Drug Absorption Flashcards
Discuss the physico-chemical factors that affect the transfer of drugs across cell membranes. Discuss the factors that affect absorption of a drug from the GI tract Discuss the medical importance of first pass metabolism. Discuss the benefits of intravenous, topical and inhaled medication.
Pharmaceutical process
Get the drug into the patient
Get the drug to the site of action
Pharmacokinetic process
Produce the correct pharmacological effect
Pharmacodynamic process
Produce the correct therapeutic effect
Therapeutic process
the 4 basic factors to determine drug pharmacokinetics.
Absorption
Distribution
Metabolism
Elimination
how can drugs be administered
oral, IV, subcutaneous (insulin injection), intramuscular, rectal, inhalation, nasal, transdermal
what is Absorption is defined as
the process of movement of unchanged drug from the site of administration to the systemic circulation.
what is therapeutic response related to
plasma concentration of a drug
what is Tmax
the time of peak concentration
Cmax
the peak concentration
what is AUC
Area under the curve - relates to the amount of drug that actually gets into the systemic tsystem
higher Tmax
the earlier the conc. peaks
what happens when dose is increased
not affect time to peak conc. - however the Cmax is increased
what is the name of the active range of a drug?
the therapeutic range
what happens above/below the the therapeutic range
above - toxicity
below - no pharmacological action
what is the therapeutic index
a measure of the range at which a drug is safe and active.
bioavailability
the proportion of a drug or other substance which enters the circulation when introduced into the body and so is able to have an active effect
what is the Henderson-Hasselbalch
The relationship between the local pH and the degree of ionisation
what is the ability of a drug to diffuse across a lipid barrier
lipid-water partition coefficient
how quickly will a highly lipid soluble drug diffuse across a membrane
rapidly diffuse
will a non lipid soluble drug be absorbed
no
how much is absorbed via inhalation
what is it better for
5-10%
volatile agents
how would a drug pass across a lipid barrier
be lipid soluble
what are the main drivers of drug filtration
the hydrostatic and osmotic pressure across the membrane
what GI factors effect adsorption
motility - speed to reach absorption site (area of bowel)
food - can enhance or impair absorption
illness - especially pain reduces absorption rate
what is first pass metabolism
its when some of the drug is metabolised before it reaches the systemic circulation (ADME becomes AMDME)
what are some of the benefits of sublingual (under tongue)
by passes first pass metabolism
what are the benefits of rectal medicine
use drugs that irritate stomach
absorption tends to be slow bypass first pass metabolism
what is transdermal
a patch on skin
controlled release
avoids first pass metabolism
what is the difference between a topical and IV drug administration
iv is more direct, less drug is needed to get same effect, absorption is more rapid higher Tmax
what should the unionised form of drugs do
pass across a membrane until it reaches equilibrium
a drug with high lipid solubility will
will rapidly diffuse across a cell membrane.
what is motility
hoe dose it effect GI absorption
Speed of gastric absorption will affect speed at which drug reaches site of absorption - small intestine
how dose food effect GI absorption
Can enhance or impair rate of absorption.
how does illness effect GI absorption
Migraine reduces rate of stomach emptying and therefore rate of absorption of analgesic drugs.
what factors affect tissue distribution
Plasma protein binding Tissue perfusion Membrane characteristics Transport mechanisms Diseases and other drugs
how does plasma protein effect distribution
the more drug that binds to protein the less that is biologically INACTIVE
what can bioavailability be effected by
Renal failure Hypoalbuminaemia Pregnancy OTHER DRUGS Saturability of binding
why is it important
if bioavalibility is low (high drug binding)
then a small change in drug binding can have a FUCKING HUGE change in free drug (toxicity?)
what is Vd
volume of distribution
volume of plasma that would be necessary to account for the total amount of drug in a patient’s body
what happens as Vd increases
the ability of the drug to diffuse into and through membranes.
if a drug could penetrate any membrane the Vd would be…
42L - volume of fluid in human
what is clearance (cl)
the theoretical volume from which a drug is completely removed
MEASURE OF ELIMINATION
what is half life
the time taken for the drug conc. to decline by half
what doses half life depend on
Vd and Cl
0.7xVd/Cl
if a half life increases so will
toxicity
what is steady state conc.
the concentration that sits in the therapeutic range after chronic administration
what dose drug elimination determine
what is it made up of
the length of drug action
metabolism
excretion
what are the primary organs for drug excretion
the kidneys
what are the 3 principles of excretion
glomerular filtration
passive tubular
reabsorption
what is glomerular filtration
is how much liquid and waste are passing through the kidneys
passive tubular excretion
what can this lead to
eliminating protein bound cationic and anionic drugs
is In high conc. so can lead to reabsorption
what is biliary secretion
liver - secreted in to the bile
some reabsorbed - entero-hepatic circulation
what dose metabolism in the liver lead to
conjugation of the drug which means its not reabsorbed
liver damage may reduce this = toxicity
what is drug metabolism
the biochemical modification of pharmaceutical substances by living organisms (ENZYMES)
what dose metabolism do
turn lipid soluble and non-polar substances
POLAR AND WATER SOLUBLE for excretion
where dose metabolism occur
LIVER, lining of the gut, the kidneys and the lungs.
what drugs might be activated after metabolism
PRODRUGS
first past metabolism
what are the two phases of metabolism
phase 1 (POLARITY) = drug becomes activated or inactivated
phase 2 (WATER SOLUBILITY) = forms conjugation products
what are the phase 1 reactions
what is their goal
oxidation
reduction
hydrolysis
to increase the polarity of a substance
what is cytochrome P-450
enzymes are the most important super family of metabolising enzymes.
what is drug specificity determined by
the isoform of the cytochrome P-450
what is a isoform
a protein formed from a gene just (different splicing)
what is CYP3A4
enzyme in human liver
diazepam, methadone
what is CYP2D6
responsible for the metabolism of some antidepressants
Reduced or absent expression is found in 5-10% of the population (immune)
what is CYP1A2
induced by smoking and is important in the metabolism of theophylline.
what is conjugation
increases the water solubility and enhances excretion of the metabolised compound.
what does conjugation attach
glucuronic acid, glutathione, sulphate or acetate
what is another name for phase 2
GLUCURONIDATION
what factors effect metabolism
Other drugs/herbals/natural substances Genetics Hepatic blood flow Liver disease Age Sex Ethnicity Pregnancy
what happens if a enzyme is endued
Increased metabolism of drugs metabolised by that enzyme
Resulting in decreased drug effect
what causes enzyme induction
othe compounds
other drugs
what happens when enzymes are inhibited
often lead to toxicity
may be irreversible
what drugs cause enzyme inhibition
common food, drugs
HERBAL MEDICINES
erythromycin
clarithromycin
what is the importance of pharmacogenetics
inter-individual differences in gene expression are common
therefore
metabolising enzymes are often expressed in multiple forms
what is the expression of multiple metabolising drugs called
Genetic Polymorphisms
how dose age effect metabolism
in the young and old
renal function might be deficient
how does sex effect metabolism
Responsiveness to certain drugs is different for men and women
Pregnancy – induction of certain drug metabolizing enzymes occurs in second and third trimester
what do monoclonal antibodies do
delivery of a toxin, cytokine or other active drug
what is a suspension
what is it good for
drug particles in a liquid phase
make a small volume
drugs that are unpalatable - in a sugary syrup
can go in a nasal gastric tube
what 3 factors determine dosage regimes
dose
frequency
timing
(administering technique?)
what is the classification of ADR onset
acute
sub-acute
latent
what is the classification of ADRs
type A - augmented tB - bizarre tC - chronic tD - delayed tE - end of treatment tF - failure of treatment
what are predisposing factors of ADRs
age sex race/genetic polymorphism inter-current disease multiple drug therapy's
what are type A reactions
entirely predictable dose dependent
pharmacological action
Easily reversible
what are examples of type A reactions
bradycardia - beta-blockers
hypoglycaemia - insulin
what are the two types of TYPE A ADRs
Augmentation of the primary effect
Secondary effect
how are ADRs reported
yellow card app
what is reported
ADRs affecting Black Triangle Drugs
All significant or unusual adverse drug reactions
what is the secondary effect
an effect that is not on the target area but still makes sense due to the pharmacology of the drug
dry mouth with tricyclic antidepressants
what are the two common reasons for Type A ADRs
when do they occur
Pharmacokinetic variation
Pharmacodynamic variation
as a result of disease
what is teratogenicity
abnormal foetus malformations due to in utero exposure
ALL DRUGS AVOIDED DURING PREGNANCY
what are the important factors in type B ADRs
more common with macromolecules
patient has history of asthma , eczema
how is a drug allergy/ hypersensitivity reaction formed
The first dose acts as the antigen
Body produces the antibody
Subsequent antigen-antibody reaction
what type of effect is teratogenicity
a delayed effect - long time after treatment
what are some teratogenic agents
Cytotoxins
Vitamin A
Anti-thyroid drugs
Steroids
what are some long term effects of ADRs
what type is this
Semi-predictable
Steroid induced osteoporosis
Opiate dependence
TYPE C
when do Type C ADRs occur
is related to the duration of treatment as well as the dose
what are some examples drugs most likely to be involved
Warfarin
Erythromicin
Clarithromicin
Cyclosporin
what type of interactions can occur
drug on drug herbal food drink pharmacogenetics
The Drug whose Activity is effected by such an Interaction is called the..
object drug
The agent which precipitates a drug-drug interaction is referred to as the
the Precipitant
what are some examples of good drug interactions
treatment of hypertension
treatment of Parkinsonism
drug - dug interactions effect how many people
3-30% in hospital
9.2-70% in GP
what traits do drugs that are most likely to be involved in drug-drug interactions
All these drugs are potent with a narrow therapeutic index
small change in blood levels can induce profound toxicity
what is a drug-drug interaction
interaction is defined as the modification of a drugs effect by prior or concomitant administration of another substance
what are some predisposing conditions
no. of medications old young very ill chronic conditions
what chronic conditions could cause drug-drug interactions
liver disease renal impairment diabetes mellitus epilepsy asthma
what is the importance of therapeutic drug monitoring
to make sure that potent drugs with narrow therapeutic windows don’t become highly toxic
