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ICU Primary Snippet – pK/pD changes at term in Pregnancy

Dr Swapnil Pawar June 11, 2023 89


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    ICU Primary Snippet – pK/pD changes at term in Pregnancy
    Dr Swapnil Pawar

Written by Dr Madhuri Anupindi

Outline the changes to drug pharmacokinetics and pharmacodynamics that occur at term in pregnancy

Pharmacokinetics Changes Effect
Absorption

Enteral

 

Decreased gastric acid production  increased gastric pH

Decreased gastric emptying

Slower GI motility + increased blood flow

 

Decreased absorption of weak acids e.g. aspirin and increased absorption of weak bases

Decreased oral absorption

Increased oral absorption

Therefore, in practice overall oral bioavailability is mostly unchanged for majority of drugs in pregnancy

Inhalational Increased pulmonary blood flow and increased respiratory rate Increased speed of onset of inhalational agents e.g. volatile anaesthetic
Epidural Engorged epidural veins Decreased spinal/epidural local anaesthetic dose required
Subcut/IM/transdermal Increased blood flow to skin and muscles May increase absorption
Distribution Increased plasma volume Increased Vd for hydrophilic drugs  lower plasma concentrations
  Decrease in serum albumin levels and total plasma protein levels due to dilution Increased free drug levels of protein bound drugs e.g. tacrolimus (but if total drug level measured may be same or decreased)
  Increased fat compartment Increased Vd for lipophilic drugs
  Increased blood flow Increased speed of onset of IV drugs e.g. muscle relaxants
  Placental circulation Increased Vd for lipophilic drugs
  Fetal pH < maternal pH Non-ionised drugs cross placenta more easily than ionised. Fetal pH being less than maternal pH can lead to ion trapping and greater drug concentrations in fetal circulation which may increase risk of toxicity e.g. local anaesthetics
Metabolism Increased activity of some hepatic enzymes e.g. CYP2D6 and CYP3A4 and UGT1A4 Increased metabolism of drugs such as metoprolol, methadone, quetiapine, lamotrigine  decreased drug concentration
  Decreased activity of enzymes such as CYPIA2 and CYP2C19 Decreased metabolism of certain drugs e.g. caffeine, rifampicin which may increase risk of toxicity
  Hepatic blood flow increases Increased clearance of drugs with high extraction ratio e.g. morphine
Elimination Increased glomerular filtration rate due to increased cardiac output Increased elimination of drugs such as amoxicillin, digoxin and lithium

 

Pharmacodynamic changes:

  • CNS:
    • Increased responsiveness to sedatives and hypnotics
  • CVS:
    • Increased risk of postural/orthostatic hypotension with anti-hypertensives, diuretics etc due to decreased baroreceptor sensitivity
  • Haematological/immunological:
    • Hypercoaguable state – increased factor VIII and fibrinogen  increased resistance to heparin
  • Endocrine
    • Increased insulin resistance
    • Higher doses of thyroid hormone needed during pregnancy  increased dose of levothyroxine in pregnant women with hypothyroidism
  • Maternofetal interface
    • Consideration of drugs which may be harmful to the fetus e.g. tetracyclines, warfarin
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