Autonomic Pharmacology Flashcards
Muscarinic ACh Receptors
Main antigen is acetylcholine
Parasympathetic post ganglionic neurons
M1, M3, M5: IP3 pathway > increase Ca2+ > SM contraction
M2, M4: inhibit adenyly cyclase and reduce cAMP
Adrenergic Receptors
Receptor antigen is norepinephrine or epinephrine (adrenaline: synthesized in adrenal medulla via enzyme phenethanolamine N-methyltransferase)
Sympathetic nervous system
Nicotinic ACh Receptors
Preganglionic neurons of parasympathetics, somatic muscle neuromuscular junction
Activation via acetylcholine (release inhibited by botulinum toxin (Botox)
Muscarinic activation
- Slows cardiovascular function
- Increases secretions
- increases intestinal activity
Cotinine
Main metabolite of nicotine in body
Used for laboratory testing to see if someone smokes
Varenicline
partial agonist of a4B2 neuronal nicotinic receptors
Used: treat nicotine dependence and reduces the cravings
Mivacurium
nicotinic receptor antagonist (competitive)
Use: neuromuscular blocker = paralyzer
Used in surgeries
Pancuronium
nicotinic receptor antagonist (competitive)
Use: neuromuscular blocker = paralyzer
Used in surgeries
Vecuronium
nicotinic receptor antagonist (competitive)
Use: neuromuscular blocker = paralyzer
Used in surgeries
Three common organophosphate AchE inhibitors in industry
pesticides, parathion, chloropyrifos, malathion (insecticide) and nerve gas (sarin, tabun, VX)
Initial binding to AChE can be reversed but after a few hours, phosphorylated enzyme ages (covalent bond formed) > irreversible
Neostigmine
AchE inhibitor
Reversal of non-depolarizing neuromuscular blockers
Use: Treatment of myasthenia gravis
SE: Poisoning > activation of both muscarinic and nicotinic receptors > fatal
Pyridostigmine
AchE inhibitor
Use: main treatment for myasthenia gravis
Donepezil (Aricept)
AChE Inhibitor
Uses: Palliative treatment of Alzheimer’s disease
Galantamine (Razadyne)
AChE Inhibitor
Uses: Palliative treatment of Alzheimer’s disease
Rivastigmine (Exelon)
AChE Inhibitor
Uses: Palliative treatment of Alzheimer’s disease
Pralidoxime (2-PAM)
Prevents irreversible binding of organophosphate AChE inhibitors to AChE if given prior to a few hours
Toxicity effects of acetylcholinesterase inhibitors
DUMBELSS: diarrhea, urination, miosis (contraction of sphincter in eye), bronchoconstrictoin, excitation of muscle (most life threatening) and CNS, lacrimation, salivation, sweating
-Overload of skeletal nicotinin Ach receptors > muscle paralysis > death
Atropine (belladonna)
Muscarinic antagonist: tertiary amine that can cross BBB (can cause sedation, behavioral excitation and hallucinations)
Uses: Dilate pupils, treat severe bradycardia
Can be given to help relieve AChE inhibitor poisoning to block muscarinic effects (diarrhea)
Bethanechol
muscarinic agonist (agonist for muscarinic receptors not often used) Use: treatment of urinary retention
Betanechol, carbachol, pilocarpine
Muscarinic agonist
Contract pupillary constrictor > allow aqueous humor to drain out of eye
Uses: Acute glaucoma attack (outflow of aqueous humor into canal of Schlemm is blocked)
SE of anti-muscarinic drugs
Decreased secretions (dry mouth), mydriasis (dilated pupil), cycloplegia (decreased accommodation), hyperthermia, tachycardia, sedation (BBB), bronchodilation, urinary retention, constipatoin, behavior excitation and hallucinations (BBB)
Scopolamine
Muscarinic antagonist (can cross BBB) Use: motion sickness due to sedative and amnesiac effects
Glycopyrrolate
Muscarinic antagonist
Use: Dry secretions to prevent aspirations of fluids
Benztropine
Muscarinic antagonist
Use: Parkinsonism (including drug induced)
Tropicamide
Muscarinic antagonist
Use: dilate pupils (shorter acting than atropine), more effective in clinical ophthalmology visit
Ipratropium
Muscarinic antagonist
Use: treat asthma and COPD
Combined with albuterol (B-agonist) as an inhaler
Tolerodine
Muscarinic antagonist
Use: treat bladder spasm and urinary incontinenct
Solifenacin
Muscarinic antagonist
Use: treat bladder spasm and urinary incontinenct
Tiotropium (Spiriva)
Muscarinic antagonist
Use: treat COPD
Capsuled form that is pierced > aerosolized and inhaled
Treatment of urinary incontinence and overactive bladder
Tolterodine, oxybuynin, solifenacin
Muscarinic antagonists
Amitriptyline (Elavil)
Tricylic antidepressant with antimuscarinic properties
Overdose > fatal due to antimuscarinic effects (cardiac arythmias)
How do you treat anti-muscarinic overdose
AChE inhibitors
How do you treat AChE overdose
Atropine
alpa Adrenergic receptors
a1: increase IP3, diacylglycerol and intraellular Ca+ > SM contraction (determinant of systemic BP)
a2: inhibit adenylyl cyclase > decreased calcium influx > decreased release of norepinephrine (located at presynaptic terminals > inhibit neurotransmitter release > reduce central adrenergic effects)
Beta adrenergic receptors
All activate adenylyl cyclase + increase intracellular cAMP
B1: expressed in heart > increase HR
B2:dilate/relax SM>vasodilation, bronchodilation and uterine relaxtation
B3: lipolysis of adipose tissue + relaxation of urinary bladder
alpha1-adrenergic receptor activation
mydriasis (pupil dilation), vasoconstriction, contraction of bladder trigone + sphincter (urinary retention), SM contraction of prostate
Phenylephrine
alpha1-adrenergic receptor agonist
Use: treat nasal congestion (constrict vessels), IV > raise BP in acute setting
Clonidine
alpha2-agonist
UsE: treat hypertension > reduce central norepinephrine release
SE: rebound hypertension if stopped abruptly
Prazosin
alpha1-adrenergic receptor antagonist (specific)
Use: treatment of hypertension via vasodilation
Terazosin
alpha1-adrenergic receptor antagonist (specific)
Use: treatment of benign prostatic hypertrophy > relaxes prostate capsular SM
Phenoxybenzamine
Non-specific (a1+a2) alpha-adrenergic antagonist
Use: manage pheochromocytoma (tumor that secretes catecholamines)
Phentolamine
Non-specific (a1+a2) alpha-adrenergic antagonist
Use: manage pheochromocytoma (tumor that secretes catecholamines)
B1-adrenergic receptor activation
Increased heart rate (SA node), increased conduction velocity (AV node), increased force of contraction (atrial + ventricular muscle)
Dobutamine
B-1 adrenergic receptor agonist
Use: treat cardiogenic shock and heart failure
B-blockers (B-1adrenergic receptor antagonist) action
Treat angina, hypertension, arrhythmias
B2-adrenergic receptor effects
vasodilation (all vessels), decreased pre-load, muscle tremor, glycogenolysis, uterine relaxation, bronchodilation
Albuterol
B2-adrenergic receptor agonist
Use: shorta acting inhaler for acute asthma attacks
SE: also activates B1 > tachycardia
Salmeterol
B2-adrenergic receptor agonist (selective)
Use: long acting (not used for asthma attacks) for chronic asthma
SE: increased risk of asthma death
Formoterol
B2-adrenergic receptor agonist (selective)
Use: long acting (not used for asthma attacks) for chronic asthma
SE: increased risk of asthma death
Bambuterol
B2-adrenergic receptor agonist (selective)
Use: long acting (not used for asthma attacks) for chronic asthma
SE: increased risk of asthma death
Terbutaline
B2- adrenergic receptor agonist
Use: no longer (black box) fast-acting bronchodilator and also use in uterine relaxation to stop premature labor
Isoproterenol
non-selective B-adrenergic agonist
Use: treatment of bradycardia (effects blocked by B-blockers)
Mechanism: B2 effect = lower vascular resistance B1 effect = increase HR and contractility
Mirabegron
B3-adrenergic receptor agonist
Use: treatment of overactive bladder
Relax urinary bladder SM + enhance lipolysis
Norepinephrine
a+B adrenergic receptor agonist (B1 more than B2)
Use: Increase BP
Effects: Increase SBP, DBP > vagal response > slow HR, increase peripheral vascular resistance
Epinephrine
a+B-adrenergic receptor agonist
Use: cardiac arrest, anaphylaxis, severe asthma (results in increase SBP, decrease DBP = increase MAP, accelerated HR)
Effects: vasoconstriction of vascular beds (precapillary vessels, a1), increase HR (B1), increase contraction (B1), bronchodilation (B2), vasodilation of large vessels in skeletal muscle (B2)
