6.0 Pharmacokinetics Flashcards
What type of drug is preferentially absorbed in the stomach?
Weak acids (pH of stomach = 1)<br></br><br></br>Most drugs are absorbed in non-ionized forms
What type of drug is preferentially absorbed in the intestine?
Weak bases (pH or intestine = 7)
What factors affect oral bioavailability?
1) Degree of ionisation (↑ → drug doesn’t get into plasma)<br></br><br></br>2) Digestion (some drugs are broken down in stomach)<br></br><br></br>3) Metabolism of drugs by enzymes in gut wall<br></br><br></br>4) First pass metabolism<br></br><br></br>5) Vomiting/Diarrhoea<br></br><br></br>6) Food in the gut (normal food → ↓ absorption, but poor water solubility drugs show ↑ absorption following high-fat meal)
What plasma proteins can drugs bind to?
<b>1) Albumin</b><br></br>- Majority<br></br>- Makes up 50% of plasma protein<br></br>- Each one has multiple binding sites<br></br>- Binds most weak acids, neurals and some weak bases<br></br><br></br><b>2) α1-glycoprotein</b><br></br>- Most weak bases bind to this<br></br>- Single high affinity site<br></br>- Levels ↑ with age/injury/surgery
What factors affect the rate of drug entry into tissues?
1) Fraction of drug molecules bound to plasma<br></br>2) Relative rates of blood flow through capillary beds<br></br>3) Permeability of capillaries for free drug molecules
What can cross the blood brain barrier?
1) Lipid soluble molecules<br></br>2) Small polar essential nutrients
What organs are involved with drug metabolism?
<b>Liver</b><br></br>Intestine<br></br>Lungs<br></br>Skin
What routes are available for excretion?
<b>Kidney</b><br></br>Biliary system<br></br>Lungs<br></br>Saliva<br></br>Perspiration<br></br>Tears<br></br>Milk<br></br>Hair<br></br>Skin
Where in the cell are the cytochrome enzymes found?
Smooth Endoplasmic reticulum (smooth ER)
What are the two phases of drug metabolism?
1) <b>Phase I</b><br></br>Catalysed by CYP enzymes<br></br>(oxidation, reduction, hydrolysis, hydroxylation)<br></br>Products of this phase can still be active<br></br><br></br>2) <b>Phase II</b><br></br>Catalysed by transferases<br></br>Rate limiting step<br></br>Products are nearly always inactive (exception = morphine)
What factors can cause the rate of drug elimination to vary between individuals?
1) Metabolism is poorly developed in neonates<br></br>2) Metabolism is ↓ in aged population<br></br>3) Different between males/females<br></br>4) Depressed by chronic hepatitis/cirrhosis<br></br>5) Genetic variation<br></br>6) Altered by drug-drug interactions
What drugs induce CYP metabolism with multiple administration (i.e. can induce tolerance)?
1) Phenobarbitone<br></br>2) Ethanol<br></br>3) Phenytoin<br></br>4) Cigarette smoking
What drugs inhibit CYP metabolism?
1) Erythromycin<br></br>2) Imidazole containing drugs
What three processes determine the rate of excretion?
1) Filtration<br></br>2) Reabsorption<br></br>3) Secretion<br></br><br></br>Rate = Filtration - reabsorption + secretion
What drugs show zero order elimination?
1) Ethanol<br></br>2) Aspirin<br></br>3) Phenytoin
