*Guanfacine, and Guanabenz: are also classified
AUTONOMIC DRUGS
Dr. Paguirigan (August 23, 2019)
DOPAMINE AGONIST DRUGS
 LEVODOPA - the most common drug used
- is it is converted to dopamine in the
body as simple drug
DOPAMINE AGONIST WITH CENTRAL ACTIONS
 These are used for Parkinsonism,
Parkinson’s disease and in cases of
prolactinemia.
SUMMARY OF SYMPATHOMIMETIC DRUGS
 ALPHA 1 AGONIST DRUGS:
1. Midocrine - activates Phospholipase C
which results in increased intracellular
calcium and vasoconstriction
2. Phenylephrine - can be used intravenously
for short term maintenance of blood
pressure in acute hypotension and
intranasally to produce local
vasoconstriction as a decongestant
 ALPHA 2 AGONIST DRUGS:
1. Clonidine - inhibits adenylyl cyclase and
interacts with other intracellular pathways
Vasoconstriction is masked by central
sympatholytic effect which lowers blood
pressure
-it is an anti-hypertensive drug that
paradoxically possess primarily alpha 2
adrenergic agonist properties
-Clonidine exerts its anti-hypertensive
effect with a predominant action in the
central nervous where it decreases the
sympathetic output of the brain
Labayog, Malazzab, Onate, Tupaz
as Alpha 2 agonist that act primarily also in the
central nervous system
- The pharmacologic properties of
Guanfacine, and Guanabenz are similar to
those of clonidine
- The possible site of action of Clonidine is
in the nucleus tactus solitarius in the lower
brain stem. This region is very rich in nerve
bodies and nerve terminals that contain
epinephrine or norepinephrine
- Side effects of Clonidine:
 Sedation
 dry mouth
 rebound hypertension - if it is
abruptly discontinued it will result
in -- most dreaded side effect if it is
abruptly discontinued
- Taper use prior to discontinuation to
avoid rebound hypertension
- To treat rebound hypertension
administer Phentolamine to counteract
the effect
2. Methyldopa- popularly known as Aldomet
in the market.
- This is also used as a central
sympatholytic drug-- it exerts its effect by
central mechanism
-Methyldopa enters the central nervous
system readily then it is beta oxidated to
alpha methlyldopamine and beta
hydroxylated to alpha
methylnorepinephrine
-In the central adrenergic neurons, the
alpha methyl norepinephrine is released
from such neurons is a very potent agonist
of the Alpha 2 receptors of central nervous
1
 system and so in the same manner like -Is a direct acting drug with selectivity
clonidine, it inhibits central sympathetic for the beta 1 adrenergic receptors
outflow relatively more effective in enhancing
the contractile force of the heart than
-The alpha methylnorepinephrine like in increasing the heart rate
clonidine is a more potent stimulator at - It does not affect conduction velocity
but it augments the conduction
the alpha 2 receptors than in alpha 1
velocity through the AV node
receptors
-There is little or no effect on the
ventricular impulse conduction
- The most popular clinical use of
-It does not produce renal vasodilation
methyldopa is for pre eclampsia
-Plasma half- life is about 2 minutes it’s
-Side effects of methyldopa: not effective in gestated ovary??
-The usual dose is 2.5-10 ng/kcal/min
 Sedation -It is rapidly metabolized in the liver to
 hemolytic anemia (positive coombs inactive conjugate glucuronic
acid 3,2 methyl docutamine
test)
-Could not be used in px with atrial
fibrillation
3. Apraclonidine and Brimonidine: these are -Side effects:
also sympatholytic Alpha 2 selective drugs  Nausea
and they decrease the secretion of  Headeache
aqueous humor that’s why it’s used in  Palpitations
 shortness of breath anginal
glaucoma
pain
-Activates alpha 2 adrenergic
-Therapeutic uses:
receptor  congestive heart failure
-Side effects:  cardiogenic shock
 blurring vision -Contraindicated in patients with
 dry mouth marked obstruction to cardiac ejection
 conjunctivitis like in idiopathic hyperthropic sub-
aortic stenosis
4. Dexmedetomidine: prominent sedative
BETA 2 AGONISTS
effects and used in anesthesia
1. Albuterol – most commonly used
5. Tizanidine: used as a muscle relaxant -activates adenylyl cyclase
-it is a bronchial smooth muscle
dilator. It used in asthma.
 BETA1 AGONIST DRUGS

1. Dobutamine - most popular member 2. Methaproterenol - is quite similar

- activates adenylyl cyclase, chemically to isoproterenol but it is
-Increases myocardial contractility it resistant to methylation by COMT it is
has a positive inotropic effect effective when given orally it has longer
duration of action than isoproterenol
Labayog, Malazzab, Onate, Tupaz 2
 -Primarily a beta 2 adrenergic agonists - After oral dose of 5mg, it produces
-Administered by inhalation it has bronchodilation after an hour and will last
relatively little effect on the beta 1 for 7 hours
receptors of the heart - Given by subcutaneous route and the
-After either oral or inhalation, effects will start within 5 minutes and it
methaproterenol will produce and increase will last for 4 hours.
in the force expiratory volume and - Side effects:
maximal rate of force expiratory flow but it  Muscle tremors
decreases the airway resistance  Nervousness
-After an oral dose you will see an  Headache
improvement of airway function an  Tachycardia
improvement in airway function will be  Palpitations
demonstrable for up to 4 hours.  Drowsiness
-After inhalation of the drug the improved  Nausea
respiratory function will be apparent for 3-  Vomiting
4 hours approximately 40% of  sweating.
metaproterenol is absorbed after oral
administration and the drug is excreted in 4. Albuterol - is selective Beta-2 adrenergic
the urine primarily as a conjugate with agonist also.
glucoronic acid - has the same pharmacologic property
and therapeutic implications similar to
-The adverse effect of methaproterenol :
those of with terbutaline.
 Tachycardia - When albuterol is given by inhalation
 Hypertension the effect will start within 15 minutes
 Nervousness and will last for 3-4 hours.
 Tremors
 Palpitation
 nausea 5. Trithotrine - which is a selective B-2
 vomiting adrenergic agonist also.
-Since it is a beta 2 adrenergic agonist it is - The clinical use of trithotrine is to
used as a bronchodilator prevent or delay the premature
parturition or premature labor.
3. Terbutaline - synthetic sympathomimetic - Trithotrine is rapidly but incompletely
agonist administered orally, absorbed, only 30% of the drug is
subcutaneously or by inhalation absorbed following administration
- Used as a treatment of reversible orally, 90% of the drug is excreted in
obstruction of the airways the urine as inactive conjugate and
- it is relatively selective beta-2 agonist about 50% of the drug is excreted
- not methylated by COMP unchanged after IV administration.

Labayog, Malazzab, Onate, Tupaz 3

(24:26) The other two mentioned is the  Urapidil
Isoetharine which is Used for thrombo-spastic  labetalol C
disease and prealterol? which is selective beta-1  chlorpromazine
adrenergic agonist use for chronic congestive  haloperidol
heart failure.  Trazodone
 Trimazosin
DOPAMINE D1 AGONIST
 Ergotamine
1. Fenoldopam - The most popular name  Dihydroergotamine
-activates the adenyl-cyclase, so it is a  Yohimbine.
vascular smooth muscle relaxant. 1. Phenoxybenxamine binds covalently to
- It relaxes the smooth muscle so the alpha receptor, so it causes irreversible
arteries, it is used for the treatment of blockade which is of long duration of 14-48
hypertension. hours or longer, it is somewhat selective
for a-1 receptor but it is less so than the
selectivity of prazosin.
DOPAMINE D2 AGONIST - the same as dimedamine? (30:05) They
block the alpha adrenergic receptors
1. bromocriptine - most popular
but they do not have alpha adrenergic
- an inhibitior, it inhibits adeny-cyclase, it
agonistic activity.
interrupts other intracellular pathways.
- It mimics or imitates the dopamine action
2. Pentolamine and tolazoline both produce a
in the Central Nervous System.
moderately effective competitive a-
- one of the drugs used for Parkinson’s
adrenergic blockade that is relatively
disease and Prolactenemia.
transient.
- It is used as a cardiac stimulant and as
a stimulant of gastrointestinal tract
ADRENOCEPTOR AGONIST DRUGS
that is blocked by atropine.
- Divided into alpha receptor agonist drugs and - It also stimulates gastric secretion and
beta receptor agonist drugs peripheral vasodilation.
- Pentolamine is more potent than
ALPHA RECEPTOR AGONIST DRUGS: tolazoline. However, both drugs can
 phenoxybenzamine cause alarming tachycardia, cardiac
 pentolamine arrhythmia and anginal pain.
 prazosin - Pentolamine is a potent competitive
 terasozine antagonist both the alpha-1 and alpha-
 Doxasozin 2 receptors.
 Tamsulosin
 Alfuzosin
 Silodosin
 Indoramin

Labayog, Malazzab, Onate, Tupaz 4

3. Prazosin is highly selective drug for a-1
receptors.
- It is anti-hypertensive drug that
appears to exert its vasodilator action
thru blockade of the post-synaptic
alpha-1 receptors.
- It can cause reversal of the pressor
responses to epinephrine and it blocks
the pressor response to
norepinephrine.
- Prazosin reduces the vascular tone in
both resistance and capacitance
vessels. Therefore, its effect is
associated with a reduction in the
venous return and reduction in the
cardiac output.
4. Terasozine is another reversible selective
a-1 receptor antagonist and it is also use as
anti-hypertensive drug.
5. Doxasozin has a long half-life of 22 hours
and it is use for hypertension and benign
prostatic hypertrophy.
6. Tamsulosin is a competitive a-1 antagonist,
it has a very high bioavailability and the
half-life is 9-15 hours
7. Alfuzosin is another a-1 selective
quinazoline derivative and it is used for
benign prostatic hypertrophy
8. Silodosin is also used for benign prostatic
hypertrophy
Labayog, Malazzab, Onate, Tupaz
9. Indoramin is another a-1 selective
antagonist that also has weak a-2
antagonist but it is used for hypertension
10. Urapidil is an a-1 antagonist also for
hypertension and BPH (pacheck sis 35:37)
11. Labetalol is a popular a-1 selective b
antagonist drug.
12. Chlorpromazine and haloperidol are both
potent dopamine receptor antagonist but
they also antagonist in the alpha receptor
13. Trazodone which is an anti-depressant has
a capacity to block the a-1 receptor
14. Trimazosin this is clinically related to
prazosin and exhibits similar
pharmacologic properties like prazosin, but
it has less potent inhibition of a-1
adrenergic receptor.
-It has half life 42 hours and it’s
extensively metabolized in the
liver.
15. Ergotamine and Dihydroergotamine these
are ergot alkaloids, they are ergot derivatives
but they can cause a-receptor blockade via a
partial agonist action.
- They act to the barrowing degree as
partial agonist or antagonist at the alpha
adrenergic, at the tryptominergic and
dopaminergic receptors.
- Ergotamine ___________ (38:06)
alkaloids produce coronary vaso-
constriction and associated ischemic
changes that are evident in ECG and it can
5
 even cause anginal pains to patients with
coronary artery disease.
- Another side effects of the ergot alkaloids
(that is not very much welcome) is that it
induces bradychardia.
- The primary therapeutic use of these
ergot alkaloids is for the stimulation of
uterine contraction post-partum, it is also
used to relief the pain of migraine.
16. chlorpromazine which is an anti-emetic drug
which can prolong and enhance also the pressor
response to norepinephrine.
17. Haloperidol inhibits dopamine induced renal
vasodilatation.
- It is an alpha-2 selective antagonist. It
produces an alpha-adrenergic blockade of
limited duration, and has little direct effect
on the smooth muscles but it readily
penetrates the CNS
18. Yohimbine is sometimes used in the
treatment of orthostatic hypotension.
BETA-RECEPTOR ANTAGONIST DRUGS
First group. blocks B1- and B-2 - These are your
nadolol, propranolol, timolol
A. NONSELECTIVE BETA-ADRENERGIC BLOCKERS
 block beta-1 and beta-2
 includes:
 Propranolol
 Nadolol
 Timolol
 Alprenolol
 Oxprenolol
 Penbutolol
Labayog, Malazzab, Onate, Tupaz
 Pindolol
 Sotalol
 uses:
 lowers BP
 slows heart rate
 reduce renin secretion

1. PROPRANOLOL
 blocks both beta-1 and beta-2 receptors
competitively
 widely used for the treatment of
hypertension
 for the prophylaxis of angina pectoris
 control certain types of cardiac
arrhythmias
 does not exhibit any intrinsic agonistic
properties
 decreases heart rate and cardiac output
 prolongs mechanical systole
 slightly decreases BP in resting subjects
 effects on the heart is more marked;
increased demand and sympathetic tone
 the total myocardial consumption in
coronary blood flow are also increased as a
result of the reduction of heart rate and
the ventricular systolic system and
contractility
 the release of renin from juxtaglomerular
apparatus is stimulated by beta adrenergic
agonists but its effect is locked by
Propranol
 also inhibits the Vasopressin and
vasodilator effect of Isoproterenol
 augments the pressor effects of
Epinephrine
 reduces the sinus rate
 decreases the spontaneous rate of
depolarization of topic pacemakers
 slows conduction of atrial endothelium
6
  blocks actions of sympathomimetic amines 2. NADOLOL
(beta adrenergic receptors - stops salivary)  long-acting nonselective beta-adrenergic
 almost completely absorbed following oral receptor blocking drug
administration  not catalyzed extensively
 much of the drug is metabolized by the  excreted largely unchanged in the urine
liver during its first passage through the  half-life: 6 to 20 hrs
circulation  given once a day (OD)
 1/3 of the dose reaches the systemic  does not possess membrane-stabilizing
circulation pigment and lacks partial agonist activity
 half-life:  does not readily pass the blood-brain
o initial: 3hrs barrier
o after chronic: 4hrs  adverse effects are same with Propranolol
 ingestion of food will reduce the first pass  available as: 40-160mg tablet
effect on Propranolol and increases its
bioavailability
 90-95% of the drug is found in the plasma 3. TIMOLOL
protein  nonselective beta-adrenergic antagonist
 It is completely metabolized before excretion without local anesthetic properties
through the urine  has minimal intrinsic sympathomimetic
 metabolites are: activity
o 4-hydroxyl propranolol  5-10x more potent than Propranolol as a
o Naphthyloxylactic acid beta adrenergic blocking drug
o N-desisopropylpropranolol  well-absorbed if given orally but
o Propranolol glucoronide undergoes considerable first pass hepatic
 Marketed as Inderal; available as 10-90 mg metabolism
tablet; also available as ampule for IV and as  Timolol and its metabolites are excreted in
sustained-release capsule the urine rapidly
 half-life in the plasma: about 4 hrs
 SE:  used in hypertension and angina pectoris
 heart failure  also effective in reducing the incidence and
 rebound hypertension death after myocardial infarction
 increase airway resistance (CI for  available as:
asthma) o 5, 10, 20 tablet
 hypoglycemia o also available as ophthalmic
 nausea preparation for chronic wide angle
 vomiting glaucoma (other type: secondary
 mild diarrhea glaucoma)
 constipation o also available as eyedrops in 0.25-0.5%
solution

Labayog, Malazzab, Onate, Tupaz 7

 initial dose: 1 drop to the affected eye twice a
day
 duration of action: more than 7 hours
 must be used with caution in patients with
asthma, heart block or heart failure
B. SELECTIVE BETA-1 ADRENERGIC BLOCKERS
 blocks beta-1 more than beta-2
 uses:
 lowers BP
 slows heart rate
 reduce renin
 safer for asthmatic patients
 includes:
 Metoprolol
 Atenolol
 Alprenolol
 Betaxolol
 Nebivolol
 Celiprolol
 Bisoprolol
 Esmolol
 Acebutolol
1. TIMOLOL: when used as an ophthalmic
drug, its effect is for 7 hours but as a beta
blockers for causes of asthma, heart block
and heart failure
2. INDOLOL - is a non-selective and beta
adrenergic antagonist drug also but it has a
considerable partial agonist activity
- it does not have a membrane stabilizing
activity with the usual dose.
- There is a smaller reduction in testing
with the one with decreased cardiac
output and heart rate than the one seen in
drugs which are partial agonist.
Labayog, Malazzab, Onate, Tupaz
3. PINDOLOL - is preferred to patient with less
cardiac reserve and those liable for severe
bradycardia.
-It will block the decrease heart rate and
cardiac output with exercise.
-efficiently absorbed under those with the
little first pass metabolism and have 50 %
of the drug is metabolized.
- The principal metabolites are contributed
with either glucoranide or intake and is
excreted in the urine.
- Half-life is short, approximately 3-4 hours
-Is available as 5 mg and 10 mg tablet
4. LABETALOL AND CARVEDILOL
- the other drug that are in this group
that are not listed
- have the same pharmacologic
characteristics as what have discussed.
GROUP THAT BLOCK BETA 1 THAN BETA 2
SELECTIVE BETA 1 BLOCKER
- They lower the heart rate and they lower
the blood pressure and reduced the renin
secretion.
Members are:
 Metoprolol
 Acebutolol
 Atenolol
 Betaxolol
 Nevibolol
 Bisoprolol
1. METOPROLOL - most popular
- Is a relatively selective beta 1 adrenergic
antagonist and it does not have many
agonist activity.
-It effectively inhibits the inotropic and
chronotropic response to isoproterenol
8
 -it reduces plasma renin activity in
hypertensive patients and in normal
subjects.
-it inhibits the rise in plasma renin activity
that is normally induced by cardiovascular
stress.
- Efficiently and rapidly absorbed in gastro
intestinal tract
- it is subject to first pass metabolism in
the liver
- 40 % of the drug will reach the general or
systemic circulation.
- Peak plasma concentration: is about the
switch of 90 minutes
- Plasma Half Life: 3 hours.
- It is effectively metabolized in the body.
- The 10 % of the drug is excreted in the
urine
- the metabolites lack significant
pharmacological activity
- Side Effect Of Toxic Reaction:
 Some reduction in post expiratory
volume in asthmatic patients
 There is a reduced glucose
tolerance in diabetes mellitus
patients and even in normal
individuals.
 fatigue, HA, dizziness and insommia
- the most common side effects
- usually given by injection
- it is used in early case of suspected or
definite acute MI
- contraindicated to patients with:
 bradycardia
 heart block
 systolic blood pressure of
less than 100 mmmhg
 those with moderate to
severe cardiac failure
 with hypertension, angina
and MI
Labayog, Malazzab, Onate, Tupaz
2. ATENOLOL - selective beta 1 adrenergic
drug
- with insignificant partial antagonist
activity
- with membrane stabilizing
property.
- It is completely absorbed if given
orally
- excreted largely in the urine
- Plasma half-life is 6-8 hours but its
anti-hypertensive effect appears to
last for a longer period of time
- Given once a day, but dosage
interval should be increase if renal
impairment is present in significant.
- does not enter the CNS to a
significant degree but fatigue and
depression are not uncommon side
effects.
- Other side effects- same as
metoprolol
- However, they found out that
atenolol does not appear to
potentiate the insulin induced
hypoglycemia.
- It is taken orally with 50-100 mg per
tablet,
- usual initial dose is 50 mg OD
3. BUTOXAMINE - the one that blocks beta 2
more than beta 1
- decreases the total peripheral
resistance and there is no current
clinical indication to this drugs
9
BETA 1 AND BETA 2 BLOCKER DRUGS  thyrotoxicosis
 myocardial cardiac ischemia
-have intrinsic sympathomimetic activity - only given parentally. Not orally.
that means they have partial agonist effect

- lower blood pressure and moderately DRUGS THAT BLOCK BETA RECEPTORS MORE
lower heart rate THAN THE ALCOHOL RECEPTORS
o They are used for remedy for heart failure.
Drugs Under this Group
o They are given orally and they have a long
 Indolol half-life.
 Acetebutolol o The most common toxic reaction is fatigue.
 clopidolol o Drugs under this:
1. Balberilol
 penbutolol
2. Medroxanol
 acebedelol
3. Mucipulol
 carteolol
4. Lametrolol
 oxypenolol
 penirolol
DRUGS THAT BLOCK BETA 1 MORE THAN BETA 2
o There is only one step that appeared. It is
BETA RECEPTORS BLOCKERS MORE THAN THE
escolol.
ALPHA 1 RECEPTORS
o Escolol – is the benedrift alpha1 beta
- they are used commonly for heart failure blocker.
- given orally It is used for:
- has a long half-life 1. Rapid control of the blood
- fatigue - Most common toxic reaction pressure
2. Arrhythmias
Drug under this: 3. Thyrotoxicosis
 Carvedilol 4. Myocardial stigma
 Medroxalol 5. It is used for the omefterol,
 mupicolol so give it orally
 methoxelol – half life: 10 minutes
 Carbedilol – Toxic effects: Bradycardia and
 Laehtelol hypotension

o Labetalol – a beta adrenergic blocking

drug.
ESMOLOL
- It is used for the protection. It is a
- only one listed drug that blocks pyrimethoxine drug with unique
beta 1 more that beta 2 receptor and complex autonomic properties.
- is a very brief cardiac beta blocker - With such goal that selective alpha
rapid control of : 1 and nonselective beta adrenergic
 hypertension blocking activity. It is also able to
 arrhythmias inhibit the reuptake of
Labayog, Malazzab, Onate, Tupaz 10
 norepinephrine into the nerve
terminals.
- 1/3 as potent as phentolamine in
blocking alpha receptors.
- 1/3 as potent as propranolol in
blocking beta receptors.
- After the ganglionic blocking,
labetalol has little effect on the
heart rate that it produces
vasodilation that is blocked by
propranolol.
- Appears to have an intrinsic
sympathomimetic activity that is
largely defined to beta 2 adrenergic
receptors.
- It is well absorbed when it is taken
orally and very large portion of the
drug is metabolized during the first
circulation in the liver. An extensive
hepatic first pass metabolism.
- Plasma half-life: 5 hours
- 5% of the drug is excreted in the
urine
- It is used for sexual hypertension,
pleochromocytoma, and abrupt
withdrawal of _____?
- Labetolol is a great
vasculoconstrictor
- Initial dose: 100 mg 2X a day
o Acebutanol – 1/3 as potent as propranolol
- It has local anesthetic activity
- It has an decreasing
sympathomimetic activity
- Plasma half-life: 3 hours
TYROSINE HYDROXYLASE INHIBITORS
o Metyrosine – blocks tyrosine hydroxylase.
- It reduces the synthesis of
dopamine, norepinephrine, and
epinephrine; therefore, it lowers
the blood pressure.
Labayog, Malazzab, Onate, Tupaz
- In the CNS, it may elicit
extrapyramidal effects due to low
dopamine.
- It is used in pleochromocytoma.
- Toxic effect: extrapyramidal
symptoms and it can also produce
orthostatic hypotension
OTHER ANS DRUGS
o Reserpine – a very old drug but it is still
used in some clinical conditions.
- One of the adrenergic neuron
blocking drugs.
- It takes this course of
catecholamine in many organs,
including the brain.
- After parenteral administration of
relatively large doses, it causes this
cholinomimetic fall in blood
pressure. It is frequently associated
with bradycardia.
- It requires up to three weeks for
full tactile, hypertensive. So,
reserpine cannot be used in
emergency purposes.
- It is rarely used. It used only but
also rarely in psychiatric patients
because they have a good effect on
the behavior of psychiatric patients.
- One dreaded effect of reserpine is
that it causes severe depression
and it even cause some suicidal
tendencies.
DRUGS THAT ARE USED FOR THE TREATMENT OF
LIPOMA are also autonomic drugs like:
o Beta blockers (Most commonly used:
Picolol)
o Osmotic agents (Most commonly used:
Sanitol)
o Alpha 2 agonists (except apraclonidin)
11
 o Carbonic anhydrase inhibitors
(Acetylamide and dosolamide)
*All of these decrease the secretion of
aqueous tumor from the single epithelium.
They decrease the secretion of aldosterone
o While the hepatic drugs – the
cholinomimetics, like pilocarpine and
physostigmine – act on the ciliary muscle
production so they open the trachidial
escort by increasing outflow … [‘Di
maintindihan –1:42:19]
o Prostaglandin, like labanofros – it
increases the outflow to the canal of
Schlemm
o Non-selective alpha agonist (Most
commonly used: epinephrine) – it
increases the outflow of aqueous tumor by
the manubrioscleral veins.

Baka lalabas sa exam according to doc

1. Esmolol is a pluropractic
betablocker, used only parenteral
2. Anulol is the longest acting beta
blocker
3. Acebutanol and adenolol are less
lipid soluble than the other beta
blockers, so they probably enter
the CNS through the …
4. high lipid solubility - Propranolol
5. Moderate lipid solubility -
Labetamol, mecoprolol, picolol, and
pimolol
6. Very low lipid solubility –
Acebutanol, adenolol, desmolol,
and anulol

Labayog, Malazzab, Onate, Tupaz 12