Brainscape's Knowledge GenomeTM

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


See full index

PPI > Pharmacokinetics > Flashcards

Pharmacokinetics Flashcards

1
Q

Absorption is the journey from administration to where?

A

Absorption is the journey from administration to distribution (bloodstream)

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

Define gating

A

Gating: the transition between open and closed states of an ion channel

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

Define potency

A

Potency: the measure of an agonist’s activity.

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

What is potency expressed as?

A

Potency is expressed as the concentration required to produce half of the maximal response

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

Define signal transduction

A

Signal transduction: The chain of events that converts the message

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What is signal transduction directed by?

A

Signal transduction is directed by the agonist binding to its receptor into the physiological response

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

What are therapeutic drugs?

A

Therapeutic drugs are drugs that are used to treat illnesses

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

In the treatment of acid indigestion, what is bicarbonate used for?

A

Bicarbonate can be used to increase the stomach’s pH by neutralising some of its acid.

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

What are the targets of most drugs?

A

Most drug targets are proteins

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Where are the targets for lipophilic molecules?

A

Lipophilic molecules tend to have intracellular targets as they can cross the cell membrane

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

Other than receptors, what are the other common protein targets for drugs?

A

Ion channels, transport proteins and enzymes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Define volume of distribution

A

Volume of distribution is the extent to which a drug is distributed throughout the body in relation to its concentration in the bloodstream. It is a useful measure as it can influence dosing considerations and can help to understand how a drug is distributed. If a drug possesses a high volume of distribution this infers that it is more distributed to the tissues, whereas a drug that possesses a low volume of distribution will be found in the bloodstream.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What are the different ways that a drug may be administered?

A

Different ways that a drug may be administered
* Injection
* Orally
* Sublingual (under tongue)
* Intravenously
* Rectal
* Inhaled (straight to the bloodstream)
* Intranasal- nasal spray
* Transdermal- (skin)
* Topically
* Intrathecal- directly into spinal canal- e.g. epidural

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Parenteral- Injections

A

Parenteral- Injections
* Intravenous i.v. - rapid, can stop if rapidly appearing adverse effect seen but cannot recover drug once administered
* absorption is always 100%
* Useful for cytotoxic drugs that would cause necrosis if given i.m. or s.c.
* Rate of injection important particularly for potential cardiotoxins

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

The absorption of parenteral injections is always what percentage?

A

The absorption of parenteral injections is always 100%

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

What are patenteral injections useful for?

A

Parenteral injections are useful for cytotoxic drugs that would cause necrosis if given i.m. or s.c.

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

What are some of the disadvantages of injections?

A

Injection disadvantages
* Distressing
* Invasive – carries some risk
* Could cause: Embolism Air/liquid/solid
* Things may come out of the solution
* Need for asepsis: needs a sterile/germ free environment

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

Factors affecting rate and extent of Absorption from the GI Tract:

A

Factors affecting rate and extent of Absorption from the GI Tract:
* Acidity – exposure to acid may breakdown drug
* gastric emptying time- reduced rate increases exposure to acid
* surface area and blood supply
* food in gut – variable effects
* Co-administered with other drugs
* Vomiting & diarrhoea – decrease absorption
* disease
* First Pass effect and bioavailability
* Hydration
* Emotions: can affect blood flow to the gut
* Reduced motility: exposes drug to possible degradation by bacteria
* Increased motility: reduces time to cross membranes
*

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

First pass metabolism only applies to what form of drug administration?

A

First pass metabolism only applies to drugs administered orally.

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

If a drug is metabolized before anything else does it make it more or less effective?

A

If a drug is metabolized before anything else it makes it less effective and a higher dose will be required

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

First Pass metabolism: Liver

A

First Pass metabolism: Liver
* Orally administered drug
* Absorbed from the small intestine to the liver via the hepatic portal vein to systemic circulation
* Some metabolism in the gut epithelium
* Metabolized in the liver: liver metabolic enzymes may modify the drug and reduce bioavailability
* Some amount enters the systemic circulation= bioavailability

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

Co-administration with other drugs that reduce GI motility will reduce absorption. Give examples of drugs that will have this effect on the GI tract.

A

Examples of drugs having this effect on the GI tract (reduce GI motility) are anticholinergics, opiates, and tricyclic antidepressants

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Bioavailability

A

Bioavailability:
* Highly variable
* How much drug is in circulation
* E.g. 20mg may be swallowed but only 9mg might be in circulation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Does sublingual administration undergo first pass metabolism?

A

No, sublingual administration does not undergo first pass metabolism

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

Sublingual

A

Sublingual
* Placement under the tongue
* Allows the drug to diffuse into the capillaries & therefore to enter the systemic circulation
* Bypasses the intestine & liver - avoids 1st pass metabolism
* Not via the GI tract
* Goes straight to the bloodstream
* Bioavailability is less than 100%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Rectal

A

Rectal
* When oral route is not recommended (e.g. vomiting)
* Bypasses the intestine & liver - avoids 1st pass metabolism
* Upper part of rectum blood supply does drain into liver

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

Which two forms of administration bypass the intestine and liver?

A

Sublingual and rectal administration bypass the intestine and liver, avoiding 1st pass metabolism.

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

Volume of distribution

A

Volume of distribution:
* Volume that would contain the total amount of administered drug at the same concentration as that seen in the plasma
* important because it helps determine drug plasma concentration from a given dose
* can be used to calculate loading dose.
* Is the fluid volume in which it seems to be distributed to account for its plasma concentration.

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

What is the average blood volume in humans?

A

The average blood volume in humans is 5L

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

How is volume of distribution calculated?

A

Volume of distribution is calculated:
dose (mg)/plasma concentration (mg/L)= Litres OR total amount in body/concentration in blood or plasma
* Drug is metabolised and excreted
* plasma conc… declines continuously
* estimate plasma conc.. in absence of decline
* extrapolate rate to zero

31
Q

What is the measurement of total body water?

A

Total body water is 70L

32
Q

Apparent Volume of Distribution

A

Apparent Volume of Distribution
* Tells you where the drug is
* E.g. 3-5L: bloodstream. 70L: TBW

33
Q

Apparent Volume of Distribution: Obesity

A

Apparent Volume of Distribution: Obesity
* Larger fraction of body weight is Fat
* TBW compartment is smaller % BW
* TBW compartment is smaller
* Vd for drugs in TBW appears smaller
* Vd for fat-soluble drugs appears larger
* In obesity, the total body water compartment is a smaller percent of the body weight and so drugs distributed in total body water will appear to have a smaller volume of distribution. However the volume of distribution of fat-soluble drugs will appear to be larger as there is more fat into which they can distribute.

34
Q

Apparent Volume of Distribution: Infants

A

Apparent Volume of Distribution: Infants
* TBW is larger % BW (77%)
* TBW compartment appears larger
* Vd appears larger

35
Q

Why is the Apparent Volume of Distribution helpful?

A

The Apparent Volume of Distribution helpful because:
* Helps to calculate dose
* Gives an indication of how much drug is needed: some may need to be adjusted depending on weight or physiological condition

36
Q

Apparent Volume of Distribution: Pregnancy

A

Apparent Volume of Distribution: Pregnancy
* Blood volume, extracellular water and subcutaneous fat increase
* Vd may increase for drugs in TBW
* The volume of distribution can be variable in pregnancy as there are several changes occurring in the body.

37
Q

Chloroquine has an apparent volume of distribution of 100 L/kg!! How can this be?
Metabolism
Diffusion into adipose tissue
Much less in plasma

A

Chloroquine has an apparent volume of distribution of 100 L/kg!! How can this be?
* If the amount on concentration don’t match then the drug is likely to be somewhere else, rapidly metabolised, lipophilic: might be fat

38
Q

High volume of distribution means the drug is where?

A

High volume of distribution means the drug isn’t in the bloodstream

39
Q

What is the bioavailibility of orally administrated drugs?

A

The bioavailibility of orally administrated drugs is highly variable and tends to be less than 100% due to slow absorption coupled with metabolism, distribution and exctreiton

40
Q

Bioavailability

A

Bioavailability
* Fraction of the amount of drug that reaches the systemic circulation
* IV is always 100%
* Oral administration is nearly always less than 100% - slow absorption coupled with metabolism/distribution/excretion. Highly variable.
* Amount available is not necessarily the amount given.
* Could be affected by: fat solubility, other drugs, foods, other things that can change the absorption rate

41
Q

Bioavailability and Food

A

Bioavailability and Food
* Bioavailability of some drugs is affected by the presence of food. E.g penicillin’s, erythromycin, rifampicin, thyroxine
* Some drugs are taken before meals to allow time for drug to act before food is taken
* Gastric irritation can be caused by drugs taken on an empty stomach
* Effect of food on the absorption of drugs

42
Q

Protein binding

A

Protein binding
* Protein can vary with nutritional status and as a consequence of liver, or kidney disease
* Mechanism of several drug interactions
* Protein bound drugs can’t be cleared or initiate pharmacological effects
* Drugs may be in plasma bound to protein: albumin, lipoproteins, a1 acid glycoprotein
* Protein binding is similar to competitive inhibition binding
* Protein binding derermined by concentration of free drug, amount of protein available, affinity of drug to bind to protein
* Examples of drugs highly protein bound: Warfarin, propanolol, phenytoin, diazepan
* Protein bound drugs can be dis[laced ny other molecules

  • Effects of decrease in protein bound fraction in plasma:
  • Higher free drug concentration… to exchange with tissue leading to:
    Greater tissue response, therapeutic and adverse effects
    Higher rates of clearance by organs of elimination, and more rapid decline in plasma levels
43
Q

What are the routes of excretion?

A

Routes of excretion:
Usually by the liver or kidneys
* Routes of excretion
- Biliary excretion and enterohepatic cycle
- Renal excretion
- Sweating
- Defaecation
- Breathing
- Urinating
- Crying
- Vomiting

44
Q

Half life of drugs

A

Half life of drugs
* Usually how drug excretion is expressed
* This is the **time required for the concentration of the drug in the plasma to decrease by one-half **of it’s initial value
* Drug half life is variable
* Repeated doses are given to raise the concentration levels to a peak
* In theory, the optimal dosage interval between drug administration is equal to the half-life of the drug

45
Q

Therapeutic range

A

Therapeutic range: where the drug is working

46
Q

Oral drugs have:

A

Oral drugs have an absorption phase, elimination phase and therapeutic range.

47
Q

1st order
elimination

A

1st order elimination: drug half life

48
Q

If a drug is absorbed too quickly it can cause toxicity if it is absorbed too slowly it might ?

A

If a drug is absorbed too quickly it can cause toxicity if it is absorbed too slowly it might not work

49
Q

Elimination of alcohol

A

Elimination of alcohol
* Follows linear elimination: only drug that does
* Can estimate alcohol for 2 hours
* 35mcg per 100ml breath
* Doesn’t have a half life
* Constant with time: vaires with time

50
Q

Excretion: Biliary excretion and Enterohepatic cycle

A

Excretion: Biliary excretion and Enterohepatic cycle
* Drugs swallowed from small intestine
* Goes to liver
* Liver metabolizes drug
* Some metabolites go back to small intestine via bile
* Some bacteria break down metabolized drug and make it original drug
* Drug is reabsorbed in liver
* Back to small intestine
* Remetabolized by bacteria
* drug stays in the body longer than it should

51
Q

Renal excretion

A

Renal excretion
Passive reabsorption:
* - only lipid soluble molecules (no charged mols)
* Dependent on concn
* gradient as water reabsorbed
* Drinking more fluid will decrease

Glomerular filtration:
* - only free molecules filtered (no protein bound)
* GFR 120ml/min

Active
* - Active transport
* Non free drugs?
* Acidic drugs (penicillin)
* Basic drugs (procainamide)
* Competition can cause toxicity

52
Q

Polyphenols

A

Polyphenols
* Extend the viability of fruits
* Toxins to cause death of animals that feed on plant
* Naringenin and bergotamin in grapefruit juice: alter P450
* Polyphenols implicated in altering metabolism of range of Phase I and Phase II reaction enzymes
* Further work needed

53
Q

Cruciferous vegetables

A

Cruciferous vegetables
* Induce CYP1A2 which can cause conversion of amines to carcinogens by induce GST which associated with decreased cancers of gut
Broccoli, brussel sprouts, cabbage, cauliflower
Induce CYP1A2 and glutathione transferases (GST) in gut resulting in rapid clearance of some compounds
CYP1A2 may convert aromatic amines to carcinogens
Induction of GST associated with decreased cancers of gut

54
Q

Barbecued meats

A

Barbecued meats
Induce P450s
Induce CYP1A1 and CYP1A2
Increased clearance of:
Paracetamol
Amitryptiline
Clozapine
Fluvoxamine
Naproxen
Haloperidol

55
Q

What is clearance?

A

Clearance is the combined effects of excretion and metabolism
Amount of drug removed
Volume of plasma cleared per unit time (ml/min)

56
Q

Glomerular filtration rate?

A

Glomerular filtration rate:
120ml/min

57
Q

Total systemic clearance:

A

Total systemic clearance
* Is related to the half life of the drug (time it takes for blood level to fall by half)
* As clearance increases, half-life decreases for a given Vd;
* As Vd decreases, half-life decreases, for a given clearance. (why? More in blood, so more available for elimination)

58
Q

Kidneys are the _______ way out for a drug

A

Kidneys are the best way out for a drug

59
Q

Clearance

A

Clearance
* Body’s way of getting drug out
* Steady state concentration of the drug (Css) is achieved when : rate of elimination = rate of adminstration.

60
Q

Use of clearance

A

Steady state concetration of drug x clearance= (dose x f)/ frequency of administration

61
Q

Metabolism

A

Metabolism:
Drugs that are not excreted
in urine or bile must be metabolised

Hepatic clearance measures rate of
hepatic metabolism

62
Q

The liver microsomal drug-metabolising system

A

The liver microsomal drug-metabolising system
* Metabolizes drugs to make them more water soluble
* Key enzymes are: NADPH-cytochrome P450 reductase and the haemoprotein cytochrome P450
* Cytochrome P450 3A4 alone is responsible for metabolising in the liver more than 60% of clinically prescribed drugs
*
* Multiple forms of the haemoprotein: e.g. CYP1A2, 2A6, 2C9, 2C19, 2D6, 2E1, 3A4
* Mediate Phase I oxidations and Phase II glucuronide conjugations
* Alcohol gravitates to TBW

63
Q

CYP450 Isoenzymes

A

CYP450 Isoenzymes
More than 30 subtypes identified.
Cause differences in the ability of an individual to metabolise drugs.
Nomenclature
Root: CYP Family: CYP2
Subfamily: CYP2D Gene: CYP2D6
All CYP isoenzymes in same family have at least 40% structural similarity, those in same subfamily have at least 60% structural similarity.

64
Q

For example, fluoxetine is metabolized by both CYP2D6 and CYP3A4.

Why is this advantageous?

A

For example, fluoxetine is metabolized by both CYP2D6 and CYP3A4.

Why is this advantageous?

  • Greater clearance/excretion
  • Another pathway to fall back on
  • Drug/food metabolized by one
65
Q

Main CYP Isoenzymes

A

Main CYP Isoenzymes
* Different P450 for different drugs
* Drugs have multiple isoenzymes
More than 90% of human drug oxidation is due to six CYP isoenzymes:
1A2, 2C9, 2C19 * , 2D6 * , 2E1, 3A4
* Many antidepressants and antipsychotic drugs are metabolized by either CYP2C19 or CYP2D6.
* CYP3A4 is involved in the metabolism of more than 50% of ALL drugs. Often serves as second isoenzyme system (‘safety net’) involved in drug metabolism.

66
Q

Isoenzymes

A

Isoenzymes
* Enzymes with similar structure
* Catalyze same reaction
* Different AAs
* Different genes encoded
* Different kM
* Can be denatured, blocked/inhibited, induced

67
Q

What do inducing agents do?

A

Inducing agents get the body to make more of something

68
Q

Inducing agents

A

Inducing agents:
* Anticonvulsants: Many CYP isoforms
* Steroids: CYP3A4
* Polycyclic aromatic hydrocarbons: CYP1A1, CYP1A2
* Antibiotics: Most CYP isoforms
* Recreational agents: CYP1A2 (NICOTINE) CYP2E1 (alcohol)
* Herbal remedies: CYP3A4 (John’s Wort)

69
Q

Grapefruit contains what?

A

Grapefruit contains a P450 inhibitor

70
Q

Induced Agents Mechanism of Action

A

Induced Agents Mechanism of Action
* Inducing agents cause alterations in transcription in the nucleus
* Results in increased expression of CYP isoforms
* Consequence – increased clearance of co-administered drugs metabolised by the isoform.

71
Q

P450 inhibition and induction

A

P450 inhibition is more dangerous because the level of the drug keeps rising
P450 induction takes longer and something can be done

72
Q

Clinical Consequences of Inducing Agents

A

Clinical Consequences of Inducing Agents
* Induction leads to therapeutic failure
* Drug levels restored to therapeutic levels by either increasing dose or
* Removal of inducing agent
* Effects on patient not serious as efficacy is easily restored

73
Q

Enzyme inhibition

A

Enzyme inhibition
Occurs through four main mechanisms:
* Competitive (Ketoconazole CYP3A4)
* Non-competitive (omeprazole and lansoprazole CYP3A4): tightly bound but not covalently
* Uncompetitive (citrus fruits e.g. tangeretin acts upon CYP3A4): creates covalent bonds
* Mechanism based (GFJ, suicide inhibitor, irreversible): destroys enzyme, more enzyme needs to be produced.

74
Q

Irreversible inhibition clinical consequences

A

Irreversible inhibition has serious clinical consequences:
Causes elevated levels of drug leading to toxicity
Worsens over time if inhibitor not stopped
Causes destruction of enzyme – not readily reversible

PPI (23 decks)

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