pharmacokinetics
what body does to drug
pharmacodynamics
what drug does to body
acid/base pH-charge relationship
Henderson-Haaselbach equation
pH =pKa + log[A-]/[HA]
pH definition
log[H+]; pKa = -log(Ka)
when is an weak acid lipid-soluble?
unprotonated: HA
pH<pKa
when pH=pKa, [HA]=[A-]
when is weak base lipid-soluble?
unprotonated: B
pH>pKa
when pH=pKa, [B]=[BH+]
bioavailability
(AUC oral/AUC iv)/100
affected by cholestyramine, resins: bind lipids
,
partition coefficient
lipid/H2O solubility
lipid sol = crosses memb; H2O = excreted
pH drug basics: weak OA, OB
weak OA: pH<pKa: uncharged: crosses memb
-phenobarbital, MTX, aspirin
weak OB: pH<pKa: charged: can't cross memb
-amphetamine, phencyclidine
carrier-mediated transport
ABC
MDR1
issues: saturation, competition
active transport
where: neurons, choroid plexus, renal tubular
cells, hepatocytes
facilitated diffusion
no ATP
sugar, aa, purines, pyrimidines
pinocytosis
<1KDa
botulinum toxin, mAb, Vit B12/IF,
Fe/Transferrin
absorption: factors
surface size
pH
solubility
blood flow
contact time
[Rx]
dissolution
drugs that can't be administered orally
enz destruction: peptides
low pH: penicillin, cephalosporin
complexing: tetracycline, fluoroquinolone, Ca2+
1st pass: morphine, nitroglycerine, lidocaine
,
transdermal patches
testosterone, estrogen, nicotine, fentanyl,
scopolamine, clonidine, nitroglycerine
rectal/sublingual
diazepam
ped + unconscious
no 1st pass metab
plasma water distribution
small Vd
0.045L/kg: 3L in 70kg avg
protein-bound Rx, large Rx: heparin
ECF: extracellular H2O distribution
0.2L/kg: 14L in 70kg avg
large H2O-sol: mannitol
TBW: total body H2O
0.6L/kg: 42L in 70kg avg
small H2O-sol: EtOH
tissue concentration
large Vd
>0.7L/kg: >49L in 70kg avg
Rx that bind tissue: chloroquine
distribution factors
gender, age, body fat, edema
in what tissues do Rx concentrate?
adipose: ^lipid-sol: thiopental, CNS Rx
tissues: muscle, liver
bone: tetracyclines
plasma-protein drugs
low Vd
only unbound Rx available for metab, filtration
ex: tolbutamide, warf, MTX, digoxin, quinidine
sites of Rx exclusion
cerebral, ocular, lymph, fetal, pleural fluid
what body does to drug
pharmacodynamics
what drug does to body
acid/base pH-charge relationship
Henderson-Haaselbach equation
pH =pKa + log[A-]/[HA]
pH definition
log[H+]; pKa = -log(Ka)
when is an weak acid lipid-soluble?
unprotonated: HA
pH<pKa
when pH=pKa, [HA]=[A-]
when is weak base lipid-soluble?
unprotonated: B
pH>pKa
when pH=pKa, [B]=[BH+]
bioavailability
(AUC oral/AUC iv)/100
affected by cholestyramine, resins: bind lipids
,
partition coefficient
lipid/H2O solubility
lipid sol = crosses memb; H2O = excreted
pH drug basics: weak OA, OB
weak OA: pH<pKa: uncharged: crosses memb
-phenobarbital, MTX, aspirin
weak OB: pH<pKa: charged: can't cross memb
-amphetamine, phencyclidine
carrier-mediated transport
ABC
MDR1
issues: saturation, competition
active transport
where: neurons, choroid plexus, renal tubular
cells, hepatocytes
facilitated diffusion
no ATP
sugar, aa, purines, pyrimidines
pinocytosis
<1KDa
botulinum toxin, mAb, Vit B12/IF,
Fe/Transferrin
absorption: factors
surface size
pH
solubility
blood flow
contact time
[Rx]
dissolution
drugs that can't be administered orally
enz destruction: peptides
low pH: penicillin, cephalosporin
complexing: tetracycline, fluoroquinolone, Ca2+
1st pass: morphine, nitroglycerine, lidocaine
,
transdermal patches
testosterone, estrogen, nicotine, fentanyl,
scopolamine, clonidine, nitroglycerine
rectal/sublingual
diazepam
ped + unconscious
no 1st pass metab
plasma water distribution
small Vd
0.045L/kg: 3L in 70kg avg
protein-bound Rx, large Rx: heparin
ECF: extracellular H2O distribution
0.2L/kg: 14L in 70kg avg
large H2O-sol: mannitol
TBW: total body H2O
0.6L/kg: 42L in 70kg avg
small H2O-sol: EtOH
tissue concentration
large Vd
>0.7L/kg: >49L in 70kg avg
Rx that bind tissue: chloroquine
distribution factors
gender, age, body fat, edema
in what tissues do Rx concentrate?
adipose: ^lipid-sol: thiopental, CNS Rx
tissues: muscle, liver
bone: tetracyclines
plasma-protein drugs
low Vd
only unbound Rx available for metab, filtration
ex: tolbutamide, warf, MTX, digoxin, quinidine
sites of Rx exclusion
cerebral, ocular, lymph, fetal, pleural fluid
