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Psychology & Neuroscience of Addiction > Introduction to pharmacokinetics and pharmacodynamics > Flashcards

Introduction to pharmacokinetics and pharmacodynamics Flashcards

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1
Q

What is psychopharmacology?

A

The study of drug induced changes in mood, cognition and behaviour

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2
Q

What are psychoactive drugs?

A

Drugs that interact with our central nervous system (CNS)

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3
Q

What are pharmacokinetics?

A

What our bodies do to the drugs

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4
Q

What are the four parameters that affect the patterns of drug use?

A

ADME

  1. Administration and Absorption
  2. Distribution
  3. Metabolism
  4. Excretion
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5
Q

What does drug administration refer to?

A

Method of getting drugs into the body

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6
Q

What does drug absorption refer to?

A

Drugs crossing cellular barriers

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7
Q

What are the different methods of drug administration?

A

> Oral (e.g. tablet)

> Injection

  • intramuscularly (IM)
  • intravenously (IV)
  • subcutaneous (SC)

> Inhalation

> Application to skin

> Via mucous membranes

  • intranasal (sniffing)
  • sublingual (under tongue)
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8
Q

What can the choice of administration depend on?

A

> Chemical characteristics of the drugs

> Personal preference

> How long the drug will persist in the body

> Concentration profile (dosage)

> Number and nature of membranes

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9
Q

Why does the intravenous injection method of administration has the fastest rate of absorption?

A

Drug goes directly into blood stream

-> no need to cross any cellular membrane

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10
Q

What happens when a drug reaches for the brain?

A

It’s longer to reach the brain

-> some of the drug will be lost

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11
Q

What are the six factors that determine the speed and success of a drug crossing a cellular barrier?

A
  1. Lipid solubility of the drug
  2. Ionisation of drug’s molecules
  3. pH of the drug
  4. Size of the drug
  5. Vehicle of the drug
  6. Concentration gradient along the membrane
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12
Q

How does the lipid solubility of a cellular membrane determine the speed and success of a drug crossing a cellular barrier?

A

Highly lipid soluble drugs (i.e. fatty drug molecules) are absorbed at increased rate

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13
Q

Why are highly lipid soluble drugs absorbed at increased rate in the cellular membrane?

A

Cell membranes predominantly consists of lipids and phospholipids

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14
Q

What is a lipid bilayer?

A

Basis of most animal cell membranes

- most abundant lipids in a membrane are phospholipids

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15
Q

Why does the ionisation of a drug’s molecules determine the speed and success of a drug crossing a cellular barrier?

A

> In a solution, part of drug’s molecules will ionise and become charged

> Increased ionisation leads to decreased rate of absorption (RoA)

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16
Q

Why does an increased ionisation of drug molecules lead to a decreased rate of movement across a membrane?

A

Due to negatively charged heads of the phospholipids in a membrane

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17
Q

How does the pH of a drug determine the speed and success of a drug crossing a cellular barrier?

A

> Similar pH between the drug and the fluids next to the membrane will result in little ionisation
-> increased rate of absorption (RoA)

> Differences in pH between drug and fluids surrounding the membrane will result in ionisation
-> decreased RoA

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18
Q

Why does the size of a drug’s molecules determine the speed and success of a drug crossing a cellular barrier?

A

Smaller molecules are absorbed a lot quicker than larger molecules (e.g. proteins)

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19
Q

What is the vehicle of a drug?

A

The solution that we dissolve our drug in

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20
Q

How does the vehicle of a drug determine the speed and success of a drug crossing a cellular barrier?

A

We can design slow or fast release vehicles to speed up or slow down the rate of absorption (RoA)

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21
Q

Why does the concentration gradient along the membrane determine the speed and success of a drug crossing a cellular barrier?

A

Force of diffusion

-> the greater the difference in concentration either side of a membrane, the greater the rate of movement across that membrane

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22
Q

What is the cellular force of diffusion?

A

Molecules tend to go from high concentration areas to low concentration areas

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23
Q

Why does the inhalation of vapours have a high rate of absorption?

A
  • Lung is specialised for absorption (large surface area)
  • Gaseous drugs have high lipid solubility and small molecular size
  • > fast rate of absorption
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24
Q

Why do the intranasal and sublingual methods of administration have medium rates of absorption?

A
  • Thin membranes BUT several layers
  • > slow rate of absorption (RoA), even though there’s rich blood supply to mouth and nose
  • It’s difficult to keep the drug in contact with the membranes
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25
Q

Why do the intramuscular and subcutaneous methods of administration have slow rates of absorption?

A
  • Rate of absorption (RoA) depends on blood flow near injection site
  • Fatty tissue would result in slow absorption
    e. g. muscle problems -> altered blood flow to muscles which affects RoA
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26
Q

Why does oral administration of drugs have the slowest rate of absorption?

A
  • In this way, absorption occurs in small intestine

- Small intestine has high blood supply, high surface area AND a range of pH levels

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27
Q

Why does the absorption with oral administration occur in the small intestine rather than the stomach?

A

Because the stomach has acidic contents

-> high degree of ionisation -> slower rate of absorption

28
Q

Which elements in blood vessels affect the distribution of the drug?

A
  • Dilution: drugs will gradually dilute in the blood stream

- Cells form various hurdles for the drug, slowing its entry into tissues/brain

29
Q

Which key element affects the degree and speed of a drug’s distribution?

A

Blood brain barrier

30
Q

What is the blood-brain barrier?

A
  • Tight junction of endothelial lining of brain capillaries

- Comprised mostly of glial cells

31
Q

What is the function of the blood-brain barrier?

A

Forms a barrier
- preventing some drugs entering the brain

  • pumping some drugs out of the brain
32
Q

What does the metabolism refer to?

A

Enzyme-mediated chemical reactions within a living organism

- that provide energy for vital processes AND for synthesising new organic material

33
Q

What does excretion of drugs refer to?

A

How we remove drugs from our bodies

34
Q

How is a drug compound converted into urine for excretion?

A
  1. Drug is lipophilic (i.e. fat soluble)
  2. Metabolism of drug in the liver
    - series of enzymatic reactions
    - active or inactive metabolites
  3. Drug compound is now hydrophilic (i.e. water soluble)
    - > Urine -> easy excretion
35
Q

What are metabolites?

A

Organic substances that enter the metabolic process

36
Q

What happens if active metabolites enter the metabolism of a drug?

A

Active metabolites extend drug action

37
Q

What happens if inactive metabolites enter the metabolism of a drug?

A

Inactive metabolites terminate drug action

AND turn it into some biological activity

38
Q

What are the cytochrome P450 (CYP450) enzymes?

A

Liver enzymes that combine a drug with another molecule (e.g. amino acid) to produce inactive, highly ionised, low lipid soluble drug

  • metabolise over 90% of drugs
39
Q

What are the isoforms (types) of cytochrome P450 (CYP450) enzymes?

A

3A, 2D and 2C

- metabolise over 90% of drugs

40
Q

What makes cytochrome P450 (CYP450) enzymes specific and inducible?

A

The more effort they have to make, the more the body makes

41
Q

What are the stages of a drug metabolisation process?

A
  1. Oxidation
    - breaks the structure of the drug molecule
    - makes intermediate compound (derivative) more reactive
  2. Conjugation
    - adds molecule to the drug’s structure
    - helps to get the intermediate compound (derivative) out drug’s structure
42
Q

What is an oxidation?

A

Chemical reaction to break the structure of a molecule

43
Q

What is a conjugation?

A

Chemical reaction that adds a molecule to the compound structure

44
Q

What are the primary routes of excretion?

A

Lungs and bodily fluids (via kidney)

45
Q

How are drug gases excreted?

A

Gases exhale via lungs

-> absorption process in reverse

46
Q

How are solvents and ethanol excreted?

A

Excreted via bodily fluids and lungs

47
Q

Why does producing a lot of bodily fluids (e.g. urine) will reduce the drug concentration in the body?

A

The amount of drug excreted by bodily fluids is almost directly proportional to the amount of that fluid produced and lost by the body

48
Q

What is the excretion process via bodily fluids?

A
  1. Blood enters kidneys
    - molecules of certain size are filtered by Bowman’s capsules
  2. Filtration involves passing a cellular membrane
  3. Non-ionised, lipid soluble drugs re-enter circulation and persist longer
49
Q

What is the plasma?

A

Liquid that forms 55% of human blood and contains blood cells

50
Q

What is the half-life (t1/2) of a drug?

A

Time required for drug concentration to reach half the peak plasma concentration (Cmax)

51
Q

What does the half-life (t1/2) of a drug depend on?

A

Chemical characteristics and metabolism of the drug

52
Q

How does the half-life (t1/2) of a drug can be used to manage dosage?

A
  • As a guide to the duration of action
  • Indication of dosing intervals
  • > how quickly you need to take the drugs to have an effect
53
Q

What is the therapeutic range of a drug?

A

Concentration range through which a drug is deemed to have a biological effect

54
Q

What is the meaning of a drug having a wide therapeutic range?

A

Drug has large concentration difference between the maximum therapeutic concentration (MTC) and minimum effective concentration (MEC)

55
Q

What is the meaning of a drug having a narrow therapeutic range?

A

Drug has small oncentration difference between the maximum therapeutic concentration (MTC) and minimum effective concentration (MEC)

56
Q

What is the risk of drugs that have a narrow therapeutic range?

A

Liable for overdose

57
Q

What does the effect duration of a drug depend on?

A
  1. Chemical characteristics of the drug
  2. Preparation of the drug (vehicle)
  3. How the body is functioning at the time
  4. General health
58
Q

How does the elimination of drug effects occur?

A

Rate of change in plasma concentration (blood stream) will change over time
- due to concentration differences across membranes

59
Q

Which drug is not eliminated by the change in plasma concentration?

A

Alcohol

60
Q

How are the effect of alcohol eliminated?

A

Alcohol dehydrogenase

- oxidation enzyme

61
Q

What is alcohol dehydrogenase and what does it do?

A

Flat rate limited enzyme (for oxidation)

  • breaks down 8g of alcohol per hour
62
Q

Which factors represent the role of individual differences in the duration and elimination of drug effects?

A

> Total volume of body fluid

> Gender

> Age

> Genetics

63
Q

How does the total volume of body fluid in an individual influence the duration and elimination of drug effects?

A

Larger fluid volume -> lower drug concentration

  • because we’re diluting this drug in a bigger volume
64
Q

How does gender influence the duration and elimination of drug effects?

A

On average, woman have smaller volume of water and higher volume of lipids than men

65
Q

How does age influence the duration and elimination of drug effects?

A

Very young AND very old people have reduced ability to metabolise and excrete different forms of drugs

66
Q

How do genetics influence the duration and elimination of drug effects?

A

Many drugs are broken down by cytochrome P450 enzymes

  • different levels of this enzyme between individuals can affect the duration of a drug’s effects

Psychology & Neuroscience of Addiction (14 decks)

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