Exam 1: Kinetics Flashcards
(115 cards)
1
Q
The scientific study of drugs and their effects on a living organism
A
Pharamcology
2
Q
Neuropharmacology
A
concerned with drug-induced changes in cell functioning in NS
3
Q
Psychopharmacology
A
emphasizes drug-induced changes in mood, thinking, and behavior
4
Q
What is the goal of neuropsychopharamacology?
A
identify chemical substances that act on NS to alter behavior. Neurobiology of behavior
5
Q
Drug ACTION
A
Specific molecular changes produced by a drug when it binds to particular target site/receptor
6
Q
Drug EFFECTS
A
widespread alterations in physiological/psychological function caused by drug action
7
Q
Drug-receptor interaction:
1) Favorable effects
2) other effects
A
1) therapeutic effects
2) side effects
8
Q
Specific drug effects
A
those based on the physical and biochemical interactions of a drug with a target site in living tissue
9
Q
Nonspecific drug effect
A
those based NOT on chemical DR but on unique characteristics of the individual
10
Q
Opposite of placebo effect
A
Nocebo
11
Q
Pharmacokinetics
A
Body –> Drug
1) Administration
2) Absorption
3) Distribution
4) Biotransfomration/Inactivation
5) Elimination
12
Q
Pharmacodynamics
A
Drug –> Body
Binding and Action
13
Q
Bioavailability
A
amount of drug in blood free to bind at specific target sites to elicit action
14
Q
Depot binding
A
drug binds to plasma proteins (IM)
15
Q
Absorption
A
movement of drug from site of administration to the blood circulation
Absorption = BLOOD CIRCULATION
16
Q
Agnoist
A
acts like NT (dynamics)
17
Q
Antagonist
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blocks NT (dynamics)
18
Q
Alimentary Canal
A
Mouth down
19
Q
GI enteral tract (gut)
A
Stomach and intestines.
20
Q
Eteral administration
A
Stomach/intestine
GI tract/alimentary canal
e.i. oral/rectal
21
Q
Parenteral administartion
A
all non enteral routes
e.i. topical injection pulmonary
22
Q
1st pass metbolism
A
portal vein –> liver, reduces drug bioavailability
23
Q
Bioavailbility
A
[drug] in blood that can interact with targets, determined by kinetics
24
Q
Drugs that effect thinking mood and behavior
A
Psychoactive drugs
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Absorption depends on
administration route, absorbing surface, cell layers, drug destroyed by metabolism, solubility/ionization, etc.
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Solubility of drugs and absorption
lipid soluble = passive diffusion across membrane
greater concentration gradient = rapid
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Prodrugs (e.i. Heroin)
drug dependent on metabolism to convert inactive drug to active one (BIOACTIVATION)
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Properties of drug that allow GI absorption
survive gastric enviornment, resist 1st pass, WS, LS
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What contribute to gastric degradation of proteins, peptides and drugs
Chemical: HCl + Pepsin --> gastric juice
Mechanical: muscle contractions (Peristasis)
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Hepatic 1st pass metabolism
Intestine --> portal vein --> liver --> hepatic vein --> circulation --> hepatic artery
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Ionization depends on
pH and pKa
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acidity/alkalinity of environment
pH
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pKa
pH of aqueous solution in which drug would be 50% ionized, 50% unionized
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Although acid favors stomach, why more in by small intestine?
absorption also determined by length of time in contact with absorptive membrane
Larger surface area/slower movement
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What drugs can't be GI tract?
highly charged drugs in both acid/basic environments
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Absorption rating limiting factor
rate at which stomach empties into intestine
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GI tract is ___ formed by ___
sealed tube formed by Epithelial cells
intracellular space ~4 A
cells tight against each other
hard for drug to leave
Lumen --> Capillaries
Simple columar
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Ionized
no diffusion water shell
| water soluble
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Passive/Facilitated rate of diffusion depends on
concentration gradient
high = higher rate of diffusion
Passive - lipids, NP
Facilitated - fructose/vitamins
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Active transport
need energy
[low]> [high]
e.i. glucose, mineral ions, amino acids
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Unionized =
GI absorption and diffusion
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Weak Acid + H+
Unionized (LS), absorption
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Weak Base + H+
Ionized (WS), no absorption
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Weak acids best absorbed at
Low pH
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Weak bases best absorbed at
High pH
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pH across GI tract
Gets higher (less H+)
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Acid Ion Trapping
ionized after passing into area with higher pH and become trapped there (opposite of best absorption pH)
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Base Ion Trapping
Base ionized and trapped in low pH area
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_____ maintains higher [unionized molecules] in original compartment promoting faster absorption
ion trapping
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____ of base allows GI absorption
deprotonization
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Small intestine surface area is given by...
cylinder, folds, microvilli, villli
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Capillaries with intestinal villi
LS drugs move through lymph vesicle to Lacteal
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Small Intestine favored by both Weak acids/base becuase
surface area
less mucous
longer transit time
high pH for weak bases
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Distribution
moving through blood vessels
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Artery
Thick outer wall
small lumen
thick layer of muscles and elastic fibers
Heart --> Tissue
effects bp
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Vein
think layer of muscle/elastic fibers
Large lumen
thin outer wall
Blood --> heart, no as muscular
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Capillaries
very small lumen
wall is single layer
drug action
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Does movement from CAPILLARIES/blood to tissue depend on solubility? Why?
No, unless bound to protein
Capillaries have a lot of pores
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Drug redistribution
Drug moving from tissues with high vasculature (heart, brain, kidneys, liver) back to plasma to maintain equilibrium
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Typically Capillary
Intracellular - small gaps
Fenestration- larger openings
Pinocytotic vesicles
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Brain Capillary
tight junctions: endothelial cells fused
carrier-mediated transport
astrocytes/glia feet to maintain the barrier, maintain tight junctions.
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BBB is ___ permeable
selectively permeable
lets in lipid soluble
WS by carrier protein
Enzymes made by endothelial/astrocytes can degrade chemicals passing by membrane
Bidirectional
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Area postrema
```
chemical trigger zone
BBB free
induces vomiting
allows WS
works with oral ingestion
located in medulla
```
WIDE SPACING BETWEEN ENDOTHELIAL CELLS
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Capillaries have single layer of ___ cells
ENDOthelial
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Capillary structure: continuous
intracellular spaces, basement membrane
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Capillary structure; fenestraed
fenstrations, pores in body of cells
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Capillary: Sinusoid
Huge gaps in some capillaries
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Plasma Protein Binding (PPB)
reduces bioavailability/drug effect
induces side effects
extends time of drug in body.
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PPB: drug interactions
free up more due to competition
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PPB: liver dysfunction
increase bioavailability
pass 1st pass
reduces liver's synthesis of proteins
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Storage depot binding
binding of drug to inactive site
Bone, fat, enamel
decrease bio-available/drug effect
bad effects:
lead/bone
thiopental/fat
tetracycline/enamel
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Functions of BBB
stable environment, prevents access of various chemicals, prevents access of many types of drugs
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BBB structure mainly determined by
tight junctions between endothelial cells
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BBB structure all parts
tight junctions
basement membrane- support
astrocytes release factors that anchor junctions
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Astrocyte jobs
1. synthesize proteins that support tight junctions between endothelial cells
2. uptake/degrade molecules that evade BBB
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Enzomatic barrier
glia cells degrade foreign stuff
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Transcytotic transport where drug and rector in vesicle to go across BBB is used by
Insulin/transferrin
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Biotransformation
Alteration in chemical structure of drug molecule by action of enzyme
Most common site: Liver
(also stomach, intestine, blood, kidney, brain)
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sinusoid
irregularly shaped liver blood vessel
allows things to access hepatocytes, large gaps
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Hepatocytes
Contain enzymes needed for drug biotransformation
Connected by tight gap junctions
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Enzymes
proteins with binding sites
reuseable
decrease energy needed for reaction
can break down/add stuff to molecules
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Phase 1
Nonsynthetic
Catabolic - tear things up
(oxidation, hydroxylation, dealkylation, deamination)
SUBTRACTIONS
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Phase 2
synthetic
Anabolic- build things up
(-COOH, -OCCH3, -CH3, -C6H10O7, methyl, amine, carboxyl, glucuronic acid, sulfhydryl)
CONJUGATIONS
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Cytochrome P450
phase 1
mixed function: oxidases
non-specific
inducible
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inducible
make more enzyme or increase affinity of enzyme
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Transferases
phase 12
transfer groups to drug molecule
specific
inducible
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Do drugs have to go through both phase 1 and 2 or in that order?
no
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Metabolism of Aspirin
Phase 1: hydrolysis CP450
Salicyclic Acid (active form)
P2: glucuronic acid transferase
Ether glucuronide
Ester glucuronide
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_______ is the most common type of P2 conjugation, catalyzed by transferase enzyme: ____
glucuronidation
UDPGT
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1/2 life
time for plasma [drug] decline by 50%
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First Order (exponential)
constant % drug removed each interval
Looks like curve
most common type
Rate of metabolism higher at higher plasma concentration of drug
at very high [drug], metabolism becomes zero order
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Zero Order
Constant AMOUNT of drug in blood removed each interval
Rare
e.i. aspirin, ethanol, phenytonin
Rate not effected by plasma [drug]
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Genetic copies cyto450
0 (PM)/ 1 (IM): adverse response, overreaction
2(EM): good
3+ (UM): too many enzyme, don't respond to medication
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Factors affecting biotransformation
```
genetic variation
age
sex
species
illness
drug history
```
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What does excretion
kidney
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Ureter
connects kidney to bladder
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Nephron
1.5 million/kidney
functional unit of kidney with renal corpuscle/tubule
H2O leaves descending loop
Na+Cl- leaves ascending limb
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Renal tubuae
in kidney
moves out, gets ride of stuff
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GLomerulus
fist of capillaries in kidney
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How do water/solutes enter kidney tubules?
Bowman's capsule, surrounds glomerulus
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_____ too large to enter kidney
blood cells/plasma proteins
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Most drugs that are LS when in kidney are
reabsorbed by blood
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Epithelial Cells:
| GI tract vs. Renal Tube
GI: simple columner
Renal: simple cuboidal
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Drug excretion: _______ are excreted in urine, _____ reabsorbed by blood.
Unionized (LS) reabsorbed
Ionized (WS) excreted urine
105
Acids excreted faster
high pH, ionized
106
Bases excreted faster
low pH, ionized
107
pH of kidney tubules
4-8 and varies
108
Factors affecting elimination by kidneys
acid/base
pKa
pH tubules
109
Anti-Diuretic Hormone (ADH)
```
Peptide
synthesized by hypothalamus
stored in posterior pituitary
facilitates water re-absorption
increases aquaporins at collecting tubules
```
Increases permeability of luminal membrane to H2O by inserting water channels
increases bp
regulates distal duct in nephron
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Aldosterone (steroid hormone)
Synthesized/release by adrenal gland
acts on collecting tube
facilitates Na+ re-absorption
111
Diuretics that increase urine output: ethanol/caffine
Ethanol: inhibit ADH, more fluid out
Caffeine: increase glomerular blood flow rate
112
Steady State Plasma level determined by
Half-life
the desired blood [drug] achieved when absorption/distribution = metabolism/excretion phase.
113
microsomal enzymes
liver enzyme that metabolize psychoactive drugs
located on smooth ER
lack specificity, metabolize variety of things
ex: CYP450
114
Enzyme induction
repeated drug uses causes increase in liver enzyme
speeds up biotransformation of this drug and toerhs
115
Enzyme inhibition
repeated drug use causes decrease in liver enzymes, reduces metabolism of drugs metabolized by that enzyme
