pharmacology Flashcards
(32 cards)
4 key concepts of pharmacokinetics?
ADME
Definitions:
Pharmacokinetics vs pharmacodynamics
Pharmacokinetics:
How the body acts on the drug (how its broken down etc)
Pharmacodynamics:
How the drug affects the body (uptake, distribution etc)
Define affinity
A measure of binding strength between an epitope (specific piece of the antigen) and an antibody binding site - the higher the affinity the better
describes how well a ligand BINDS to the receptor
Define efficacy
(Does an antagonist show efficacy?)
What on a graph shows this??
Maximum effect that can be achieved by drug
/ how well the ligand activates the receptor
No. An antagonist has affinity but zero efficacy. Bc antagonists don’t activate receptors!! An agonist however demonstrates affinity and efficacy.
Emax
Define potency
Value on graph?
What is the effect of fewer receptors on drug potency?
= drug strength/weakness aka how well a drug works
Or = Aka the strength of a drug at a particular dosage
Or = Or concentration/dosage required to produce 50% of the maximal effect
EC50
Fewer receptors will shift the dose-response curve to the RHS, this means drug potency will be reduced.
Would a drug with a lower EC50 have a lower or greater potency?
Greater potency.
partial vs full agonist?
A full agonist has high efficacy, producing a full response while occupying a relatively low proportion of receptors (they’ll also go up to 100%) on graphs
Vs
Apartial agonisthas lower efficacy than a full agonist. It produces sub-maximal activation even when occupying the total receptor population, therefore cannot produce the maximal response, irrespective of the concentration applied. Also (Partial agonists don’t have receptor reserve).
competitive vs non competitive inhibitors?
Can they reach max rate of reaction?
Competitive inhibitor = inhibitor may bind to an enzyme and block binding of the substrate, for example, by attaching to the active site.
B)—— Will decrease reaction rate but can be ‘out-competed’ if there is lots of substrate so can sill reach max reaction rate if enough substrate
Non-competitive inhibitor = inhibitor doesn’t block the substrate from binding to the active site. Instead, it attaches at allosteric site and blocks the enzyme from doing its job. This inhibition is said to be “noncompetitive” because the inhibitor and substrate can both be bound at the same time.
B)——-
Specificity vs selectivity?
Can aspirin be described as a selective drug?
Specificity:
Drugs with a specific action act directly on their receptor so not through another molecule
eg exenatide is specific for the GLP-1 receptor
Selectivity:
Acts on one target ad one target alone
(No compound is truly ever specific )
No. Aspirin is non-selective, it acts on COX1 and COX2.
Name 5 local routes of drug administration:
Name all routes of systemic routes of drug administration inc the 2 categories?
What route of drug administration has a bioavailability of 1?
- Topical - directly onto skin/mucosa
- intranasal
- Eye drops
- inhalation
- transdermal
Systemic -> enteral
- oral
- rectal
- sublingual
And -> parenteral
- IV
- IM
- SC
- inhalation
- transdermal
IV infusion, all the drug administered will go into the plasma.
What is the effect of an increase in pH on a weak acid?`
give an example of a weak acid
The weak acid will become more ionised.
aspirin
In terms of ionisation, what happens to Aspirin in the stomach?
What is the advantage of aspirin doing this in the stomach?
Explain what would happen to the bioavailability of aspirin if gastric pH increased.
Aspirin is a weak acid and so becomes less ionised in the stomach due to the low gastric pH.
This allows rapid non-ionic diffusion across the gut membrane into the plasma. Once in the plasma aspirin becomes more ionised again.
The bioavailability would decrease. Aspirin would be more ionised and so wouldn’t diffuse across the gut into the plasma as rapidly this would mean aspirin uptake would decrease.
bioavailability: define
formula?
The proportion of the drug that enters circulation and so can exert an effect on the body
= AUC oral / AUC IV x 100
area under the plasma drug concentration-time curve (AUC) reflects the actual body exposure to drug after administration of a dose of the drug and is expressed in mg*h/L.
What is the bioavailability of morphine taken orally?
50%.
What are the two ways by which drugs can be eliminated in the kidneys?
- Glomerular filtration.
2. Active secretion.
GFR: define
normal gfr?
GFR stands for glomerular filtration rate. GFR is a measure of how well your kidneys filter blood.-
Normal GFR is about 120ml/min
- Rate of urine production is about 1-2mL/min.
- Drugs can be filtered at the glomerulus
Now usually use eGFR (estimated GFR)
eGFR uses serum creatinine, age, sex and race (for African-Caribbean patients).
- This is normalised to a body surface area of 1.73m2 and derived from a specific formula.
Formula: Absolute GFR = eGFR x individual’s body surface area /1.73
creatinine clearance: define?
Estimation of creatinine clearance means =
Creatinine is a substance produced in skeletal muscle which is excreted through the kidneys
neither passively reabsorbed nor actively secreted
= estimates clearance of drugs filtered at glomerulus
cockcroft-gault equation?
estimated creatinine clearance (ml/min) = (140-age) x weight x constant
/ serum creatinine
- Constant 1.23 for men 1.04 for women
- Age in years
- Weight in kilograms
- Serum creatinine in micromol/litre
hepatic extraction ratio: (HER)
define
What is the limiting factor when a drug has a high HER?
What is the limiting factor when a drug has a low HER?
The proportion of a drug removed by one passage through the liver.
Hepatic blood flow, perfusion limited.
Diffusion limited. A low HER is slow and not efficient.
What happens to high and low HER drugs when enzyme induction is increased?
The clearance of low HER drugs increases. There is minimal effect on high HER drugs.
Divisions of PNS?
CNS and PNS
PNS -> autonomic and somatic
autonomic -> sympathetic and parasympathetic
Describe the gate control theory.
Non-noxious stimuli trigger larger A beta fibres, these override smaller pain fibres and ‘close the gate’ to pain transmissions to the CNS.
adverse drug reaction: define
Rawlins-Thompson system: Describe a type A adverse drug reaction.
Treatment for type A?
A noxious and unintended response to a drug.
Type A adverse reaction:
- Augmented.
- Very common.
- Predictable from physiological effects of the drug.
- Often dose related.
treatment: reduce dose
Rawlins-Thompson system: Describe a type B adverse drug reaction.
treatment?
- Bizarre.
- Unpredictable.
- Immunological mechanisms and hypersensitivity.
- Often there is a history of allergy.
treatment: withdraw drug immediately
