Basic Concepts of Physiology Flashcards
1
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‘what the BODY does to drugs”
A
pharmacokinetics
2
Q
absorption, distribution, metabolism, and excretion of drugs
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pharmacokinetics
3
Q
determines the concentration of a given drug at its target receptors, may reflect individual differences between patients
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pharmacokinetics
4
Q
“what a DRUG does to the body”
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pharmacodynamics
5
Q
intrinsic sensitivity/responsiveness of the body’s receptors to a drug
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pharmacodynamics
6
Q
chemical structure influences what plasma concentration of a drug is necessary to evoke a response
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pharmacodynamics
7
Q
INTRINSIC SENSITIVITY also varies among patients, and is determined by measuring the concentration needed for the desired effect because the sensitivity varies from person to person
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pharmacodynamics
8
Q
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pharmacokinetics
9
Q
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pharmacodynamics
10
Q
- Specific protein molecule of lipid bilayer of cell membrane with which an administered drug interacts
- interaction with drug causes changes in the cell to produce drug’s effects
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receptor
11
Q
- Different types cause drugs to exert their effects in different ways
- concentration (number) at site of action may change
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receptor
12
Q
___________ __________ receptors change conductance of cell, altering ion influx/efflux
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voltage-sensitive
13
Q
____________ ___________ receptors cause conformational change and thus alter cell membrane. Effects may INHIBIT or ENHANCE the functions of cells
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ligand-gated
14
Q
will cause downregulation of receptors to try and avoid the abundance of catecholamines
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pheochromocytoma
15
Q
___________ will upregulate the number of receptors. if you abruptly discontinue use, you will get an exaggerated effect
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Beta antagonists
16
Q
FOUR TYPES OF RECEPTORS
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- MEMBRANE RECEPTORS
- LIGAND-GATED ION CHANNEL
- VOLTAGE-GATED ION CHANNEL
- ENZYME
17
Q
ex: Beta-AR
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membrane receptor
18
Q
ex: GABAa
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ligand-gated ion channel
19
Q
ex: Na+ channel
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voltage-gated ion channel
20
Q
ex: phosphodiesterase inhibitors
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enzyme
21
Q
3D structural orientation of molecules
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stereochemistry
22
Q
2 molecules having the same chemical composition but different orientations around a central atom – mirror images
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entantiomers
23
Q
- may bind to receptor sites differently, contribute to differnces in absoption, distribution, clearnce, potency, toxicity.
- one may cause clinical effect, the other may cause side effects
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entantiomers in racemic mixture
24
Q
2 entantiomers present in EQUAL proportion
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racemic mixture
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"S" entantiomer: tetragenic, peripheral neuritis
"R" entantiomer: effective sedative, sleep med, and cure for morning sickness
Thalidomide
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* a drug that produces its clinical effect by binding to a receptor and activating it
* mimetic
agonist
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* a drug that produces its clinical effect by binding to a receptor WITHOUT activating it and simultaneously prevents an agonist from stimulating it
* blocking
antagonist
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drug that combines directly with its receptor to trigger its physiologic response
direct-acting receptor agonist
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drug that produces its physiologic response by:
1. inducing the release/increasing the concentration of ENDOGENOUS substrate (neurotransmitter or hormone) at receptor site
2. OR inhibits inactivation of neurotransmitter, (inhibiting reuptake or degadative metabolism)
3. DRUG ITSELF DOES NO INTERACT WITH RECEPTOR
indirect-acting receptor agonist
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* Example of direct-acting receptor agonist
* binds to alpha receptors in the peripheral vascular system and directly activates them to cause vasoconstriction
Phenylephrine
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Example of indirect-acting receptor agonist
* induces the RELEASE of norepinephrine from post synaptic nerve endings
* denervation or depletion of teh neurotransmitter (after repeated doses, for example) will cause the administered drug to have less effect
ephedrine
amphetamines
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receptor inhibition which can be overcome by INCREASING the concentration of the agonist at the receptor site (reversible blockade)
competitive receptor antagonism
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receptor inhibition which CANNOT be overcome by increasing the concentration of the agonist (irreversible blockade)
noncompetitive receptor antagonism
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drug response: unusually low dose triggers pharmoacological effect – very sensitive patients
hyperactive drug response
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drug response: allergic to drug
hypersensitive drug response
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drug response: patient requires large dose for desired effect, often due to chronic exposure (tolerance)
hyporeactive drug response
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drug response: decreased effectiveness of a drug with multiple doses (ex. Ephedrine)
tachyphylaxis
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drug response: second drug administered with the first will produce an effect EQUAL to the sum of the 2 doses if administered independently
additive drug response
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drug response: 2 drugs administered together may produce a greater effect than either drug given alone
synergistic drug response
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drug response: 2 drugs administered together have LESSER effect than either given alone
antagonistic drug response
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drug response: pharmacologically inactive compounds designed to maximize the amount of active species that reaches its site of action (ACE inhibitors)
prodrug drug response
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route of administration: via the alimentary tract
* oral (PO)
* Sublingual
* rectal
Enteral
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route of administration: "aside from" the alinentary tract
* IV
* IM
* SC
* pulmonary
* intraarterial
* intrathecal
* nasal
* transdermal, topical
parenteral
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routes of administration:
PO drugs from GI enter PORTAL VENOUS blood and travel to liver before being delivered to tissue
LIVER begins breakdown, accounting for differences between IV and PO administration of drug
oral administration of drugs
FIRST PASS HEPATIC METABOLISM
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routes of administration:
ADVANTAGES: convenient, cheap
DISADVANTAGES: GI irritation, destruction of drug by gastric acid, alterations with food
Oral administration:
FIRST PASS HEPATIC METABOLISM
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routes of administration: rapid absorption through buccal mucosa, no first pass metabolism
(nitroglycerine: if swallowed, NO EFFECT)
sublingual administration
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route of administration: absorbed into superior hemrrhoidal veins, good for vomitting pts and peds
rectal administration
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routes of administration: immediate onset, CANNOT RETRIEVE AN OVERDOSE
IV administration
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routes of administration: absorption rate depends on blood flow;nutrition for comatose or uncooperative pts
IM and SC administration
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routes of administration: volatile drugs and aerosols
pulmonary administration
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routes of administration: FEW DRUGS GIVEN THIS WAY!!! DON'T GIVE DRUGS THROUGH A-LINE!!!
intraarterial administration
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routes of administration: into CSF
intrathecal admnistration
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routes of administration: for LOCAL effect at application site
topical administration
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routes of administration: for SYSTEMIC effect but given on skin (patch)
transdermal administration
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Name each layer ![]()
epidermis
dermis
subcutaneous tissue
muscle (with vein)
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site-specific factors affecting absorption
1.
2.
3.
1. blood flow from site
2. surace area for absorption
3. solubility of drug at site
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(theory) the body is composed of multiple compartments having calculated volumes
circulating blood
central nervous system
liver
fat
(etc.)
Compartment models
we can examine the pharmacokinetics of drugs we administer in terms of what compartments they travel to and what happens when they reach those compartments (clinical effect, metabolism, storage, etc.)
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components of 2-compartment model
1.
2.
1. Central component
2. Peripheral component
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2-compartment model: rapid uptake of drug
* includes intravascular fluid and highly perfused tissues like the lungs, heart, brain, kidneys, and liver
* 75% of cardiac output, 10% of body mass
Central compartment
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2-compartment model: slower uptake of drug
* includes less vascular tissues like fat, bone, and inactive skeletal muscle
peripheral compartment
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drugs equilibrate between compartments and are eventually eliminated from the central compartment
2-compartment model
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(concept) the total approximation of all the compartments to which a drug goes
relates the amount of drug in the body to the concentration of drug in the blood or plasma
volume of distribution (Vd)
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indicates that a drug is extensively taken up by the tissues
large volume of distribution (Vd)
(the greater the Vd, the longer the elimination half-life)
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indicates that the majority of drug remains in plasma
small volume of distribution
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plasma concentration curve phases: immediately after administration of drug
movement from central to peripheral compartments
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distribution phase
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plasma concentration curve phases: more gradual as drug is removed from circulation
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elimination phase
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ex: drugs travel on proteins in the blood
1.
2.
1. albumin
2. alpha-1-acid glycoproteins
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protein binding: binds acidic drugs (eg, barbiturates)
albumin
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protein binding: binds basic drugs (eg, local anesthetics)
AGP (alpha-1-acid glycoproteins)
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proportional relation: protein binding vs. volume of distribution
degree of protein binding is INVERSELY PROPOTIONAL to volume of distribution
degree of protein binding = 1/Vd
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pharmacologic implication of drug-protein binding
1.
2.
3.
1. only unbound drug crosses cell membranes to reach its site of action
2. free drug is more readily available for elimination
3. drug that is protein bound is NOT pharmacologically inert
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drug-protein binding: as soon as unbound drug leaves circulation, some drug will dissociate from binding sites, which tends to restore the free drug concentration
law of mass action
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what determines the degree of ionization of a drug?
* pK of substrate
* pH of surrounding fluid
whether or not a drug exists predominately in an ionized vs. nonionized state affects how well it permeates membranes
if a drug can't diffuse through a cell membrane, its travel is limited
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\_\_\_\_\_\_\_\_\_\_\_\_ __________ drugs have:
* impaired absorption from GI
* limited hepatic metabolism
* increased excretion (in unchanged form) facilitated by kidneys (drug will not be reabsorbed)
* poor lipid solubility
highly ionized
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what form of ionization of a drug is more lipid soluble and can readily diffuse across a cell membrane?
non-ionized drugs
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what form of ionization of a drug is less lipid soluble and can not readily diffuse across a cell membrane?
ionized
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when ________ & _________ are \_\_\_\_\_\_\_\_\_\_, 50% of the drug exists in both the IONIZED and NONIONIZED from
when _pK_ & _pH_ are _IDENTICAL_
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ACIDIC drugs are _________ \_\_\_\_\_\_\_\_\_ at alkaline pH
ex., barbituates
highly ionized
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BASIC drugs are __________ \_\_\_\_\_\_\_\_\_\_\_ at acidic pH
ex., opioids, local anesthetics
highly ionized
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if membrane separates areas of differing pHs, then the nonionized portion of a drug diffuses and equilibrates, but the ionized form does not, resulting in large concentration differences on either side of membrane
ion trapping
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ex., organ systems that induce ion trapping:
1.
2.
3.
1. stomach
2. renal tubules
3. placenta
degree of ionization is different on each side of the membrane, and nonionized form equilibrates
82
opioids and local anesthetics are ___________ drugs that ___________ the placenta to fetus.
Fetal pH is \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_, thus drug is converted to ________________ form and accumulates...can result in fetal distress
basic
cross
acidic
ionized
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chemical process where drug is altered in the body
biotransformation
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biotransformation: drug is converted to polar metabolite
* oxydation, reduction, hydrolysis, acetylation
* can result in activation, change, or inactivation of drug
metabolic biotransformation
Phase I
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biotransformation: drug forms conjugate with endogenous substrates (carbohydrates, amino acids) to form water soluble metabolites, readily excreted from body
results in loss of biological activity of a compound
metabolic biotransformation
phase II
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removal of drug from plasma
important concept to achieve steady state: want to dose amount that is leaving
clearance
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ester hydrolysis
clearance: kidneys
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hoffman elimination
clearance: liver
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ezymatic alteration of drug's chemical structure
4 major types of reactions:
1.
2.
3.
4.
metabolism
1. oxidation
2. reduction
3. conjugation
4. hydrolysis
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refers to all the processes that remove drugs from the body, either excretion of unchanged drug or metabolism and subsequent excretion of metabolites
elimination
91
a temperature- and pH-dependent process
(rate of degradation in vivo is highly influenced by body pH and temperature)
Hofmann eliminiation
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Hofmann elimination: an increase in body temp favors \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_
elimination
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Hofmann elimination: a decrease in temperature _____________ \_\_\_\_\_\_\_\_\_\_ \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_
slows down elimination
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clearance: drugs that are cleared efficiently by the liver are restricted in their rate of elimination not by intrahepatic process, but by
\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_
the rate at which they can be transported in the blood to the liver
95
metabolism: typically conversion from ACTIVE, LIPID SOLUBLE drugs into \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_
INACTIVE, WATER SOLUBLE metabolites
drugs must be transformed into hydrophilic metabolites for elimination
96
drug clearance from liver dependent on:
1.
2.
3.
1. hepatic blood flow
2. intrinsic ability of liver to irreversibly eliminate drug from the blood
3. the extent of drug binding to plasma proteins or other blood constituents
