Drug Therapy Flashcards
Physico-chemical factors that affect the transfer of drugs across cell membranes
Ionisation - changes in pH
Lipid solubility - must be lipid soluble in order to diffuse across phospholipid bilayer
Structure - Must resemble naturally occurring substances to be able to fit through the pumps
Factors affecting absorption of a drug from the GI tract
Motility (speed of gastric activity)
Food (impairs or enhances absorption)
Illness (malabsorption, migraines reduce rate of stomach emptying
First pass metabolism
Metabolism of the drug prior to it reaching the site of absorption
Benefits of IV medication
Avoids first pass metabolism
100% bioavailability
Benefits of topical medication
Can achieve local or systemic effects
Able to achieve controlled, sustained doses of the drug
Avoids first pass metabolism
Benefits of inhaled medication
Drug delivered directly to site of action Rapid effect Small doses used Little systemic absorption Reduced adverse effects
Bioavailability
Amount of drug that reaches circulation and is available for action
Factors that determine bioavailability
Formulation Ability to pass physiological barriers GI effects First pass metabolism Particle size pH and ionisation Food Illness
Preparation forms of oral administration
Solutions
Suspensions
Tablets and capsules
Enteric coated tablets
Phase 1 drug metabolism
Involves oxidation, reduction or hydrolysis
Increases polarity
Provides active site for phase 2
Mainly carried out by P-450 family of enzymes
Phase 2 metabolism
Involves conjugation
Increases water solubility of compound, makes excretion easier
Most drugs inactivated by conjugation but some may remain active
Factors that inhibit or induce drug metabolism
Other drugs/substances Genetics Hepatic blood flow Liver disease Age Sex Ethnicity
Factors that determine drug metabolism
MUST LEAVE CIRCULATION AND ENTER TISSUES Plasma protein binding Tissue perfusion Membrane characteristics Blood-brain barrier Transport mechanisms Diseases/other drugs
Renal drug excretion
Glomerular filtration
Active tubular secretion
Passive tubular reabsorption
Glomerular filtration
All unbound drugs are filtered at the glomerulus as long as their size or charge does not prevent this
Active tubular secretion
Some drugs are actively secreted into the proximal tubules of the kidneys
Main method of excretion for protein bound cationic and an ionic drugs
Passive tubular reabsorption
As filtrate moves down kidney tubules, becomes more positive => body reabsorbs some of the drug (only unionised drug though)
Also affected by renal failure
Factors that predispose a patient to drug interactions
Patient specific - advanced age (young/old), genetic polymorphisms, concomitant diseases
Drug specific - polypharmacy, narrow therapeutic range, dose
Classification of drug-drug interactions
Direct
Indirect
Antagonistic
Synergistic/agonistic
Types of adverse drug reaction
Augmented Bizarre Chronic Delayed End of treatment Failure of treatment
Augmented (ADR)
Predictable
Dose dependent
Resolved when drug is stopped
Recognised before drug is available
Bizarre (ADR)
Unpredictable
Rare
Serious illness/death
Unrelated to dose
Chronic (ADR)
Related to dose
Related to length of treatment
Semi-predictable
Delayed (ADR)
Occurs years after treatment, or in children of patient
End of treatment (ADR)
Effects caused when drug is stopped, especially suddenly
Failure of treatment (ADR)
Common
Frequently caused by drug interactions
