Autonomic Drugs Flashcards
Nicotinic ACh receptors - type of receptor?
Ligand-gated Na/K channel
What are the two subtypes of nicotinic ACh receptors and where are they found?
Nn - autonomic ganglia, adrenal medulla
Nm - NMJ of skeletal muscle
Muscarinic ACh - type of receptor?
G-protein-coupled receptors; usually act through 2nd messengers
Where are muscarinic ACh receptors found?
Smooth muscle, gland cells, nerve terminals, cardiac muscle, sweat glands (cholinergic sympathetic)
What receptors do NE bind to? Where are these found?
A1, A2, B1 (smooth muscle, gland cells, nerve terminals, cardiac muscle, vessels)
What receptors does EPI bind to? Where are these found?
A1, A2, B1, B2 (cardiac muscle, vessels)
List the receptors + the G protein class associated with it. (Use the pneumonic)
“after QISSeS, you get a QIQ out of SIQ SQS (super qinky sex)”
A1, A2, B1, B2, B3
M1, M2, M3
D1, D2, H1
H2, V1, V2
What are the effects of binding to Gq receptors?
Activates PLC
Lipids -> PIP2; PLC converts this to DAG and IP3
DAG activates PKC; IP3 increases intracellular calcium, which leads to smooth muscle contraction (and further activates PKC)
What are the effects of binding to Gs receptors? Gi?
Gs activates AC, which converts ATP to cAMP -> PKA -> increased intracellular calcium in the heart and activation of MLCK in smooth muscle; Gi inhibits this
Function of A1
Increases contraction of: vascular smooth muscle, pupillary dilator (mydriasis), intestinal/bladder sphincters
Function of A2
Decreases sympathetic outflow, insulin release, lipolysis, aqueous humor production
Increases platelet aggregation
Function of B1
Increased HR, contractility, renin release, lipolysis
Function of B2
Dilation of vascular smooth muscle, bronchi, ciliary muscle (relaxation)
Increases lipolysis, insulin release, aqueous humor production
Decreases uterine tone
Function of B3
Increases lipolysis, thermogenesis in skeletal muscle, bladder relaxation
Function of M1
Mediates higher cognitive function
Stimulates enteric nervous sytem
Function of M2
Decreases HR/atrial contractility
Function of M3
Increases exocrine gland secretions, peristalsis, bladder contraction, bronchoconstriction, pupillary sphincter contraction (miosis), ciliary muscle contraction (accommodation), insulin release
Function of D1
Relax renal vascular smooth muscle
Activate direct striatum pathway
Function of D2
Modulates transmitter release; inhibits indirect striatum pathway
Function of H1
Increase nasal/bronchial mucus production, vascular permeability, contraction of bronchioles, pruritis, pain
Function of H2
Increase gastric acid secretion
Function of V1
Increase vascular smooth muscle contraction
Function of V2
Increase water permeability and reabsorption in collecting tubules of kidneys
List the 4 cholinomimetics - direct agonists.
- Bethanechol
- Carbachol
- Methacholine
- Pilocarpine
List the 5 (+3) cholinomimetics - indirect agonists (anticholinesterase)
- Galantamine, donepezil, rivastigmine, tacrine
- Edrophonium
- Neostigmine
- Physostigmine
- Pyridostigmine
What is the general AE of any cholinomimetic?
May exacerbate COPD, asthma, peptid ulcers
MOA and indications of bethanechol
Activates bowel and bladder smooth muscle
Postoperative or neurogenic ileus, urinary retention
MOA and indication of methacholine
Bronchoconstriction via stimulation of muscarinic receptors; inhaled to diagnose asthma (challenge test)
Edrophonium- indication?
Diagnose myasthenia gravis (historically)
Neostigmine - indication?
Postoperative/neurogenic ileus
Urinary retention
Myasthenic gravis
Reversal of NMJ blockade postoperatively
Physostigmine - indication?
Anticholinergic toxicity antidote (ie, atropine overdose)?
Pyridostigmine - indication?
Myasthenia gravis (long-acting)
List the muscarinic antagonists.
- Atropine (homatropine, tropicamide)
- Benztropine, trihexyphenidyl
- Glycopyrrolate
- Hyoscyamine/dicyclomine
- Ipratropium/tiotropium
- Oxybutynin, solifenacin/tolterodine
- Scoplamine
Which muscarinic antagonists decrease ACh activity in the CNS primarily?
- Benztropine/trihexyphenidyl
2. Scopolamine
Which muscarinic antagonists decrease ACh activity in the GI system?
- Glycopyrrolate (and respiratory)
2. Hyoscyamine, dicyclomine
Which muscarinic antagonists decrease ACh activity in the respiratory system?
- Glycopyrrolate
2. Ipratropium/tiotropium
Which muscarinic antagonists decrease ACh activity in the GU system?
Oxybutynin, solifenacin, tolterodine
Indications for atropine?
Cholinesterase inhibitor poisoning (too much ACh), bradycardia, ophthalmic uses to produce mydriasis and cycloplegia
What are the key AE of atropine?
Hot as a hare, dry as a bone, red as a beet, blind as a bat, mad as a hatter (increased body temperature, decreased sweating, rapid pulse, dry mouth, dry flushed skin, cycloplegia (paralysis of ciliary muscle), constipation, disorientation
What specific AE can atropine have on the elderly, men with prostatic hyperplasia, and hyperthermia in infants?
Elderly - acute angle-closure glaucoma (mydriasis)
Men - prostatic hyperplasia
Infants - hyperthermia
Indications - glycopyrrolate?
Parenteral - reduce airway secretions pre-op
Oral - drooling, peptic ulcer disease
Indication - oxybutynin, solifenacin, tolterodine
Reduce bladder spasms and urge incontinence by inhibiting M3 receptors on smooth muscle in the bladder (decreases involuntary detrusor contraction)
Indication - scopolamine?
Motion sickness
Sympathomimetic effect of albuterol/salmeterol?
B2 > B1
Sympathomimetic effect of dobutamine?
B1 > B2, A1, A2
Inotropic > chronotropic (contractility increases more than HR)
Indication of dobutamine?
Heart failure, cardiac stress testing
Sympathomimetic effect of dopamine (low dose vs. high dose)?
D1 = D2 > B1, B2 > A1, A2
Low - inotropic and chronotropic
High - vasoconstriction
Indications of dopamine?
Unstable bradycardia, HF, shock
Sympathomimetic effect of epinephrine?
B1, B2 > A1, A2
Which receptor effect predominates at a higher dose of EPI?
Alpha
Indications of epinephrine?
Anaphylaxis, asthma, open-angle glaucoma
Sympathomimetic effect of fenoldopam?
D1
Sympathomimetic (direct) effect of isoproterenol?
B1 = B2 (non-selective)
Indication of isoproterenol?
Electrophysiologic evaluation of tachyarrhythmias (caution, as it can worsen ischemia)
Sympathomimetic (direct) effectof midodrine?
A1 agonist
Indications of midodrine?
Autonomic insufficiency Postural hypotension (may exacerbate supine HTN)
Sympathomimetic (direct) effect of mirabegron?
B3
Indication of mirabegron?
Urge incontinence
Sympathomimetic (direct) effect of NE?
A1 > A2 > B1
Indications of NE?
Hypotension, septic shock
Sympathomimetic (direct) effect of phenylephrine?
A1 > A2
List the 3 indirect sympathomimetics.
- Amphetamine
- Cocaine
- Ephedrine
MOA - amphetamine; what other sympathomimetic has the same MOA?
Uses the NE transporter to enter the presynaptic terminal, uses VMAT to enter vesicles, which displaces NE, increasing the [NE] in the terminal, leading to transporter reversal; ultimately increases release and inhibits reuptake
Same as ephedrine
Three indications for amphetamines?
ADHD
Narcolepsy
Obesity
MOA - cocaine?
Inhibits reuptake of NE
What is strongly contraindicated if cocaine intoxication is suspected and why?
Beta-blockers - can lead to unopposed A1 activation and extreme hypertension
Indications - ephedrine?
Nasal decongestion (pseudoephedrine)
Urinary incontinence
Hypotension
MOA - clonidine, guanfacine, alpha-methyldopa
A2 agonist (sympatholytic)
Indications - clonidine, guanfacine?
Hypertensive urgency (limited situations) ADHD, Tourette syndrome
Indication - alpha-methyldopa?
Hypertension in pregnancy
Major AE - clonidine, guanfacine?
Rebound hypertension with abrupt cessation
CNS depression, bradycardia, hypotension, respiratory depression, miosis
What are the two non-selective alpha antagonists? Which is irreversible?
Phenoxybenzamine - irreversible
Phentolamine - reversible
Indication - phenoxybenzamine?
Pre-operatively in pheochromocytoma to prevent catecholamine (hypertensive) crisis
Indication - phentolamine?
Given to patients on MAOIs who eat tyramine containing food
AE - non-selective alpha blockers?
Orthostatic hypotension, reflex tachycardia
List the 4 alpha-1-selective blockers.
Prazosin
Terazosin
Doxazosin
Tamsulosin
What are the 3 indications of alpha-1-selective blockers?
Urinary symptoms of BPH
PTSD (prazosin)
HTN (except tamsulosin)
What AE may occur with the first dose of an A1 selective blocker?
Orthostatic hypotension
What is the one A2 blocker?
Mirtazapine
List the 6 beta blockers with B1 selectivity (B1>B2).
- Acebutolol
- Atenolol
- Betaxolol
- Bisoprolol
- Esmolol
- Metoprolol
(A-M)
List the major indications of beta-blockers.
- Angina pectoris
- MI
- SV tachycardia
- HTN
- Glaucoma
- Variceal bleeding
- Decrease mortality of heart failure (some)
How do beta-blockers address angina pectoris?
Decrease HR and contractility, resulting in decreased O2 consumption
What is the MOA of beta-blockers in treating HTN?
Decreases CO, decreases renin secretion via blockade on JGA cells
How do beta-blockers treat variceal bleeding?
Decrease hepatic venous pressure gradient and portal hypertension
Which three beta-blockers decrease mortality of heart failure?
Bisoprolol
Esmolol
Metoprolol
List the non-selective beta blockers (4).
- Nadolol
- Pindolol
- Propranolol
- Timolol
(N-Z)
What is the unique indication/mechanism of propranolol?
Inhibits 5’ monodeiodinase in peripheral tissue, reducing the conversion of T4 to T3; treats thyroid storm
List the two non-selective alpha and beta blockers.
Carvedilol
Labetalol
List the two partial beta agonists.
Acebutolol
Pindolol
List the B1 blocker/B3 agonist.
Nebivolol