adrenergic pharmacology Flashcards
how sensitive are adrenoceptors to adrenaline, noradrenaline and isoprenaline
alpha receptors: adrenaline>noradrenaline»> isoprenaline
beta receptors: isoprenaline> adrenaline»> noradrenaline
how do beta receptors differ
beta 1 is excitatory and innervated (synaptic activation)
beta 2 is inhibitory (usually) non innervated (responds to circulating adrenaline)
what are main cotransmitters in sympathetic system
ATP, others such as NPY
what sympathetic innervation is mediated via Ach
innervation of adrenal medulla via preganglionic neurones, termed a modified ganglion
innervation of sweat glands in skin on muscarinic receptors
what is the name of the group that contains adrenalines and dopamine
catecholamines
where are beta 1 receptors found and what are the physiological effects of stimulating them
in the heart, juxtaglomerular aparatus and adipose tissue,
heart: increase in rate and contractility
juxtaglomerular apparatus: release of renin
adipose tissue: lipolysis
where are beta 2 receptors found and what is effect of stimulating them
bronchial smooth muscle, uterine smooth muscle and skeletal muscle vasculature,
relaxation of smooth muscle
in liver and muscle:
in liver: breakdown of glycogen to glucose via acitvation of protein kinase A
muscle: mediates breakdown of glycogen to lactic acid (may cause hyperlactic academia), also causes increased activation of sodium/potassium ATPase pump, causes blood potassium to drop
what type of receptors are adrenoreceptors
all GPCRs
alpha 1 coupled to phospholipase C, so causes increase in IP3 and DAG, Gq
alpha 2 are Go, so inhibit adenylate cyclase
beta receptors activate adenylate cyclase and protein phosphorylation via protein kinase A, both are Gs
what effect do alpha 1 receptors have on liver
cause release of potassium from liver to blood
where are alpha 2 receptors used post junctionally
(almost always autoreceptors for negative feedback)
post junctionally: cause platelet aggregation
what receptors are adrenaline, noradrenaline and isoprenaline selective for
adrenaline: all adrenoreceptors
noradrenaline: all except beta 2
isoprenaline: beta receptors
what are clinical uses of adrenaline
treatment of:
anaphylactic shock
glaucoma: acts on alpha 2 receptors, causes vasoconstriction of afferent arterioles, reduces aqueous humour production, so reduces pressure in the eye, also act on veins which drains the canal of schlemm which aids in absorption of the aqeuous humour
cardiac arrest
prolongation of action of local anaesthetics (by vasoconstriction)
what action does clonidine have, how is it used therapeutically
alpha 2 agonist
used as antihypertensive drug
what are therapeutic effects of alpha 1 agonists
cause vasoconstriction
phenylepherine used as nasal decongestant
used to prolonged local anaesthetic action
what is dobutamine
a beta 1 agonist, used for treatment of cardiogenic shock
how are beta 2 selective agonists used therapeutically?
what are unwanted effects
salbutamol: used in asthma to produce bronchodilation, in premature labour to relax uterus
unwanted effects: hypokalaemia, tremor, vasodilation leads to fall in blood pressure causing reflex tachycardia
what effect do ergot alkaloids have
they are alpha adrenoceptor agonists
derivatives of LSD
are also agonists of 5HT and dopamine receptors
used to treat migraine and postpartum haemorrhage
name classic antagonists of adrenoceptors and which ones they work on
phentolamine: alpha 1 and alpha 2 antagonist
prazosin: alpha 1 antagonist (minor alpha 2 antagonism)
propranolol: competitive reversible antagonist for beta receptors
atenolol: beta 1 antagonist (minor beta 2 antagonism)
what action does phenoxybenzamine have
irreversible non competitive antagonist for alpha adrenoceptors
acts by forming covalent bond
this type of antagonism shows reduction in slope of log dose response curve and decrease in max response to agonist
what are physiological consequences of alpha adrenoceptor blockade
fall in blood pressure, causes sympathetic drive on beta receptors causing reflex tachycardia and sodium and water retention by renin
postural hypotension
nasal congestion
miosis (constriction of pupil)
what are therapeutic uses of alpha adrenoceptor blockade
treatment of hypertension and benign prostatic hyperplasia
what action does atenolol have
cardio selective beta 1 antagonist
what are therapeutic uses of beta antagonists
treatment of angina, hypertension, glaucoma, myocardial infarction, arrhythmias
what effect does disulfiram have
is a copper chelating agent;
prevents synthesis of NA by inhibiting dopamine beta hydroxylase, which converts dopamine to noradrenaline
giving L-DOPA increases rate of synthesis
what effect does reserpine have?
depletes vesicular storage of NA by preventing passage of catecholamines into storage vesicles
what effect does tetrabenazine have, how is it used
short acting noradrenaline and dopamine depletory, used in treatment of hyperkinetic disorders such as huntingtons
what effect does clonidine have
alpha 2 agonist, inhibits NA release, is an antihypertensive drug
what effect does guanethidine have
enters via uptake and inhibits release of NA, also blocks sodium channels
used as local anaesthetic, has tyramine like actions
what are MAO inhibitors used for
treatment of depression
phenelzine is a non selective MAO inhibitor used to treat depression
what effect does catechol-O-methyl transferase
only breaks down catechols
found in neuronal and non neuronal tissues
breaks down NA after it is broken down by MAO
what are indirect acting sympathomimetics, name one and how does it work
tyramine causes effects of nerve stimulation in absence of nerve stimulation (indirect acting sympathomimetic) by displacement of neuronal NA from cytoplasmic pool
tyramine is taken up by NET (norepinepherine transporter) into terminal
it is then taken into vesicle by vesicular monoamine transporter (VMAT), in exchange for noradrenaline which escapes into cytoplasm
some of this cytoplasmic NA is metabolised by MAO, the rest escapes by retrotransport
this process does not require calcium or exocytosis
