Adrenergics

Shah, M

Alpha1
PostSyn

Alpha2
PreSyn

Beta1
HEART

Beta2
Blood vessels

Vasoconstriction: all blood

vessels
Increase TPR & BP
Mucosa Decongestion

Presynaptic: reduce
release of NorE

Increase rate, force of

contraction, velocity of
conduction

Vasodilation: skeletal
muscle, pulmonary,
coronary

Eye: radial muscle,

mydriatic

CNS: reduce symp

outflow

Skin: pilomotor muscles

contraction

Prolonged stress > alpha receptors can

override beta receptors

Bronchodilation
DA: renal vasodilation
(DIRECT)

Hyperglycemia

Uterus: relaxation
Hyperglycemia
Lactic acidemia
Lipolysis

AGONISTS
Drugs Acting at Alpha Receptors
mech: Phosphatidylinosotol, Second Messenger System
IP3 turnover
Drug
Norepinephrine
(Levarterenol)

Phenylephrine
(Neo-Synephrine)

Effects

Clinical X

IV
Pressor effect: increases BP
Increase in TPR
Rise in both systolic and diastolic > MAP
increases
HR may or may not change

Serious hypotensive
states but not if its
from a loss of blood
__ if you have a really
low volume and you
increase the BP you
will decrease the
blood supply to vital
organs

ADR

PO, Nasal, IV
Pressor
Decongestant (Primary Use)
Mydriatic

Anxiety

Class Notes
It is also endogenous

Resp difficulty

Forceful HB

Headache

Decongestant !

Severe HTN w/ violent

headache (overdose/
sensitive person)
Infiltr. Necrosis (IV)

Rebound nasal
congestion (people
taking too much and it
ends up doing the
reverse)

Methoxamine
(Vasoxyl)

IV
Pressor

Metaraminal
(Aramine)

IV
Pressor
acts at alpha1 BUT ALSO stimulates release of
endogenous NorE

Phenylpropanolamine
(Dexatrim)

She didnt talk about this one at all in class but its in her list

Psuedoephedrine
(Sudafed, Novafed)

PO
Decongestant

Used mostly in the

hospital not used at
home

Meth drug
Specific Alpha2 Agonist
mech: decreased central outflow of impulses in the symp. NS
activation of alpha2 in the NTS

Drug

Effects

Clinical X

ADR

Class Notes

Clonidine (Catapres)

PO, Transdermal
HypoTN
Sedation
Bradycardia

Drugs Acting at Beta Receptors

mech: Adenylyl Cyclase; Second Messenger System
Drug
Isoproterenol (Isuprel)

Effects

Clinical X

Skeletal muscle
tremor (beta2)

Beta1 and Beta2

Tachy (systemic B1)

Relaxation of smooth muscles
* bronchioles, intestinal tract
Skeletal Muscle vasodilation
* TPR drop, concurrent drop in diastolic
Increase CO
* + inotropes
* chronotropic axs
* rise in systolic
Glycogenolysis & Hyperlipemia
Myometrial Relaxation

Dobutamine (Dobutrex)

Parenteral, Inhaltion, Sublingual

ADR

Class Notes
Classic and original
drug

Hyperglycemia (B2)

Continuous IV infusion

Short term tx of
Cardiac
decompensation
* cardiac surgery
* CHF
* Acute MI

Increases CO and SV
No marked increase in HR
Minor alterations in BP or TPR
t 1/2 = 2 min

Drugs Acting at Beta 2

Shes not too keen on these for us to know
Drug

Method

ADR

Isoetharine
(Bronkosol, Bronkometer)

Inhalation

Skeletal muscle
tremor (beta2)

Metaproterenol
(Alupent, Metaprel)

PO, inhaltion

Tachy (systemic B1)

Terbutaline
(Brethine, Bricanyl)

PO, SC inhalation

Albuterol
(Proventil, Ventolin)

PO, inhaltion

Bitolterol
(Tornalate)

Inhalation

Class Notes

Hyperglycemia (B2)

Used Most often to

treat asthma

Specific Agonists
Drug
Epinephrine
(Adrenaline)

Effects

Clinical X

Dose-dependent effects
low dose = B
high dose = A & B
> A > B bc higher number and wider
distribution

Relieve resp distress

due to bronchospasm

Prolong ax of local
anasthetics
* vessels constrict so
the anasthetic will
stick around

Class Notes

Dopamine (Intropin)

Dose dependent effects

low dose = activate D1 (DA)
> vasodilation of renal, mesenteric,
and coronary beds
moderate = act at B1
> + inotropic effect on the
myocardium
high doses = release of norE from A1
> vasoconstriction

Ephedrine
(Primatene Tablets)

A: increase in HR, CO, TPR, BP

B: bronchodilation (class B)

Asthma, nasal
congestion

has multiple different

types of OTC
formulations

Enhances release of NorE

Antagonists
Drugs BLOCKING Alpha Receptors
Effects:
Decrease TPR/ BP
Increase HR and CO through baroreceptor reflex
Enhance release of NorE
Orthostatic hypoTN through efferent baroreceptor reflex
Most : competitive antagonists
Mixed Alpha1 and Alpha2 Blockers
Drug

Mech

Clinical X

ADR

Class Notes

Phenoxybenzamine
(Dibenzyline)

A1: decrease BP
A2: tachy
Inhibits uptake1

Pheochromocytoma=
tumor of the
chromaffin cells
(adrenals)

Postural hypoTN
Tachy
Inhibition of sperm
pd(x)
Inhibition of
ejaculation

Irreversible alpha
antagonist

Phentolamine (Regitine)

A1, A2, 5-HT, histamine release

CV effects similar to Phenoxybenzamine

Short term control

HTN in
pheochromocytoma

HypoTN
Tachy

Dont see male SE

Alpha 1 Blockers
- zosin !
Use:
Drug

Effects

Clinical X

Prazosin (Minipress)

TPR, VR, BP, Preload decrease

No effect on baroreflex (hTN pts)

Terazosin (Hytrin)

Less potent
High specificity
Longer t1/2
Higher bioavailability

Doxazosin (Cardura)

Longer t1/2

1 systemic HTN

ADR

Class Notes

first dose
phenomenon marked postural
hypoTN, syncope

tolerance develops to
these SEs

She just wants us to

know that Terazosin
and Doxazosin are
analogs of Prazosin

ADR

Class Notes

Alpha 2 Competitive Antagonist

Drug
Yohimbine

Mech

Clinical X

CNS mediated effects:

* BP, HR increase
* Antagonize 5-HT

Original use:
Psychogenic
impotence

Enhances motor ax
Tremor

Easily obtained and

can buy it at
supplement stores

Drugs BLOCKING Beta Receptors

-olol
Cardiac Effects of Beta Block:
decrease HR & contractility > decrease CO, BP
Improve ship b/t cardiac oxygen supply and demand > decrease work , increase O2 supply (increase mechl efficiency)
Influence cardiac rhythm > decrease sinus rate, spontaneous depol. of ectopic pacemakers (automatacity);
increase RP of AV node (anti-arrhyth)
Attenuate release of renin
diminish release of NorE from sympathetic neurons
Bronchoconstriction
Metabolic: decrease glucose, lactate, FFAs
Drug

Mech

Clinical X

Propranolol (Inderal)

B1 and B2 competitive antagonist

Membrane stabilizing effect: if person is going
into arrhythmias
No intrinsic sympathomimetic ax

Timolol (Blocadren,
Timoptic)

Non selective B1 and B2 antag

short acting
potent
NO intrinsic sympatho. ax
NO membrane stabilizing effect

Nadolol (Corgard)

CV:
induce CHF
Life-threatening
bradyarrhythmia

Intrinsic sympathomimetic ax
Low membrane stabilizing ax

Carteolol (Cartrol)

Some intrinsic symp. ax

Class Notes
Prototype!

Ophthalmic soln used

to lower intraocular
pressure in glaucoma

Pulm:
bronchoconstriction

CNS:
Fatigue, insomnia,
nightmares,
depression

B1 and B2 antagonist
longer acting than prop.
NO intrinsic sympatho. ax
NO membrane stabilizing effect

Pindolol (Visken)

ADR

Metabolism:
blunt recognition of
hypoglycemia
delay recovery from
insulin-induced
hypoglycemia

Penbutolol (Levatol)
Selective Beta1 Blockers
Block most ax of Epi and NorE on the heart
little - no effect on B2 (bronchial)
no effect on vasoconstrictor actions of A
Drug

Mech

Clinical X

Metoprolol (Lopressor)

No intrinsic symp. ax
Low Membrane stab. ax

Atenolol (Tenormin)

No intrinsic symp. ax
No Membrane stab. ax

Acebutolol (Sectral)

Some intrinsic symp. ax

Some Membrane stab. ax

Esmolol (Brevibloc)

LITTLE intrinsic symp. ax

LITTLE Membrane stab. ax

ADR

Class Notes

Look up!
Somewhat longer t1/2
than meto

v. short t1/2

Other Adrenergic Blocking Drugs

Drug

Mech

Labetalol (Normodyne,
Trandate)

Decrease BP

Block A1, B1, and B2

Partial agonist at B2

Clinical X

A: because it can also block

Alpha!

Inhibits uptake of NorE

B >>> 5-10x>> A block

A1: relax arterial SmMusc; vasodilator

B1: block reflex simp stim. of heart
B2: vasodilate

ADR

Class Notes

Drugs Affecting NT Metab

Drug

Mech

Clinical X

ADR

Reserpine (Serpasil)

Blocks transx of catechols into storage

vesicles
> vesicles lose ability to conc and store
> catechols leak into cytoplasm
> MAO metab. catechols

Decrease BP

CNS:
sedation, inability to
concentrate or
perform complex
tasks, depression bc
decreased 5-Ht and
NorE

Guanethidine (Ismelin)

Binds to storage vesicles and inhibits NorE

release > NorE leak > MAO does its thing

Decrease BP

Sexual dysf(x) in
males (delayed/ retro
ejaculation)

Bretylium (Bretylol)

Prevents release of NorE from terminal

Anti-arrhythmic

Methyldopa (Aldomet)

Methylated catelchols displace nL catechols

> MAO BLOCKED

Decrease BP

Sedation,
forgetfullness,
decreased mental
acuity, postural
hypoTN

Periphery: act same as DA or NorE

CNS: depletion of Epi form brainstem nuclei

Class Notes
Both of these affect
vesicles differ in the
type of NT

DOPA w/ a
methylated A carbon

Hemolytic anemia,
leukopenia,
thrombocytopenia,
hepatitis
Tyramine

Displaces the transmitter form axonal terminal

HTN crisis (tyramine)

Sympathetic agonist effect

Pargyline,
Tranylcypromine,
Phenelzine

Irreversibly inactivate MAO

Antidepressant
Anti-parks

Increase levels of catechols and 5-HT

Orthostatic hypoTN
Weight gain
Sex dysf(x)
insomnia
Bipedal edema

Agonists
Alpha

Alpha1

Beta

Beta2

Dose Dependent

Mixed

NorE

Clonidine

Isoproterenol

Isoetharine

Epinephrine

Ephedrine

Dobutamine

Metaproterenol

DA

Phenylephrine
Methoxamine

Terbutaline

Metaraminal

Albuterol

Phenylpranolamine

Bitolterol

Pseudoephedrine
Antagonists
Alpha

Alpha1

Alpha 2

Beta

Beta1

Mixed

Phenoxybenzamine

-Zosine

Yohimbine

Propranolol

Metoprolol

Labetalol

Timolol

Atenolol

Nadolol

Acebutolol

Pindolol

Esmolol

Phentolamine

Cartelol
Penbutol