Pharmacokinetics- Distribution Flashcards
Drug Factors affecting distribution?
Lipid/water solubility Molecular size Ionisation Cellular/protein binding Drug interaction
Physiological factors affecting distribution?
Bloody flow Disease Age Special barriers Plasma protein binding Organ binding
Volume of distribution?
VD = total amount of drug in plasma (mg) / initial plasma concentration (mg/l)
Digoxin
Binds to Na/K ATPase (inhibitor)
-Heart -Skeletal muscle
Chloroquine
-Eye. -Spleen
Warfarin
Anticoagulant
Highly bound to albumin
Narrow therapeutic index
Drug displacement interaction
Plasma proteins
Only unbound are pharmacologically active and can be distributed, metabolised and excreted
Most important is albumin which binds acidic drugs
Others include B-globulin and acid glycoprotein -basic drugs
A source of drug interactions
Blood brain barrier transport routes?
A- Paracelullar aqueous pathway
B- Trancellular lipophilic pathway
C- Transport proteins
D- Efflux pumps
E- Receptor mediated pathways
F- Absorptive transcytosis
G- Cell mediated transcytosis
Parkinson’s disease
Destruction of dopaminergic neurones in substantia nigra
Lack of dopamine
Dopamine does not cross the blood brain barrier
Give L-Dopa
Kernicterus
Decreased Awareness Floppy Poor feeding Can include seizures Can develop serious Brian damage
Placental barrier and characteristics?
Un-ionised
Lipid soluble
Low protein binding
Blood flow
pH slightly acidic
Nutrient transporters
Developing metabolism
The advancement of pregnancy- thinning and ageing of barrier
Increasing surface area
Decrease maternal albumin
Thalidomide
Sedative
Nausea
inhibits angiogenesis
Malformation of limbs
Sodium Valproate
- 10 in 100 babies will have a birth defect
- 30/40 in 100 will have developmental problems
