Kupdf.net Topnotch Supplement Pharmacology Handout

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TOPNOTCH MEDICAL BOARD PREP ANATOMY SUPPLEMENT BY THE TOPNOTCH TEAM For inquiries visit www.topnotchboardprep.com.ph or email us at [email protected]  Aqueous Diffusion Diffusion Passive movement of non-protein-bound drugs between the blood and extravascular space through small waterfilled pores (exceptions: Brain, Testes, Eye and Placenta) Affected by drug concentration and charge Governed by Fick’s Law of Diffusion

Dissocation of Weak Acids

HA Protonated R – COOH

A+ ↔ ↔ unprotonated + + ↔ R – COO-

H+ H+ H+

Lipid Diffusion Movement of drugs through lipid memebranes (i.e. BBB, Placenta) separating body compartment, and from the ECF to the ICF Most important limiting factor for permeation Governed by Fick’s Law of Diffusion Very important for the diffusion of weak acids and weak bases 

unprotonated (A-) form is more water-soluble and undergoes better clearance protonated (HA) form is more lipid-soluble and more likely to cross biological membranes

Dissocation of Weak Bases

 

Transport by Special Carriers Drugs that do not readily cross through membranes membranes may be transported across barriers by mechanisms that carry similar endogenous substances Ions through Na/K pump o Neurotransmitter through reuptake transporters o Metabolites such as glucose through GLUT o Carriers for foreign molecules or xenobiotics or xenobiotics o NOT governed by Fick’s Law of   Diffusion and is capacitylimited 

BH Protonated R – NH3

B + ↔ ↔ unprotonated + R- NH2 + ↔

Weak Acids and Bases

H+ H+ H+

Above pKa: Unprotonated > protonated

At pH = pKa Unprotonated = protonated

Endocytosis Endocytosis: large drugs bind to receptors, are internalized and released after vesicle breakdown (exocytosis is the 

Below pKa: Protonated > unprotonated

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