DR. LEAL - AUTONOMIC DRUGS PART2 Flashcards
activates receptor for adrenaline or epinephrine or norepinephrine
ADRENOCEPTOR AGONIST
mimics the sympathetic nervous system
SYMPATHOMIMETIC DRUGS
− Directly interact with and activate adrenoceptors.
− eg, NOREPINEPHRINE and EPINEPHRINE
DIRECT AGONISTS
− Actions are dependent on their ability to enhance the actions of endogenous (naturally occurring in the body) catecholamines (norepinephrine, epinephrine, dopamine)
INDIRECT AGONISTS
Inducing the release of catecholamines by displacing them from adrenergic nerve endings (mechanism of action of ______)
TYRAMINE
not physiologically important in humans but if under the treatment of monoamine oxidase inhibitors, THIS can accumulate. If medicating with MAO inhibitors, avoid cheese or protein-rich foods.
TYRAMINE
Decreasing the clearance of catecholamines by inhibiting their neuronal reuptake (mechanism of action of ____ & _____)
COCAINE
TCA
Receptors for acetylcholine
NICOTINIC
MUSCARINIC
Pharmacologic effects of INDIRECT SYMPATHOMIMETICS are greater under conditions of:
a. Increased sympathetic activity.
b. Norepinephrine storage and release.
Receptors for noradrenergic
ALPHA
BETA
sublingually administered for emergency treatment of hypertensive urgency. If BP is 180/100, it is used to acutely decrease the BP of the patient.
CLONIDINE (CATAPRES)
used if BP is decreased
PHENYLEPHRINE
has atropine, it can increase the heart rate so avoid giving it to patients with arrhythmia.
LOMOTIL
greater affinity in α1 > α2
PHENYLEPHRINE
greater affinity in α2 > α1
CLONIDINE
have the same affinity to both α1 and α2
NE
EPINEP
mostly found in blood vessels = contraction = increase BP
α1 (ALPHA1)
NE or Epi (will attach to β1 in the heart) is used in CPR to increase the force or contraction of the heart
β1 (BETA 1)
given to asthmatic patients to relieve bronchial smooth muscles but still has a side effect to increase the heart rate of patients.
ISOPROTERENOL
Used in CPR to increase contractility of the heart, and increase heart rate, stroke volume, cardiac output, and blood pressure of the patient.
EPINEPHRINE
GIVEN to patients with decreased blood pressure and increased heart rate to increase BP without increasing the heart rate.
PHENYLEPHRINE
• Agonist at both α and β receptors
• Very potent vasoconstrictor and cardiac stimulant
EPINEPHRINE (ADRENALINE)
The rise in systolic blood pressure that occurs after
epinephrine release or administration is caused by its
positive inotropic and chronotropic actions on the heart (predominantly β 1receptors) and the vasoconstriction induced in many vascular beds (α receptors).
epinephrine functions largely as a _____; it is released from the adrenal medulla and carried in the blood to distant sites of action.
HORMONE
• Agonist at both α1 and α2 receptors
• Also activates β1 receptors with similar potency as
epinephrine, but has relatively little effect on β2 receptors.
• Increases peripheral resistance and both diastolic and
systolic blood pressure.
NOREPINEPHRINE (LEVARTERENOL, NORADRENALINE)
• Immediate precursor in the synthesis of norepinephrine.
DOPAMINE
Rate-limiting step in the formation of NE
CONVERSION OF TYROSINE TO DOPAMINE
Endogenous dopamine may have more important effects in
regulating sodium excretion and renal function.
Deficiency in the basal ganglia leads to Parkinson’s disease, which is treated with its precursor Levodopa.
DOPAMINE
• A prodrug that is enzymatically hydrolyzed to desglymidodrine, a selective α1-receptor agonist (peak concentration of desglymidodrine is achieved about 1 hour after midodrine is administered orally)
MIDODRINE
Treatment of orthostatic hypotension, typically due to impaired autonomic nervous system function.
• Increases upright blood pressure and improves orthostatic tolerance, but it may cause hypertension when the subject is supine
MIDODRINE
Decrease blood pressure through actions in the CNS that
reduce sympathetic tone (“sympatholytics”) even though direct application to a blood vessel may cause
vasoconstriction.
ALPHA 2-SELECTIVE AGONISTS
are useful in the treatment of hypertension.
SE (side effects): Sedation
CLONIDINE
METHYLDOPA (for pregnant with high BP)
GUANFACINE
GUANABENZ
for sedation in an intensive care setting or before anesthesia. Can be given to patients who will undergo MRI or CT scan.
DEXMEDETOMIDINE
used as a centrally-acting muscle relaxant.
TIZANIDINE
• Topical decongestant - ability to promote constriction of
the vessels in the nasal mucosa and conjunctiva.
• Large doses may cause hypotension, presumably because of a central clonidine-like effect. Should not be given to
already hypotensive patients.
OXYMETAZOLINE
- Has positive chronotropic and inotropic actions.
- Because IT activates β receptors almost
exclusively, it is a potent vasodilator.
ISOPROTERENOL (ISOPRENALINE)
• Positive inotropic action caused by the isomer with
predominantly β-receptor activity
DOBUTAMINE
• Component of many decongestant mixtures.
• Precursor in the illicit manufacture of methamphetamine. • Given to ongoing operation to increase BP especially if
becoming hypotensive due to blood loss.
EPHEDRINE & PSEUDOEPHEDRINE
TRUTH SERUM
KETAMINE
• Racemic mixture of phenylisopropylamine.
• Use and misuse as a CNS stimulant.
AMPHETAMINE
• Pharmacokinetically similar to EPHEDRINE; however, enters the CNS even more readily, where it has marked stimulant effects on mood and alertness and a depressant effect on appetite
• Actions are mediated through the release of NOREPINEPHRINE and, to some extent, dopamine.
AMPHETAMINE
• Very similar to amphetamine, with an even higher ratio of central to peripheral actions.
METHAMPHETAMINE (N-methylamphetamine)
• An amphetamine variant
• Major pharmacologic effects and abuse potential are
similar to those of amphetamine
METHYLPHENIDATE
used to increase BP.
Methamphetamine
Methylphenidate
Shabu users: decreased sleep, hyperactive and some had heart failures because of increased heart rate and BP.
METHYLPHENIDATE
• A psychostimulant that differs from amphetamine in
structure, neurochemical profile, and behavioral effects
MODAFINIL
• Primarily to improve wakefulness in narcolepsy and some other conditions
MODAFINIL
• Anormal byproduct of tyrosine metabolism in the body
• An indirect sympathomimetic, inducing the release of
catecholamines from noradrenergic neurons
TYRAMINE
In patients treated with MAO inhibitors—particularly inhibitors of the MAO-A isoform—the sympathomimetic effect of tyramine may be greatly intensified, leading to marked increases in blood pressure. This occurs because of increased bioavailability of tyramine and increased neuronal stores of catecholamines.
TYRAMINE
Patients taking MAO inhibitors should avoid tyramine-
containing foods
aged cheese
cured meats
pickled food
• A selective inhibitor of the norepinephrine uptake
• Actions are mediated by the potentiation of
norepinephrine levels in noradrenergic synapses
• Used in the treatment of ATTENTION DEFICIT DISORDERS.
ATOMOXETINE
• Has similar characteristics to Atomoxetine but is used mainly for MAJOR DEPRESSION DISORDER.
• Reuptake inhibitors potentiate norepinephrine actions (cardiovascular safety)
REBOXETINE
• Serotonin and norepinephrine reuptake inhibitors used as an appetite suppressant.
SIBUTRAMINE
• Widely used antidepressant with balanced serotonin and norepinephrine reuptake inhibitory effects
• Treatment of pain in fibromyalgia.
DULOXETINE
• A local anesthetic with a peripheral sympathomimetic
action that results from the inhibition of transmitter
reuptake at noradrenergic synapses.
COCAINE
• Readily enters the CNS and produces an amphetamine-
like psychological effect that is shorter lasting and more
intense than amphetamine
COCAINE
- Major action of ____ in the CNS is to inhibit dopamine
reuptake into neurons in the “pleasure centers” of the brain.
COCAINE
- Converted to dopamine in the body
- Dopamine agonists
- Treatment of Parkinson’s disease and prolactinemia.
LEVODOPA
D1-receptor agonist that selectively leads to peripheral vasodilation in some vascular beds
• IV treatment of severe hypertension.
FENOLDOPAM
may be required in cases of sustained hypotension with evidence of tissue hypoperfusion.
Sympathomimetics
Treatment of Acute Hypotension
• A complex acute cardiovascular syndrome that results in a critical reduction in perfusion of vital tissues and a wide range of systemic effects
SHOCK
The mainstay of treatment especially in hypovolemic shock
replacement of volume example severe diarrhea / bleeding = hypovolemic shoc
k
vasopressor of first choice to increase BP
NOREPINEPHRINE
• •
Impairment of autonomic reflexes that regulate blood pressure
Increasing peripheral resistance is one of the strategies to treat chronic orthostatic
hypotension (drugs activating α receptors can be used for this purpose)
Chronic Orthostatic Hypotension
o A prodrug that is converted to norepinephrine by
the aromatic L-amino acid decarboxylase (dopa- decarboxylase), the enzyme that converts L-dopa to dopamine.
DROXIDOPA
o Improves the chance of returning to spontaneous circulation.
CARDIAC APPLICATIONS
EPINEPHRINE
o Used as a pharmacologic cardiac stress test
o Augments myocardial contractility and promotes
coronary and systemic vasodilation.
DOBUTAMINE
used in the nares for vasoconstriction to avoid excessive bleeding
Oxymetazoline
o Effective mydriatic agent frequently used to facilitate examination of the retina
o Decongestant for minor allergic hyperemia and itching of the conjunctival membranes.
PHENYLEPHRINE
dissociate from receptors, and the block can be surmounted with sufficiently high concentrations of agonists
• Phentolamine and Prazosin
• Labetalol
• Several Ergot derivatives
REVERSIBLE ANTAGONISTS
• Management of hypertension
• Highly selective for α1 receptors and typically 1000-fold
less potent at α2 receptors
PRAZOSIN
• Reversible α1-selective antagonist that is effective in
hypertension.
• Men with urinary retention symptoms due to BENIGN
PROSTATIC HYPERPLASIA (BPH)
TERAZOSIN
• Treatment of Hypertension and BPH
DOXAZOSIN
• Binds covalently to α receptors, causing irreversible
blockade of long duration (14–48 hours or longer)
• Somewhat selective for α1 receptors but less so than
Prazosin
PHENOXYBENZAMINE
• Most significant effect is attenuation of catecholamine-
induced vasoconstriction.
• It reduces blood pressure when sympathetic tone is high,
eg, as a result of upright posture or because of reduced
blood volume
PHENOXYBENZAMINE
Adverse Effects:
a. Orthostatic Hypotension and Tachycardia
b. Nasal stuffiness and inhibition of ejaculation
c. Enters the CNS (may cause fatigue, sedation and
nausea
PHENOXYBENZAMINE
Treatment of PHEOCHROMOCYTOMA.
PHENTOLAMINE
Treatment of ORTHOSTATIC HYPOTENSION
Treat MALE ERECTILE DYSFUNCTION
YOHIMBINE
• Greater potency in inhibiting contraction in PROSTATE
smooth muscle versus vascular smooth muscle compared
with other α1-selective antagonists
• Drug’s efficacy in BPH (benign prostatic hyperplasia)
TAMSULOSIN
• α1-selective quinazoline derivative that is approved for
use in BPH
ALFUZOSIN
• Resembles Tamsulosin in blocking the α1A receptor and is
also used in the treatment of BPH.
SILODOSIN
• α1- selective antagonist that also has efficacy as an
antihypertensive.
INDORAMIN
• α1 antagonist (its primary effect) that also has weak α2-
agonist and 5-HT1A-agonist actions and weak antagonist
action at β1 receptors
• Antihypertensive agent and for BPH.
URAPIDIL
Have both α1-selective and β-antagonistic effects
Somewhat selective for β1 and β2 receptors than α receptors.
(MIXED ANTAGONISTS)
LABETALOL and CARVEDILOL
PHARMACODYNAMICS OF THE BETA-RECEPTOR ANTAGONIST DRUGS
EFFECTS ON THE CARDIOVASCULAR SYSTEM
• Lower blood pressure in patients with hypertension
• Suppression of renin release and effects in the CNS
• Treatment of angina, chronic heart failure and following
myocardial infarction
PHARMACODYNAMICS OF THE BETA-RECEPTOR ANTAGONIST DRUGS
EFFECTS ON THE RESPIRATORY TRACT
INCREASE IN AIRWAY RESISTANCE
PHARMACODYNAMICS OF THE BETA-RECEPTOR ANTAGONIST DRUGS
EFFECTS ON EYE
• Reduce intraocular pressure, especially in GLAUCOMA.
• Mechanism: DECREASED AQUEOUS HUMOR
PRODUCTION
inhibits sympathetic nervous system
stimulation of lipolysis.
PROPANOLOL
much safer in those TYPE 2
DIABETIC patients who do not have hypoglycemic
episodes.
Beta-receptor antagonists
• Has negligible effects at α and muscarinic receptors;
however, it may block some serotonin receptors in the brain.
PROPANOLOL
• SAFER in patients who experience bronchoconstriction in
response to propranolol
• Preferable in patients with DIABETES or PERIPHERAL
VASCULAR DISEASE when therapy with a β blocker is required.
METOPROLOL & ATENOLOL
• Most highly selective β1-adrenergic receptor blocker.
- ADDITIONAL QUALITY OF VASODILATION
- MAY INCREASE INSULIN SENSITIVITY
NEBIVOLOL
• Non selective agent with no local anesthetic activity
• Has excellent ocular hypotensive effects when
administered topically in the eye.
TIMOLOL
• Very long duration of action
• Spectrum of action is similar to that of TIMOLOL.
NADOLOL
Used for topical ophthalmic application in GLAUCOMA.
LEVOBUNOLOL
BETAXOLOL
• Effective in the major cardiovascular applications of the β-
blocking group (HYPERTENSION AND ANGINA)
PINDOLOL, ACEBUTOLOL, CARTEOLOL, BOPINDOLOL, OXPRENOLOL, CELIPROLOL, AND PENBUTOLOL
• Hypotension induced is accompanied by LESS TACHYCARDIA than occurs with phentolamine and similar α blockers.
LABETALOL
• Ultra-short-acting β1-selective adrenoceptor antagonist
• Useful in controlling SUPRAVENTRICULAR ARRHYTHMIAS, ARRHYTHMIAS associated with thyrotoxicosis, perioperative hypertension, and myocardial ischemia in acutely ill patients
ESMOLOL
- An effective mydriatic and decongestant that can be used to raise the blood pressure, an effective ophthalmic drug
a. Amphetamine
b. Phenylephrine
c. Tizanidine
d. Midodrine
B
- Treatment for Parkinson’s disease and Prolactinemia
a. Fenoldopam
b. Tyramine
c. Levodopa
d. BothAandC
C
- Treatment of pheochromocytoma, it is used to reverse local anesthesia in soft tissue sites
a. Yohimbine
b. Talozoline
c. Phentolamine
d. Phenoxybenzamine
C
- Major action in the CNS is to inhibit dopamine reuptake into neurons in the ‘pleasure centers’ of the brain.
a. Atomoxetine
b. Cocaine
c. Fenoldopam
d. Sibutramine
B
- Used for topical ophthalmic application in glaucoma
a. Levobunolol
b. Bopindolol
c. Betaxolol
d. BothAandC
D
- A prodrug that is used for treatment of orthostatic hypotension, it increases upright blood pressure and improves orthostatic tolerance, but may cause hypertension when the subject is supine
a. Phenmetrazine
b. Phenylephrine
c. Tizanidine
d. Midodrine
D
- Most common on effector cell membranes, especially glandular and smooth muscle cells
a. M1 receptor
b. M2 receptor
c. M3 receptor
d. M4 receptor and M5 receptor
C
- Less prominent and appear to play a greater role in the CNS than in the periphery
a. M1 receptor
b. M2 receptor
c. M3 receptor
d. M4 receptor and M5 receptor
D
- Inhibits both norepinephrine and dopamine transporters, improves wakefulness in narcolepsy.
A. Modafinil
B. Tyramine
C. Methylphenidate
D. Methamphetamine
A
- In noradrenergic nerve ending by a sodium-dependent carrier and then converted to dopamine.
adrenergic transmission, _____ is transported into the
a. Choline
b. Tyrosine
c. Norepinephrine
d. Leucine
B
- Which of the following agents produces a vasopressor effect that can relieve nasal congestion?
a. Atropine
b. Reserpine
c. Cocaine
d. Mecamylamine
C
- What is the predominant adrenoceptor in heart muscle?
A. α1-adrenoceptor
B. α2-adrenoceptor
C. β1-adrenoceptor
D. β2-adrenoceptor
C.
- THE prototype of beta-receptor antagonist drugs
A. Atenolol
B. Propranolol
C. Timolol
D. Metoprolol
B
- THE following has local anesthetic action except:
A. Labetalol
B. Esmolol
C. Metoprolol
D. Propranolol
B
- This drug may elicit extrapyramidal effects.
a. Carvedilol
b. Butoxamine
c. Metyrosine
d. Esmolol
C
- Antimuscarinic drug used in ophthalmology with the shortest duration of effect
a. Atropine
b. Tropicamide
c. Scopolamine
d. Cyclopentolate
B
- What is the main clinical use for agonists of the β2- adrenoceptor?
A. Treatment of hypertension
B. Treatment of angina
C. Treatment of asthma
D. Treatment of pain
E. All of the above
C
- Ultra-short–acting β1-selective adrenoceptor antagonist that is rapidly metabolized by esterases in red blood cells.
a. Esmolol
b. Metoprolol
c. Labetalol
d. Carvedilol
A
- What part of a neuron is responsible for receiving information?
A. Axon
B. Terminal fiber
C. Dendrite
D. Myelin sheath
E. Nucleus
C
- Preparing the body for “flight-or-fight” response during threatening situations is the role of the?
a. Autonomicnervoussystem
b. Somatic nervous system
c. Parasympathetic nervous system
d. Sympathetic nervous system
e. cerebrum
D.
