Drugs Flashcards
What is absorption?
Process of movement of the unchanged drug from the site of administration to the systemic circulation
What is Cmax?
Drug concentration peak
What is Tmax?
The time at which Cmax us observed
What is bioavailability?
The amount of the drug available for action in the systemic circulation
What factors affect bioavailability?
Formulation
Ability of drug to pass physiological barriers
GI effects
First pass metabolism
What are some physiological barriers drugs encounter?
Lipid solubility
pH
Ionisation
How does ionisation affect drug diffusion?
An ionised drug will not cross the cell membrane
What is the Henderson-Hasselbalch equation used to show?
The relationship between local pH and the degree of ionisation
What is the Henderson-Hasselbalch equation?
pH=pKa+log10([A-]/[HA])
What is the lipid water partition coefficient?
The ratio of the amount of drug which dissolves in the lipid and water phase when they are in contact
How does lipid solubility affect diffusion across a membrane?
A drug must be lipid soluble to diffuse across a membrane
By what methods can drugs pass across the membrane?
Passive diffusion Filtration Bulk flow Active transport Facilitated diffusion Ion pair transport Endocytosis
What drugs cross the membrane via facilitated diffusion?
Monosaccharides, amino acids, vitamins
What is the driving force for filtration, bulk flow and pore transport?
The difference in hydrostatic or osmotic pressure
What gastrointestinal factors affect drug absorption?
Motility
Food
Illness
What is first pass metabolism?
Metabolism of drug prior to it reaching the systemic circulation
What are the 4 primary systems that affect first pass metabolism?
GI lumen
Gut wall enzymes
Bacterial enzymes
Hepatic enzymes
What are the benefits of subcutaneous and IM administration?
Only a small volume required
Avoids first pass metabolism
Water soluble drugs absorbed well
What are the benefits of buccal and sublingual administration?
Avoids first pass metabolism
Enter circulation directly
What are the benefits and disadvantages of suppositories?
Avoids first pass metabolism
Can be used for drugs that irritate stomach
Absorption tends to be slow
What are the benefits of inhalation of drugs?
Can be used for volatile agents
Relatively rapid action
Can be used for topical or systemic effects
What are the advantages and disadvantages of transdermal administration?
Avoids first pass metabolism
Controlled release
Few substances well absorbed
Needs to be nonirritant
What is drug distribution?
Reversible transfer of a drug between the blood and extravascular fluids and tissues of the body
What factor affect tissue distribution?
Plasma protein binding Tissue perfusion Membrane characteristics Transport mechanisms Diseases and other drugs Elimination
What is the effect of plasma protein binding?
Only unbound drugs are biologically active
What factors affect the amount of a drug that binds to plasma proteins?
Renal failure Hypoalbuminaemia Pregnancy Other drugs Saturability of binding
What is the apparent volume of distribution (Vd)?
Theoretical volume that would be necessary to contain the amount of the administered drug at the same concentration as it is in the plasma
What is the correlation between Vd and the ability of a drug to diffuse?
The higher the Vd, the better the drug is at diffusing
What is clearance?
The theoretical volume from which a set amount of a drug is completely removed over time
What is drug clearance dependent on?
Urine flow rate for renal clearance
Metabolism and biliary secretion for hepatic clearance
What is half life (t1/2)?
Time taken for the drug concentration in the blood to half
What is the half life dependent on?
Volume of distribution and rate of clearance
What does prolongation of the half life cause?
Toxicity
When is steady state reached in chronic administration?
Usually after approx 4 half lives
What is elimination?
Removal of the active drug and its metabolites from the body
What are the 3 stages of drug elimination?
Metabolism and excretion
Where does most of drug metabolism take place?
Liver
What is the primary organ of drug excretion?
Kidneys
What are the 3 principle mechanisms of drug excretion?
Glomerular filtration
Passive tubular reabsorption
Active tubular secretion
What drugs are filtered during glomerular filtration?
All unbound drugs, as long as they size, charge or shape are not excessively large
What happens in active tubular secretion?
Acidic and basic compounds are actively secreted into the proximal tubule
Why is active tubular secretion important?
Eliminating protein bound cationic and anionic drugs
What is the process of passive tubular reabsorption?
As the filtrate moves down the renal tubule, any drug present is concentrated and passive diffusion allows some of the drug to diffuse across the membrane back into circulation
Where does passive tubular reabsorption tale place?
Distal tubule and collecting duct
What is biliary secretion?
Secretion of the drug into the bile where it can then be reabsorbed into the enter-hepatic circulation
What does metabolism in the liver lead to and what does this cause?
Conjugation of the drug
Cannot be reabsorbed into the circulation
What ways are drugs delivered to patients?
Tablets or capsules Solutions or suspensions Ointments and creams Inhalation Injections Suppositories Pessaries
Why are there different drug formulations?
To allow selective targeting, avoid pre or systemic metabolism, allow for fast or slow release
Where are oral medications absorbed?
GI tract
Who are solutions or suspensions used for?
Young, old, those with difficulty swallowing
What is the rate limiting step in absorption of tablets?
Break down of the tablet
What are the advantages of tablets and capsules?
Convenient Accurate dose Reproducability Drug stability Ease of mass production
What are enteric coated tablets?
A drug with a protective coating to protect the drug from the stomach and the stomach from the drug
Why are prolonged or delayed release formulations useful?
Most conditions require prolonged therapy
Maintains drug levels within therapeutic range
Reduces need for frequent dosing
Improved compliance
What are prodrugs?
Synthesised inactive derivatives of an inactive drug which requires to be metabolically activated after administration
What are buccal and sublingual administration ideal for?
Drugs with extensive first pass metabolism
Who is the rectal route useful for?
Young, old, patients unable to swallow
What can the rectal route be used to treat?
Local conditions, or systemic absorption
What are pessaries used for?
To treat local conditions
What are the 3 forms of injection based administration?
IV
IM
Subcutaneous
When is IV used?
When rapid onset of action id required
Careful control of plasma levels required
Drug has short half life
How can IV be given?
Rapidly
Slowly- to prevent toxic effects
Continuoisly- ensure accurate controls of plasma levels
What does IM allow for?
More sustained duration of action
What are subcutaneous injections used to administer?
Insulin
Heparin
Narcotic analgesics
What are 2 types of subcutaneous administration?
Dermojet
Pellet implantation
Why is subcutaneous injection uses?
Bypasses need for venous access
Slow absorption
What is transdermal drug delivery?
Adhesive patched containing the drug are applied to the skin, drug crosses the surface by diffusion and goes into systemic circulation
What is the benefit of transdermal drug delivery?
Bypasses first hepatic inactivation
What can percutaneous drugs be used for?
Local or systemic
Give an example of a systemic percutaneous drug?
Transderm-SCOP
Give an example of a local percutaneous drug?
Hydrogel transdermal patch
How can inhalation drugs be administered?
Pressurised aerosol, breath activated aerosol, nebuliser, dry powder device
What are the advantages of inhalation?
Delivered directly to site of action Rapid effect Small doses uses Little systemic absorption Reduced adverse effects
What are the 3 types of carrier based drug delivery?
Monoclonal antibodies
Liposomal drug delivery
Nanoparticle based drug delivery
How do monoclonal antibodies work as a carrier based drug delivery system?
Modified antibodies with attached toxins cytokines etc act directly when binding to a cancer specific antigen and induce immunological response
How does a liposomal drug delivery system work?
Allows for drug accumulation at disease sites and avoidance of sensitive sites
How do nanoparticles work as a carrier based drug delivery system?
Drug can be targeted to precise location, making the drug more effective and reduce side effects
What are the 3 types of nano carriers?
Nanoparticle
Nanotubule
Nanoshell
What are carbon nanotubes used to treat?
Bronchial asthma
What are gold nano tubules used to treat?
Chemo
What are nanoerythrosomes and what are they used for?
Resealed erythrocytes that carry proteins, enzymes and macromolecules
Used in treatment of liver tumour and enzyme and pancreatic diseases
What is an adverse drug reaction?
Any response to a drug which is harmful, unintended and occurs in doses used for prophylaxis, diagnosis or treatment
What are the classifications of onset of adverse drug reactions?
Acute- within 60 minutes
Sub-acute- 1-24 hours
Latent- >2days
What are the classifications of severity of adverse drug reactions?
Mild= bothersome but requires no change in treatment Moderate= Requires change in therapy, additional treatment, hospitalisation Severe= Disabling, life threatening
What are the classifications of adverse drug reactions?
Augmented Bizarre Chronic Delayed End of treatment Failure of treatment
What is a type A drug reaction?
Augmented
Dose related and predictable
Resolve when drug is reduced or stopped
What causes a type A drug reaction?
Too high a dose
Pharmaceutical variation
Pharmacokinetic variation
Pharmacodynamic variation
What is a type B drug reaction?
Bizarre
Rare and unrelated to dose
Can cause serious illness
What causes a type B drug reaction?
Immunological or genetic response
When are type B drug reactions more common?
With macromolecules
Patients with history of asthma or eczema
Presence of leukocyte antigen
Sex linked G6P deficiency
What is a type C drug reaction?
Chronic
Does not occur with single dose
Semi predictable
What is a type D drug reaction?
Delayed
Occur in children of patients or patients years after end of treatment
What are some examples of type D drug reactions?
Second cancers in those treated with alkylating agent or immunosuppressants
Graniofacial malformations in children of those treated with isotrtinoin
What is a type E drug reaction?
End of treatment
Adverse reaction when treatment is stopped, particularly when it was stopped suddenly
What are some examples of type E drug reactions?
Unstable angina or MI when taken off beta blockers
Withdrawal seizures when taken off anti-epileptics
What are type F drug reactions?
Failure of treatment
Common and dose related
Frequently caused by drug interactions
What are the 4 steps in diagnosis a type F drug reaction?
Differential diagnosis
Medication history
Assess time of onset and dose relationship
Lap investigations
What are the risk factors of adverse drug reactions?
Age Multiple medications Inappropriate medication prescribing, use or monitoring End organ dysfunction Altered physiology History of adverse drug reactions Dose and duration of exposure Genetic predisposition
