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.
1
Q
Pharmaceutical process
A
Get the drug into the patient
2
Q
Get the drug to the site of action
A
Pharmacokinetic process
3
Q
Produce the correct pharmacological effect
A
Pharmacodynamic process
4
Q
Produce the correct therapeutic effect
A
Therapeutic process
5
Q
the 4 basic factors to determine drug pharmacokinetics.
A
Absorption
Distribution
Metabolism
Elimination
6
Q
how can drugs be administered
A
oral, IV, subcutaneous (insulin injection), intramuscular, rectal, inhalation, nasal, transdermal
7
Q
what is Absorption is defined as
A
the process of movement of unchanged drug from the site of administration to the systemic circulation.
8
Q
what is therapeutic response related to
A
plasma concentration of a drug
9
Q
what is Tmax
A
the time of peak concentration
10
Q
Cmax
A
the peak concentration
11
Q
what is AUC
A
Area under the curve - relates to the amount of drug that actually gets into the systemic tsystem
12
Q
higher Tmax
A
the earlier the conc. peaks
13
Q
what happens when dose is increased
A
not affect time to peak conc. - however the Cmax is increased
14
Q
what is the name of the active range of a drug?
A
the therapeutic range
15
Q
what happens above/below the the therapeutic range
A
above - toxicity
below - no pharmacological action
16
Q
what is the therapeutic index
A
a measure of the range at which a drug is safe and active.
17
Q
bioavailability
A
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
18
Q
what is the Henderson-Hasselbalch
A
The relationship between the local pH and the degree of ionisation
19
Q
what is the ability of a drug to diffuse across a lipid barrier
A
lipid-water partition coefficient
20
Q
how quickly will a highly lipid soluble drug diffuse across a membrane
A
rapidly diffuse
21
Q
will a non lipid soluble drug be absorbed
A
no
22
Q
how much is absorbed via inhalation
what is it better for
A
5-10%
volatile agents
23
Q
how would a drug pass across a lipid barrier
A
be lipid soluble
24
Q
what are the main drivers of drug filtration
A
the hydrostatic and osmotic pressure across the membrane
25
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
26
what is first pass metabolism
its when some of the drug is metabolised before it reaches the systemic circulation (ADME becomes AMDME)
27
what are some of the benefits of sublingual (under tongue)
by passes first pass metabolism
28
what are the benefits of rectal medicine
use drugs that irritate stomach
| absorption tends to be slow bypass first pass metabolism
29
what is transdermal
a patch on skin
controlled release
avoids first pass metabolism
30
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
31
what should the unionised form of drugs do
pass across a membrane until it reaches equilibrium
32
a drug with high lipid solubility will
will rapidly diffuse across a cell membrane.
33
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
34
how dose food effect GI absorption
Can enhance or impair rate of absorption.
35
how does illness effect GI absorption
Migraine reduces rate of stomach emptying and therefore rate of absorption of analgesic drugs.
36
what factors affect tissue distribution
```
Plasma protein binding
Tissue perfusion
Membrane characteristics
Transport mechanisms
Diseases and other drugs
```
37
how does plasma protein effect distribution
the more drug that binds to protein the less that is biologically INACTIVE
38
what can bioavailability be effected by
```
Renal failure
Hypoalbuminaemia
Pregnancy
OTHER DRUGS
Saturability of binding
```
39
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?)
40
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
41
what happens as Vd increases
the ability of the drug to diffuse into and through membranes.
42
if a drug could penetrate any membrane the Vd would be...
42L - volume of fluid in human
43
what is clearance (cl)
the theoretical volume from which a drug is completely removed
MEASURE OF ELIMINATION
44
what is half life
the time taken for the drug conc. to decline by half
45
what doses half life depend on
Vd and Cl
0.7xVd/Cl
46
if a half life increases so will
toxicity
47
what is steady state conc.
the concentration that sits in the therapeutic range after chronic administration
48
what dose drug elimination determine
what is it made up of
the length of drug action
metabolism
excretion
49
what are the primary organs for drug excretion
the kidneys
50
what are the 3 principles of excretion
glomerular filtration
passive tubular
reabsorption
51
what is glomerular filtration
is how much liquid and waste are passing through the kidneys
52
passive tubular excretion
what can this lead to
eliminating protein bound cationic and anionic drugs
is In high conc. so can lead to reabsorption
53
what is biliary secretion
liver - secreted in to the bile
some reabsorbed - entero-hepatic circulation
54
what dose metabolism in the liver lead to
conjugation of the drug which means its not reabsorbed
liver damage may reduce this = toxicity
55
what is drug metabolism
the biochemical modification of pharmaceutical substances by living organisms (ENZYMES)
56
what dose metabolism do
turn lipid soluble and non-polar substances
POLAR AND WATER SOLUBLE for excretion
57
where dose metabolism occur
LIVER, lining of the gut, the kidneys and the lungs.
58
what drugs might be activated after metabolism
PRODRUGS
| first past metabolism
59
what are the two phases of metabolism
phase 1 (POLARITY) = drug becomes activated or inactivated
phase 2 (WATER SOLUBILITY) = forms conjugation products
60
what are the phase 1 reactions
what is their goal
oxidation
reduction
hydrolysis
to increase the polarity of a substance
61
what is cytochrome P-450
enzymes are the most important super family of metabolising enzymes.
62
what is drug specificity determined by
the isoform of the cytochrome P-450
63
what is a isoform
a protein formed from a gene just (different splicing)
64
what is CYP3A4
enzyme in human liver
| diazepam, methadone
65
what is CYP2D6
responsible for the metabolism of some antidepressants
Reduced or absent expression is found in 5-10% of the population (immune)
66
what is CYP1A2
induced by smoking and is important in the metabolism of theophylline.
67
what is conjugation
increases the water solubility and enhances excretion of the metabolised compound.
68
what does conjugation attach
glucuronic acid, glutathione, sulphate or acetate
69
what is another name for phase 2
GLUCURONIDATION
70
what factors effect metabolism
```
Other drugs/herbals/natural substances
Genetics
Hepatic blood flow
Liver disease
Age
Sex
Ethnicity
Pregnancy
```
71
what happens if a enzyme is endued
Increased metabolism of drugs metabolised by that enzyme
| Resulting in decreased drug effect
72
what causes enzyme induction
othe compounds
other drugs
73
what happens when enzymes are inhibited
often lead to toxicity
may be irreversible
74
what drugs cause enzyme inhibition
common food, drugs
HERBAL MEDICINES
erythromycin
clarithromycin
75
what is the importance of pharmacogenetics
inter-individual differences in gene expression are common
therefore
metabolising enzymes are often expressed in multiple forms
76
what is the expression of multiple metabolising drugs called
Genetic Polymorphisms
77
how dose age effect metabolism
in the young and old
| renal function might be deficient
78
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
79
what do monoclonal antibodies do
delivery of a toxin, cytokine or other active drug
80
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
81
what 3 factors determine dosage regimes
dose
frequency
timing
(administering technique?)
82
what is the classification of ADR onset
acute
sub-acute
latent
83
what is the classification of ADRs
```
type A - augmented
tB - bizarre
tC - chronic
tD - delayed
tE - end of treatment
tF - failure of treatment
```
84
what are predisposing factors of ADRs
```
age
sex
race/genetic polymorphism
inter-current disease
multiple drug therapy's
```
85
what are type A reactions
entirely predictable dose dependent
pharmacological action
Easily reversible
86
what are examples of type A reactions
bradycardia - beta-blockers
hypoglycaemia - insulin
87
what are the two types of TYPE A ADRs
Augmentation of the primary effect
Secondary effect
88
how are ADRs reported
yellow card app
89
what is reported
ADRs affecting Black Triangle Drugs
All significant or unusual adverse drug reactions
90
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
91
what are the two common reasons for Type A ADRs
when do they occur
Pharmacokinetic variation
Pharmacodynamic variation
as a result of disease
92
what is teratogenicity
abnormal foetus malformations due to in utero exposure
ALL DRUGS AVOIDED DURING PREGNANCY
93
what are the important factors in type B ADRs
more common with macromolecules
patient has history of asthma , eczema
94
how is a drug allergy/ hypersensitivity reaction formed
The first dose acts as the antigen
Body produces the antibody
Subsequent antigen-antibody reaction
95
what type of effect is teratogenicity
a delayed effect - long time after treatment
96
what are some teratogenic agents
Cytotoxins
Vitamin A
Anti-thyroid drugs
Steroids
97
what are some long term effects of ADRs
what type is this
Semi-predictable
Steroid induced osteoporosis
Opiate dependence
TYPE C
98
when do Type C ADRs occur
is related to the duration of treatment as well as the dose
99
what are some examples drugs most likely to be involved
Warfarin
Erythromicin
Clarithromicin
Cyclosporin
100
what type of interactions can occur
```
drug on drug
herbal
food
drink
pharmacogenetics
```
101
The Drug whose Activity is effected by such an Interaction is called the..
object drug
102
The agent which precipitates a drug-drug interaction is referred to as the
the Precipitant
103
what are some examples of good drug interactions
treatment of hypertension
treatment of Parkinsonism
104
drug - dug interactions effect how many people
3-30% in hospital
9.2-70% in GP
105
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
106
what is a drug-drug interaction
interaction is defined as the modification of a drugs effect by prior or concomitant administration of another substance
107
what are some predisposing conditions
```
no. of medications
old
young
very ill
chronic conditions
```
108
what chronic conditions could cause drug-drug interactions
```
liver disease
renal impairment
diabetes mellitus
epilepsy
asthma
```
109
what is the importance of therapeutic drug monitoring
to make sure that potent drugs with narrow therapeutic windows don't become highly toxic
