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
nonmicrosomal enzymes
* 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
Vd influenced by:
* Volume of distribution
* influenced by the physiochemical characteristics of the drug:
* lipid solubility
* binding to plasma proteins
* molecular size
27
antagonist drugs
* bind to receptors and change the configuration of the agonist site or bind to it, preventing effect from cell signaling molecules
28
transdermal
* 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
enantiomer
* two stable forms of a molecule slightly differently shaped.
* interaction with receptors can differ greatly
30
Volume of distribution
* sum of the volumes of the compartments
* Vd = dose of IV drug/Plasma [] before elimination
31
Sites of metabolism
1. plasma (adenosine, esmolol)
2. kidneys
3. lungs
4. GI tract
5. liver
32
hyper-reactive
* people who have desired effect of drug from an unusually low dose
33
how do drugs exert effects without using receptors?
* antacids neutralize gastric acid by a direct action
* adding a base to an acid to form a salt
34
Ionization
* most drugs are weak acids or bases
* can be ionized and non-ionized
35
context sensitive half time
* 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
Compartmental models
* divides the body into compartments that represent theoretical spaces with calculated volumes
* 2 compartments:
* central
* peripheral
37
hydrolysis
water added to substance causes chemical reaction
38
metabolism
* 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
zero order kinetics
* 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
phase 1 of metabolism
* oxidation, reduction, hydrolysis
41
efficacy
* the ability of a drug to produce the desired effect
42
elimination half **time**
* 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
absorption
* systemic absorption depends on the drug's solubility
* no matter how it is administered
44
hepatic microsomal enzymes
* 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
state of receptor activation theory
* non-activated receptors are converted to active by the drug
46
pathways of metabolism
1. oxidation
2. reduction
3. hydrolysis
4. conjugation
47
perfusion dependent elimination
* if the hepatic extraction for a drug is high (\>0.7) the clearance of the drug will depend on hepatic blood flow
48
Ke0
* the rate constant of drug elimination from the effect site
49
oral administration advantages vs disadvantages
* advantages
* most convenient
* most economic
* disadvantages
* emesis
* destruction by enzymes or acidic gastric fluid
* irregular absorption with food or other drugs
50
Degree of ionization
* 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
51
Central compartment
* 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
ED 50 vs LD 50
* 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
Pharmacodynamics
* What a drug does to the body
* mechanism of effect
* sensitivity
* responsiveness
54
receptor occupancy theory
* the more receptors occupied by drug the more effect
55
elimination half **life**
* 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
hypersensitivity
* allergy to drug
57
how do drugs exert effects?
* 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
Sublingual, transmucosal
* rapid onset
* bypasses liver and prevents first pass effect
59
reduction
gaining an electron
60
CNS distribution
* 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
Capacity dependent elimination
* 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
agonist drugs
* mimic cell signaling molecules by activating the same receptor sites and causing similar effects
63
Therapeutic index
LD50/ED50
64
Steady state plasma concentration of drug
equation
steady state plasma concentration of drug =
dose rate/clearance
