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LEAH FCP > Drug regimes > Flashcards

Drug regimes Flashcards

1
Q

What are the key determinants of a dosage regimen?

A

Activity/toxicity (therapeutic window, side effects, dose-response relationships)

Clinical factors (state of patient, compliance, convenience)

Pharmacokinetics (dose, onset, loading dose, maintenance dose, time to steady-state)

Other factors (dosage form, route of administration, drug interactions).

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2
Q

Define dosage

A

The administration of medicine in prescribed amounts over time

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3
Q

What factors influence the onset of drug action

A

Route of administration

Bioavailability and first-pass metabolism

Clinical situations (pathologies, blood perfusion, changes in pH, etc.)

Chemical structure and formulation.

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4
Q

Describe the main routes of drug administration & elimination

A
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5
Q

What pharmacokinetic factors influence drug regimens?

A

Dose: potency and efficacy

Onset: Absorption & distribution

Loading dose: Vd

Maintenance dose: clearance
Time to steady-state: half-life

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6
Q

What factors affect the dosage of a drug given?

A

potency
absorption
Bioavailability and 1st pass metabolism
Distribution

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7
Q

What factors influence the onset of action of a drug?

A

Route of administration

Chemical structure and formulation (slow or fast release)

Clinical situations (pH change, shock, tissue blood perfusion)

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8
Q

If a drug is given orally what factors affect onset of action?

A

Polypharmacy (other drugs)
Gut content
Splanchnic blood flow

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9
Q

What is loading dose and how is it calculated

A

An initial higher dose to enable therapeutic concentrations sooner
Dose = Vd x plasma conc

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10
Q

What is a maintenance dose?

A

The dose given to maintain drug conc at therapeutic conc
= clearance (CL) x steady state conc (Css)

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11
Q

How can steady state concentrations be maintained?

A

Constant IV infusion (impractical)

Increased dose frequency (beware of owner compliance)

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12
Q

What is saturation kinetics?

A

At high doses, increases in drug concentration result in disproportionate rises in steady-state levels due to enzyme saturation (e.g., phenytoin).

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13
Q

How does β€œnormal” kinetics differ from saturation kinetics?

A

In normal kinetics, plasma concentrations increase proportionally with dose

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14
Q

What is plasma protein binding?

A

Only free drugs are active, distributed, metabolized, or excreted

Drugs bind to plasma albumin (acidic drugs) or Ξ²-globulin (basic drugs)

Extensive binding slows drug elimination.

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15
Q

What happens in cases of saturable binding?

A

At high drug concentrations, binding sites may saturate, leading to non-linear drug concentration increases.

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16
Q

What drug-related factors affect absorption?

A

High absorption for lipid-soluble drugs.

Low absorption for drugs with molecular weight > 1000 Da or high ionization.

Formulation can improve absorption

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17
Q

What body-related factors affect absorption?

A

Increased absorption with larger absorptive surface area.

Altered by pH, GI motility, absorptive surface integrity, and diseases

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18
Q

What drug-related factors affect distribution?

A

High for lipid-soluble and weak base drugs.

Low for water-soluble and weak acid drugs

19
Q

What body-related factors affect distribution?

A

Higher body fat increases 𝑉𝑑 for lipid-soluble drugs.

Higher body water increases 𝑉𝑑 for water-soluble drugs.

Low for drugs highly bound to plasma proteins.

20
Q

What drug-related factors affect metabolism?

A

High metabolism for lipid-soluble drugs.

Protective chemical groups (e.g., F, CN) can reduce metabolism.

CYP inhibition reduces clearance, and CYP induction increases clearance

21
Q

What body-related factors affect metabolism?

A

Enzyme quantity (e.g., P450 enzymes).

Polymorphisms in metabolizing enzymes.

Decreased blood flow to metabolizing organs reduces clearance.

Diseases

22
Q

What drug-related factors affect excretion?

A

High for water-soluble and ionizable drugs

Low for lipid-soluble drugs.

Inhibitory drug-drug interactions reduce excretion

Drug with low plasma protein binding have increased clearance

23
Q

What body-related factors affect excretion?

A

Drug transporter quantity.

Blood flow and GFR in kidneys.

Diseases affecting excretory organs

24
Q

How does absorption in neonates differ from adults?

A
25
Q

How does distribution in neonates differ from adults?

A
26
Q

How does metabolism in neonates differ from adults?

A
27
Q

How does excretion in neonates differ from adults?

A
28
Q

What dosing adjustments are needed for neonates?

A

Usually lower doses to prevent toxicity.
- Adult doses may result in accumulation due to differences in distribution
- Blood brain barrier not fully complete – risk of undesired CNS penetration

Avoid drugs like fluoroquinolones and tetracyclines

29
Q

How does absorption in geriatrics differ from adults?

A
30
Q

How does distribution in geriatrics differ from adults?

A
31
Q

How does metabolism in geriatrics differ from adults?

A
32
Q

How does excretion in geriatrics differ from adults?

A
33
Q

What dosing adjustments are needed for geriatrics for drugs mainly eliminated by kidney?

A
  • Reduce dose or dosing frequency (increase dosing interval)
  • Use alternative drug that is predominantly metabolised in liver
34
Q

What dosing adjustments are needed for geriatrics for lipid-soluble drugs

A

Average adult dosing regimens may result in accumulation due to increased fat distribution - more likely to produce β€œhang over effect” and toxicity

Reduce dose or dosing frequency (increase dosing interval)

35
Q

What dosing adjustments are needed for geriatrics for water-soluble drugs

A

Rarely change dosing regimen as reduction in Vd and therefore half-life tends to be small

36
Q

How does chronic cardiovascular disease affect drug PK? What changes would you make to dosing regimen?

A

Decreased blood flow: lower clearance for highly cleared drugs (eg anesthetics)

Avoid drugs with high clearance or reduce dose

37
Q

How does respiratory disease affect drug PK? What changes would you make to dosing regimen?

A

Altered serum pH and protein binding

Adjust dose down for intravenous anaesthetics

38
Q

How does liver disease affect drug PK? What changes would you make to dosing regimen?

A

Content and activity of phase I/II reactions is decreased

Little effect on drug metabolism until 80% functional loss

No adequate functional tests

Most antimicrobials are well tolerated

Rarely an issue but reduce dose if necessary for severe cases or use a drug that is primarily renally cleared

39
Q

How does renal disease affect drug PK? What changes would you make to dosing regimen?

A

Potentially most profound changes in PK

gradual loss of urine concentrating ability & ability to acidify

Altered drug distribution patterns

Change in acid base balance

Uraemia: chronic acidosis, reduced albumin binding of drug, less hepatic metabolism

Avoid renally cleared drugs?
Adjust dose down for changes in GFR?

40
Q

What is therapeutic index?

A

comparison of amount of therapeutic agent that causes therapeutic effect to amount that causes toxic effects

Ideal drug has high therapeutic index

41
Q

Name some drugs with a high therapeutic index

A

NSAIDs - aspirin, tylenol, ibuprofen
Sedatives - benzodiazepines
Most antibiotics
beta-blockers

42
Q

Name some drugs with a low therapeutic index

A

Neuroleptics - phenytoin, phenobarbital
Lithium
Some antibiotics - vancomycin
Digoxin
Immunosuppressives

Drugs with low therapeutic indexes used in chronic therapy may require therapeutic monitoring for altered physiological states

43
Q

What is therapeutic monitoring?

A

Measure plasma drug concentrations to:
- Detect changes in pharmacokinetics
- Optimize dose/therapeutic response
- Monitor compliance
- Avert toxicity

44
Q

When should blood samples be taken?

A

At steady-state levels (after 5 half-lives)

Peak concentration (Cmax) for toxicity monitoring

Trough concentration (Cmin) for efficacy monitoring.

LEAH FCP (49 decks)

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