FA.Pharm.AutonomicDrugs Flashcards
Nicotinic ACh receptors are….
Nn are found in _____.
Nm are found in _____.
Nicotinic ACh receptors are LIGAND-GATED Na+ / K+ channels;
Nn receptors are found in AUTONOMIC GANGLIA
Nm receptors are found in NEUROMUSCULAR JUNCTIONS
What is odd about the adrenal medulla and sweat glands?
Both are part of SANS, but are innvervated by cholinergic fibers.
Botulinum toxin _____ the release of _____ at all _______ terminals.
Botulinum toxin PREVENTS the release of NEUROTRANSMITTER at all CHOLINERGIC TERMINALS.
Muscarinic ACh receptors:
General mechanism
Subtypes
Muscarinic ACh receptors are G-protein–coupled receptors that act thru 2nd MESSENGERS
Subtypes: M1-M5
However, only M1, M2, and M3 are of concern
G-protein–linked 2nd messengers
Receptor:
G-protein class:
Major functions:
¶ QISS and QIQ till you’re SIQ of SQS
{ SANS } { PANS }{ Dopa } { Hista }{ ADH }
[A1] [A2] [ß1] [ß2] [M1] [M2] [M3] [D1] [D2] [H1] [H2] [V1] [V2]
[ q ] [ i ] [ s ] [ s ] [ q ] [ i ] [ q ] [ s ] [ i ] [ q ] [ s ] [ q ] [ s ]
Receptor: A1
G-protein class:
Major functions:
Receptor: A1
G-protein class: Gq
Major functions:
/\ Vascular smooth muscle contraction,
/\ pupilary dilator muscle contraction (mydriasis),
/\ intestinal and bladder sphincter muscle contraction
Receptor: A2
G-protein class:
Major functions:
A2
Gi
\/ sympathetic outflow
\/ insulin release
Receptor: ß1
G-protein class:
Major functions:
ß1
Gs
/\ Heart Rate
/\ Contractility
/\ Renin release
/\ Lipolysis
Receptor: ß2
G-protein class:
Major functions:
ß2
Gs
Vasodilation Bronchodilation /\ Heart rate /\ Contractility /\ Lipolysis /\ INSULIN RELEASE \/ uterine tone
Receptor: M1
G-protein class:
Major functions:
M1
Gq
CNS
Enteric nervous system
Receptor: M2
G-protein class:
Major functions:
M2
Gi
\/ Heart rate
\/ contractility of atria ( ø by atropine)
Receptor: M3
G-protein class:
Major functions:
M3
Gq
/\ Exocrine gland secretions (sweat, GASTRIC ACID)
/\ Gut peristalsis
/\ Bladder contraction
BronchoCONSTRICTION
/\ Pupillary sphincter muscle contraction (miosis)
Ciliary muscle contraction (accomodation)
Receptor: D1
G-protein class:
Major functions:
D1
Gs
Relaxes renal vascular smooth muscle
Receptor: D2
G-protein class:
Major functions:
D2
Gi
Modulates transmitter release, especially in the brain
Receptor: H1
G-protein class:
Major functions:
H1
Gq
/\ Nasal and bronchial mucus production
/\ Bronchiole contraction
Pruritis (itching)
Pain
Receptor: H2
G-protein class:
Major functions:
H2
Gs
/\ Gastric acid secretion
Receptor: V1
G-protein class:
Major functions:
V1
Gq
/\ Vascular smooth muscle contraction
Receptor: V2
G-protein class:
Major functions:
V2
Gs
/\ H2O permeability and reabsorption in the COLLECTING TUBULES of the kidney
¶ V …2… is found in the …2… kidneys
Gq coupled receptors and their MOA
H1, A1, V1, M1, M3
Gq lipids Receptor—>Phospholipase C—> | DAG—> Protein Kinase C
V /
PIP2
\
IP3 —> /\ [Ca++] in cell
¶ hey cutesy! HAV 1 M&M
q C
Gs and Gi coupled receptors and their MOA
Receptor
ß1,ß2,D1 \ Gs
H2,V2 \ (+) ATP /\ [Ca++] in heart
Adenylyl Cyclase—> | /
/ (-) \/ / (+)
/ Gi cAMP—>p.k.A
Receptor \ (-)
M2,A2,D2 \
Myosin light-chain kinase
¶MAD 2’s (smooth muscle)
CHOLINERGIC Neuron
Drug that blocks reuptake of Choline
Hemicholinium
CHOLINERGIC Neuron
Drug that blocks ACh from entering vesicles
Vesamicol
CHOLINERGIC Neuron
What is needed for NT release from vesicles
Ca++
CHOLINERGIC Neuron
What blocks the release of ACh from vessicles?
Botulinum toxin
CHOLINERGIC Neuron
Postsynaptically, what breaks down ACh, and what does it break it down into?
ACh-esterase
ACh —> Acetate + Choline
NORADRENERGIC Neuron
Drug that blocks Tyrosine Hydroxylase.
This drug prevents _____ from becoming ______.
Metyrosine blocks Tyrosine hydroxylase
(-)
Metyrosine ——| Tyrosine
hydroxylase
Phenylalanine——>Tyrosine———X———> DOPA
/’ \,
THB DHB
NORADRENERGIC Neuron
Drug that blocks entry of dopamine into vessicles
Reserpine
NORADRENERGIC Neuron
Drug that blocks release of NE from vessicles
Guanethidine
NORADRENERGIC Neuron
Drug that causes NE to be released from vessicles
Amphetamine
NORADRENERGIC Neuron
3 drugs that block reuptake of NE at nerve terminal
- Cocaine
- TCAs
- Amphetamine
NORADRENERGIC Neuron
Name 3 release modifying, presynaptic receptors, and whether they inhibit or stimulate neuron.
- M2 — inhibit
- Angiotensin II — stimulate
- A2 — inhibit
All are presynaptic and found in cardiac muscle (SA node)
In general, cholinomimetic agents make you…
ooze from every orifice.
Drug: Bethanechol
Class :: Subclass
Clinical applications
Action
BethaneCHOL
Cholinomimetic, direct agonist
Postoperative and neurogenic ileus
Urinary retention
Activates Bowel and Bladder smooth muscle
Resistant to AChE
¶ BETHANY, CALL me if you want to activate your Bowels and Bladder
Drug: Carbachol
Class :: Subclass
Clinical applications
Action
CarbACHOL
Cholinomimetic, direct agonist
Glaucoma
Pupillary contraction
Relieve of intraocular pressure
¶CARBon copy of acetylcholine
Drug: Pilocarpine
Class :: Subclass
Clinical applications
Action
Pilocarpine
Cholinomimetic, direct agonist
Potent stimulator of SWEAT, TEARS, SALIVA
Contracts ciliary muscle of eye (open angle)
Contract pupillary sphincter (narrow angle)
Resistant to AChE
¶You cry, drool, and sweat on your PILOw
Drug: Methacholine
Class :: Subclass
Clinical applications
Action
Methacholine
Cholinomimetic, direct agonist
Challenge test for DX of ASTHMA
Stimulates muscarinic receptors in airway when inhaled
Drug: Neostigmine
Class :: Subclass
Clinical applications
Action
Neostigmine
Cholinomimetic, INdirect agonist
Postoperative and neurogenic ileus
Urinary retention
Myasthenia gravis
Reversal of neuromuscular junction blockade (postoperative)
/\ endogenous ACh; no CNS penetration
¶ NEO CNS! = NO CNS
Drug: Pyridostigmine
Class :: Subclass
Clinical applications
Action
Pyridostigmine
Cholinomimetic, INdirect agonist
Myasthenia gravis (b/c long acting) Does NOT penetrate CNS
/\ endogenous ACh
/\ Strength
¶ Py…RID…ostigmine get …RID… of myasthenia gravis
Drug: Edrophonium
Class :: Subclass
Clinical applications
Action
Edrophonium
Cholinomimetic, INdirect agonist
DIAGNOSIS (not Tx) of myasthenia gravis (extremely short acting)
/\ endogenous ACh
¶ I called my friend EDRO on the PHONE to see if he has myasthenia gravis
Drug: Physostigmine
Class :: Subclass
Clinical applications
Action
Physostigmine
Cholinomimetic agent, INdirect agonist
Glaucoma (b/c it crosses blood-brain barrier —> CNS)
Atropine OD
/\ endogenous ACh
¶ PHY…sostigmine PHY…xes atropine OD
¶ PH-YS…ostigmine is for your eyes (Fuh-yh-eyes-ostigmine): glaucoma. Did I see an ECHO? (echothiophate also for glaucoma)
Drug: Echothiophate
Class :: Subclass
Clinical applications
Action
Echothiophate
Cholinomimetic, INdirect agonist
Glaucoma
/\ endogenous ACh
¶ Fuh-yh-eyes-ostigmine. Did i see an ECHO? Echo is also for glaucoma
Drug: Donepezil
Class :: Subclass
Clinical applications
Action
Donepizil
Cholinomimetic, INdirect agonist
Alzheimer’s Dz (only transient, NOT a cure)
/\ Endogenous ACh
¶ DONE with al…Z…heimers. donepe…Z…il
When given to susceptible px, all cholinomimetics carry risk of exacerbating…
COPD
Asthma
Peptic Ulcers
Drug: Parathion
Class :: Subclass
Clinical applications
Action
Parathion
Organophosphate, cholinesterase inhibitor POISON
Commonly used as pesticide: case will probably involve FARMER
Antidote — ATROPINE + PRALIDOXIME (regenerates active AChE, must use within a few hours before toxin “ages” [ leaves phosphate on receptor, R group is hydrolyzed — irreversable]
Causes Diarrhea, Urination, Miosis, Bronchospasm, Bradycardia, Excitation of skeletal muscle and cns, Lacrimation, Sweating, and Salivation (oozing from every oriface)
¶ DUMBBELSS
Drug: Atropine
Class
Organ system
Clinical applications
Atropine
Muscarinic antagonist
Eye————————— /\ Pupil dilation, cycloplegia Airway———————-- \/ Secretions Stomach——————— \/ Acid secretion Gut————————— \/ Motility Bladder———————- \/ Urgency in cystitis
Used to Tx BRADYcardia, and for ophthalmic applications
Produces MYDRIASIS and CYCLOPLEGIA
¶Blocks DUMBBELSS
Atropine
TOXICITY
/\ Body temp (due to \/ sweating) Rapid Pulse Dry Mouth Dry, flushed skin Cycloplegia Constipation Disorientation ¶think about Alz Dz with \/ ACh
Can cause acute ANGLE CLOSURE glaucoma in elderly,
Urinary retention in men with BPH
Hyperthermia in infants
¶ Hot as a hare…Dry as a bone…Red as a beet…blind as a bat… Mad as a hatter
Name a plant toxicity that mimics that of atropine
Jimson weed
Drug: Homatropine
Class :: Subclass
Clinical applications
Action
Homatropine
Muscarinic antagonists
Produces MYDRIASIS and CYCLOPLEGIA (paralysis of ciliary muscle –> ø accommodation)
EYE
Drug: Tropicamide
Class :: Subclass
Clinical applications
Action
TROPicamide (like aTROPine)
Muscarinic antagonist
Produces mydriasis and cycloplegia
Eye
Drug: Benztropine
Class :: Subclass
Clinical applications
Action
benzTROPINE
Muscarinic antagonist
Parkinson’s disease ¶ PARK my BENZ
CNS
Drug: Scopolamine
Class :: Subclass
Clinical applications
Action
Scopolamine
Muscarinic antagonist
Motion sickness ¶ Think about riding in a gyroSCOPE
CNS
Drug: Ipratropium
Class :: Subclass
Clinical applications
Action
Ipratropium
Muscarinic antagonist
Asthma, COPD ¶ I PRAy i can breathe again
Respiratory
Drug: Oxybutynin
Class :: Subclass
Clinical applications
Action
Oxybutynin (same use as Glycopyrrolate)
Muscarinic antagonist
Reduces urgency in mild cystitis and reduces bladder spasms
Genitourinary
¶ GLYCO PYRO’s can’t pee because they have an OXY BUTT
Drug: Glycopyrrolate
Class :: Subclass
Clinical applications
Action
Glycopyrrolate (same use as Oxybutynin)
Muscarinic antagonist
Reduce urgency in mild cystitis and reduce bladder spasms
Genitourinary
¶GLYCO PYRO’s can’t pee because they have an OXY BUTT
Drug: Methscopolamine
Class :: Subclass
Clinical applications
Action
Methscopolamine (along with Pirenzepine, and Propantheline)
Muscarinic antagonist
Peptic ulcer treatment
Gastrointestinal
[methscopolamine] [pirenzepine] ¶ use your METH SCOPE to PEER IN ZE gastric ulcer to see the PROPAN (proton) pump, and block the muscarinic receptor
Drug: Pirenzepine
Class :: Subclass
Clinical applications
Action
PirenzePINE (similar to Methscopolamine, and propantheline)
[atroPINE]
Muscarinic antagonist
Peptic ulcer treatment
Gastrointestinal
Drug: Propantheline
Class :: Subclass
Clinical applications
Action
Propantheline (along with Methscopolamine and Pirenzepine)
Muscarinic antagonist
Peptic ulcer disease
Gastrointestinal
Drug: Epinephrine
Class :: Subclass
Clinical applications
Action
Epinephrine
Direct sympathomimetic
Anaphylaxis
Glaucoma (open angle)
Asthma
Hypotension
[ a1 ][ a2 ][ ß1 ][ ß2 ][ D1 ]
+ + + + + + + + + + + + + +
Drug: Norepinephrine
Class :: Subclass
Clinical applications
Action
Norepinephrine
Direct sympathomimetic
Hypotension (but \/ renal perfusion [esp. when given w/ NSAIDS]
[ a1 ][ a2 ][ ß1 ][ ß2 ][ D1 ]
+ + + + + + + + + + +
Drug: Isoproterenol
Class :: Subclass
Clinical applications
Action
ISOproterenol
Direct sympathomimetic
AV block (rare)
Isolated ß agonist
ß1, ß2
Drug: Dopamine
Class :: Subclass
Clinical applications
Action
Dopamine
Direct sympathomimetic
Shock (renal perfusion)
Heart failure:
inotropic
chronotropid
D1 > ß > a
D1 —- low dose
ß —— medium dose
a —— high dose
Drug: Dobutamine
Class :: Subclass
Clinical applications
Action
Dobutamine
Direct sympathomimetic
Heart failure
Cardiac stress testing
Inotropic AND chronotropic
a1 a2 ß1 ß2 D
\+ + + + + + +
Drug: Phenylephrine
Class :: Subclass
Clinical applications
Action
Phenylephrine
Direct sympathomimetic
Pupilary dilation (w/o cycloplegia) Vasoconstriction Nasal decongestion
a1 a2 ß1 ß2 D1 \+ + + + + +
Drug: Metaproterenol
Class :: Subclass
Clinical applications
Action
Metaproterenol ¶ MAST
\_______________________/
Direct sympathomimetic
Acute asthma
a1 a2 ß1 ß2 D1
\+ + + + + +
Drug: Albuterol
Class :: Subclass
Clinical applications
Action
Albuterol ¶ MAST
\__________________/
Direct sympathomimetic
Acute asthma
a1 a2 ß1 ß2 D1
\+ + + + + +
Drug: Salmeterol
Class :: Subclass
Clinical applications
Action
Salmeterol ¶ MAST
\____________________/
Direct sympathomimetic
LONG TERM tx of ASTHMA
a1 a2 ß1 ß2 D1
\+ + + + + +
Drug: Terbutaline
Class :: Subclass
Clinical applications
Action
Terbutaline ¶ MAST
\______________________/
Direct sympathomimetic
\/ Premature uterine contraction
a1 a2 ß1 ß2 D1
\+ + + + + +
Drug: Ritodrine
Class :: Subclass
Clinical applications
Action
Ritodrine
Direct sympathomimetics
\/ Premature uterine contractions
a1 a2 ß1 ß2 D1
\+ + + +
Drug: Amphetamine
Class :: Subclass
Clinical applications
Action
Amphetamine
INdirect sympathomimetic
Narcolepsy
Obesity
Attention deficit disorder
Indirect general agonist
RELEASES stored catecholamine
Drug: Ephedrine
Class :: Subclass
Clinical applications
Action
Ephedrine
INdirect sympathomimetic
Nasal decongestion
Urinary incontinence
Hypotension
Indirect general agonist
Releases stored catecholamines
Drug: Cocaine
Class :: Subclass
Clinical applications
Action
Cocaine
INdirect sympathomimetic
Vasoconstriction
Local anethesia
TOX: Stroke, nasal septum perforation
Indirect general agonist
ø uptake
Drug: Clonidine
Class :: Subclass
Clinical applications
Action
Clonidine
Sympatheplegics
Hyptertension (esp. w/ renal dz)
NO \/ in blood flow to kidney
Centrally acting a2-agonists
\/ Central adrenergic outflow
Drug: a-methyldopa
Class :: Subclass
Clinical applications
Action
a-methyldopa
Sympathoplegic
Hypertension (like Clonidine: esp. w/ kidney dz b/c no \/ in blood
to kidney
Centrally acting a2-agonists
\/ Central adrenergic outflow
Drug: Phenoxybenzamine
Class :: Subclass
Clinical applications
Action
Phenoxybenzamine (irreversible)
Nonselective alpha blocker
PHEOCHROMOCYTOMA (use this drug before removing tumor, since high levels of released catecholamine will never overcome block)
TOX: Orthostatic hypotension
Reflex TACHYcardia
Drug: Phentolamine
Class :: Subclass
Clinical applications
Action
Phentolamine (reversible)
Nonselective alpha-blocker
Give to patients on MAO inhibitors who eat TYRAMINE-containing foods
TOX: Orthostatic hypotension
Reflex TACHYcardia
Drug: Prazosin, Terazosin, Doxazosin
Class :: Subclass
Clinical applications
Action
-ZOSIN ending
a1 selective blocker
Hypertension
Urinary retention in BPH
TOX: 1st dose orthostatic hypotension
Dizziness
Headache
Drug: Mirtazapine
Class :: Subclass
Clinical applications
Action
Mirtazapine
a2 selective blocker
Use for DEPRESSION
Tox: Sedation
/\ Serum cholesterol
/\ appetite
Name drug that causes /\ blood pressure that can be reversed (cause \/ pressure) after Phentolamine administration
Epinephrine
Alpha-blockade causes unmasking of the ß2 vasodilatory fx
Name drug that causes an /\ BP but whose effect can be cancelled after phentolamine administration.
Phenylephrine
A selective alpha-agonist.
Alpha blockade cancels its physiological effect.
ß-blockers end in…
-olol
ex.
Acebutolol
ß-blockers clinical applications… (6)
- Hypertension \/ Cardiac output
\/ RENIN secretion
(due to ß block of JGA cells) - Angina pectoris \/ Heart rate / contractility
‘–> \/ O2 consumption - MI \/ mortalitly
- SVT Class II anti-arrhythmic
(Propranolol & Esmolol) \/ AV conduction vel. - CHF Slows progression of chronic failure
- Glaucoma \/ secretions of aqueous humor
(timolol eye drops)
ß blocker TOX (5)
- Impotence
- Exacerbation of asthma/COPD
- Adverse CARDIAC fx
› Bradycardia
› AV block
› CHF - Adverse CNS fx
› Sedation
› Sleep alterations - Use with caution in DIABETICS
ß1 selective antagonists…
What px would benefit most from these as opposed to non selective ß blockers?
ß1 selective antagonists
¶Begin with letters A-M
Acebutolol (partial agonist) Betaxolol ) Esmolol ) > Short acting Atenolol Metoprolol
¶ A BEAM of ß1 blockers
Good for px with pulmonary dz!!!
Nonselective ß antagonists
Begin with letters N-Z
¶ Please Try Not ßeing Picky
/ / / /
Propranolol————–’ / / /
Timolol—————————–’ / /
Nadolol———————————’ /
Pindolol——————————————–’
Nonselective (vasodilatory)
a- and ß-antagonists
Carved…ILOL
Labet…ALOL
¶ The weird one’s that don’t end in -OLOL
Partial ß-Agonists
Pindolol ——.
Acebutolol—–-—————–.
\ \
¶ …P…artial ß …A…gonists
¶ PAPA
