Phrama Week 2 Flashcards
5 mechanism of transport the drug across cell membrane
1- Passive diffusion ( lipid)
2- Facilitated diffusion
3-filtration or Aqueous diffusion
4- Active transport
5- pinocytosis
Examples of carrier or transporter
1- ATP binding cassette transporter
1- P-glycoprotein, MDR type 1 transporter, found in some drug resistance neoplastic cells
2- multi drug resistance associated protein : important for excretion of some drugs or their metabolites in urine and bile
Non ATP binding transporter : Solute carrier family , important in the uptake of neurotransmitters
3 examples of high molecular weight drugs
1- iron
2- hormones
3- vitamin B12
Permeation of drug depend on 3
1- solubility
2- concentration gradient
3- surface area and vascularity
6 factors for distribution of drugs
1- regional blood flow ( brain receive fast )
2- chemical properties of drug ( hydrophilic, hydrophobic )
3- special barrier
4- some drugs show selective accumulation in particular tissue ( iodides in thyroid , tetracycline in bone , chlorinated insecticides in fat )
5- plasma proteins binding
6- tissue protein binding
3 Drugs compete for plasma protein binding
1- sulfonamides & bilirubin
2- quinidine & digoxin
3- coumarin anticoagulants & NSAIDs
Example of phase 1 genetic polymorphism and phase 2
Deficiency of CYP2D6 lead to failure of activation of tamoxifen to endoxifen
Deficiency in enzyme responsible for acetylation lead to accumulation of isoniazid lead to peripheral nueropathy
3 functions of volume of distribution
And 3 for Elimination half life t1/2
1- how to treat drug toxicity
High VD as digoxin = distributed in muscles = no value of haemodialysis
Low VD as aspirin = haemodialysis is good
2- calculation of loading dose
LD = VD * Css
3- calculation of plasma clearance
CL = VD * kel ( elimination rate constant)
1- indicates the time required to attain Css
2- in drugs with long t1/2 we use loading dose to attain Css
3- determines the dosage intervals for maintenance therapy
2 drugs doesn’t cross placental barrier
1- propylthiouracil
2- methimazole
3 drugs with zero order kinetic
1- ethanol ( except low doses)
2- phenytoin
3- salicylates
3 clinical significance of t1/2
1- it indicates the time required to attain CSS
2- in cases of drug with long t 1/2 we may use loading dose to reach Css rapidly
3- it determines the dosage intervals for maintenance therapy
What is TDM and mention 6 indicators to use it
Therapeutic drug monitoring is the process of measuring plasma concentrations of drug in biological fluid
1- drugs of narrow therapeutic index as digoxin , antiepileptics ( phenytoin , carbamazapine , phenobarbital ) anticancer , aminoglycosides
2- failure of therapeutic response at usual effective does
3- organ dysfunction to adjust dafe dose
4- multidrug therapy to avoid drug drug interactions
5- Diagnosis of drug toxicity
6- identify of addicting drugs
