fundamentals of pharmacology Flashcards
what is a drug ?
a chemical substance of know structure, other than a nutrient or an essential dietary ingredient, which, when administered to a living organism, produces a biological effect
what makes a good medicinal drug ?
- drug can be delivered to its site of action
- it will act once at the site of action
- the drug will stay in that place
how are drugs named ?
- chemical name
- common name
- proprietary (trade) name
- therapeutic uses
- mechanism of action
how do drugs produce their effects ?
exogenous molecules that mimic or block the actions of endogenous molecules
bind to molecular targets ( receptors)
what are some examples of receptors in the body ?
- receptors for neurotransmitters or hormone
- enzyme
- ion channels
- carrier or transporter molecules
what effects the binding of a drug ?
- the size and flexibility of the drug
- ## nature of chemical bonds that form between drug molecule and its binding site
why do drugs have side effects ?
- drug binding isnt completely specific
what is pharmacodynamics
what drugs does to the body
what is pharmacokinetics ?
what the body does to the drug
how drug is handled by the organism
what are the critical elements of pharmacokinetics
- absorption
- distribution
- metabolism
- excretion
what is absorption ?
determines how much and how quickly the drug enters the blood
what is absorption influenced by ?
- drugs molecular size
- lipid solubility
- chemical stability
- the route by which the drug is adminstered
what is distribution?
where the drug goes after its been absorbed
what determines the drugs distribution ?
- drugs need to circulate in blood plasma and diffuse into tissue through ECF
- ability to do this is determined by a drugs water solubility
what can interfere with a drugs distribution ?
- circulation of patient
- drug sticking to proteins in blood plasma
- drugs partitioning into fat stores
what is the volume of distribution ?
- the volume the drug would occupy if the total amount administered was dissolved in solution at the same concentration as that found in the blood plasma
what 2 factors determine how long the drug effect will last ?
- metabolism happen in liver
- excretion by the kidneys
what are some routes of excretion ?
- urine
- faeces
- sweat
- bile
- breath
what is a drugs half life ?
the time it takes for the plasma concentration to fall by half
concentration follows monoexponential decline
what is clearance ?
the volume of blood plasma cleared of the drug in unit time
how long does the preclinical stages of a drug take ?
5-10 years
how many phases is there in clinical development of a drug ?
4 phases
what is the first clinical stage ?
- exploratory phase first look into drug reaction on humans
- last 6 months to a year
- purpose is to check for safety + tolerability
who is the drugs tested on in phase 1 ?
- healthy volunteers
what is phase II ?
divided into 2 :
- phase IIa
- phase IIb
what is phase IIa ?
- exploratory phase
- 50 - 200 patients
- checks how drug acts
- dosage and treatment regimen established
what is phase IIb ?
confirmatory stage
- 200 - 500 patients
- last approx 2 years
- safety + efficacy compared to placebo/ current treatment
what is phase III ?
drug tested in 2000-10,000
- evaluation to see how effctive + safe treatment actually is
what is phase IV ?
- on going
- continues when drug is licensed and on market
- mointers consequences of drug
give some examples of drug regulatory bodies :
medicines and healthcare regulatory agency (MHRA)
european medicine agency (EMA)
food and drug administration (FDA)
What is a concentration- response relationship
- quantified drug effects
- relationship between drug conc and response of drug
What is Emax
Maximum effect that a drug can produce
What is EC50 ?
Concentration of drug that produces 50% of maximum response
Where do receptors usually insert ?
Across the lipid bilayer
What 2 main functions can receptors perform ?
- recognition or detection of extracellular molecules
- can bring changes into cell activity
What are receptors often named after ?
The drugs they bind to
What does highly selective receptors lead to ?
Less side effects
Describe the binding of drugs to receptors
Is reversible
D+ R <> DR
What is the affinity of a drug for its receptor quantified as ?
The molar concentration of drug required to occupy 50% of the receptors at equilibrium
What is KD ?
The concentration of a drug
Describe the relationship of drug affinity and KD :
Drugs with hugh affinity have a low KD
What do k+1 and k-1 tell ?
- rate constants
- likelihood of forward and backwards reactions occuring
How do you calculate rate of forward reactions ?
Rate of forward reaction = k+1 [D][R]
How do you calculate rate of backward reactions ?
Rate of backward reaction = k-1[DR]
What happens at equilibrium?
Backward rate = forward rate
k-1[DR] = k+1 [D][R]
KD = k-1/k+1 = [D][R]/[DR]
What do agonists do ?
Bind and activate the receptor
Produces a change in shape of receptor
What does efficacy describe ?
The ability of drug to activate the receptor
What do agonist have ?
- affinity and efficacy
What are some examples of natural agonists ?
- adrenaline
- acetylcholine
- insulin
What are the 2 types of agonists ?
- partial agonists
- full agonists
What are full agonists ?
- have high efficacy
- very effective at activating receptors and producing a biological response
What are partial agonists ?
- low efficacy
- less effective at activating receptors and producing a biological response
How many other receptors do full agonists activate
Only a fraction if available receptors
How many other receptors are occupied by partial agonists
Occupy all available receptors
What are antagonist?
Act to inhibit the effects of a neurotransmitter or another drug
What are competitive antagonist?
Compete with the agonist for the same site on receptor molecule
But dont activate it
What are non-competitive antagonist?
Act at a different site on the receptor
Or another molecule closely associated with it
What are reversible competitive antagonist?
Used to inhibit the effcets of a neurotransmitter or hormone
What are some examples of reversible competitive antagonist?
- pancurobium
- cetirizine
- propranolol
How can you overcome the inhibitory effects of reversible competitive antagonist?
Increase concentration of agonist
How do antagonists impact the concentration vs response curve
Produce a parallel shift to the right
What is the dose ratio ?
The ratio of the concentration of agonist producing the same response in the presence and absence of the antagonist
What can the dose ratio been used to measure ?
Extent of the shift in the position of the agonist curve
What is the extent of the shift ?
Measures the affinity of the antagonist for the receptor
What is pA2 ?
The affinity of an antagonist
What are the effects of irreversible competitive antagonist on a concentration response curve
Shift to the right which isnt parallel
