Uptake and Distribution of IV Agents Flashcards
1
Q
synergetic effect
A
- two drugs interact to produce an effect greater than their sum
- 1+1 = 3
2
Q
potency
A
- how strong the drug is.
- the dose necessary to achieve therapeutic effect
- ex. hormones
3
Q
Pharmacokinetics
A
- what the body does to the drug
- absorption
- distribution
- metabolism
- excretion
- Commonly measured:
- elimination half-time
- bioavailability
- clearance
- volume of distribution
4
Q
bases bind to:
A
alpha acid glycoprotein
5
Q
enzyme induction
A
- drugs and chemicals stimulate activity of the hepatic microsomal enzymes
6
Q
acids bind to:
A
albumin
7
Q
Clearance
A
- volume of plasma cleared of drug by metabolism and excretion
8
Q
Hepatic clearance
A
- equals the hepatic blood flow and hepatic extraction ratio.
- if hepatic extraction for a drug is high (>0.7) the clearance will depend on hepatic blood flow.
9
Q
Peripheral compartment
A
- large calculated volume
- extensive uptake of drug
**Rate of transfer between compartments decreases with aging, leading to greater plasma concentration in certain drugs
10
Q
additive effect
A
- second drug acting with the first will produce effect equal to the sum of both
- 1+1 = 2
11
Q
Non-ionized
A
- usually lipid soluble and can diffuse across lipid cell membranes
- BBB
- renal
- tubules
- GI epithelium
- hepatocytes
- pharmacologically active
- gets re-absorbed across renal tubules, is absorbed from GI tract and is metabolized by the liver
12
Q
rectal
A
- proximal rectum transports to the portal system via superior hemorrhoidal veins
- therefore experiences first-pass effect
- distal rectum bypasses portal system
**this is why rectal administration provides unpredictable responses.
13
Q
Distribution
A
- after systemic absorption of drug, the highly perfused tissues (heart, brain, kidneys, liver) receive a large amt of drug.
- as plasma level of drug decreases below these tissues, drug leaves and is redistributed to less well perfused sites (muscle, fat)
- plasma level decreases below these sites (muscle and fat) and drug leaves tissue to reenter circulation
- tissues that accumulate drug act as reservoir and prolong effect
- large or repeated doses saturate inactive tissue negating redistribution and prolonging action
- b/c now reduction of effect depends on metabolism instead of redistribution
14
Q
Renal clearance
A
- water soluble compounds are excreted more efficiently than lipid soluble drugs
- highly lipid soluble drugs are reabsorbed so little or no unchanged drug is excreted in urine
15
Q
Lung uptake
A
- lung uptakes basic lipophilic drugs and acts as a reservoir to release drug back into the systemic circulation
- lidocaine
- fentanyl
- demeol
16
Q
IV
A
- achieve therapeutic plasma levels precisely and rapidly
17
Q
First-pass effect re oral administration
A
- drugs absorbed from GI system enter the portal venous blood and pass through the liver before entering the systemic circulation for delivery to tissue receptors
- in GI system they are extensively extracted and metabolized.
18
Q
Effect site
A
- drugs exert their biological effect at the “biophase”
- biophase aka “effect site”
- the place where the drug acts upon the body
- membranes
- receptors
- enzymes
19
Q
First-Order Kinetics
A
- almost all drugs administered in the therapeutic dose ranges are cleared at a rate proportional to the amount of drug in plasma
- (Think about this like the enzyme chart when there are more enzymes than substrate)
- most common
20
Q
phase 2 metabolism
A
- covalently links drug or metabolite with highly polar molecule, making a more water soluble conjugate
21
Q
oxidation
A
losing an electron
22
Q
Ion trapping
A
- concentration difference of total drug can develop on two sides of a membrane that separates fluids with different pHs
- ex: placenta
23
Q
Protein binding
A
- most drugs bind to plasma proteins
- only free or unbound fraction of drug is easily and readily available to cross cell membranes
- Vd is inversely proportional to protein binding
- proteins are:
- albumin
- alpha acid glycoprotein
- lipoproteins
24
Q
Ionized drugs
A
- poorly lipid soluble
- can not penetrate lipid cell membranes
- repelled from portions of the cell with similar changes
- excreted by the kidneys unchanged
25
Q
nonmicrosomal enzymes
A
- metabolize drugs mostly by conjugation and hydrolysis
- some oxidation and reduction too
- present in liver, plasma, GI tract
- responsible for hydrolysis of drugs that contain ester bonds
- succhs, esmolol
- some people dont have them, which cannot be affected by enzyme induction
- determined genetically
26
Q
Vd influenced by:
A
- Volume of distribution
- influenced by the physiochemical characteristics of the drug:
- lipid solubility
- binding to plasma proteins
- molecular size
27
Q
antagonist drugs
A
- bind to receptors and change the configuration of the agonist site or bind to it, preventing effect from cell signaling molecules
28
Q
transdermal
A
- provides sustained therapeutic plasma [] of drug
- absorption occurs along sweat ducts and hair follicles that function as diffusion shunts
- rate-limiting step is diffusion across the stratum corneum of the epidermis (thick part of skin)
- thickness and blood flow are factors reflected in the skin’s permeability for drugs
- contact dermatitis can occur at the site.
29
Q
enantiomer
A
- two stable forms of a molecule slightly differently shaped.
- interaction with receptors can differ greatly
30
Q
Volume of distribution
A
- sum of the volumes of the compartments
- Vd = dose of IV drug/Plasma [] before elimination
31
Q
Sites of metabolism
A
- plasma (adenosine, esmolol)
- kidneys
- lungs
- GI tract
- liver
32
Q
hyper-reactive
A
- people who have desired effect of drug from an unusually low dose
33
Q
how do drugs exert effects without using receptors?
A
- antacids neutralize gastric acid by a direct action
- adding a base to an acid to form a salt
34
Q
Ionization
A
- most drugs are weak acids or bases
- can be ionized and non-ionized
35
Q
context sensitive half time
A
- the time required for plasma concentrations of a drug to decrease by 50% after discontinuation of drug administration
- in reference to discontinuation of an infusion
- depends on:
- distribution
- excretion
- physiochemical properties of the drug
- length of infusion
36
Q
Compartmental models
A
- divides the body into compartments that represent theoretical spaces with calculated volumes
- 2 compartments:
- central
- peripheral
- 2 compartments:
37
Q
hydrolysis
A
water added to substance causes chemical reaction
38
Q
metabolism
A
- transforms the drugs to make them water soluble and (often) inactive drugs
- increased water solubility reduces the Vd for a drug and enhances its renal excretion
- metabolism is not aways synonymous with inactivation or detoxification as some metabolites of certain drugs are active. (metabolite of versed)
39
Q
zero order kinetics
A
- constant amount of drug is cleard per unit of time because the drug will exceed the metabolic or excretory capacity even at therapeutic doses
- ex: aspirin, dilantin, ETOH
40
Q
phase 1 of metabolism
A
- oxidation, reduction, hydrolysis
41
Q
efficacy
A
- the ability of a drug to produce the desired effect
42
Q
elimination half time
A
- time necessary for the plasma [] of drug to decline 50% during the elimination phase
- directly proportional to its Vd and inversely proportional to its clearance
- elimination half time is independent of the dose of drug administered.
43
Q
absorption
A
- systemic absorption depends on the drug’s solubility
- no matter how it is administered
44
Q
hepatic microsomal enzymes
A
- located in hepatic smooth ER
- cytochrome P-450: large amount of different protein enzymes involved in oxidation and reduction and conjugation of a large number of drugs
- (enzymes in the liver)
45
Q
state of receptor activation theory
A
- non-activated receptors are converted to active by the drug
46
Q
pathways of metabolism
A
- oxidation
- reduction
- hydrolysis
- conjugation
47
Q
perfusion dependent elimination
A
- if the hepatic extraction for a drug is high (>0.7) the clearance of the drug will depend on hepatic blood flow
48
Q
Ke0
A
- the rate constant of drug elimination from the effect site
49
Q
oral administration advantages vs disadvantages
A
- advantages
- most convenient
- most economic
- disadvantages
- emesis
- destruction by enzymes or acidic gastric fluid
- irregular absorption with food or other drugs
50
Q
Degree of ionization
A
- depends on its dissociation constant (pK) and the Ph of the surrounding fluid
- changes in pH can result in large degree of ionization
- i.e. acidic drugs are highly ionized at alkaline pH and vice versa
- giving an acidic med to an acidic pt requires less drug b/c there will be less ionized
- i.e. acidic drugs are highly ionized at alkaline pH and vice versa
51
Q
Central compartment
A
- highly perfused tissues
- rapid uptake of drug
- drug first introduced into the central compartment distributes to the 2nd compartment and returns to central compartment for clearance
- kindney, liver, lungs, heart, brain
- receives 75% of CO
- represents only 10% of the body mass
52
Q
ED 50 vs LD 50
A
- ED 50: median effective dose
- LD 50: median lethal dose
- ratio of LD 50 and ED 50 indicates the therapeutic indes of a drug
53
Q
Pharmacodynamics
A
- What a drug does to the body
- mechanism of effect
- sensitivity
- responsiveness
54
Q
receptor occupancy theory
A
- the more receptors occupied by drug the more effect
55
Q
elimination half life
A
- time necessary to eliminate 50% of the drug from the body
- drug accumulation occurs if dosing intervals are ess than the elimination half times
- elimination half-time and elimination half-life are not equal when the decrease in the drug’s plasma [] does not parallel its elimination from the body.
56
Q
hypersensitivity
A
- allergy to drug
57
Q
how do drugs exert effects?
A
- interaction with specific macromolecules in the lipid bi-layer of cell membranes called receptors
- can increase or decrease in number in response to specific stimuli
58
Q
Sublingual, transmucosal
A
- rapid onset
- bypasses liver and prevents first pass effect
59
Q
reduction
A
gaining an electron
60
Q
CNS distribution
A
- blood-brain barrier (BBB) prevents ionized, water soluble drugs from crossing the barrier into the brain circulation
- BBB can be overcome with large doses of drug, in head injury, and hypoxemia
61
Q
Capacity dependent elimination
A
- if hepatic exraction ratio is low (<0.3) a decrease in protein binding or an increase in enzyme activity will increase hepatic clearance
- changes in hepatic blood flow will have minimal changes in its clearance
62
Q
agonist drugs
A
- mimic cell signaling molecules by activating the same receptor sites and causing similar effects
63
Q
Therapeutic index
A
LD50/ED50
64
Q
Steady state plasma concentration of drug
equation
A
steady state plasma concentration of drug =
dose rate/clearance
