Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Basic Pharmacology > 7. Kinetics > Flashcards

7. Kinetics Flashcards

1
Q

What is Vd?

A

volume of disttribution

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Equation for Vd

A

conc of drug in body/conc of drug in plasma

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Drugs distributed through body water are …

A
  • lipid-soluble
  • readily cross cell membranes e.g phenytoin, ethanol
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Drugs distributed through body water have low or high Vd?

A

relatively high

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Drugs confined to plasma compartment are …

A
  • too large to cross capillary wall easily
  • e.g heparin
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Drugs confined to plasma compartment have low/high Vd?

A

low

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Drugs distributed in extracellular compartment are …

A
  • cannot easily enter cells
  • due to low lipid solubility
  • e.g gentamicin
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Drugs distributed in extracellular compartment have high/low Vd?

A

relatively low

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Drugs that accumulate outside plasma compartment are …

A
  • bound to tissues or stored in fat
  • e.g chloriquine, tricyclic, antidepressants
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Drugs that accumulate outside the plasma compartment have high/low Vd?

A

high

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Compare Vd of
- drugs distributed in body water
- drugs confined to plasma conpartment
- drugs distributed in extracellular compartment
- drugs that accumulate outside plasma compartment

A
  • confined to plasma is low
  • drugs in extracellular relatively low but higher
  • drugs in body water relatively high
  • drugs outside plasma comp is high
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Define ‘Vd’

A
  • what volume of your body have to be for a given amount of drug
  • to yield a concentration equal to that seen in plasma
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Define ‘distribution’

A
  • pharmacological term used to quantify the distribution of medication
  • between plasma and rest of body
  • after oral or parentaral dose
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

List the 4 mathematics of processes governing amount of drug in body and how it changes over time

A
  • absorption
  • distribution
  • metabolism
  • excretion
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Define ‘absorption’

A

movement of drug across membranes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Define ‘distribution’

A

where drug goes within body

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Define ‘metabolism’

A

how drug is broken down

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Define ‘excretion’

A

how drug is removed from body

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Define ‘bioavailibility’

A

the fraction of administered dose which enters systemic circulation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Define ‘first pass metabolism’

A
  • process occurring in intestine and liver before drug reaches systemic circulation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Where does first pass metabolism occur?

A
  • intestine
  • liver
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Explain enterohepatic recirculation/HER

A
  • drugs that are eliminated in bile can be reabsorbed in the GI tract
  • may occur after any route of administration
  • secreted into bile which is then stored in gall bladder and reduced into duodenum
  • many drugs undergo some degree of this - hard to generalize characteristics
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Examples of drugs that undergo enterohepatic recirculation

A
  • morphine
  • erythromycin
  • oral contraceptives
  • lorazepam
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Elimination is the sum of what 2 processes?

A
  • metabolism
  • excretion
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

What are the main systems involved with elimination?

A
  • kidneys
  • hepato-biliary system
  • lungs
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Define ‘metabolism’ in relation to drugs

A
  • most drugs are lipophilic
  • must be made more water soluble prior to elimination (makes it more polar)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

Drug metabolism is … … of the drug, in … phases

A

enzymatic modification
2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

Major site of metabolism for drugs is …

A

liver

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

Where does phase 2 of drug metabolism occur?

A

cytosol

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

Why is drug metabolism needed?
Give what is formed at each stage

A
  • drug to a derivative in phase one (ensures it’s lipophilic to get into target area)
  • phase 2 is derivative to conjugate (makes it polar for excretion)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

What chemical reactions are involved with drug to derivative?

A
  • oxidation
  • hydroxylation
  • dealkylation
  • deamination
  • hydrolysis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

What chemical reaction occurs in derivative to conjugate?

A
  • conjugation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

Give the chemicals formed in drug metabolism of aspirin

A
  • aspirin is the drug
  • becomes salicylic acid as derivative
  • glucoronide as conjugate
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

Which stage of aspirin metabolism is the active NSAID drug?

A
  • derivative stage
  • salicylic acid
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

Phase 1 reactions usually consist of …, … and …
… are important enzymes but others are involved like …
Often involves introduction of …

A
  • oxidation, reduction, hydrolysis (oxidation most common)
  • cytochromes P450
  • plasma cholinesterase
  • or exposing of a functional group (like hydroxyl) - called functionalisation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

Role of phase 1 reactions

A
  • decrease lipid solubility but may increase pharmacological/toxicological activity
  • many benzodiazepenes form metabolites which are more pharmacologically active than parent drug
  • important for activation of pro-drugs
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

… speed up phase 1 reactions

A

cytochromes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

Phase 1 reactions are cata/anabolic

A

catabolic - makes smaller molecule from larger one

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

Explain the cytochrome P450 enzyme family

A
  • often called CYPs
  • large superfamily of heme co-factor-containing enzymes
  • metabolise thousands of endogenous and exogenous compounds
  • individual members referred to as isozymes
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

Where are CYPs found? What kind?

A
  • mainly in intestine and liver - in liver hepatocytes (highest amount in body), enterocytes in intestine
  • small amounts in kidneys, white blood cells and nasal passages
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

Where are CYPs found in cells?

A

always in endoplasmic reticulum

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

Give basic CYP reaction

A

RH + O2 + NADPH + H+ -> ROH + H2O + NADP+

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

What is redox potential?

A
  • reduce, reoxidise and regenerate activity
  • as ionic form of haem group
44
Q

How does a basic CYP reaction occur?

A
  • enzyme is the haem group attached to a polypeptide
  • combine and creates a functional drug complex
  • driven by enzyme, needs cofactors and byproduct is production of water and functionalised drug
45
Q

where does ethanol metabolism occur?

A

almost entirely in liver

46
Q

Explain ethanol metabolism

A
  • ethanol to acetaldehyde
  • by alcohol dehydrogenase 2/3
  • and CYP2E1 1/3 (but in chronic administration)
  • acetaldehyde to acetic acid by aldehyde dehydrogenase
47
Q

What inhibits stage 2 of ethanol metabolism?

A

metronidazole

48
Q

CYP2E1 is a … and is only used in ethanol metabolism when?

A
  • P450
  • lots of ethanol is given/chronic administration
49
Q

Phase 2 metabolism is mainly … reactions and the functional group serves as …
What happens?

A
  • conjugation
  • point of attack for conjugation systems
  • large group e.g glucuronyl, sulphate and acetyl is attached
50
Q

Role of phase 2 metabolism

A
  • further decreases lipid solubility
  • almost always results in pharmacologically inactive metabolite
  • conjugate is excreted in urine or bile
51
Q

Explain glucuronidation
Mediated by?
Characteristics?

A
  • commonest conjugation reaction
  • important for endogenous compounds like bilirubin and exogenous compounds
  • mediated by UDP- glucuronyl transferases, an enzyme system with broad substrate specificity
  • due to polar nature, glucuronides are usually pharmacologically inactive and rapidly excreted
52
Q

Drug in phase 0 has … and …
How does this change after phase 1 and 2?

A
  • activity and toxicity
  • after phase 1, some activity and toxicity
  • after phase 2, larger water soluble compound has been added so no activity and toxicity
53
Q

Glucuronide conjugation reaction is … dependent

A

enzyme - need to drive high energy

54
Q

How does paracetamol metabolism occur for therapeutic doses?

A
  • mainly by conjugation with sulphate and glucuronic acid
  • only a minor proportion metabolised by CYP450 to a toxic metabolite
  • toxic metabolite normally detoxified by glutathione (another phase 2 reaction)
  • detoxification with glucuronic acid and sulfation and glutathione-5-transferase
  • finally becomes mercapturic acid
55
Q

Does paracetamol metabolism have a phase 1?

A
  • no
  • straight to phase 2
  • add big molecules to make it water soluble then when oxidised makes NAPQI which is toxic
56
Q

What happens in an overdose of paracetamol metabolism?

A
  • pathways of conjugation are saturated and co-factors are depleted
  • as such, more paracetamol is metabolised via CYP450
  • toxic metabolite reacts with liver proteins instead of glutathione (depleted)
  • tissue damage occurs leading to hepatic necrosis
57
Q

Phase 2 is good for … but what’s the drawback?

A
  • removing drugs from system
  • rate limited and depends on amount of conjugates we have
58
Q

For the average person in UK, daily intake of food additives is …

A

8g

59
Q

Additives in our lives include …

A
  • cosmetics
  • food additives
  • smoking
  • alcohol
60
Q

How do we excrete things?

A
  • urine
  • bile
  • lung
  • milk
  • sweat
61
Q

Explain renal excretion

A
  • wide variation in rate at which drugs are excreted by kidneys
  • rapidly cleared from blood e.g penicillin
  • slowly cleared from blood e.g diazepam
  • metabolites cleared faster than parental compound
62
Q

When drugs come out in urine, they are … or…

A
  • unchanged
  • more polar
63
Q

3 processes of renal excretion

A
  • glomerular filtration
  • tubular reabsorption
  • tubular secretion
64
Q

Water soluble drugs/metabolites are excreted …

A

through the kidneys

65
Q

How do lipid soluble drugs get to be excreted in urine?

A
  • filtered in glomeruli
  • reabsorbed on distal portion of nephron
  • metabolism to more polar compounds
  • excretion in urine
66
Q

Even the most lipophilic drugs that undergo metabolism will have …

A

a small fraction of administered dose appearing unchanged in urine

67
Q

…% of renal blood flow is filtered through glomerulus

A

20

68
Q

Explain glomerular filtration

A
  • drugs of molecular weight less than 20,000 diffuse into glomerular filtrate (most drugs)
  • plasma albumin (MR 68,000) almost completely held back
  • highly ppb drugs found in lower concs in filtrate than in plasma (like warfarin) 98% ppb conc in filtrate, 2% in plasma
69
Q

2 factors that don’t affect glomerular filtration

A
  • lipid solubility
  • pH
70
Q

Rate of entry to glomerular filtration depends on 2 things?

A
  • concentration of free drug in plasma
  • molecular weight
71
Q

…% of renal blood flow and therefore what? passes onto peritubular capillaries of proximal tubule

A
  • 80
  • 80% of drug
72
Q

Explain active tubular secretion

A
  • drug molecules transferred to tubular lumen by two carrier systems
  • which can transport against an electrochemical gradient
  • acidic drugs and endogenous acids e.g penicillins, uric acid
  • organic bases e.g morphine
73
Q

What is the most effective mechanism of drug elimination?

A

active tubular secretion

74
Q

ppb is not a barrier to …
Many drugs share same … which can lead to …

A
  • carrier mediated transport
  • transporter
  • competition
75
Q

2 systems for tubular secretion

A
  • for acids like penicillin, furosemide, probenecid
  • for bases like amiloride, amphetamine, cimetidine, procainamide
76
Q

Volume of urine is about … of the filtrate

A

1%

77
Q

Explain passive diffusion/tubular reabsorption

A
  • drug concentration increases as water is reabsorbed
  • highly lipid soluble drugs have high tubular permeability and are slowly excreted
  • highly water soluble drugs have low tubular permeability and concentrate in urine (100x that in plasma)
78
Q

Extent of absorption in tubular reabsorption depends on …

A
  • drug lipid solubility (i.e pKa)
  • pH of tubular fluid
79
Q

If the fluid becomes more alkaline in tubular reabsorption what happens?

A
  • then an acidic drug ionises, becomes less lipid soluble - reabsorption diminishes
  • a basic drug becomes un-ionised and reabsorption increases
80
Q

How does tubular reabsorption apply to patients?

A
  • helps with excretion in emergency situations
  • increase/decrease excretion by adding acid or base
81
Q

For weak bases e.g …, ionisation is greatest at …
For weak acids e.g …, ionsisation is greatest at …

A
  • pethidine, acid pH
  • aspirin, alkaline pH
82
Q

pH partition impacts what of drugs?

A
  • rate at which drugs permeate membranes - and distribution of drug between aqueous compartments
  • weak acids accumulate in compartments of relatively high pH whereas weak bases do the reverse
83
Q

How does pH partition affect urine excretion?

A
  • weak bases more rapidly excreted in acidic urine (drug is largely ionised and thus not reabsorbed)
  • weak acid more rapidly excreted in alkaline urine
84
Q

Urinary acidification does what?
It’s important in what?

A

accelerates excretion of weak bases and vice versa
- important in overdose - ion trapping

85
Q

Mechanisms of elimination depend on…

A

physiochemical properties of the compound

86
Q

Methods of elimination for different properties
- volatile
- water-soluble
- lipid-soluble

A
  • volatile gases are eliminated by exhalation
  • water-soluble compounds are done to some degree unchanged in urine (or excreted in bile)
  • lipid-soluble compounds undergo metabolism to more water-soluble metabolites that are excreted in urine/bile
87
Q

Define and explain ‘saturable elimination’

A
  • elimination mechanisms like enzymes are typically not saturated at therapeutic doses od drugs but some exceptions like phenytoin
  • increasing dose disproportionately increasing conc (linear to non-linear kinetics)
  • often called Michaelis-Menten kinetics
88
Q

What are Michaelis-Menten kinetics?

A
  • when dose is increased and disproportionately increases concentration
  • linear to non-linear kinetics
89
Q

Clearance is an … parameter

A

elimination

90
Q

Define ‘clearance’

A

best measure of ability of the eliminating organs to remove a compound from the body

91
Q

How to work out total body clearance or CL?

A
  • sum of all organ CL processes
  • e.g hepatic CL + renal CL + other CL
92
Q

How can clearance be defined using volume?

A
  • volume of plasma/blood cleared of compound per unit of time (mainly L/hr but can be any)
93
Q

Equation for CL after IV dosing

A

IV dose/IV AUC 0-> infinity

94
Q

Equation for clearance after oral dosing

A

oral dose x F/oral AUC 0-> infinity

95
Q

Dose/AUC after oral administration gives what?

A
  • CL/F (often called oral clearance)
  • can be calculated with CL = Ke x Vd
96
Q

Give another elimination parameter that isnt clearance

A
  • elimination rate constant or Ke
  • half life
97
Q

Define ‘half life’

A
  • time taken for conc of a compound to reach 50% of current value
  • units are time
98
Q

Equation for half life

A

0.693/Ke

99
Q

Rule of thumb for half life

A
  • takes 5 half lives for a compound to reach a steady state
  • rate in = rate out after chronic exposure
100
Q

Half life is the reciprocal of …

A

elimination constant
- rate of elimination under same conditions is the same

101
Q

How does exposure to chemicals and additives affect drugs?

A
  • important factor in perturbation of drug metabolising enzymes
  • compounds can induce or inhibit them
102
Q

Explain induction of drug metabolising enzymes

A
  • increased synthesis of enzymes of phase 1 and 2
  • increased metabolism therefore of inducing agent (autoinduction) and other drugs
  • inducers include enzymes and isozymes
  • over 200 drugs can be inducers like rifampicin, ethanol or carbamazepine
  • smoking and ethanol chronic exposure are inducers too
103
Q

Implications of induction of drug metabolising enzymes

A
  • decreased drug effectiveness on chronic exposure
  • need to increase drug dose
  • in multiple drug therapy, can be problems when inducer is withdrawn from regimen
  • basis of drug-drug interaction like oral contraceptives and rifampicin
104
Q

Paracetamol metabolism is induced how?

A
  • CYP450 metabolism to a toxic metabolite enhanced by ethanol or isoniazid consumption
105
Q

Explain inhibition of drug metabolising enzymes

A
  • inhibition of CYP system done by many drugs
  • reduced rate of metabolism and increased pharmacological effect
  • basis of several drug-drug interactions e.g terfenadine and ketoconazole
  • ethanol acts acutely to inhibit drug metabolism
106
Q

How is grapefruit juice a inhibitor of drug metabolising enzymes?

A
  • a component of the juice inhibits CYP3A4
  • as such inhibits the metabolism of CYP3A4 substrates including terfenadine and nifedipine

Basic Pharmacology (16 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions