PHAR3911 - Sympathetic and parasympathetic NS, beta receptors, and beta-blockers

differentiate between the sympathetic and parasympathetic nervous system

symp: stimulates activity to prepare body for action (fight or flight)

para: promotes relaxation and energy conservation (restore homeostasis)

what is the role of epinephrine in regulation of the sympathetic nervous system?

catecholamine

hormone secreted by adrenal gland

stimulates sympathetic nervous system to induce action

what is the role of norepinephrine in regulation of the sympathetic nervous system?

catecholamine

transmitter release by sympathetic nerve terminals

dominates the CNS

released by Ca2+ from storage

what is the mechanism of biosynthesis of epinephrine?

in adrenergic neurons (adrenal medulla)

Norepinephrine -> epinephrine

what is the mechanism of biosynthesis of norepinephrine?

L-tyrosine -> L-Dopa -> Dopamine -storage vesicle-> norepinephrine

what is the mechanism of norepinephrine breakdown?

termination of neurotransmission

MAO to DOPGAL or COMT to NMEP

then alternate to degrade more

what does targeting MAO and COMT increase and what condition does it treat?

MAO: dopamine, serotonin, norepinephrine

COMT: dopamine

treat Parkinson's

what receptors are involved in the adrenergic synapse and their role?

a1 adrenergic: activate phospholipase C

a2 adrenergic: inhibit adenylate cyclase + cAMP

β-adrenergic: activate adenylate cyclase + cAMP

what is the relationship between a2 adrenoreceptors and beta receptors?

a2 and b-adrenergic have opposite coupling so alternate effects

a2 agonist same effect as b-antagonist

what is the action of a1, a2, b1, b2, b3 adrenergic receptors?

a1: vasoconstriction, pupil dilation

a2: inhibit norepinephrine release

b1: increase HR

b2: bronchodilation

b3: lipolysis

what receptors are found in the parasympathetic nervous system and their role?

ACh neurotransmitter and cholinergic receptors

Nicotinic receptors: ligand-gated channels stimulated by ACh (para and symp)

Muscarinic receptors: m1 (CNS, gastric) m2 (heart), m3 (gland secretion), m4/5 (brain)

where are beta receptors found in the body?

b1: heart b2: lungs b3: adipose tissue

what are the key structural features of alpha adrenoreceptor agonists?

small R' increases half-life

small N-group increase activity

flexible R'' group

what are the key structural features of beta adrenoreceptor agonists?

4' OH or 3'+5' OH

large N-group substituents

what are examples of beta-adrenoreceptor agonists?

norepinephrine

dopamine

dobutamine

how does structure determine the selectivity of bronchodilators + examples?

long molecule -> sticks in lungs longer -> increases duration of action -> less likely to leave lung and cause SE

examples: formoterol and salmeterol

what are the cardiovascular effects of beta blockers?

reduce HR, lower BP, anti-arrhythmic

what are the respiratory effects of beta blockers?

bronchoconstriction from non-selective b-blockers

caution in asthma and COPD

what are the metabolic effects of beta blockers?

mask hypoglycemia

caution in diabetic patients

what are the CNS effects of beta blockers?

cross BBB

caution in migraines and mental health

differentiate between non-selective, selective and mixed blockers

non-selective bind to b1 and b2 receptors

selective bind to b1 >> b2

mixed blockers bind to b1, b2, a2

what is the structural significance of non-selective beta blockers and examples?

structural resemble norepinephrine and epinephrine

examples: propranolol, sotalol, timolol

Examples of selective beta blockers?

atenolol

metoprolol

examples of mixed beta blockers?

carvedilol

labetalol