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

Dr Swapnil Pawar June 11, 2023 125

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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Dr Swapnil Pawar

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