principles pharmacology Flashcards
paracrine signals
produces by cell, targets nearby cells
what are autocrine signals
cell to its own receptors
endocrine signals
targets specific cells far away from source (hormones)
hydrophobic ligands
cannot freely stay in ECM, brought into cells via carrier proteins
hydrophilic ligands
signals move freely through ECM, bind to surface receptors on cell
what are the stages of cell signalling
reception - recetor binds to ligand
transduction - receptor protein changes, activates intracellular molecules
cell response
what are the 3 classes of signalling pathways
- G-protein coupled receptors
- enzyme coupled receptors
- ion channel receptors
describe ligand-gated ion channels
- response within milliseconds
Steps
- Ligand binds to the receptor, channel opens
- Ions (Ca2+, Na+, K+) flow through passively
- Triggers signalling pathway
ex
- Nicontinic acetylcholine receptors
describe G-protein coupled receptors
- response happens in seconds
signal travels far due to signal amplification
describe the steps for turning a G-protein coupled receptor on
- Agonist (ligand) activates G-coupled receptor
- ⍺ subunit leaves G-protein
- GDP exchanged for GTP (guanine nucleotide exchange)
- Triggers other proteins in signaling pathway
describe the steps for turning a G-protein coupled receptor off
- ⍺ subunit hydrolyses GTP → GDP
- disactivating G-protein
- ⍺ subunit recombines with β𝛾 subunit
example of G-protein coupled receptors
- Adrenoceptors – bound and activated by the neurotransmitters/hormones adrenaline and noradrenaline
- Adrenalinebinding tob2-adrenoreceptors→ Causes bronchodilation
describe enzyme coupled receptors
- Response occurs in hours
- Single pass transmembrane proteins
- multiple pathways activated
what are the functions of the autonomic nervous system
Mediates output from whole body except skeletal muscle, regulated by external and internal sensory input, via reflexes
- maintained homeostasis through negative feedback loop
sympathetic transmitter for preganglionic neurones and postganglionic neurones
- acetylcholine (ACh)
- noradrenaline (NA)
parasympathetic transmitter for both
acetylcholine (ACh)
β1: Gs stimulation of adenylyl cyclase →
inc HR and force of contraction
β2: Gs stimulation of adenylyl cyclase →
bronchodilation
M1: Gq (stimulation of phospholipase C) →
inc stomach acid secretion
M2: Gi (inhibition of adenyl cyclase; opening of K+ channels, closure of Ca2+ channels) →
decreased HR
M3: Gq (stimulation of phospholipase C) →
bronchoconstriction
what does action potential allow
signalling over long distances
lower Ka =
greater affinity of ligand for receptor
antagonist
drug that reduces or inhibits the actions of an agonist by binding to the same receptor
potency
amount of drug required to produce a desired effect
efficacy
maximum response achievable from drug
EC50
concentration of drug where 50% of effect is produced
smaller EC50 =
more potent
partial agonist
response is sub-maximal, even when all receptors occupied
if both the agonist and partial agonist have similar affinities which one has the greater efficacy
the full agonist
describe reversible competitive antagonist
antagonist competes with agonist for same binding site on receptor
- inhibition can be overcome with increased ligand concentration
what is the pKa
pH at which 50% of drug is ionised and 50% is unionised
lower pKa =
stronger acid
weak bases are absorbed better in
acidic environments
weak acids are absorbed better in
alkaline environments
low Vd =
drugs retained in vascular compartments - mostly in plasma
high Vd
drugs retained in non-vascular compartments – adipose, muscle etc.
Vd calculation
Vd = Dose / [drug] x plasma
what Is albumin
most abundant plasma protein, high affinity for hydrophobic drugs
where do phase I and II of drug metabolism take place
the liver
what is the equation for bioavailability (F)
quantity of drug reaching systemic circulation (AUC)
divided by
quantity of drug administered (DOSE)
what is phase I metabolism
change in the drug by oxidation, reduction or hydrolysis
what is phase II metabolism
involves combination of the drug with polar molecules to form a water-soluble metabolite - conjugate
name a drug which goes straight to phase II metabolism
Codeine
what is drug elimination accomplished by
renal filtration of blood plasma
what is clearance
volume of plasma cleared of drug per unit time
clearance equation
clearance = rate of drug elimination / [Drug] plasma
what is Vmax
max. rate of the drug elimination
what is Km
half of max. rate of elimination
t1/2 =
0.693 x Vd / CL
how many half lives are required to reach steady state
5
necrosis =
cell death
internal necrosis
ischemia
when does coagulative necrosis occur
when the tissue becomes hypoxic
Liquefactive necrosis
Occurs when hydrolytic enzymes completely digest dead cells leaving behind a creamy substance (pus) and dead cells
- brain injury
caseous necrosis
Occurs when the dead cells disintegrate but are not fully digested
- cheesy
TB
