Principles Flashcards
Define pharmacokinetics
What the body does to the drug (absorption, distribution, metabolism, and excretion)
Define pharmacodynamics
What a drug does to the body and how it does it (biological effects and mechanism of action)
Define the term agonist
A drug that binds to a receptor to produce a cellular response
Define the term antagonist
A drug that blocks the actions of an agonist and normal body chemical
Define affinity
The strength of association between ligand and receptor
Define efficacy
The ability of an agonist to evoke a cellular response
Define EC50
The concentration of agonist that elicits a half maximal response
Define potency
The most potent is the drug that produces a response at the lowest concentration
Define orthosteric
The primary binding site of a ligand
Define allosteric
When an antagonist binds to the receptor not at the active site preventing activation
Define pKa
The pH at which 50% of the drug is ionised and 50% is unionised.
What are the 5 factors affecting GI absorption.
GI motility pH at the absorption site Blood flow to stomach and intestines The way in which the table is manufactured Physicochemical interactions
Define GI motility
The rate of stomach emptying and movement through the intestines
Why does the way the tablet/capsule is manufactured affect absorption?
They can be customised to release drugs at different rates and sites
Define systemic availability
The % of drug absorbed into systemic circulation -
IV = 100%
Oral has to go through first-pass metabolism
Define the term efferent signals
Signals going away from the CNS
Define the term afferent signals
Signals moving towards the CNS
What is the ANS responsible for?
Carrying output from the CNS to the whole body apart from skeletal muscles
What does the sympathetic ANS do?
Responsible for body’s response to stress. Fight or flight?
What does parasympathetic ANS do?
Coordinates the body’s basic homeostatic functions
What is the transmitter in the preganglionic neurones?
Acetylcholine
What is the usual transmitter in postganglionic neurones in the sympathetic division?
Noradrenaline
What is the transmitter in postganglionic neurones of the parasympathetic system?
Acetylcholine
What are cholinergic neurones?
Neurones that use acetylcholine as the transmitter
Are postganglionic neurones longer in sympathetic or parasympathetic system?
Sympathetic
Which ganglionic synapse used noradrenaline opposed to acetylcholine?
Sympathetic Postganglionic neuron
What are the postganglionic receptors of the sympathetic nervous system?
Adrenoceptors
What are the postganglionic receptors of parasympathetic nervous system?
G-protein Muscarinic acetylcholine
Where do M1 muscarinic ACh receptors act and what G protein couples with it?
M1 couples with Gq in the stomach to stimulate phospholipase C which causes increased acid secretion.
What G protein couples with M2 muscarinic receptors (parasympathetic) and what effect does this have?
Gi couples with M2 muscarinic ACh receptors in the heart resulting in inhibition of andeylyl Cyclase, opening K+ channels causing decreased heart rate (vagus nerve)
What G protein couples with M3 muscarinic receptors (parasympathetic) and what effect does this have?
Gq couples with M3 muscarinic ACh receptors resulting in stimulation of phospholipase C causing increased secretion of saliva in the mouth
Which muscarinic ACh receptor (parasympathetic) doesn’t couple with Gq
M2 - it couples with Gi in the heart
Which G protein couples with beta 1 and 2 sympathetic adrenoceptors at the neuroeffector junction?
Gs
Which G protein does sympathetic adrenoceptor beta 1 couple with at the neuroeffector junction and what does this cause?
Gs causing stimulation of adenylyl Cyclase resulting in increased rate and force of the heart
Which G protein does sympathetic adrenoceptor beta 2 couple with at the neuroeffector junction and what does this cause?
Gs causing stimulation of adenylyl Cyclase resulting in relaxation of the bronchial and vascular smooth muscle
Which G protein does sympathetic adrenoceptor alpha 1 couple with at the neuroeffector junction and what does this cause?
Gq causing stimulation of phospholipase C resulting in contraction of vascular smooth muscle
Which G protein does sympathetic adrenoceptor alpha 2 couple with at the neuroeffector junction and what does this cause?
Gi causing inhibition of adenylyl Cyclase resulting in inhibition of NA release
Does the sympathetic or parasympathetic nervous system cause contraction and relaxation of the vascular smooth muscle?
Sympathetic - beta 2 receptor caused relaxation
Alpha 1 causes contraction
What do Gs, Gq and Gi proteins do?
Gs stimulates adenylyl Cyclase
Gq stimulates phospholipase C
Gi inhibits adenylyl Cyclase
What action does cocaine have on the sympathetic post-ganglionic neurone
Blocks U1 preventing re-uptake of NA into post-ganglionic neurone resulting in large amounts of NA in the synapse increasing adrenoceptor stimulation :(i.e. Increased vasoconstriction and increased heart rate)
What effect do amphetamines have on the sympathetic post-ganglionic neurone?
Enters post-ganglionic neurone via U1 and blocks the NA degradation MAO enzyme preventing NA breakdown. It then causes U1 to run backwards and NA goes in a loop, leaving the cell at U1 as well as entering it resulting in a build up of NA in the synapse and increased adrenoceptor stimulation
(i.e. Increased vasoconstriction and heart rate)
What do prazosin, atenolol and salbutamol act on and do?
Prazosin - alpha 1 antagonist
Atenolol - beta 1 antagonsit
Salbutamol - beta 2 agonist
What effect does atropine have on the parasympathetic post-ganglionic neurone?
It blocks muscarinic ACh receptors preventing release of adenylyl Cyclase from M2 therefore causing an increase in heart rate. Therefore used to reverse bradycardia.
What is the therapeutic ratio and how is it calculated?
The window between minimum and maximum concentrations of drugs in which they are effective
Calculated by maximum tolerated dose divided by minimum effective concentration
What are first order kinetics?
Rate of elimination is directly proportional to the drug concentration (half life)
What are zero order kinetics?
When a drug is eliminated at a constant rate rather than a half life.
I.e. Ethanol - lose a set volume per hour regardless of concentration
Define membrane difference
The difference in potential (charge) between the inside and the outside of the cell
Define depolarization
When the membrane potential becomes less negative (or more positive)
Define hyperpolarization
When the membrane potential becomes more negative
What charge is the inside of a cell usually?
Negative
What is the normal membrane potential for neurones?
-80mV
What happens to K+ and Na+ to cause a change in membrane potential?
K+ leaves the cell
Na+ enters the cell
Define ENa and what is it’s value?
The membrane potential at which Na enters and leaves the cell at the same rate (equilibrium). This is +60mV
Define EK and what is it’s value?
The membrane potential at which K enters and leaves the cell at the same rate (equilibrium). This is -100mV
What type of channels are responsible for Na+ and K+ movement?
Voltage-activated Na+/K+ channels
What are action potentials?
Brief electrical signals in which the polarity of the nerve cell membrane is reversed (goes from negative to positive)
What is the refractory period?
A period in which no stimulus can elicit a second action potential as the voltage-activated Na+ channels are inactivated
