Basics of PK Flashcards

1
Q

What is Absorption?

A
  • The transfer of a drug from its site of administration to the bloodstream
    • rate and efficiency of absorption depend on the route of administration
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2
Q

What is Distribution?

A
  • The reversible transfer of drug from one location to another within the body
    • once a drug enters the systemic circulation by absorption or direct administration, it must be distributed into interstitial and intracellular fluids
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3
Q

What is Metabolism?

A
  • The metabolism of drugs into more hydrophilic metabolites is essential for the elimination of these compounds from the body and termination of their biological activity
    • the objective of drug metabolism is to create hydrophilic products for kidney excretion
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4
Q

What is Elimination?

A

Irreversible loss of drug from the body by excretion of metabolism

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5
Q

Factors Affecting Drug Absorption: Drug

A
  • Molecular size
  • Particle size
  • Degree of Ionisation
  • Lipid/water solubility
  • Physical structure
  • Chemical structure
  • Dosage forms
  • Formulation/concentration
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6
Q

Factors Affecting Drug Absorption: Body

A
  • Surface area
  • Vascularity
  • pH
  • Presence of food
  • Gastric emptying rate
  • Integrity of absorptive surface
  • Disease
  • Secreted substances
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7
Q

What are the three ways drugs use to cross cell barriers?

A
  1. Direct penetration of lipid membrane
  2. Diffusion through aqueous channels
  3. Transporters (influx & efflux)
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8
Q

What is the importance of BBB?

A
  • Specific characteristics of blood vessels within the brain
  • Protects brain from molecules that are potentially harmful and are in the blood
  • BBB has specific processes that takes up important molecules from the blood
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9
Q

What are the processes drugs use to pass BBB?

A
  • Move freely if drug is water soluble with small molecular weight
  • Lipophilic pathway is easiest, because drugs move straight through
  • Specific transport proteins
  • Complex proteins
  • Very large proteins such as albumin use absorptive transcytosis

*if drugs cannot pass BBB, then they cannot be used to treat the CNS

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10
Q

What processes are involved in drug distribution?

A
  • Excretion
  • Metabolism
  • Tissue
  • Tissue and receptor sites
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11
Q

What is the process of drug binding to plasma proteins?

A
  • Once a drug has been absorbed into the circulation it may bind to plasma proteins
    • rapidly reversible and non-specific
  • Once the drug is bound to plasma proteins, it is not active
    • the only drug that is active is the free drug because only then can it bind to the receptors
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12
Q

What are the main characteristics of liver drug metabolism?

A
  • Oral medication is transported to GI which dissolves and gets absorbed
  • Transported to portal vein
  • Metabolism in the liver starts immediately
    • continues into systemic circulation via hepatic vein
    • comes back via hepatic artery
  • Goes back to second entry to the liver (second pass), then third etc. causing exponential decay of drug level in the blood
    • each pass causes metabolism of the same % of original drug amount
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13
Q

What are the Phases of Liver Drug Metabolism?

A

Phase 1 and 2

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14
Q

Describe Phase I: functionalisation reactions (CYP)

A
  • Convert a parant drug to more polar metabolite by oxidation introducing or unmasking a functional group
    • results in loss of pharmalogical activity
    • may be equally or more active than parent
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15
Q

Describe Phase II: conjugation reactions

A
  • Subsequent reaction in which a covalent linkage is formed between a functional group on the parent compound of Phase I metabolite and endogenous substrate
  • Highly polar, usually inactive
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16
Q

What are endogenous substrates used in Phase II metabolism?

A
  • Glucuronic acid
  • Sulfate
  • Acetate
  • Amino acids
17
Q

What are the characteristics of drug elimination by kidneys?

A
  • Filtration
  • Secretion
  • Reabsorption
18
Q

Characteristics of drug elimination by kidneys: Filtration

A
  • Drugs are transported by the capillaries to the tubule by glomerular filtration at the renal corpuscle
    • allowing small drugs and those not bound to plasma protein to filter from the blood into the Bowman’s Capsule
19
Q

Characteristics of drug elimination by kidneys: Secretion

A
  • Majority of drugs enter kidneys by tubule secretion (active process)
    • involves two carrier systems
      • basic carriers: transport basic drugs
      • acidic carriers: transport acidic
20
Q

Characteristics of drug elimination by kidneys: Reabsorption

A
  • Some drugs and metabolites may be reabsorbed back into the blood stream
  • Passive diffusion
21
Q

What is a prodrug?

A

Originally pharmacologically inactive, has to be metabolised by the liver first in order to be activated

22
Q

Define Drug Half-Life

A

The time necessary for blood levels to drop from Cmax to 50% of Cmax

23
Q

Define Therapeutic Range

A
  • Useful range of concentration over which a drug is therapeutically beneficial
    • narrow therapeutic windows require smaller and more frequent doses/or a different method of administration
    • drugs with slow elimination rates may rapidly accumulate to toxic levels
24
Q

What is the Inhibition of Drug Metabolism?

A

Drugs and other substances can inhibit the metabolism of other drugs

25
Q

What are the consequences of Inhibition of Drug Metabolism?

A
  • Increase in plasma concentration of parent drug
  • Reduction in metabolite concentration
  • Exaggerated and prolonged pharmalogical effects
  • Increased likelihood of drug-induced toxicity
26
Q

Induction of Drug Metabolism

A

Induces its own metabolism or the metabolism of other drugs

27
Q

What are the consequences of Induction of Drug Metabolism?

A
  • Increased metabolism rate
  • Decrease in drug plasma concentration
  • Enhanced oral first pass metabolism
  • If metabolite is more active than drug, increased drug effects or toxicity