not provide the high but also prevents withdrawls.
____ Agonist that have the oppiste effects from a full agonist
decrease basline receptor
Inverse Agonist
What are the 3 drug receptor bonds
- Covalent (strong)
- Electrostatic (weak)
- Hydrophobic (weakest)
What bond?
very strong and in many cases not reversible under biologic conditions
Covalent
What bond?
weaker then covalent bonds and more common
vary from relatively strong linkages between permanently charged ionic molecules to weaker hydrogen bonds and very weak induced dipole interactions such as van der Waals forces
Electrostatic
What bond?
usually quite weak
important in the interactions of highly lipid-soluble drugs with the lipids of cell membranes
Hydrophobic
Drugs that bind through weak bonds are more ____ than drugs that bind in strong bonds.
weak bonds= selective drug
* weak bonds require precise fit
the measure of drug safety
Theraputic Index
High TI vs Low TI?
- High/wider TI= safer
- Low/narrower TI= less safe
TD50/ED50 4+ good
The further the TD 50 and ED50 the higher the TI
The maximal response that a drug can produce
Efficacy
The measure of the dose that is required to produce the response
Potency
Drug that requires smaller does and stops issue entirly
More potent drug
Drug that requires higher does and only stops issue 60%
Less efficacy and less potancy
The **lower the EC(50) **which is the concentration of drug to reach 50% response
what does this** mean for potency?**
The higher the potency, drug reaches EC50 faster!
