Fichas
Pharm I - Pharmacokinetics
Fichas del conjunto (34)
- 1Volume of Distribution VdVd= Amt of drug/ desired plasma concen
- 2Vd Lipo/hydro PHILICVd TBW > 0.6 L/kg or > 42 L = LIPOPHILIC
Vd TBW < 0.6 L/kg or < 42 L = HYDROPHILIC - 3Loading dose calcLoading dose= Vd x Desired Plasma Conce
Bioavailability (1) - 4Clearance: Directly vs InverselyDirectly: Blood flow to organ
Extraction ratio
Drug dose
Inversely: Half-life
Drug concen in central compartment - 5Elimination Half-LifeHalf life Drug Elim% Drug Remaining%
0 - 0 - 100
1 - 50 - 50
2 - 75 - 25
3 - 87.5 - 12.5
4 - 93.75 - 6.25
5 - 96.875 - 3.125 - 6Half life vs Half timeHalf life: time it takes for 50% of the drug to be removed from the BODY
Half time: time it takes for 50% of the drug to be removed from the PLASMA - 7Like Dissolves LikeDrug: Solution
Acid: Basic sol = Highly ionized
Acid: Acidic sol = Unionized
Base: Acidic = Highly ionized
Base: Basic = Unionized - 8Ion TrappingMaternal Alkalosis & fetal acidosis
^Union fraction of locals crosses placenta
Fetal acidosis - protonates the LA+ "trapping" the LA in the fetus - 9Plasma Protein BindingDrug storage in the blood
Albumin: negative charge; acidic >basic
Alpha-1 acid glycoprotein: basic drugs
Beta-globulin: binds basic drugs - 10Plasma Concen: Albumin & Alpha-1 acid glycoproteinDecreased
Albumin: Liver/renal dz, Age, malnutrition, prego
a-1 acid glycoprotein: Neonates, prego
Increased a-1 acid glycoprotein: Sx stress, MI, pain, RA, Age - 11Plasma Protein Binding & VdVd is INVERSELY r/t plasma protein binding
Highly protein bound drugs slower metabolism and elimination - 12Metabolism Phases (3)1- Oxidation: + O2
- reduction: + e-
- hydrolysis: + H2O
2 - Conjugation (H2O soluble, inactive)
3 - Elimination (kidney, liver, GI) - 13Perfusion dependent vs Capacity dependentPerfusion dependent: Fenta, lido, Prop
Capacity dependent: Diazepam & Roc - 14Extraction Ratio formulaExtraction Ratio =
Arterial - Venous concen
Arterial concen - 15ER > 0.7 ER < 0.3Flow limited elimination ER > 0.7
blood flow
Capacity limited elimination ER < 0.3
enzyme induction - 16LOW ER DrugsRoc
Benzo's (most)
Methadone
Thiopental
Theophylline
Phenytoin - 17P450 Enzymes: Inducers vs InhibitorsInduce: Tobacco, Barbs, Phenytoin, ethanol, Rifampin, carbamazepine
Inhibitor: grapefruit, SSRIs, cimetidine, omperazole, isoniazid, erythromyocin,
-azole - 18Other enzymesCYP 3A4: Opioids
Benzos
LA's
CYP 2D6: Codeine, oxy-hydrocodone
CYP 1A2: Theophylline - 19Polarity & EliminationHydrophilic drugs - excreted unchanged
Lipophilic drugs - biotransformation to ^H2O solubility - 20Transport drugs to urine:1- Glomerular filtration: non-protein bound drugs & free fraction are filtered
2 - Organic Anion/Cation transporters:
OAT-anion: furosemide, thiazide, PCN
OCT-cation: morphine, meperidine, dopa - 21Urine pH Reabsorption & ExcretionAcidic Urine: AAA
Reabsorption of acidic
Excretion of basic
Basic Urine: BBB
Reabsorption of acidic
Excretion of basic - 22Metabolism in the Plasma
- 23Difference between: Kinetics Biophasics Dynamics
- 24Dose Response Curve: Efficacy & Potency
- 25Dose Response Curve: Affinity for receptor
- 26Agonists Partial Agonists Antagonists Inverse Agonists (graph)
- 27Drugs administered togetherAddition: 1+ 1 = 2
Synergism: 1 + 1 = 3
Potentiation: 1 + 0 = 3
Antagonism = 1 + 1 = 0 - 28Therapeutic IndexMeasure of drug safety
TI =
Lethal dose50/Effective dose50 - 29ED 50Effective dose 50 = dose that produces expected clinical response in 50% of pop.
POTENCY - 30LD 50Lethal dose 50 = dose that produces death in 50% of pop.
- 31ChiralityMolecule with 3D asymmetry
1chiral carbon = 2 enantiomers - 32EnantiomerismMolecules that are Mirror images & can't be superimposed
Dextrorotary clockwise: R (rectus) d or +
Levorotary counterclock: S (sinister) l or - - 33Enantiomerism in AnesthesiaKetamine & Thiopental
Methohexital
Iso & Des
Mepivacaine, Prilo, Bupi, CisAtra
Morphine & Methadone
Ibuprofen & Toradol
(* Bupi & Cardiac toxicity: R > S) - 34—