Lecture 10: Sympathetic Modulation Flashcards
Effects of B1 sympathetic modulation innervation on pacemaker in SA node?
B1 can increase cAMP and PKA increase Ca2+ depolarization reach threshold faster steeper
Role of protein kinase phosphorylation on 4 components
- Voltage gated calcium channel
- Sarcoplasmic reticulum
- Myosin actin crossbridge
- Ca/ATPase pump
Leads to increase heart contractility
IPE
VASODILATOR non-selective Beta agonist low affinity at Alpha receptor decrease peripheral vascular resistance increase cardiac output via B1 positive inotropic and chronotropic effect
EPI
Vasodilation and vasoconstriction
vasoconstriction of skin renal FI blood vessels via a1
low dose- dilation in skeletal muscle vasculature as B2 more sensitive than a1
high dose- epi used to treat shock, urticaria, hay fever and angioneurotic edema
adrenergic modulation on insulin
B2 increase insulin release and uptake
A2 decrease insulin release
A1 decrease GLUT4 transporters
A1 and A2 can lead to hyperglycemia
Phenylephrine (PE)
selective A1 agonist
no catecholamine transferase activation, longer half life
activate B receptor at very high doses
less potent than NE
Increase blood pressure
decongestant
mydriatic (dilation of eyes)
Clonidine and Apraclonidine
Selective a2 agonist
treats hypertension
IV - decrease BP and heart rate (bradycardia)
rebound hypertension if sudden withdrawal
adverse effect: anticholinergic: dry mouth, constipation, bradycardia, sedation
Apraclonidine- more selective and used for adjunct glaucoma (increased pressure within eyeball)
Dobutamine
selective B1 agonist
greater positive inotropic effect than chronotropic
increase contractility more than heart rate
long term increase mortality because increase O2 demand
short term treatment of heart failure
Salbutamol and Salmeterol
selective B2 agonist ASTHMA TREATMENT bronchodilators decrease TPR can be used to delay premature labor
Salmeterol (longer action)
Terbutaline only used short term for premature labour
Mirabegron
selective B3 agonist
treat overactive bladder
Cocaine and Desimipramine
increase neurotransmitter by blocking DAT and NET (block reuptake of NE or EPI)
Clorgyline
MAO-A inhibitor: anti-depressant by increasing Dopamine and Norepinephrine
Amphetamine
increase NE and DA at synaptic cleft
block Na/Cl dependent reuptake
Tyramine
no direct effect, VMAT substrate
naturally occur in fermented foods
degraded rapidly by MAO with poor oral absorption
CANT BE USED WITH MAO INHIBITORS: SUDDEN AND SEVERE INCREASE OF BLOOD PRESSURE
Ephedrine and Pseudoephedrine
bind to a1, b1 and b2
vasopressor
increase HR, bronchodilation and skeletal muscle tone
pseudoephedrine: a1 and b2 agonist
OTC decongestant
METH can be created from this
Phenoxybenzamine
non-selective A antagonist
irreversible
decrease BP, DP VR
baroreceptor can lead to tachycardia
Phentolamine
reversible and competitive inhibitors for a1
similar to phenoxybenzamine
use for short term hypertension treatment
BARORECEPTOR reflex increase heart rate, tachycardia
Prazosin
selective a1 antagonist
treat moderate hypertension
BARORECEPTOR reflex
first dose can lead to orthostatic hypotension
First Dose Phenomenon
Tamsulosin
selective a1 antagonist
treat moderate HT and benign prostatic hyperplasia (BPH)
Yohimbine
selective a2 antagonist at low dose
reversible competitive a2 antagonist at low dose
increase BP, HR, excitation, tremor, ADH release
blocks clonidine
HIGH doses: block a1 to decrease BP
binds to 5HT receptor
Propranolol
non-selective B antagonist
equal affinity for B1 and B2
treat hypertension, arrhythmia and angina
Nadolol, Pindolol and Timolol
non-selective B antagonist
Nadolol - longest acting, slow absorption
Timolol- used in glaucoma
Labetalol
antagonist at a1/b1
partial agonist at b2
decrease BP without reflex tachycardia and increase cardiac output
Carvediol
antagonist at a1 and B with higher affinity for B
reduce TPR improve LV ejection fraction
Metoprolol and Atenolol
selective b1 antagonist
less activity at b2
angina, HT and Heart failure
Reserpine
binds to VMAT
depletes NE, 5-HT and DA
chronic treatment leads to receptor upregulation (super sensitivity to catecholamines)
decrease HR CO and BP (bradycardia)
antihypertensive effect
increase parasympathetic tone
Guanethidine
competition for NAT with NE
depletion of NE
super sensitivity to NE
used in patient with severe HT
a-Methyldopa
substrate for dopa decarboxylase: FALSE TRANSMITTER
activates a2 receptors
decrease HR BP CO TPR
adverse effect: drowsiness depression parkinsons dry mouth nasal stuffness GI disturbance
hypersensitivity
a-methyltyrosine
inhibits biosynthesis of catecholamines centrally
competitive inhibitor of tyrosine hydroxylase
decrease sympathetic tone
adverse effect: sedation, severe diarrhea
excreted in urine, can lead to urine crystals
