Pharmacology Flashcards
What is pharmacodynamics?
What the drug does to the body
What is pharmacokinetics?
What the body does to a drug - ADME
What does ADME stand for?
Absorption
Distribution
Metabolism
Excretion
What is an agonist?
A drug which binds to a receptor to produce a cellular response
What is an antagonist?
A drug which binds to the same receptor as the agonist in order to block it
An agonist has both affinity and efficacy, true or false?
True
What is affinity?
The strength of association between a ligand and a receptor
What is efficacy?
The ability of an agonist to evoke a cellular response
What is the EC50?
The concentration that an agonist produces a half max response
What are the different types of receptor?
LGIC
GPCR
Kinase linked
Nuclear receptors
What nucleotide binding site is present on the G protein binding site?
Guanine
What is a receptor?
A macromolecule (mostly protein) on or within cells that mediate the biological actions of endogenous substances.
Give an example of an agonist
adrenaline - increases the cardiac rate
A high efficacy favours a bigger response, true or false?
True
What is the relationship between the concentration of the agonist and the effect this has, when plotted logarithmically?
Sigmoidal - s-shaped
if an agonist is more potent, what does this mean?
that it will carry out an effect over a smaller agonist concentration range
when is antagonism reversible?
when the agonist and antagonist bind to the same site - orthosteric - as this is competitive
when is antagonism non-reversible
in non-competative antagonism: the agonist and antagonist bind to different sites, meaning the agonist cannot activate as the agonist is bound
what effect does a non-competitive antagonism have graphically? (on a logarithmic plot)
the curve is decreased as the full effect of the agonist cannot be reached
what effect does competitive antagonism have graphically? (on a logarithmic plot)
the curve moves to the right but maintains the same height, meaning the agonist can still carry out its full effect, it just needs to be at a higher concentration
what are the different ways drugs can move around the body?
- Bulk flow (via circulatory system)
- Diffusion (only over short distances)
- solubility (eg: lipid soluble molecules are more likely to diffuse across the lipid bilayer membranes)
what are the 4 ways something can cross the membrane?
endocytosis
passive diffusion
facilitated diffusion
active transport
Facilitated diffusion requires energy. True or false?
False
what is saturation kinetics?
A build up of drug in the extracellular compartment due to a limited amount of carrier proteins
Where in the body is there a high density of carrier proteins?
blood brain barrier GI tract placenta renal tubule biliary tract
Ions/charged particles can easily cross the membrane. True or false?
False
what is pKa?
the pH where half of the drug is ionised and half is un-ionised
what is the Henderson Hasselbalch equation?
pH-pKa = log (A-/AH)
or
pH-pKa = log (B/BH+)
B= base A = acid
what is the apparent volume of distribution?
Volume into which drug appears to be distributed with a concentration equal to that of plasma.
(REMEMBER: drug is not evenly distributed)
Eg: Lipophilic drugs cross membranes easily therefore Vd is normally greater than the total body volume
Where do low Vd drugs have access to?
the blood, normally retained in vascular compartments as it has high plasma protein binding, so has an increased drug plasma concentration
Where is the primary site for drug metabolism?
the liver
sometimes the kidney
what is drug metabolism?
the enzymatic conversion of the drug to form a metabolite that is normally less pharmacologically active than the OG compound.
what is bioavailability?
the amount of drug that is available in systemic circulation to do its job
why does IV give a higher bioavailability?
because it bypasses the liver
what happens during phase 1 metabolism?
the drug is either oxidised, hydrolysed or reduced forming a reactive metabolite that is pharmacologically active
what enzymes allow oxidation in phase 1 metabolism?
cytochrome P450 enzymes
what happens to aspirin during phase 1 metabolism?
it is hydrolised
what happens during phase 2 metabolism?
the drug combines with polar molecules (that are naturally present) to form a water soluble metabolite. This terminates biological activity
Give an example of a drug that bipasses phase 1 metabolism and goes straight to phase 2.
codeine
where can the drug or drug metabolites be excreted?
in the urine, faeces or bile
what role do the kidneys play in excretion of a drug?
this is the main organ where the drug is eliminated via renal filtration of the blood plasma
What is clearance?
the volume of blood removed of drug per unit of time
what determines the half life or a drug
its volume of distribution and its clearance
What is the steady state of a drug?
when the rate of drug administration is equal to the rate of drug elimination
How can you figure out the dosage rate?
dosage rate = drug plasma concentration X the clearance
How is the half life of a drug calculated?
half life = (0.693xVd)/CL
what does the half life of a drug determine?
the time required for the drug plasma concentration to achieve the drug plasma concentration steady state
what is the normal number of half lives needed for a drug to reach its steady state?
5 half lives
what is oral availability?
the fraction of drug that reaches systemic circulation after oral ingestion
what is systemic availability?
the fraction of drug that reaches systemic circulation after absorption
The threapeutic ratio = MTC/MEC. What do these stand for and what does the ratio mean?
MTC = maximum tolerated concentration MEC = minimum effective concentration
the higher the TR, the safer the drug.
what is first order kinetics of drug elimination?
the rate of elimination directly proportional to the drug concentration.
Half life is inversely proportional to elimination rate constant.
What does clearance refer to in drug elimination?
The volume of plasma cleared of drug in unit time
What is the equation for rate of elimination?
rate of elimination = clearance x plasma concentration
what is a loading dose?
the initial higher dose of drug before stepping down to lower maintenance dose.
what is the half life dependent on?
volume of distribution and clearance
What 3 processes occur in the kidney to excrete drugs and drug metabolites?
Glomerular filtration
active tubular secretion
passive reabsorption across tubular epithelium.
describe what happens in depolarisation and repolarisation.
Depolarisation: membrane potential becomes less negative (more positive)
Repolarisation: membrane potential returns to normal more -ve state.
What way do Na ions move through Na channels?
Inwardly as there is a higher concentration of Na ions outside the cell, compared to inside the cell.
What way do K ions move through K channels?
Outwardly
What do voltage activated channels cause?
Depolarisation
What do voltage activated K channels cause?
Hyperpolarisation
How are voltage activated Na and K channels activated?
by membrane depolarisation
Na channels activate more rapidly than K channels, true or false?
True
In an AP what causes the upstroke and what causes the downstroke? And why is there an undershoot?
Upstroke due to cell becoming more +ve due to influx of Na ions.
Downstroke due to cell repolarising due to efflux of K ions.
Undershoot is due to delayed closure of K channels
How can a Na channel go from being inactivated to closed?
Repolarisation of the cell
What is the refractory period?
Time when the Na channels are inactivated, at this point they are non conducting, to close the cell needs to repolarise.
What do oligodendrocytes do?
Produce myelinated cells in CNS
What produces myelinated cells in the PNS?
schwann cells
What are microglia?
Immune surveillance, the marcrophages of the CNS
What are the pre and postganglionic neurones of the sympathetic system?
Pre-ganglionic = acetyl choline (always) Post-ganglionic = noradrenaline (usually)
what does sympathetic stimulation do to the HR, bronchi, mucus production and arterioles?
increases HR
dilates/relaxed bronchi
decreases mucous production
vasoconstriction
Ejaculation is regulated by which ANS response?
Sympathetic
What are the pre and post-ganglionic neurones for the parasympathetic system?
Both acetyl choline
From where do the sympathetic chains derive from?
Thoraco-lumbar outflow (T1-L2)
Where does parasympathetic activity originate from?
CN 3, 7, 9 and 10
What does parasympathetic stimulation cause on the heart, bronchi, and blood vessels?
Decreased HR
Bronchoconstriction
Stimulates mucus production
NO effect on blood vessels
What type of ANS causes erection?
Parasympathetic
Describe the chemical transmission allowing a sympathetic response.
AP from CNS
Travels to pre-synaptic terminal of perganglionic neuron.
Triggers Ca entry and ACh release
ACh opens ligand-gated ion channels in the postganglionic neurone.
This causes depolarisation and generation of APs which travel to the presynaptic terminal of the neurone triggering Ca entry and release of noradrenaline.
What are the two key differences in chemical transmission in the sympathetic vs parasympathetic system?
In parasympathetic ACh is released by both pre and post-ganglionic neurones.
ACh (para) activates muscarinic G-protein receptors.
Noradrenaline actives G- protein adrenoceptors
Describe the structure of G-protein coupled receptor in response to the receptor part.
It is an integral membrane protein.
Has extracellular NH2 and intracellular COOH termini.
7 transmembrane spanse joined by 3 extracellular and 3 connecting loops.
Describe the structure of the G-protein part of the GPCR.
Peripheral membrane protein.
3 polypeptide subunits (alpha = binding site)
Contains guanine nucleotide binding site which holds GTP.
How do GPCR work when there is no signalling?
The receptor is unoccupied.
G protein binds GDP.
Effector not modulated
How is the signal turned on in a GPCR?
Agonist activates receptor.
G protein couples with receptor.
GDP dissociated and GTP binds instead to alpha subunit
G protein dissociates.
Alpha subunit combines with and modifies activity of effector.
(agonist may dissociate from receptor but signalling continues)
Describe how the signal is turned off in a GPCR?
Alpha subunit hydrolyses GTP -> GDP.
It then rejoins the beta gamma subunit
what do nicotinic acetylcholine receptors consist of?
5 glycoprotein subunits that form a central, cation conducting channel
describe what happens during the cholinergic (ACh) transmission at parasympathetic neuroeffector junctions
Uptake of chlorine, synthesising and storing ACh.
Depolarisation by AP, causing Ca influx and Ca induced release of ACh.
ACh muscarinic receptors (M1-3) are activated causing a cellular response.
ACh is degraded to choline and acetate by AChE which terminates transmissions.
Reuptake and reuse of choline.
What degrades ACh?
AChE
Describe what G-protein muscarinic ACh receptor subtype M1 does and its alpha subunit’s name.
Alpha subunit Gq
Stinulates phopholipase C causing increased stomach acid secretion.
Describe what G-protein muscarinic ACh receptor subtype M2 does and its alpha subunit’s name.
Alpha subunit Gi.
Inhibits adenylyl cyclase, opening K channels, causing decreased HR
Describe what G-protein muscarinic ACh receptor subtype M3 does and its alpha subunit’s name.
Alpha subunit Gq
Stimulates phospholipase C, causing increased saliva secretion and bronchoconstriction
Describe what happens in noradrenergic transmission at sympathetic neuroeffector junctions.
Synthesis and storage of NA
Depolarization by AP
Ca influx causing release of NA.
Activation of adrenoceptor subtypes causing cellular response.
Reuptake of NA by transporters.
Metabolism of NA by monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT)
What are the adrenoceptor subtypes at sympathetic neuroeffector junctions?
beta 1 and 2 and alpha 1 and 2
What is adrenoceptor beta 1’s alpha subunit called and what does it do?
Gs alpha subunit
Stimulation of adenylyl cyclase causing increased HR and force
What is adrenoceptor beta 2’s alpha subunit called and what does it do?
Gs alpha subunit.
Stimulates adenylyl cyclase causing relaxation of bronchial and vascular smooth muscle
What is adrenoceptor alpha 1’s alpha subunit called and what does it do?
Gq alpha subunit
Stimulation of phospholipase C causing contraction of vascular smooth muscle
What is adrenoceptor alpha 2’s alpha subunit called and what does it do?
Gi
Inhibition of adenylyl cyclase causing inhibition of NA release.
Describe what amphetamine is and what it does.
Is a U1 substrate.
Works by inhibiting MAO, which displaces NA into the cytoplasm.
NA accumulates in synaptic cleft causing increased adrenoceptor stimulation
describe what prazosin is and what it is used for.
Selective, competative antagonist of alpha 1 adrenoceptors. Causes vasodilation and used as anti-hypertensive
describe what atenolol is and what it does.
Selective, competative antagonist of beta 1. Therefore will decrease HR and so used as anti-anginal and anti-hypertensive agent.
Describe what salbutamol is and used for.
Selective agonist for beta 2 adrenoceptor. Used as a bronchodilator in asthma as will increase the relaxation action of the sympathetic adrenoceptor
describe what atropine is and what it does.
Competitive antagonist of muscarinic ACh receptors, blocks the parasympathetic division of ANS. So is used to reverse bradycardia post MI
