carbons → alteration of activity and function of

drug
ADRENERGIC AGONIST/ SYMPATHOMIMETICS
- parent drug- origin or precursor of
sympathomimetic drug
- They mimic the effects of neurotransmitters
such as norepinephrine, epinephrine, and
dopamine
- They are adrenergic agonists because they A. Substitutions on the AMINO GROUP
activate the adrenoceptor such as alpha, beta,
and dopaminergic receptors. increasing the size of alkyl substituents on the
amino group 🡪 increases B-receptor activity
Four main receptors - B receptor activity: Isoproterenol- propyl/
- Alpha 1 CH(CH3)2 > epinephrine methyl/ CH(CH3)2 >
- Alpha2 norepinephrine- unsubstituted
- Beta 1 - Norepinephrine is unsubstituted meaning
- Beta 2 walang nasubstitute or nalagay na alkyl group
sa kanyang amine group but nung naging
α1 epinephrine siya, nagkaroon ng methyl
- vasoconstriction 🡪 increase resistance group or CH3 doon sa epinephrine
- increase BP - Isoproterenol- has propyl group in the amino
- closure of bladder sphincter group of phenylethylamine (norepinephrine is
- mydriasis unsubstituted, epinephrine has methyl group,
α2 isoproterenol has propyl group, which has a
greater activity in the beta receptor?
- inhibition of NE (norepinephrine) release
ANSWER; ISOPROTERENOL 🡪 the longer
- inhibit insulin release
β1 the alkyl substituent is, the greater the
- increase heart rate, contractility beta receptor activity. It is more selective
- lipolysis in beta receptor compared to epinephrine and
norepinephrine
- causes positive ino, chrono and
- increase alkyl substituent, increase beta
dromotropic effect
receptor activity
β2
- 4 Substitution- results in alkylation of function or
- bronchodilation
activity of the drug
- uterine relaxation
- glucagon release -> glycogenolysis -> increase
glucose levels
B. Substitutions on the BENZENE RING
ADRENERGIC DRUGS
- stimulate the sympathetic NS Catecholamines
- AKA adrenergic agonist, sympathomimetic, o contain OH at 3, 4 (catechol ring)
adrenomimetic o ex. epinephrine, norepinephrine, isoproterenol,
- they mimic NE and Epinephrine dobutamine, dopamine
- act on one or more receptor sites o Maximal a, B activity (alpha, beta) 🡪 equal
activity of alpha and beta receptor
PHENYLETHYLAMINE o because of presence of OH, rapid inactivation
- Considered as the PARENT compound from by COMT in the intestines so cannot be
which sympathomimetic drugs are derived given orally (given in injections)
- Consists of benzene ring with an ethylamine o COMT- enzyme used to break down
catecholamines
o Can be given through injections
o polar- poor CNS penetration
-
o has catechol ring 🡪 a benzene/catechol ring
- Alpha carbon- nearby amine
which has an OH at carbon 3 and 4
- Beta carbon- nearby benzene
o AKA 1,2 Dihydroxybenzene
- Substitutions may be made on the terminal amino
group, benzene ring, and on the alpha or beta
Non-catecholamines
o absence of one or both OH in 3,4
o ex. phenylephrine, ephedrine, amphetamine
o longer duration of action since it is not
inactivated by COMT
o can be given orally
o good CNS penetration 🡪 lipid soluble
C. Substitution on the ALPHA CARBON
Methylation (adding methyl grp) blocks oxidation by
MAO
- ex. ephedrine, amphetamine 🡪 have methyl group
that blocks the oxidation by MAO so they ay
resistant with the action of MAO.
- may promote NE release- indirect-acting
activity
- carbon nearby the amino group
- 2 enzymes responsible for metabolism of
neurotransmitter in SNS 🡪 MAO and COMT
D. Substitutions on the BETA CARBON
- addition OH- direct-acting activity
- OH substitute can produce a direct-acting
activity
NOTE:
- Methylation in alpha carbon causes indirect-acting
activity
- Addition of OH group in beta carbon causes
direct-acting activity
CLASSIFICATION OF ADRENERGIC DRUGS
MOA of sympathomimetic drugs:
According to their effect on organ cells:
1. Direct-acting
- acts on the receptor such as alpha, beta, and
dopaminergic receptor
- directly stimulate the adrenergic receptors
(Epinephrine and Norepinephrine)
2. Indirect-acting
- They will not act on the enzyme
- It will affect the release of the
neurotransmitter
- Will increase the release of the
neurotransmitter
- Actions are dependent on the release of
endogenous catecholamine. Example:
Amphetamine stimulates the release of NE
from the terminal nerve ending.
3. Mixed–acting
- Affects both the receptor and the release of
the neurotransmitter
- Direct and Indirect-Stimulates receptor site
and release of NE from nerve endings. Ex.
Ephedrine
ADRENERGIC AGONISTS
DIRECT ACTING
- Directly bind to the receptor
a. α, β agonists
- Epinephrine, NE, Dopamine
b. α agonists
- α1-agonist- Phenylephrine,
Phenylpropanolamine, Methoxamine.
- a2-agonist- Clonidine
c. β agonists
- β1 agonists- Dobutamine.
- β2 agonists – Salbutamol, Terbutaline.
- β1 agonists and β2 agonists- Isoproterenol
Α, Β AGONISTS
1. Epinephrine/ adrenaline
- DOC: anaphylactic shock 🡪 symptoms: flushing,
bronchoconstriction, redness of skin, hypotension
- Bronchodilator in lungs
- anaphylaxis (bronchodilator)
- treatment for cardiac arrest
- local anesthetics 🡪 adjunct drug for local
anesthetics
- epinephrine will prevent systemic absorption
of local anesthetic
- eg. lidocaine (1:100,000)- prolongs effect of
local anesthetic
- S/E (side effect): HTN, arrhythmia, MI (myocardial
infarction), pulmonary edema/hemorrhage
2. Norepinephrine (Levophed)/ Noradrenaline
- DOC: septic shock
- Tx. shock/ hypotension
- increase heart rate, contractility;
vasoconstriction 🡪 increase BP
- kapag naiinhibit and NE, bumababa and blood
pressure
3. Dopamine (Docard)
- DOC: for cardiogenic shock 🡪 congestive heart
failure, the inability of the heart to pump blood
- a cardiogenic drug
- tx. shock/ hypotension
- can produce increase in the blood flow and
cause dilation of renal blood vessel
- renal failure to increase blood flow
- dopamine receptors- dilation of renal vessels
- binds both in dopamine 1 and dopamine 2 receptor
- Low dose: dopamine receptors 🡪 may cause
vasodilation
- Moderate dose: β-receptors
- High dose: α-receptors 🡪 may cause
vasoconstriction
Dopamine 1 Agonist: Fenoldopam
- effect: peripheral vasodilation in some vascular
beds.
- for the treatment of severe hypertension (IV)
- D1 >> D2 (fenoldopam has greater activity in D1
than in D2 receptor)
- Dopamine 1 Agonist- acts on the vasodilation of
blood vessel
Dopamine 2 Agonist: Bromocriptine
- MOA: Inhibits adenylyl cyclase and interacts
with other intracellular pathways
- A decrease in the amount of CAMP that causes
vasodilation and bronchoconstriction.
- adenylyl cyclase- converts ATP into CAMP
- increase adenylyl cyclase, increase in CAMP
(causes contraction in heart, bronchodilation
in lungs)
- Effects: Mimics dopamine actions in the CNS
- Uses: Parkinson’s disease, prolactinemia
- Parkinson’s disease- depleted yung
dopamine, prolactinemia is an excessive
amount of prolactin causing increase in milk
secretion
In pharmacology, iisa lang ang effect ng ex. Alpha 1
agonists, but used in different conditions
ALPHA 1 AGONISTS
1. Phenylephrine
- (Neo-Synephrine, Dimetapp)
- Tx. nasal decongestant, shock, mydriatic
(dilation of pupil 🡪 treatment of glaucoma)
- Causes vasoconstriction
- S/E: HTN 🡪 hypertension
2. Phenylpropanolamine
- (Neozep, Decolgen, Tuseran, Disudrin, Sinutab),
Pseudoephedrine (Sudafed): nasal decongestant
- Withdrawn in the US because it causes
hemorrhagic stroke
3. Methoxamine
- For hypotension (during surgery) induced by
halothane
- Causes vasoconstriction and nasal decongestant
OTHER ALPHA 1 AGONISTS
4. Midodrine
- MOA: Activates phospholipase C, resulting in
increased intracellular calcium and
vasoconstriction
- phospholipase C- enzyme converting
phosphatidylcholine into IP3 and DAG
- Effects: Vascular smooth muscle contraction
increasing BP
- Used in the treatment of postural hypotension /
orthostatic hypotension 🡪 common side effect
of alpha 1 blocker (a sudden decrease in the blood
pressure through sudden change of position. Ex.
From lying position to standing position) → ung
nag gagalaxy pag bigla ka tumayo
5. Xylometazoline & oxymetazoline (topical)
- When taken in large doses, oxymetazoline may
cause hypotension, presumably because of a
central clonidine-like effect
- Used for hypotension
ALPHA 2 AGONISTS
1. Clonidine (Catapres) – SE: rebound hypertension
(a sudden increase in blood pressure)
2. methyldopa (Aldomet) – a false
neurotransmitter (related to dopamine). It gives a
false positive result at coomb’s test (a test for
hemolytic anemia)
3. Guanfacine
4. Guanabenz
o treatment of Hypertension 🡪 decrease NE
release 🡪 decrease BP
- MOA: Inhibits adenylyl cyclase thereby
inhibiting the release of Norepinephrine from
sympathetic nerve endings
- Inhibits release of norepinephrine 🡪 decreases
blood pressure, that is why it is used in the tx. Of
hypertension
BETA 1 AGONISTS
1. Dobutamine (Dobutrex)
- congestive heart failure
- USED in cardiogenic shock
- S/E: tachycardia, arrhythmia
BETA 2 AGONISTS
- Bronchodilation in lungs and relaxation of
uterus causing tocolytic effect
- Bronchodilator for the treatment of asthma and a
tocolytic drug or a drug that prevents premature
labor.
1. albuterol/ salbutamol (Ventolin)
OTHER SYMPATHOMIMETICS (indirect-acting-
- Terbutaline (Bricanyl), metaproterenol
acts only on release)
- Salmeterol, Formoterol 🡪 bronchodilators
o asthma
2. terbutaline- prevents premature labor acting as 1. Methylphenidate and Pemoline
tocolytic drug – decrease uterine contraction 🡪 - For ADHD
relaxes uterus 2. Modafinil
- S/E: stimulates B1 at high doses: palpitations, - new drug with both similarities to and differences
tremor from amphetamine.
- has significant effects on central 1B receptors but
MIXED BETA 1 AND BETA 2 AGONISTS in addition appears to affect GABAergic,
1. Isoproterenol AKA isoprenaline glutaminergic, and serotonergic synapses
- Has both an activity with b1 and b2 receptor - approved for use in Narcolepsy
- Treatment of cardiac arrest, asthma (rare) (masa-masandal-tulog)
- S/E: Hypertension, palpitations, arrhythmia - it increase norepinephrine release that is why it
- Non-selective beta agonist can be used as a stimulant

INDIRECT ACTING MIXED/ DIRECT AND INDIRECT AGONISTS

promotes NE release - both acting on the receptor and on the release of

- they will not affect the receptor but are neurotransmitter
promoting the norepinephrine release
Ephedrine
1. Tyramine - alkaloid from ma huang (Ephedra sinica)
- rich in tyramine: red wine, beer, cheese, - tx. For urinary incontinence,
chocolates (bawal sa depressed) bronchospasm, hypotension, nasal
- can cause Hypertension in patients taking MAO congestion, narcolepsy
inhibitors (MAO inhibitors are antidepressant - a stimulant and a bronchodilator
drugs) - S/E: HTN, tachycardia, arrhythmia, insomnia
- abundant amount of norepinephrine will cause
hypertensive crisis, cannot be given in patients Metaraminol
taking MAO - Used in tx. Of Hypotension
- MAO: cannot be given in tyramine because - Used to increase blood pressure
tyramine will increase norepinephrine (if taken with - Used when norepinephrine and dopamine is not
maoi) NO POPULAR MEDS possible for the treatment of shock (a
- Nardil (phenelzine) substitute)
- Parnate (tranylcypromine)
- Marplan (isocarboxazid)
ADRENERGIC ANTAGONIST
2. Amphetamines 🡪 increase norepinephrine
release
- For attention deficit hyperactivity disorder - Direct acting- acts on receptor
(ADHD), appetite suppression - Indirect Acting – acts on enzymes or the release
- Used as an appetite suppressant (pag uminom ka of neurotransmitter
nito feeling mo busog ka and hyper ka)
- S/E: HTN, tachycardia, dependence, insomnia,
seizures psychosis
Alpha blockers
- Alpha 1 receptor will cause vasoconstriction, upon
blocking A1, it will cause vasodilation.
- Vasodilation, decrease in peripheral vascular
resistance (PVR), decrease blood pressure
causing hypotension
- Postural hypotension- a condition wherein a
sudden change in position will cause a sudden
drop in blood pressure (causes decrease BP
and dizziness)
- Compensatory: increase the pulse rate to
produce a reflex tachycardia (para mapataas ng
konti yung blood pressure)
- Most common effects of alpha blockers are
orthostatic hypotension (AKA postural
hypotension) causing increased pulse rate to
produce reflex tachycardia.
ALPHA 1 BLOCKERS 🡪 ends in “osin”
- Ex. prazosin, doxazosin, terazosin
- Since alpha 1 agonist causes vasoconstriction,
alpha 1 blocker causes vasodilation
- Used in the treatment of Hypertension- decrease
vasoconstriction
- dec. resistance -> dec. BP
- tx. For benign prostatic hyperplasia-
enlargement of prostate gland that 🡪 prevents
urinary retention
- S/E: orthostatic hypotension especially after the
first dose of the drug/ syncope
- Syncope- first dose phenomenon 🡪 characterized
as fainting at the administration of first dose
- To avoid syncope- trim down the dose into 1/3
or ¼ or the dose to prevent excessive
dropping of blood pressure
ALPHA 2 BLOCKERS
1. Yohimbine
- tx. Of impotence- penile injection
- MOA: used to inhibit PDE 5
(phosphodiesterase) 🡪 an enzyme used for
metabolism of CAMP producing a decrease in
amount of CAMP
- It increases the amount of CAMP producing
contraction
- Pag madaming CAMP it produces erection
specifically in the penis that it why it can treat
impotence through penile injection
- One of the drug for male erectile dysfunction
MIXED ALPHA 1 AND ALPHA 2 BLOCKERS
1. phenoxybenzamine
- irreversible, long-acting
- HTN due to pheochromocytoma 🡪 tumor in the
adrenal medulla
- (adrenal medulla tumor 🡪 increase epinephrine
release producing increase in blood pressure)
- S/E: postural hypotension
2. Phentolamine
- reversible, short-acting
- pheochromocytoma induced HTN
- S/E: postural hypotension
BETA BLOCKERS
1. Non Selective blockers
- Blocks both beta 1 and beta 2 receptors causing
decrease in blood pressure and
bronchoconstriction
- Ex. propranolol, timolol, nadolol
- used for HTN, post-MI (myocardial infarction),
angina pectoris, SVT (supra ventricular
tachycardia), heart failure
a) Propranolol- tx. Of migraine, stage fright,
hyperthyroidism. it promotes bradycardia and
lowers thyroid hormone
- PROTOTYPE DRUG
- has negative chronotropic and inotropic
effect
- used for decreasing heart rate
- cause decrease in oxygen consumption 🡪 for
tx. Of angina
- decrease cardiac output 🡪 decrease blood
pressure
- contraindicated in px with asthma because it
can cause bronchoconstriction
- tx. Of migraine because it can block the
catecholamine induced vasodilation
b) Timolol
- tx. For glaucoma
- S/E: bradycardia, heart block, bronchospasm
in patients with COPD/asthma
- S/E: Bronchoconstriction- contraindicated for
asthmatics
2. Selective blockers
- Can block beta 1 receptor only 🡪 For the tx. Of
hypertension, not contraindicated in patients with
asthma
- EX. metoprolol, atenolol, esmolol, acebutolol,
nebivolol, BETAXOLOL
- Acronym: BEAAMN- betaxolol, esmolol, atenolol,
acebutolol, metoprolol, nebivolol.
- Most selective beta blocker is nebivolol
- also blocks B2 receptors at high doses

3. Combined/mixed alpha and beta blockers

a) Labetalol 🡪 alternative drug for hydralazine in
the tx. Of pregnancy induced hypertension
b) Carvedilol

4. beta blocker with partial agonist activity

- intrinsic sympathomimetic activity
- ex. Pindolol, acebutolol, labetalol (PAL)
- Cause some bronchodilation
- For treating patients with asthma 🡪 causes
bronchodilation
- A beta 1 blocker but may also produce some
intrinsic sympathomimetic activity. Can be an
agonist at some receptor (a beta 1 blocker
but a beta 2 agonist)

5. beta blocker with MSA (MEMBRANE

STABILIZING ACTIVITY)
- Anesthetic Effect: ex. Pindolol, Propranolol,
Acebutolol, Metoprolol, Labetalol (PAL PM)

INDIRECT ACTING
1. Guanethidine- inhibits release of neurotransmitter,
for tx. Of hypertension
- HTN
- rarely used
2. Reserpine – inhibits VMAT ( a protein responsible
for storage of dopamine in the storage vesicle)
- alkaloid from Rauwolfia serpentina
- tx. For hypertension but is rarely used
- rarely use

RECAP:
Adrenergic
1. direct – acts on receptor
- a1 blocker
- a2 blocker
- mixed alpha 1 and a2 blocker
- beta blocker (5 types)
2. indirect – acts on the release