Pharmacology Flashcards
what is pharmacodynamics?
what a drug does to the body
what is pharmacokinetics?
what the body does to a drug
What do agonists do?
bind to a receptor to produce a cellular response
what do agonists possess?
affinity and efficacy
what do antagonists do?
bind to receptors and block activation by agonists
what do antagonists possess?
affinity
four processes that occur in drug disposition?
absorption
distribution
metabolism
excretion
what form of drug readily diffuses?
unionised forms
what is oral availability?
the fraction of drug that reaches the systemic circulation after oral ingestion
what is systemic availability?
this is the fraction that reaches the systemic circulation after absorption (IV drugs have 100% systemic availability)
factors affecting drug absorption?
solubility
chemical stability
lipid to water partition coefficient
degree of ionisation
factors affecting GI absorption?
GI motility pH blood flow physicochemical interactions transporters present in membranes
when is Css (steady state concentration) reached?
after 5 half lives
what is steady state?
when drug administration is equal to drug elimination
what is a loading dose and when is it given?
a loading dose is an initial higher dose of a drug, given at the start of treatment so it decreases the time taken to reach steady state
what three reaction types occur in Phase 1 drug metabolism?
oxidation
reduction
hydrolysis
what does Phase 1 drug metabolism aim to do?
make the drug more polar and add a chemically reactive group, so conjugation (phase 2) can occur
what family of proteins mediate Phase 1 drug metabolism?
cytochrome P450 Monooxygenases
what happens in the monooxygenase P450 cycle?
drug (RH) enters and joins with P450
drug combines with one O of Oxygen, to produce ROH
other oxygen combines with H+ to form H20
what does Phase 2 drug metabolism aim to do ?
add an endogenous product, which is called conjugation, and inactivate the drug
what is glucoronidation?
transfer of glucoronic acid to the substrate
what drugs can be excreted by glomerular filtration?
unbound drugs
what facilitates tubular secretion?
organic anion transporter (against electrochemical)
organic cation transporter (with electrochem)
in tubular secretion, what influences drug excretion?
concentration (pH) of urine
what pH of urine favours excretion of acids/bases?
alkaline favours excretion of acids
acidic favours excretion of bases
direction of Na concentration and electrochemical gradient
IN
IN
direction of K concentration and electrochemical gradient
OUT
IN
what is the equilibrium potential for EK?
- 100mV
what is the equilibrium potential for ENa?
+60mV
positive feedback is shown by what channels?
sodium
negative feedback is shown by what channels?
potassium
what causes the refractory period?
Na+ channels enter a non conducting state when maintained depolarisation occurs
where is sympathetic outflow from and what is it called?
T1-L2, thoracolumbar
where is parasympathetic outflow from and what is it called?
CN 3, 7, 9 and 10
craniosacral
in sympathetic, what are the two neurotransmitters and the receptors they work on?
acetylcholine (cholinergic)
Noradrenaline (adrenergic)
in parasympathetic, what is the neurotransmitters and the receptors it works on?
acetylcholine (cholinergic)
what type of channels are activated in effector cells, in the sympathetic? what activates them?
g protein coupled adrenoreceptors, noradrenaline
what type of channels are activated in effector cells, in the parasympathetic? what activates them?
g protein coupled muscarinic acetylcholine receptors, acetylcholine
in g protein coupled receptors, what does the receptor consist of?
7 transmembrane spans, joined by 3 extracellular and 3 intracellular loops
in g protein coupled receptors, what does the g protein consist of?
alpha, beta and gamma subunits
a guanine nucleotide binding site for GTP/GDP
how do g protein coupled receptors work?
- alpha subunit binds to GDP
- agonist binds to the receptor, causing the g protein to also
- GDP->GTP in the guanine nucleotide binding subunit
- g protein dissociated to alpha and beta/gamma subunits, with the alpha combining to the effector (with GTP attached)
- this modifies the effector
TO INACTIVATE..
- alpha subunit catalyses GTP->GDP +Pi, so the signal is turned off
- g protein detaches from the effector and reassembles
steps of cholinergic transmission and degradation
- choline is uptaken
- ACh is synthesised, via CAT, which is then stored in vesicles
- depolarisation via an AP occurs
- Ca2+ influx, causing release of ACh
- ACh acts on receptors to cause a cellular response
degradation of ACh
- ACh -> choline and acetate by AChE
- choline is re uptaken and reused
what receptors does ACh act on?
nicotinic ACh receptors (ligand gated ion channels)
g protein couples muscarinic ACh receptors
3 types of g protein couples muscarinic ACh receptors and their effects
M1 Gq - stimulation of phospholipase C, causes increased acid secretion in the stomach
M2 Gi - inhibits adenylyl cyclase, decreases HR
M3 Gq - stimulation of phospholipase C, relaxes vascular smooth muscle and increases saliva production
steps of noradrenergic transmission and degradation
- synthesis of NA and storage in vesicles
- depolarisation via an AP
- Ca2+ influx, which causes release of NA
- activation of G protein couples adrenoreceptors
- reuptake of NA
in presynaptic, what happens to NA?
U1 uptakes it
metabolised to MAO
in postsynaptic, what happens to NA?
U2 uptakes it
metabolised to COMT
4 types of G protein coupled adrenoreceptors and their effects
beta 1 Gs - stimulates adenylyl cyclase, increases HR and force
beta 2 Gs - stimulates adenylyl cyclase, relaxes bronchial and vascular smooth muscle
alpha 1 Gq - stimulates phospholipase C, contracts vascular smooth muscle
alpha 2 Gi - inhibits adenylyl cyclase, inhibits NA release
what do presynaptic autoreceptors do?
act as a negative feedback system
increased neurotransmitter in the synaptic cleft is sensed by autoreceptors
they halt Ca2+ influx into the cell
effects of agonist and antagonist on function of presynaptic autoreceptors?
agonist decrease release by autoreceptor (more neurotransmitter)
antagonist increase release by autoreceptor (less neurotransmitter)
