Adrenergic Receptor Agonists and Antagonists

Question 1

Where do pre-ganglionic cells arise from? Where do they project?

Answer 1

Pre-ganglionic cells arise from the IML cell column of spinal cord and project to clusters of cell bodies, or “ganglia” that give rise to post ganglionic cells that innervate the effector organ

Question 2

The sympathetic and parasympathetic systems are comprised of two sets of fibers arranged in series with the exception of the adrenal gland. Describe the adrenal gland.

Answer 2

Acts like a ganglion but releases hormone into circulation

Question 3

Describe sympathetic vs parasympathetic.

Answer 3

Thoracolumbar- sympathetic (short pre-ganglionic cells and long post ganglionic cells)

craniosacral- parasympathetic (long pre-ganglionic cells and short post ganglionic cells)

Question 4

What do pre-ganglionic fibers release?

Answer 4

Ach

Question 5

What do Post ganglionic parasympathetic/sympathetic fibers release?

What are the exceptions?

Answer 5

Parasympathic - Ach
Sympathetic- NE (noradrenaline; hence “adrenergic”)

Exceptions: post-ganglionic sympathetic fibers that innervate sweat glands and some skeletal blood vessels release Ach

Question 6

Describe parasympathetic effects on the following organs:

Eye
Heart
Bronchioles
GI tract
Bladder

Answer 6

Eye- constrinction of sphincter muscles of pupil, constriction (miosis), constriction of ciliary muscle regulates accommodation

Heart- sinoatrial node to reduce heart rate, and AV node to slow conduction

Bronchioles- smooth muscle of bronchi - constriction

GI tract- GI tract to promote secretions and motility

Bladder- contraction of detrusor muscle, causes bladder emptying

Question 7

Describe sympathetic effects on the following organs:

Eye
Heart
Bronchioles
Blood vessels
GI tract
Bladder

Answer 7

Eye - activation of dilator muscle causes mydriasis, innervation of ciliary epithelium regulates production of aqueous humor

Heart- accelerated SA node pacemaker depolarization (increased heart rate)

Bronchioles- relaxation of smooth muscle lining the bronchioles

Blood vessels- contraction and relaxation - dep on receptor population expressed in vascular bed (alpha 1 vs beta 2) as well as ligand mediating the vascular response

GI tract- decreased motility, can override normal enteric nervous system during fight or flight

Bladder- inhibits emptying by contracting urethral sphincters and relaxing body of bladder (detrusor muscle) during urine storage

Metabolic functions- increase blood sugar (gluconeogenesis, glycongenolysis, lipolysis)

Question 8

What three currents contribute to SA node membrane potential?

Answer 8

1) inward Ca current
2) hyperpolarization-induced inward current or “funny current” (mediated by hyperpolarization activated cyclic nucleotide gated channel, a non-selective cation channel
3) outward K+ current

Sympathetic activation increases inward Ca current and the funny current to promote faster spontaneous depolarization during phase 4 of SA node action potential and lower threshold for activation.

Also stimulates greater Ca influx into myocytes during depolarization culminating in greater contractile force of the heart

Question 9

Describe in detail the following component of adrenergic function:

synthesis

Answer 9

Tyrosine hydroxylase (the rate
limiting step in DOPA formation. DOPA is metabolized to dopamine (DA). 

Half the DA produced is transported into storage vesicles via the vesicle monoamine transporter
(VMAT), the other half is metabolized.

Question 10

Describe in detail the following component of adrenergic function:

Storage in vesicles

Answer 10

Synaptic vesicles contain ATP and dopamine beta-hydroxylase the latter of which converts dopamine to norepinephrine.

Adrenal medullary cells
produce norepinephrine (NE), or epinephrine (EPI). EPI containing cells also synthesize an additional enzyme, phenylethanolamine-N-methyltransferase, that converts NE to EPI.

Question 11

Describe in detail the following component of adrenergic function:

release of catecholamines

Answer 11

Voltage dependent opening of calcium channels elevates intracellular calcium and stimulates the interaction of SNARE proteins to enable vesicle fusion with post-synaptic membrane and
exocytosis of the vesicle contents.

Question 12

Describe in detail the following component of adrenergic function:

binding of neurotransmitter to post-synaptic or pre-synaptic sites

Answer 12

Neurotransmitters bind to receptors localized on pre-synaptic or post-synaptic cell membranes.

The action of neurotransmitter binding depends upon the receptor type, the second messenger system as well as the machinery of the cell type.

Question 13

Describe in detail the following component of adrenergic function:

Termination of action

Answer 13

three mechanisms account for termination of action in
sympathetic neurons:

1) re-uptake into nerve terminals or post-synaptic cell
2) diffusion out of
synaptic cleft
3) metabolic transformation

Inhibition of reuptake produces potent sympathomimetic effects indicating the importance of this process for normal termination of the
neurotransmitter’s effects.

Inhibitors of metabolism, i.e., inhibitors of monoamine oxidase (MAO) and catechol-o-methyltransferase (COMT) are very important in the metabolism of catecholamines within the nerve terminal and circulation respectively.

Question 14

What type of receptors do adrenergic neurons couple to?

Answer 14

Adrenergic receptors are coupled to G proteins that mediate receptor signaling by altering ion channel conductance, adenylyl cyclase activity and phospholipase C activation, as well as gene
expression.

Several adrenergic receptor subtypes are targeted in clinical pharmacology including
alpha1-, alpha2-, beta1- and beta2-receptor subtypes. beta3 receptors are involved in fat metabolism and will
become an important therapeutic target in the future.

Question 15

What tissue is the following receptor found in and what actions does it mediate?

Explain mechanism.

alpha 1

Answer 15

tissue:

most vascular smooth muscle
pupillary dilator muscle
pilomotor smooth muscle

contracts (increases vascular resistance)
contracts (mydriasis)
contracts (erects hair)

are positively coupled to Phospholipase C (PLC) via
Gq/11 alpha protein of the heterotrimeric G protein
family to increase IP3/DAG.
IP3 activates IP3 receptor that acts as Ca release channel in SR. When activated, it releases stored Ca into intracellular space and increasing Ca concentrations stimulate smooth muscle contraction

Question 16

What tissue is the following receptor found in and what actions does it mediate?

Explain mechanism.

alpha 2

Answer 16

tissue:

adrenergic and cholinergic nerve terminals- inhibits neurotransmitter release

platelets- stimulate aggregation

some vascular smooth muscle- contracts

negatively couple to adenylyl cyclase via Galphai subunit which inhibits cAMP formation, so reduces activation of PKA..(so phosphorylation of N type Ca channels on nerve terminals is reduced and thereby reducing Ca influx during membrane depolarization and reducing vesicular release of neurotransmitter

alpha2-adrenergic receptors produce peripheral vasoconstriction through the opposite mechanism of
beta2-adrenergic receptors. In this case, the Galphai subunit, to which the alpha2 adrenergic receptor is coupled, inhibits adenylyl cyclase, which, in turn, inhibits cAMP production and PKA activity. Loss of PKA activity leads to activation of MLCK and vascular smooth muscle constriction.

Question 17

What tissue is the following receptor found in and what actions does it mediate?

beta 1

Answer 17

heart- stimulates rate and force

juxtaglomerular cells- stimulates renin release

positively couple to adenylyl cyclase via Galphas-proteins –
increases cAMP

Positive chronotropy. Activation of adenylyl cyclase and increase of cAMP can activate PKA to promote phosphorylation of calcium channels in the membrane of sinoatrial node cells
leading to increased inward calcium current and thus faster nodal cell depolarization to the firing threshold.

EX: Positive Inotropy: Increased cAMP leads to increased PKA-dependent phosphorylation of L-type calcium channels in myocyte membrane which leads to enhanced calcium influx and larger trigger signal for release of calcium from the sarcoplasmic reticulum into the
intracellular space. Trigger calcium also enters the sarcoplasmic reticulum (SR)
increasing calcium storage such that the next trigger initiates larger efflux of calcium into the cytoplasm from the SR.

Question 18

What tissue is the following receptor found in and what actions does it mediate?

beta 2

Answer 18

respiratory uterine and vascular smooth muscle- relaxes

liver- stimulate glycogenolysis

pancreatic beta cells- stimulate insulin release

somatic motor nerve terminals (voluntary muscle) - causes tremor

positively couple to adenylyl cyclase via
Galphas protein - increases cAMP

Vascular smooth muscle relaxation: cAMP activates PKA which phosphorylates and
inactivates myosin light chain kinase (MLCK). Normally MLCK phosphorylates the light chain
of myosin enabling actin and myosin cross-bridge formation and smooth muscle contraction.
Phosphorylation of the MLCK enzyme by PKA reduces the affinity of MLCK for Ca-calmodulin resulting in reduced activity of the enzyme so its ability to phosphorylate myosin light chain is inhibited. In this case, PKA inactivates MLCK. Therefore, beta2 adrenergic receptor activation
leads to reduced smooth muscle contraction. beta2 adrenergic receptors are highly expressed on
smooth muscle of the bronchi and some vascular beds and therefore regulates the degree of airway constriction as well as peripheral vascular resistance.

Question 19

What tissue is the following receptor found in and what actions does it mediate?

beta 3
(beta 1 and 2 may also contribute)

Answer 19

fat cells- stimulate lipolysis

Question 20

What tissue is the following receptor found in and what actions does it mediate?

dopamine 1

Answer 20

renal and other splanchic blood vessels- relaxes (reduces resistance)

Question 21

What tissue is the following receptor found in and what actions does it mediate?

dopamine 2

Answer 21

nerve terminals - inhibits adenylyl cyclase

Question 22

There are direct and indirect acting adrenomimetic agonists; alpha and beta agonists are direct acting; what are indirect-acting drugs?

Answer 22

releasers and reuptake inhibitors

Question 23

Sympathomimetic agents have different affinities for adrenergic receptor subtypes. What are the pharmacodynamic implications?

Answer 23

Thus, a specific compound may be more or less potent in producing a specific effect depending upon the affinity of the compound for a specific receptor subtype.

Question 24

What are the endogenous ligands for adrenergic receptors?

Answer 24

NE, EPI and dopamine (DA).

Question 25

What makes catecholamine susceptible to degradation by metabolic enzymes?

Answer 25

Catecholamines contain two hydroxyl groups on a phenyl ring.

Catecholamines differ in the
substitutions present on the terminal amine and the two methyl groups.

Adrenergic agonists can
be made more or less selective for various adrenergic receptors by altering the substitutions on
the methyl and amine groups.

Question 26

Isoproterenol (ISO), a synthetic catecholamine, has a

particularly large substitution on the amine group. How does this affect its selectivity for receptors?

Answer 26

This gives the compound selectivity for the beta-
adrenergic receptors. Compounds may also be more or less susceptible to degradation or be
more or less lipophilic by altering the hydroxyl groups on the phenyl ring.

Question 27

It is important to recognize the difference in efficacy of the various catecholamines at different receptors in order to correctly anticipate their physiological effects.

Alpha1 adrenergic

Answer 27

1. epinephrine
2. NE
3. isoproterenol

Question 28

It is important to recognize the difference in efficacy of the various catecholamines at different receptors in order to correctly anticipate their physiological effects.

Alpha2 adrenergic

Answer 28

1. epi
2. NE
3. isoproterenol

Question 29

It is important to recognize the difference in efficacy of the various catecholamines at different receptors in order to correctly anticipate their physiological effects.

beta2 adrenergic

Answer 29

1. isoproterenol
2. epi
3. NE

Question 30

It is important to recognize the difference in efficacy of the various catecholamines at different receptors in order to correctly anticipate their physiological effects.

beta1 adrenergic

Answer 30

1. isoproterenol

2. epi=NE

Question 31

TPR has a predominant effect on diastolic pressure (prevailing arterial pressure after the systolic wave has passed is mediated by arterial vasoconstriction)

CO has a predominant effect on systolic pressure (acute increase during systole due to contractile force of the heart and blood volume passing through the arterial tree)

So which is affected more by adrenergic expressed in vasculature vs cardiac tissue?

Answer 31

Therefore TPR and diastolic pressure are affected more by adrenergic receptors expressed in vasculature while CO and systolic pressure are affected more by adrenergic receptors in cardiac tissue.

Question 32

Epinephrine

What receptors does it stimulate and which predominates at low concentrations?

Answer 32

a1, a2, b1, b2 (beta receptor effects predominate at low concentrations)

short acting due to suceptibility and to degradation

at low infusion rates B2 receptor activation causes peripheral vasodilation, thereby decreasing diastolic BP

B1 has positive iontropic and chronotropic effects increasing CO and systolic BP

Question 33

What are the CV effects of epinephrine at high and lower doses?

Answer 33

at low infusion rates B2 receptor activation causes peripheral vasodilation, thereby decreasing diastolic BP

B1 has positive iontropic and chronotropic effects increasing CO and systolic BP

at higher doses
effects of a1 predominate (more receptors) producing peripheral vasoconstriction, elevated systolic pressure and elevated diastolic pressure

Overall, the cardiovascular effect is a slight increase in mean BP at lower doses, with quite robust increases at higher concentrations.

Question 34

What is the bronchiole effect of epinephrine interacting w Beta2 and alpha1 receptor?

Answer 34

beta2 receptor - bronchodilation

alpha1 receptor - decrease in bronchial secretions

Question 35

What toxicity can result from epinephrine?

Therapeutic uses?

Contraindications?

Answer 35

Toxicity: Arrhythmias, cerebral hemorrhage, anxiety, cold extremities, pulmonary edema

Therapeutic Uses: Anaphylaxis, cardiac arrest, bronchospasm

Contraindications: late term pregnancy due to unpredictable effects on fetal blood flow

Question 36

Describe the CV effects of Norepinephrine. Effects on bronchiole smooth muscle?

Answer 36

has high affinity
and efficacy at a1 a2 and b1 receptors with little
affinity for b2 receptors, susceptible to
degradation by metabolic enzymes, short halflife
give by controlled infusion

due primarily to a1-
receptor activation which leads to vasoconstriction - increase in TPR, and diastolic
BP; also produces significant positive inotropic
and chronotropic effects on heart and increased
systolic BP due to b1 receptor binding; large rise
in pressure leads to reflex baroreceptor response
and decrease in HR which predominates over the
direct chronotropic effects; Overall increase in
MAP; NE has limited affinity for b2 receptors
and so has limited effects on bronchiole smooth
muscle.

Question 37

What are the toxicity, therapeutic use and contraindications for NE?

Answer 37

Toxicity: Arrhythmias, ischemia, hypertension

Therapeutic Use: Limited to vasodilatory shock

Contraindications: pre-existing excessive vasoconstriction and ischemia and late term pregnancy

Question 38

What is the affinity of dopamine for the various receptors? CV effects?

Answer 38

stimulates D1 receptors at low concentrations, but also has affinity for b1 and alpha receptors which may be activated at higher infusion rates; readily metabolized.

Cardiovascular Effects: activates D1-receptors at low infusion rates leading
to decreased TPR; at medium infusion rates activates b1-receptors leading to increased cardiac
contractility and increased HR; at still higher infusion rates it stimulates alpha- receptors leading to increased BP and TPR.

Question 39

What are the toxicity, therapeutic uses and contraindications for dopamine?

Answer 39

Toxicity: low infusion rates – hypotension, high infusion rates – ischemia

Therapeutic Use: Hypotension due to low cardiac output during cardiogenic shock- may be advantageous due to vasodilatory effect in renal and mesenteric vascular beds

Contraindications: uncorrected tachyarrhythmias or ventricular fibrillation

Question 40

Describe the affinity of receptors, CV and bronchiole affects of isoproterenol.

Answer 40

synthetic compound; non selective B-adrenergic agonist

potent neta-receptor agonist with no appreciable affinity for alpha receptors. Catecholamine structure means it is susceptible to
degradation.

Cardiovascular effects: beta2 receptor activation
promotes peripheral vasodilation, decreased
diastolic BP; beta1 receptor - positive inotropy and chronotropy, leads to transient increased systolic BP. Overcome by vasodilatory effect; Overall small decrease in MAP which may contribute to
further reflex HR increase.

Bronchioles: beta2 receptor – bronchodilation

Question 41

What is the toxicity, therapeutic uses and contraindications for isoproterenol?

Answer 41

Toxicity: Tachyarrhythmias

Therapeutic uses: Cardiac stimulation during
bradycardia or heart block when peripheral
resistance is high.

Contraindications: Angina, particularly with arrhythmias

Question 42

What type of drug is dobutamine?

Affinity for receptors?
CV effects?
Toxicity?
Therapeutic use?

Answer 42

Selective B1-adrenergic receptor agonist

(adrenergic receptor
affinity: B1>B2>alpha), though considered by most to be a B1 selective agonist. dobutamine is a catecholamine that is rapidly degraded by COMT.

Cardiovascular effects: increased CO, usually little effect on peripheral vasculature or lung; unique in that positive inotropic effect is greater than positive chronotropic effect due to lack of B2-mediated
vasodilation and reflex tachycardia.

However, no agonist is purely selective so at higher doses,
Beta2 agonist activity may cause hypotension with reflex tachycardia.

Toxicity: Arrhythmias, hypotension (vasodilation), hypertension (inotropic and chronotropic effects).

Therapeutic Use: Short-term treatment of cardiac insufficiency in CHF, cardiogenic shock or
excess beta-blockade

Question 43

What type of drugs are terbutaline and albuterol?

CV effects? Bronchioles?
Pregnant uterus?
Toxicity?
Therapeutic use?

Answer 43

Selective beta2 adrenergic agonists:

Cardiovascular Effects: negligible in most patients due to lack of beta1 activity. However, can cause some beta1 agonist-like response

Bronchioles: Bronchodilation

Pregnant Uterus: Relaxation

Toxicity (see Fig): Tachycardia, tolerance, skeletal muscle tremor, activation of beta2-receptors expressed on pre-synaptic nerve terminals of cholinergic somatomotor neurons increases release of
neurotransmitter. This can lead to muscle tremor, a side
effect of beta-agonist therapy.

Tolerance to drug can
develop with chronic use.

Therapeutic Use: Bronchospasm, chronic treatment of obstructive airway disease.

Question 44

Describe the following for phenylephrine:

Type of drug
CV effects
Ophthalmic effects
Bronchioles
Toxicity
Therapeutic use
Contraindications

Answer 44

Cardiovascular Effects: Peripheral vasoconstriction and increased BP, activates baroreceptor reflex and thereby decreases HR.

Ophthalmic Effects: Dilates pupil

Bronchioles: Decrease bronchial (and upper airway) secretions

Toxicity: Hypertension

Therapeutic Use: Hypotension during anesthesia or shock, paroxysmal supraventricular
tachycardia, mydriatic agent, nasal decongestant

NOTE: Phenylephrine is not a catecholamine and therefore is not subject to rapid degradation by COMT. It is metabolized more slowly; therefore it has a much longer duration of action than
endogenous catecholamines.

Contraindications: Hypertension, ….not effective in ventricular tachycardia

Question 45

Describe the following for clonidine:

Type of drug
CV effects
Toxicity
Therapeutic use

Answer 45

Cardiovascular Effects: Peripherally, clonidine causes mild vasoconstriction and slight increase in BP, also crosses BBB to cause reduced sympathetic outflow thereby reducing vasoconstriction
and BP (see figure at right). The loss of sympathetic activity predominates over the direct vasoconstrictor effects of the drug leading to overall reduction in blood pressure.

Activation of alpha2-receptors on pre-motor neurons that normally provide tonic activation of sympathetic pre-ganglionic cells reduces pre-motor neural activity
by unknown mechanism. Reduction of tonic excitatory input to the sympathetic
cells reduces sympathetic output to vascular smooth muscle.

Toxicity: Dry mouth, sedation,
bradycardia, withdrawal after chronic use can result in life-threatening hypertensive crisis (increases
sympathetic activity).

Therapeutic Use: Hypertension when
cause is due to excess sympathetic drive.

Question 46

What is the mechanism of indirectly acting sympathomimetics?

What is the mechanism?

Examples of releasing agents?

Answer 46

Indirect acting sympathomimetic agents increase the concentration of endogenous catecholamines in the synapse and circulation leading to activation of adrenergic receptors. This occurs via either:

1) release of cytoplasmic
catecholamines
2) blockade of re-uptake transporters

Releasing agents: amphetamine, methamphetamine, methylphenidate,
ephedrine, pseudoephedrine, tyramine.

Question 47

Describe the half life of the following releasing agents; amphetamine, methamphetamine, methylphenidate,
ephedrine, pseudoephedrine, tyramine.

Answer 47

Most are resistant to degradation by COMT and MAO and therefore have relatively long half lives
(exception is tyramine which is
highly susceptible to degradation by MAO and thus has little effect unless
patient is taking MAO inhibitor).

Amphetamine-like drugs are taken up by re-uptake proteins and subsequently
cause reversal of the re-uptake mechanism resulting in release of neurotransmitter in a calcium-independent manner.

The resulting increase in synaptic NE mediates the drugs’ effects. Amphetamine-like drugs readily cross the blood brain barrier leading to high abuse potential due to reinforcing effects of central dopamine release.

Question 48

What are the CV effects, CNS, toxicity, therapeutic uses, contraindications of the following?

Releasing agents: amphetamine, methamphetamine, methylphenidate,
ephedrine, pseudoephedrine, tyramine.

Answer 48

Cardiovascular Effects: due to NE release, α adrenergic receptor activation causes peripheral vasoconstriction and increased diastolic BP; beta receptor activation of heart leads to positive
inotropy and increased conduction velocity and increased systolic BP; increased BP can cause
decreased HR due to baroreceptor activation, but this can be masked by direct chronotropic effect.

Central Nervous System: Stimulant, anorexic agent

Toxicity: Anxiety, tachycardia

Therapeutic use: Attention Deficit Disorder, narcolepsy, nasal congestion

Contraindications: Hypertension, severe atherosclerosis, history of drug abuse, Rx with MAO
inhibitors within previous 2 weeks.

Question 49

Describe the following for: propranolol, timolol, nadolol

Heart rate and force of contraction 
Peripheral resistance 
Renin release
Bronchioles
Glucose metabolism

Answer 49

non-selective b1 and b2 antagonists (Blockers)

Heart rate and force of contraction (B1)- decrease both rate and force of contraction

Peripheral resistance (B2)- increase, due to unopposed vasoconstriction by a1 receptors

Renin release (B1)- decreased release

Bronchioles (B2)- bronchoconstriction, particularly in asthmatics

Glucose metabolism (B2)- inhibits effects of epi like hyperglycemia, anxiety, sweating. Use caution in diabetics using insulin, since masks symptoms of hypoglycemia (normally due to epi release)

Question 50

Describe the following for: atenolol, metoprolol

Heart rate and force of contraction 
Peripheral resistance
Renin release 
Bronchioles 
Glucose metabolism

Answer 50

cardioselective b1 antagonists (Blockers)

Heart rate and force of contraction (B1)- decrease both rate and force of contraction

Peripheral resistance (B2)- little effect bc B2 receptors are not blocked

Renin release (B1)- decreased release

Bronchioles (B2)- less bronchoconstriction in asthmatics, but still not recommended in these patients

Glucose metabolism (B2) -little effect

Question 51

Describe the following for: pindolol

Heart rate and force of contraction 
Peripheral resistance 
Renin release 
Bronchioles
Glucose metabolism

Answer 51

partial agonist b1 and B2

Heart rate and force of contraction (B1)- decreases both rate and force of contraction. However, bradycardic response is limited due to partial agonist activity

Peripheral resistance (B2)- may be slight decrease because of partial B2 agonist properties

Renin release (B1)- decreased release

Bronchioles (B2)- asthmatics have a reduced capacity to dilate bronchioles

Glucose metabolism (B2)- reduced response to epi bc partial agonist activity is not as potent as endogenously-released epi

Question 52

What are the CV effects, bronchioles, therapeutic uses, Describe the following for : propranolol, nadolol, timolol

CV effects
Bronchioles
Therapeutic uses
Toxicity 
Contraindications

Answer 52

non-selective beta-blockers

first generation beta-blockers
with potentially harmful side effects for patients with respiratory disease.

Cardiovascular effects: reduced heart rate and contractility, reduced renin release leads to
reduced angiotensin II production and thus reduced vasoconstriction, probably reduced sympathetic activation due to central effects of lipid soluble drugs. Some peripheral
vasoconstriction due to blockade of beta2 adrenergic receptors.

Bronchioles: can cause bronchiole constriction in those with asthma or chronic obstructive pulmonary disease.

Therapeutic Use:
Hypertension, angina, glaucoma, heart failure, arrhythmia, thyrotoxicosis,
anxiety

Toxicity: Bronchospasm, masks symptoms of hypoglycemia, CNS effects including insomnia
and depression (most significant with lipid soluble drugs), some can raise triglycerides, bradycardia.

Contraindications: Bronchial Asthma, sinus bradycardia, 2nd and 3rd degree heart block, cardiogenic shock

Question 53

Describe the following for: metoprolol, atenolol, esmolol

CV effects
Bronchioles
Therapeutic uses
Toxicity 
Contraindications

Answer 53

non-selective beta-blockers

second generation beta-
blockers developed for their ability to reduce respiratory side effects.

Cardiovascular Effects: Same as for non-selective beta-blockers with limited effects on peripheral
resistance.

Therapeutic Use:

Hypertension (metoprolol, atenolol), angina (metoprolol, atenolol), arrhythmia
(esmolol-emergent control). Esmolol has very short half-life (~9 min) so is given i.v. in hypertensive crisis, unstable angina or arrhythmias when longer acting beta blockers may be
problematic.

Toxicity: (typically mild and transient), Dizziness, depression, insomnia, hypotension,
bradycardia.

Contraindications: Sinus bradycardia, 2nd or 3rd degree heart block, cardiogenic shock

Question 54

What kind of drug is pindolol? Explain.

Answer 54

partial agonist activity at both B1 and B2 adrenergic
receptors;

Therapeutic benefit is good when hypertension is due to high sympathetic output since blockade of endogenous agonist (i.e., NE and EPI) will predominate over partial agonist effect of drug.

Partial agonists have less bradycardic effect since
some beta signal remains, while betasignal is blocked by agonists without agonist activity

Used when patients are less tolerant of bradycardic effects.

Question 55

Describe the following for pindolol.

CV effects
Bronchioles
Therapeutic uses
Toxicity 
Contraindications

Answer 55

partial agonist Cardiovascular Effects: Same as above for non-selective beta-blockers, particularly when sympathetic activity is high.

Therapeutic Use: Hypertension in those who are less tolerant of bradycardia and reduced
exercise capacity caused by other beta blockers without partial agonist activity

Toxicity: dizziness, depression, insomnia, hypotension

Contraindications: sinus bradycardia, 2nd and 3rd degree heart block, cardiogenic shock

Contraindications: Same as above

Question 56

Draw graphs comparing phenoxybenzamine to phentolamine.

Answer 56

See p 18 h/o

Non-selective alpha-receptor antagonists: phenoxybenazmine (irreversible) and
phentolamine (reversible).

Question 57

Describe the following for phenoxybenzamine and phentolamine.

CV effects
Therapeutic uses
Toxicity
Contraindications

Answer 57

Cardiovascular Effects: Inhibit vasoconstriction therefore, decreases BP, increased inotropy and chronotropy due to blockade of pre-synaptic alpha2-receptor and increased release of NE from nerve terminals, reflex increase in NE release also occurs in response to hypotension, unmasks
vasodilatory effect of EPI (which has both alpha and beta2 effects.)

Therapeutic Use: Hypertension associated with perioperative treatment of pheochromocytoma,
test for pheochromocytoma, dermal necrosis and sloughing with vasoconstrictor extravasation

Toxicity: Prolonged hypotension, reflex tachycardia, nasal congestion

Contraindications: Coronary artery disease

Question 58

Describe the following for prazosin, doxazosin, and terazosin:

What type of drug?

CV effects
Therapeutic uses
Toxicity
Contraindications

Answer 58

Selective alpha 1-receptor blockers:

Cardiovascular Effects: Inhibit vasoconstriction, resulting in vasodilation and decreased BP, produces less cardiac stimulation than non-selective a-blockers due to preservation of a2-
adrenergic function

Therapeutic Use: Hypertension, benign prostatic hyperplasia

Toxicity: Syncope, orthostatic hypotension

Question 59

How can you distinguish when to use dobutamine vs dopamine?

Answer 59

if patient has LOW bp use dopamine bc can titrate up

if higher mean arterial bp- 80mmHg or above then use dobutamine
dopamine tends to be more arrythmagenic so unstable pt dobutamine may be better choice