2 - Translocation of drugs Flashcards
Bull flow transfer
In blood stream
Chemical properties don’t affect
Diffusional transfer
Molecule by molecule over short distance
Chem properties affect (hydrophobicity & aqueous)
What does the vascular endothelium do
Acts as a filter
Gaps between them have tightly packed protein matrix
What do tight junctions do in the CNS / placenta
Blocks charged (ionised) drugs
What drugs do tight junctions let through
Lipid soluble
What are pinocytes
When drug from vesicles inside cells to transport macromolecules through membranes
Ways in which drugs cross membranes (4)
Diffuse through lipid
Diffuse through aqueous pores
Carrier protein
Pinocytes
Name the factors is the permeability coefficient equation (J=P/_\C)
J = no. molecules crossing membrane per unit area in unit time
P = permeability coefficient
/_\C = conc difference over membrane
Low lipid solubility =
Polar drug
So weak acids pass through the membrane easily
Yes because they are highly protonated
What drug increases aspirin absorption
Metoclopramide - increases gastric emptying
What drug decreases aspirin absorption
Propantheline
Consequences of urinary acidification
Increased excretion of weak acids
Decreased excretion of weak bases (check)
Consequences of urinary alkalisation
Increased excretion of weak bases
Decreased excretion of weak acids
Increased plasma pH causes extraction of …
weakly acidic drugs from CNS to plasma
Decreased plasma pH causes …
accumulation of weakly acidic drugs in the CNS
What happens after aspirin overdose
(ETC, RR, CAC)
Inhibits electron transport chain
Increased respiration rate - hyperventilation
Increase citric acid cycle
Urinary alkalisation increases excretion of aspirin
What happens to salicylate at normal urinary pH
It is unionised
Can be absorbed back into systemic circulation in nephron
What happens to salicylate in alkaline urine
It is charged and reabsorption in reduced
What is cisplatin
Anti cancer drug
What happens if there’s high exposure to cisplatin
Destruction of mitochondria
Proximal tubular cell death
Organic solutes, Na, H2O loss
Fanconi syndrome
How is cisplatin administered without causing death
With an uptake blocker
_ is transported by carrier responsible for phenylalanine
Levodopa
_ is transported by a carrier for pyrimidines
Flurouracil
_’s carrier system is in the jejunum
Iron
_ has a vitamin D dependent carrier system
Calcium
2 other factors affection distribution / elimination
Binding to plasma proteins
Partition into body fat & other tissues
