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PT3001: Introduction to Pharmacology > Pharmacokinetics I: Drug Absorption & Distribution > Flashcards

Pharmacokinetics I: Drug Absorption & Distribution Flashcards

1
Q

What is Pharmacokinetics?

A

What the body does to the drug and the interaction with the receptor

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2
Q

What are the FOUR stages in Pharmacokinetics?

A
  1. Absorption
  2. Distribution
  3. Metabolism
  4. Elimination
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3
Q

Do drug concentrations stay the same or change throughout each pharmacokinetic process?

A

Drug concentrations change

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4
Q

What is Drug Absorption?

A

The movement of a drug from its site of administration into the bloodstream

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5
Q

What is Bioavailability?

A

The fraction of drug administered that reaches the systemic circulation

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6
Q

What is the Bioavailability for intravascular drugs?

A

1
(100% absorption)

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7
Q

What is the Bioavailability for oral drugs?

A

Less than 1

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8
Q

What is the most common method of absorption for drugs?

A

Passive Diffusion

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9
Q

Which transporter absorbs Levodopa (L-DOPA) by active transport?

A

Amino Acid Transporter

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10
Q

Which transporter absorbs 5-Fluorouracil (5-FU) by active transport?

A

Pyrimidine Transporter

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11
Q

What type of drugs REDUCE gut motility and therefore drug absorption?

A

Muscarinic Receptor Antagonists

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12
Q

What is an example of a drug that INCREASES gut motility and therefore drug absorption?

A

Metoclopramide
(Pro-Kinetic)

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13
Q

How is drug absorption DECREASED with food intake?

A
  • DECREASED stomach emptying
  • INCREASED gut motility
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14
Q

How is drug absorption INCREASED with food intake?

A

INCREASED splanchnic blood flow

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15
Q

How does particle size affect drug absorption?

A

Large size = DECREASED absorption

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16
Q

Is drug administration by mouth fast or slow absorption?

A

Fast

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17
Q

Why is the absorption speed for drug administration by mouth what it is?

A

By-passes gastric pH and first-pass metabolism

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18
Q

What are TWO examples of drugs that are administered in the mouth?

A
  1. Glyceryl Trinitrate - for angina
  2. Benzodiazepines - epilepsy
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19
Q

What drugs are administered rectally in ulcerative colitis?

A

NSAIDs

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20
Q

What is Parenteral administration of a drug?

A

Drug given by a route that does not involve GI tract

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21
Q

What FOUR ways can drug molecules cross membranes?

A
  1. Passive Diffusion
  2. Facilitated Diffusion
  3. Active Transport
  4. Endocytosis
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22
Q

Are Polar or Non-Polar drugs more likely to cross a membrane by Passive Diffusion?

A

Non-Polar
(Lipophilic)

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23
Q

What TWO factors does Diffusion depend on?

A
  1. Concentration gradient
  2. Membrane surface area
24
Q

What are the TWO requirements need for Facilitated Diffusion of drug molecules across a membrane?

A
  1. Carrier Protein
  2. Ion Channel
25
What is a clinical example of Facilitated Diffusion?
Fludeoxyglucose (FDG) * Glucose analog with radio labelled fluorine * Used in PET imaging as marker of cellular metabolism in tumours
26
What are the FOUR requirements needed for Carrier-Mediated Transport?
1. Specific Receptor 2. Metabolic Energy (e.g. ATP) 3. Against Conc. Gradient 4. Saturation at High Conc.
27
What are the FOUR main sites of Carrier-Mediated Transport?
1. Renal Tubule 2. Biliary Tract 3. Blood Brain Barrier 4. GI Tract
28
What are the THREE forms of Endocytosis?
1. Phagocytosis 2. Pinocytosis 3. Receptor-Mediated Endocytosis
29
Which form of Endocytosis is the most selective?
Receptor-Mediated Endocytosis
30
What TWO drugs are examples of drugs that cross the membrane by Endocytosis?
1. Trastuzumab (Herceptin) 2. Antibody-Drug Conjugates (both used in cancer treatments)
31
Do charged or uncharged drugs diffuse passively across the membrane?
Uncharged
32
What THREE factors alter the ratio of unionised:ionised forms of a drug?
1. pH of a body compartment 2. Whether the drug is an acid or base 3. pKa of the drug
33
What is pKa?
A property of a chemical compound relating to its affinity for protons E.g. Stong Acid = Weak Affinity Strong Base = Strong Affinity
34
What body compartment are ACIDIC drugs best absorbed in in terms of pH and pKa?
Unionised and better absorbed in compartments where **pH < pKa** E.g. Stomach
35
What is an example of an ACIDIC drug?
Aspirin (pKa = 3.5); Weak Acid
36
What body compartment are BASIC drugs best absorbed in in terms of pH and pKa?
Unionised and better absorbed in compartments where **pH > pKa** E.g. Small Intestine
37
What is an example of an BASIC drug?
Pethidine (pKa = 8.6); Weak Base
38
The ionisation state of a drug affects which TWO factors?
1. Initial absorption into the blood stream 2. Elimination from the blood
39
How does ingestion of Sodium Bicarbonate affect Amphetamine (weak base) absorption?
* INCREASES stomach pH * INCREASES amphetamine absorption
40
How does ingestion of Vitamin C affect Amphetamine (weak base) absorption?
* DECREASE urine pH * INCREASE weak base ionisation * DECREASE amphetamine absorption and enhances elimination
41
What are the THREE main proteins involved in Drug-Plasma Protein Binding?
1. Albumin 2. β-Globulin 3. Glycoprotein
42
Which plasma protein(s) binds predominantly ACIDIC drugs?
Albumin
43
Which plasma protein(s) binds mainly BASIC drugs?
* β-Globulin * Glycoprotein
44
TRUE OR FALSE: Only unbound drugs can cross membranes and distribute into tissues?
True
45
What happens when two drugs compete for the same plasma protein binding site?
INCREASE in free drug plasma conc. for both drugs
46
What is Drug Distribution?
How a drug accesses extracellular space i.e. organs, tissues, cells and sub-cellular comparments
47
The Blood Brain Barrier restricts entry to which types of molecules?
* Bacteria & Toxins * Large hydrophilic molecules
48
The Blood Brain Barrier allows DIFFUSION of which types of molecules?
* Gases e.g. O2 and CO2 * Small hydrophobic molecules * Fat soluble molecules
49
The Blood Brain Barrier allows ACTIVE TRANSPORT of which types of molecules?
Nutrients e.g. glucose, amino acids and vitamins
50
What is the Volume of Distribution?
Theoretical volume necessary to contain drug at same concentration as that observed in plasma
51
What is the equation for Volume of Distribution?
52
What are the FIVE major fluid compartments in the body?
1. Plasma (5%) 2. Intracellular Fluid (35%) 3. Fat (20%) 4. Interstitial Fluid (16%) 5. Transcellular Fluid (2%)
53
What does a Vd value of < 3.5 L indicate?
Drug RETAINED in blood plasma e.g. heparin
54
What does a Vd value of < 13.5 L indicate?
* Drug RESTRICTED to extracellular fluid * Drug does not enter cells easily e.g. gentamycin
55
What does a Vd value of > 13.5 L indicate?
Drug DISTRIBUTED through total body water or concentrated in certain tissues (most drugs)
56
What is an example of a lipophilic drug with the potential to accumulate in body fat?
Thiopental

PT3001: Introduction to Pharmacology (18 decks)

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