S3M1 pharm

- most ionized: pKa > pH (H2O sol)

- least ionized: pKa < pH

- most ionized: pKa < pH (H2O sol)

- least ionized: pKa > pH

- 4 t1/2 (4 half lives)

• - most common way drugs cross cell membrance
• -

- restricted to solutes with MW < 100

• 0= 50%
• 0.5= 76%
• 1= 90%
• 2= 99%
• 3= 99.9%
• >3= >99.9%

• - process by which [drug] can climb very high compared to the [drug] outside the cell. This can be the result of change in pH and b/t ionized and non-ionized forms once it reached the inside of the cell
• - ie ASA mostly lipid solube(non ionized) in the gut lumen (low pH) and then mostly H2O soluble in the cells (pH=7), this results in the ions being trapped within the cell

- mostly ionized/H2O soluble when pKa<pH

- 2000-100,000 MW

• - up to 40,000 MW
• - passive
• - non selective

- a contant fraction (or percentage) of a drug is absorbed, distributed or eliminated per unit time

• - a constant amount of the drug is absorbed, distributed or eliminated per unit time
• - accounts for very few drugs

- F= AUCx/AUCiv

• - most rapid
• - acheive systemic effects
• - absorption is directly proportional to the Px of the gas in the alveoli

• - absorption is usually slow and very limited
• - acheive local effects

• - absorption occurs mainly via bulk-flow transfer thru intercellular pores of endothelium of b/v
• - SM (10-30 min)

• Vd = D x F/ C_p0 (independent of dose)
• D = dose, F = bioavailability, C_p0 = [drug]pl at zero time
• Vd~3L: distribution restricted to vascular compartment
• Vd~13L: distibution thruout EC fluid, cant penetrate cells
• Vd~42L: distribution is in total body water
• Vd>42L: drug extensively stored w/in specific cells/tissue

• - D = (Vd x C₀)/F
• - desired [drug]pl must be known

• - albumin if acidic
• - alpha1-acid glycoprotein if basic
• - binding is a constant percentage (independent of dose)
• - saturable
• -**competition can occur**(very relevant if binding is >90-95%, because a competitor can cause a large increase in [drug]pl

• - posterior pituitary
• - median eminence of the HT
• - Supraoptic crest
• - Subfornical organ
• - area postrema

• - <1000 MW
• - greater with lipophilic drugs
• - highly ionized drugs 200MW or higher cross slowly andpoorly
• - greater with un-protein bound drugs
• - easier in 3rd trimester

- NAPDH- cytochrome P450 reductase and ctyochrome P450

- microsomal enzyme in the liver responsible for glucuronidation, the most common conjugation reaction of xenobiotics

• - SER of the liver cyt P450
• - very low substrate specificity
• - only works with lipid soluble xenobiotics
• - mainly oxidations and glucuronidations
• - inhibited by cimetidine, amiodarone and SSRI's
• - induced by barbituates and rifampin

• - catalyze mainly conjugations, hydrolysis and redox
• - synthesis is under genetic control
• - can be inhibited, but NOT induced
• - products usually more H2O sol
• -variable substrate specificity

• CL = (F x Ud)/ Pd
• F= urine flow rate
• Ud= [drug]urine
• Pd= [drug]pl

• CL= 100-150 ml/min: glomerular filtration
• CL>150 ml/min: tubular secretion
• CL<100 ml/min: reabsorption (or protein binding)

• t1/2 = 0.7 (Vd/CL)
• **a drug is considered to be essentially eliminated from teh body after four half-lives**

• Css = (F x D)/ (Cl x T)
• F= bioavailability D= dose
• Cl= total clearance T= infusion time
• **TIME to reach Css is determined by elimination half-life only

• = 4t1/2
• - 94% plasma concentration is reached after 4 half lives
• - Css = 2 x [drug]pl after 1 half life
• *if dosing interval is <4t1/2, than accumulation will occur*

Css = (F x D x t1/2)/ (T x 0.7 x Vd)

Loading dose= (Vd x Cp)/F

Maitenance dose/T = (Cl x Css)/F

D/T = Css x CL

- EtOH, salicylic acid and phenytion

DR = Css x total CL

• - TD₁/ED₉₉ **margin of safety**
• -TD₅₀/ED₅₀

have a MW or 6000 or higher or can function as a hapten (covalently bond to a protein forming an immunogenic compound)

• blastogenesis= death of embryo or total recovery
• organogenesis= most sensitive to morphological effects
• histogenesis= most sensitive to metabolic/fuctional effects (often appear only after many years)
• **TOXIC effects are most frequent in last months of prego*

• - dosage dependent
• - prego stage very important
• - category D and X drugs should be avoided

• - dose dependent, additive and irreversible
• - many are also mutagenic (malformation that can be passed on in gametes)