Exam 2: Bosco Lectures: Autonomic Drugs

Question 1

Lecture 14 and 15

Name some adrenergic agonists: alpha and beta 1 and 2

Answer 1

α1 = EPI, NE, phenylephrine

α2 = Medetomidine

β1 = EPI, NE, dopamine, dobutamine

β2 = bronchodilation EPI, albuterol, clenbuterol

Question 2

Lecture 12

What are the four ways that NT can be metabolized and which NT is dominant in the PNS and its main form of metabolism?

Answer 2

reuptake, uptake, degradation, diffusion.

Acetylcholine dominates the parasympathetic division and is metabolized via degradation.

Question 3

Lecture 12

What is NANC transmission?

Answer 3

Smooth muscles innervated by ANS
some ANS effects in the presence of adrenergic and cholinergic blockade.

Non-adrenergic, non-cholinergic transmission
primarily inhibitory effects

Purinergic neurotransmission
adenosine receptors (P1)
ATP receptors (P2X and P2Y)
ATP often released as a co-transmitter with ACh or NE

Nitric oxide
AKA endothelium-derived relaxation factor
nitrergic nerves
talk about this more later

Question 4

Lecture 12: ANS target organ effects

How does sympathetic and parasympathetic affect the heart, blood vessels, lungs, GI, urinary bladder, eye, salivary glands and autonomic nerve endings?

Answer 4

• Heart
  sympathetic (B1): increase cardiac output
  parasympathetic (M2): decrease cardiac output
• Blood vessels
  sympathetic (a1 constriction, B2 dilation): directs blood flow to skeletal muscles
  parasympathetic (M3): no/little innervation
• Lungs
  sympathetic (B2): increase ventilation
  parasympathetic (M3,M2): decrease ventilation
• Gastrointestinal system
  sympathetic: decrease activity
  parasympathetic (M3, M2): increase activity
• Urinary bladder
  sympathetic: inhibit voiding
  parasympathetic (M3): promote voiding
• Eye
  sympathetic (midriasis a1, aqueous humor B2): enhance vision
  parasympathetic (M3,M2): limit vision
• Salivary glands
  sympathetic: small increase in viscous secretions (minimal)
  parasympathetic (M3,M2): increase watery secretions
• Autonomic nerve endings
  sympathetic (a2) and parasympathetic: limit NT release (autoreceptors and heteroreceptors)

Question 5

Lecture 12: Direct acting (and endogenous) cholinergic agonists

Acetylcholine

Answer 5

Rarely used clinically (ophthalmic)
muscarinic and nicotinic stimulation

rapid degradation by AChE and plasma butyrylcholinesterase

Question 6

Lecture 12: Direct acting cholinergic agonists

Muscarine

Answer 6

Muscarine (an alkaloid)

stimulates muscarinic receptors

not used clinically

found in certain mushrooms (contributes to some cases of mushroom poisoning)

Question 7

Lecture 12: Direct acting cholinergic agonists

Pilocarpine

Answer 7

Pilocarpine (an alkaloid)

muscarinic stimulation

topical ophthalmic used to induce pupil constriction and decrease intraocular pressure during glaucoma

rarely used systemically to promote salivation (sialogogue)

Question 8

Lecture 12: Direct acting cholinergic agonists

Bethanechol

Answer 8

Bethanechol (synthetic choline ester)

muscarinic stimulation, some GI / urinary bladder selectivity (some M3 selectivity)

promotes voiding by contraction of the detrusor and relaxation of the trigone and sphincter

used to treat urinary retention when obstruction is absent.

Question 9

Lecture 12: Indirect acting cholinergic agonists

Physostigmine and Neostigmine

Answer 9

• stimulate visceral smooth muscle (neostigmine)
• counter anticholinergic toxicity (physostigmine)

**Acetylcholinesterase (AChE) inhibitors
**
prevent hydrolysis of acetylcholine to choline and acetate, the primary mechanism terminating ACh signaling

**accumulation of ACh at sites of release: **
autonomic effector organs and ganglia, skeletal muscle, cholinergic synapses in the CNS

“reversible” covalent inhibitors: physostigmine (a quaternary compound that can cross the blood-brain barrier), neostigmine, and pyridostigmine

Clinical uses of “reversible” covalent inhibitors:
* smooth muscle atony (GI tract and urinary bladder)
* glaucoma (topical)
* reversal of competitive non-depolarizing neuromuscular blocking agents (more later)
* myasthenia gravis (ACh receptor deficiency)
* counter CNS symptoms of anticholinergic intoxication (physostigmine)

“Irreversible” covalent inhibitors:
* organophosphate compounds
* insecticides (e.g. malathion)
* “nerve gases” (e.g. sarin)

Question 10

What is the general synaptic organization, major receptors and neurotransmitters of the autonomic nervous system?

parasympathetic, sympathetic, and somatic

Answer 10

The symapthetic nervous system: CNS releases ACh to nicotinic cholinergic receptors that release NE to alpha and beta receptors and a nictotine receptor in the adrenal medulla that release E to the blood to reach alpaha and beta receptors.

The CNS of the parasympathetic nervous system releases Ach to nicotinic receptors that release Ah to Muscarinic receptors.

The somtatic system, the CNS releases Ach to Nitcotinic recptors and it ends there.

Question 11

How is acetylcholine and norepinephrine/epinephrine metabolized?

Answer 11

ACh mainly degredation by AChE

Catecholamines are metabolized from tyrosine to dopa to dopamine to NE to E. They are not degraded but can undergo uptake, reuptake and diffusion. NET reuptakes NE

Question 12

What are the general receptor signal transduction mechanisms of nicotinic, muscarinic, cholinergic, and adrenergic receptors?

Answer 12

Nicotinic cholinergic receptors
are a ionotropic ligand-gated cation channel. ACh binding opens the channel pore to cause a sodium influx which leads to depolarization. Nicotinic receptors excite post-synaptic neurons

Muscarinic cholinergic receptors M1 – M5 Inhibit or excite postsynaptic neurons. Adrenergic alpha receptors have α1 and α2 and Adrenergic beta receptors have β1 and β2 (and β3). All of these are G protein coupled receptors. Alpha receptors are mostly involved in the stimulation of effector cells and constriction of blood vessels. On the other hand, beta receptors are mostly involved in the relaxation of effector cells and dilatation of blood vessels

depolarize = more positive

Question 13

acetylcholine (direct; endogenous)

• generic name and drug class (i.e. what receptors they influence)
• target organ effects (desired and undesired)
• general clinical considerations (emphasize critical care)

Answer 13

Acetylcholine

Rarely used clinically (ophthalmic)
muscarinic and nicotinic stimulation

rapid degradation by AChE and plasma butyrylcholinesterase

*reverse NMJ blockade (AChE inhibitors)

Question 14

bethanechol (direct; some M3 selectivity)

• generic name and drug class (i.e. what receptors they influence)
• target organ effects (desired and undesired)
• general clinical considerations (emphasize critical care)

Answer 14

Bethanechol (synthetic choline ester)

muscarinic stimulation, some GI / urinary bladder selectivity (some M3 selectivity)

promotes voiding by contraction of the detrusor and relaxation of the trigone and sphincter

used to treat urinary retention when obstruction is absent.

*empty urinary bladder

Question 15

Muscarine

• generic name and drug class (i.e. what receptors they influence)
• target organ effects (desired and undesired)
• general clinical considerations (emphasize critical care)

Answer 15

Muscarine (an alkaloid)

stimulates muscarinic receptors

not used clinically

found in certain mushrooms (contributes to some cases of mushroom poisoning)

Question 16

Pilocarpine

• generic name and drug class (i.e. what receptors they influence)
• target organ effects (desired and undesired)
• general clinical considerations (emphasize critical care)

Answer 16

Pilocarpine (an alkaloid)

muscarinic stimulation

topical ophthalmic used to induce pupil constriction and decrease intraocular pressure during glaucoma

rarely used systemically to promote salivation (sialogogue)

*induce miosis in the eye

Question 17

physostigmine

• generic name and drug class (i.e. what receptors they influence)
• target organ effects (desired and undesired)
• general clinical considerations (emphasize critical care)

Answer 17

Clinical uses of “reversible” covalent inhibitors:

smooth muscle atony (GI tract and urinary bladder)

glaucoma (topical)

reversal of competitive non-depolarizing neuromuscular blocking agents (more later)

crosses the blood-brain barrier
*counter anticholinergic toxicity

Question 18

neostigmine

• generic name and drug class (i.e. what receptors they influence)
• target organ effects (desired and undesired)
• general clinical considerations (emphasize critical care)

Answer 18

Clinical uses of “reversible” covalent inhibitors:

smooth muscle atony (GI tract and urinary bladder)

glaucoma (topical)

reversal of competitive non-depolarizing neuromuscular blocking agents (more later)

*stimulate visceral smooth muscle

Question 19

glycopyrrolate

• generic name and drug class (i.e. what receptors they influence)
• target organ effects (desired and undesired)
• general clinical considerations (emphasize critical care)

Answer 19

Glycopyrrolate (synthetic)

Similar to atropine but quaternary so Does not cross BBB: little CNS effects

Used as adjunct to general anesthesia
decrease salivary and airway secretions
prevent vagally-mediated bradycardia

*decrease secretions, prevent bradycardia

quaternary: to big to cross BBB

Question 20

ipratropium

• generic name and drug class (i.e. what receptors they influence)
• target organ effects (desired and undesired)
• general clinical considerations (emphasize critical care)

Answer 20

Ipratropium
↓ bronchoconstriction and airway secretions

Quaternary: restricted distribution, administer via inhalation, limit systemic effects

Uses for asthma (cats) and chronic bronchitis (dogs) and horses with recurrent airway inflammation

*promote bronchodilation

Question 20

scopolamine

• generic name and drug class (i.e. what receptors they influence)
• target organ effects (desired and undesired)
• general clinical considerations (emphasize critical care)

Question 21

atropine

• generic name and drug class (i.e. what receptors they influence)
• target organ effects (desired and undesired)
• general clinical considerations (emphasize critical care)

Answer 21

Atropine (natural alkaloid)

Competitively inhibits the binding and stimulation of muscarinic receptors by ACh and other muscarinic agonists

Prototypical anticholinergic isolated from Atropa belladonna (deadly nightshade)

Used as adjunct during general anesthesia to decrease salivary and airway secretions

*decrease secretions

Question 22

propantheline

• generic name and drug class (i.e. what receptors they influence)
• target organ effects (desired and undesired)
• general clinical considerations (emphasize critical care)

Answer 22

Propantheline
**↓ detrusor contraction
↑ trigone and sphincter contraction **
promotes urine retention

Uses:
treat incontinence due to detrusor instability

*promote urine retention

Question 22

tropicamide

• generic name and drug class (i.e. what receptors they influence)
• target organ effects (desired and undesired)
• general clinical considerations (emphasize critical care)

Answer 22

Tropicamide (synthetic)

Used topically in the eye to produce mydriasis and cycloplegia (loss of ability to maintain focus on an object as it draws near the eye) in an ophthalmic examination and has a shorter duration of action than atropine

*induce mydriasis & cycloplegia

Question 23

epinephrine (α1, β1, β2; endogenous)

• generic name and drug class (i.e. what receptors they influence)
• target organ effects (desired and undesired)
• general clinical considerations (emphasize critical care)

Answer 23

Epinephrine (AKA adrenaline)
potent α and β agonist
released by adrenal chromaffin cells
complex action: summation of α and β agonist activity
cardiovascular effects (very important)

Cardiac effects (β1)
↑ contractility (positive inotrope)
↑ heart rate (positive chronotrope)
↑ O2 consumption
general result: ↑ cardiac output (CO)

Vascular effects
↓ **cutaneous, visceral, renal blood flow via vasoconstriction **(α1)
↑ skeletal muscle blood flow via dilation (β2)
Vascular effects are dose dependent
Can be given IV, IM or subcutaneously (not orally active)

Respiratory effects (important):
powerful bronchodilator (β2)
especially if bronchioles pre-constricted
e.g. anaphylaxis or asthma
small decrease in bronchial secretions

Rapid relief of hypersensitivity reactions (e.g. anaphylaxis and asthma) cardiovascular support (e.g. BP) and bronchodilation.
Restoring cardiac rhythm during cardiac arrest or an atrioventricular (AV) node block

α1 = vasoconstriction (EPI, NE, phenylephrine)

α2 = presynaptic inhibition (medetomidine)

β1 = ↑ HR and contractile force (EPI, NE, dopamine, dobutamine)

β2 = bronchodilation (EPI, albuterol, clenbuterol)

Question 24

norepinephrine (α1, β1; endogenous)

• generic name and drug class (i.e. what receptors they influence)
• target organ effects (desired and undesired)
• general clinical considerations (emphasize critical care)

Answer 24

Major NT released by post-ganglionic sympathetic nerves
AKA noradrenaline
Differs from epinephrine by lacking a single methyl group

NE is a direct α and β receptor agonist (as with EPI)
NE and EPI have different potencies on α and β receptors
* β1: EPI ≈ NE
* β2: EPI&raquo_space;»> NE
* α1: EPI > NE

NE effects and toxicity similar to EPI in most respects:
differences result from lack of β2 stimulation
intense vasoconstriction and increase in blood pressure,
initiates baroreceptor reflex (negative feedback mechanism) which slows heart rate

Limited use
cardiovascular support (maintain BP) during shock via α1 (vasculature) and β1 (heart) effects
Sometimes used during cardiac resuscitation
Minimal β2 effect = no bronchodilation

α1 = vasoconstriction (EPI, NE, phenylephrine)

α2 = presynaptic inhibition (medetomidine)

β1 = ↑ HR and contractile force (EPI, NE, dopamine, dobutamine)

β2 = bronchodilation (EPI, albuterol, clenbuterol)

Question 25

dopamine (D1, β1, (α1); endogenous)

• generic name and drug class (i.e. what receptors they influence)
• target organ effects (desired and undesired)
• general clinical considerations (emphasize critical care)

Answer 25

Endogenous catecholamine
Precursor to NE and EPI
Given IV (infusion), short half-life

DOSE DEPENDENT EFFECTS:
low dose (1-10 µg/kg)
stimulates vascular** D1 dopamine receptors**
coupled to Gαs = ↑ cAMP = vasodilation
** increased renal blood flow and sodium excretion**
stimulates cardiac β1 receptors
**positive inotropic effect **

Higher dose (>10 µg/kg): stimulate vascular α1 receptors, vasoconstriction, ↓ renal blood flow, etc.
Use low dose IV infusion for congestive heart failure with compromised renal function - short term only
Often used to treat hypotension during anesthesia

α1 = vasoconstriction (EPI, NE, phenylephrine)

α2 = presynaptic inhibition (medetomidine)

β1 = ↑ HR and contractile force (EPI, NE, dopamine, dobutamine)

β2 = bronchodilation (EPI, albuterol, clenbuterol)

Question 26

dobutamine

• generic name and drug class (i.e. what receptors they influence)
• target organ effects (desired and undesired)
• general clinical considerations (emphasize critical care)

Answer 26

Dobutamine
structurally related to dopamine
available as a racemic mixture of optical isomers with different properties
complex agonist activity on β1, β2 and α1 receptors (β1 > β2 and α1)
(but not D1 receptors as with dopamine)

Dobutamine cardiovascular effects:
increased cardiac contractility (β1 agonist) with minimal changes in heart rate
minimal change in BP as α1 and β2 agonist activities are weaker and counterbalance
use as positive inotrope during heart failure (IV only, short term)

General adverse effects/toxicity of non-selective β agonists: unwanted and/or excess β stimulation, e.g. ↑ HR (β1) when used as bronchodilator (β2)

nonselective but acts selective

α1 = vasoconstriction (EPI, NE, phenylephrine)

α2 = presynaptic inhibition (medetomidine)

β1 = ↑ HR and contractile force (EPI, NE, dopamine, dobutamine)

β2 = bronchodilation (EPI, albuterol, clenbuterol)

Question 27

albuterol

• generic name and drug class (i.e. what receptors they influence)
• target organ effects (desired and undesired)
• general clinical considerations (emphasize critical care)

Answer 27

Albuterol (AKA salbutamol)
for bronchospasm in dogs, cats, horses

selective B2 adrenergic agonists
β2 agonist = bronchodilator
Gαs = ↑ cAMP = relax bronchial smooth muscle
Cardiovascular effects (i.e. stimulation) less evident than with the non-selective β agonist isoproterenol
minimize further with aerosol administration

General adverse effects/toxicity of selective β2 agonists
unwanted and/or excess β stimulation
tremor, restlessness, cardiac excitation (β1)
minimize with inhalation

β receptor down-regulation
following chronic, long-term administration of β agonists (especially with over-usage)
leads to loss of pharmacological efficacy
minimize with proper dose, dosing schedule

α1 = vasoconstriction (EPI, NE, phenylephrine)

α2 = presynaptic inhibition (medetomidine)

β1 = ↑ HR and contractile force (EPI, NE, dopamine, dobutamine)

β2 = bronchodilation (EPI, albuterol, clenbuterol)

Question 28

clenbuterol

• generic name and drug class (i.e. what receptors they influence)
• target organ effects (desired and undesired)
• general clinical considerations (emphasize critical care)

Answer 28

Clenbuterol
used for allergic bronchitis, recurrent airway obstruction (“heaves”), and broncho-constriction in horses

selective B2 adrenergic agonists
β2 agonist = bronchodilator
Gαs = ↑ cAMP = relax bronchial smooth muscle
Cardiovascular effects (i.e. stimulation) less evident than with the non-selective β agonist isoproterenol
minimize further with aerosol administration

General adverse effects/toxicity of selective β2 agonists
unwanted and/or excess β stimulation
tremor, restlessness, cardiac excitation (β1)
minimize with inhalation

β receptor down-regulation
following chronic, long-term administration of β agonists (especially with over-usage)
leads to loss of pharmacological efficacy
minimize with proper dose, dosing schedule

α1 = vasoconstriction (EPI, NE, phenylephrine)

α2 = presynaptic inhibition (medetomidine)

β1 = ↑ HR and contractile force (EPI, NE, dopamine, dobutamine)

β2 = bronchodilation (EPI, albuterol, clenbuterol)

Question 29

phenylephrine

• generic name and drug class (i.e. what receptors they influence)
• target organ effects (desired and undesired)
• general clinical considerations (emphasize critical care)

Answer 29

Primary effect of α1 stimulation is constriction of vascular smooth muscle
increased total peripheral resistance
increased blood pressure (pressor agents)
limited use in hypotension and shock
nasal decongestant (systemic & topical)

Phenylephrine
prototypical α1 agonist
topical, oral, parenteral
**decongestant, vasopressor **
Methoxamine, metaraminol, mephentermine, midodrine
Toxicity = excess α1 activity (hypertension)

*α1 = vasoconstrictor

α1 = vasoconstriction (EPI, NE, phenylephrine)

α2 = presynaptic inhibition (medetomidine)

β1 = ↑ HR and contractile force (EPI, NE, dopamine, dobutamine)

β2 = bronchodilation (EPI, albuterol, clenbuterol)

Question 30

medetomidine

• generic name and drug class (i.e. what receptors they influence)
• target organ effects (desired and undesired)
• general clinical considerations (emphasize critical care)

Answer 30

selective a2 adrenergic receptors
Effect primarily central (CNS) and pre-synaptic inhibition of sympathetic neurons
sedation, analgesia
decreased sympathetic outflow from brain
decreased NE release

↓ sympathetic activity
(CNS inhibition)

(Dex)medetomidine & xylazine
α2 agonists = CNS depression
widely used as adjunct for sedation, anesthesia, and analgesia in veterinary medicine

pre-anesthetic, light anesthesia by itself
relatively high safety profile (i.e. therapeutic index)
allows for a lower dose of other anesthetic/analgesic agents with lower safety profiles

Overall effect is a decrease in blood pressure (and sedation/analgesia)
stimulation of pre-synaptic α2 receptors
Transient increase in blood pressure
stimulation of post-synaptic α2 receptors on arterial smooth muscle cells

*α2 = sedative, also decreases sympathetic outflow
(also xylazine)

α1 = vasoconstriction (EPI, NE, phenylephrine)

α2 = presynaptic inhibition (medetomidine)

β1 = ↑ HR and contractile force (EPI, NE, dopamine, dobutamine)

β2 = bronchodilation (EPI, albuterol, clenbuterol)

Question 31

phenoxybenzamine (α1, α2; non-competitive)

• generic name and drug class (i.e. what receptors they influence)
• target organ effects (desired and undesired)
• general clinical considerations (emphasize critical care)

Answer 31

Non-selective α antagonists

irreversibly blocks α1 and α2 receptors

Phenoxybenzamine, phentolamine
non-selective α antagonists
reduces urethral sphincter tone
manage urethral blockage

α1 antagonist = vasodilation (prazosin)

α2 antagonist = reverse α2 agonists
atipamezole reversal of medetomidine

non-selective α antagonists
phenoxybenzamine (non-comp, irreversible)
phentolamine (competitive, reversible)

Question 32

phentolamine (α1, α2; competitive)

• generic name and drug class (i.e. what receptors they influence)
• target organ effects (desired and undesired)
• general clinical considerations (emphasize critical care)

Answer 32

Direct acting competitive antagonists
reversibly block the stimulation of α and β receptors by endogenous NTs
varying degree of selectivity at different receptors
most adrenergic antagonists

Non-selective α antagonists

reversibly blocks α1 and α2 receptors

Phenoxybenzamine, phentolamine
non-selective α antagonists
reduces urethral sphincter tone
manage urethral blockage

α1 antagonist = vasodilation (prazosin)

α2 antagonist = reverse α2 agonists
atipamezole reversal of medetomidine

non-selective α antagonists
phenoxybenzamine (non-comp, irreversible)
phentolamine (competitive, reversible)

Question 33

prazosin (α1)

• generic name and drug class (i.e. what receptors they influence)
• target organ effects (desired and undesired)
• general clinical considerations (emphasize critical care)

Answer 33

Prazosin, terazosin, doxazosin
major effect is to relax arterial and venous smooth muscle = vasodilation
decrease in total peripheral resistance (after-load)
decrease in venous return (pre-load)

used as antihypertensive and in congestive heart failure (reduced pre-and after-load)
produce less reflex tachycardia than other vasodilation agents
prominent postural (orthostatic) hypotension in humans at start of therapy (1st dose-effect)
In vet med, most commonly used to treat urethral spasm in cats and dogs

α1 antagonist = vasodilation (prazosin)

α2 antagonist = reverse α2 agonists
atipamezole reversal of medetomidine

non-selective α antagonists
phenoxybenzamine (non-comp, irreversible)
phentolamine (competitive, reversible)

Question 34

Atipamezole

• generic name and drug class (i.e. what receptors they influence)
• target organ effects (desired and undesired)
• general clinical considerations (emphasize critical care)

Answer 34

sleective a2 adrenergic antagonists:
Antagonist effect primarily relieving central (CNS) and pre-synaptic inhibition
less sedation, analgesia
increased sympathetic outflow from brain
increased NE release

↑ sympathetic activity
↓ CNS inhibition

Atipamezole, yohimbine

selective α2 antagonists (competitive)

used to reverse sedative and analgesic effects of medetomidine (α2 agonist)
clinical reversal (i.e. planned)
toxicological reversal (i.e. not planned)

Rapid reversal of sedation (minutes) with minimal risk for relapse into sedation
Consider half-life of each.
atipamezole ≈ 2X that of medetomidine
timing, species differences
do not want re-sedation

**also increases sympathetic activity
**
do not use in patients with cardiac and respiratory disease or other conditions where excessive sympathetic stimulation is contraindicated

α1 antagonist = vasodilation (prazosin)

α2 antagonist = reverse α2 agonists
atipamezole reversal of medetomidine

non-selective α antagonists
phenoxybenzamine (non-comp, irreversible)
phentolamine (competitive, reversible)

Question 35

Propranolol

• generic name and drug class (i.e. what receptors they influence)
• target organ effects (desired and undesired)
• general clinical considerations (emphasize critical care)

Answer 35

nonselective B adrenergic antagonists:
Propranolol
prototypical β antagonist with equal affinity for β1 and β2 receptors
decreases cardiac output (β1 blockade)
more pronounced during exercise (increased sympathetic tone)

antiarrhythmic action from decreased sympathetic stimulation and non-adrenergic effects (e.g. “membrane stabilization”)
limited use because of β2 blockade and availability relatively selective β1 inhibitors

β1 antagonists: decrease heart rate
propranolol (non-selective), atenolol (selective)
decrease heart rate, reduce cardiac oxygen demand, decrease blood pressure

β2 antagonists: bronchoconstriction
propranolol (non-selective)
not helpful, limitation of non-selective agents

Question 36

timolol

• generic name and drug class (i.e. what receptors they influence)
• target organ effects (desired and undesired)
• general clinical considerations (emphasize critical care)

Answer 36

Timolol: ocular use to decrease aqueous humor production during glaucoma
nadolol, penbutolol, pindolol, etc. etc.
carvedilol, labetalol, bucindolol: also block α1 receptors (plus multiple other effects).

Question 37

atenolol

• generic name and drug class (i.e. what receptors they influence)
• target organ effects (desired and undesired)
• general clinical considerations (emphasize critical care)

Answer 37

selective B1 adrenergic antagonists:
Selectivity is relative, block β2 receptors at higher doses.
Advantage: safer to use in patients with bronchospastic disease.
Atenolol, metoprolol, acebutolol, esmolol, etc., etc.

Decreased heart rate and cardiac contractility.
↓ cardiac output, ↓ cardiac oxygen demand
BP = CO x PR, ↓ blood pressure
excessive sympathetic stimulation is pro-arrythmogenic, ↓ cardiac arrhythmias

potentially useful in feline hypertrophic cardiomyopathy (↓ HR, oxygen demand, etc.)
newer concept
beta blockers used to be contraindicated in heart failure

decreased heart rate
counteract anticholinergic tachycardia
anticholinergic toxicity (e.g. atropine)
e.g. during pancuronium NMJ block

β1 antagonists: decrease heart rate
propranolol (non-selective), atenolol (selective)
decrease heart rate, reduce cardiac oxygen demand, decrease blood pressure

β2 antagonists: bronchoconstriction
propranolol (non-selective)
not helpful, limitation of non-selective agents