GANGLIONIC BLOCKERS • Competitive pharmacologic antagonists at nicotinic acetylcholine receptors
(NN) of both sympathetic and parasympathetic autonomic ganglia • First successful agents for the
treatment of hypertension but were abandoned due to severe adverse effects Hexamethonium,
Trimethaphan, Mecamylamine MOA Competitive Nn blocker Uses Hypertension (Obsolete),
Hypertensive emergencies SE Postural Hypotension, Dry mouth, Blurred vision, Constipation, Sexual
dysfunction, Tachycardia Let’s use this section as a learning point to help you remember an
important neurotransmitter. What is the important neurotransmitter for (1) pre-ganglionic
sympathetic nerve fiber? (2) post-ganglionic para-sympathetic nerve fiber? Answer: You should
answer ACh for both. This would make sense again, because the receptors in the ganglion are Nn
which is a type receptor for Ach. Hence if you can notice sabi na mabblock niya both sympathetic and
parasympathetic ANS kasi Nn is seen in the ganglion of both sympa or parasympa. Dr. Rodriguez
NEUROMUSCULAR BLOCKERS The curare compounds “-curiums” and “curoniums” Tubocurarine,
Pancuronium, Atracurium, Vecuronium, MOA Nm blocker Uses Skeletal muscle relaxation prior to
surgery SE Tachycardia, confusion, urinary retention, increased IOP SECTION SYNTHESIS Quick
synthesis. Kindly fill out the table below. Name as much drug as you can. Try to push this exercise
further by recalling the use. Dr. Rodriguez DESCRIPTION DRUGS CHOLINERGIC AGONISTS: DIRECT
ACTING Non-selective M3 selective Nn and Nm Agonist Selective Nm agonist CHOLINERGIC AGONIST:
INDIRECT ACTING An alcohol Carbamates Organophosphates Drugs for Alzheimer’s CHOLINERGIC
ANTAGONIST: MUSCARINIC BLOCKERS Non-selective blockers M3 receptor blockers M1 selective
blockers CHOLINERGIC ANTAGONIST: NICOTINIC BLOCKERS Ganglionic blockers Neuromuscular
blockers Answers: On purpose won’t be placing here the answers for this table. Because I want this
to be a learning opportunity for you. The table is made in the same chronology as how we discussed
it and I want you to go back to the previous pages to complete this table J Dr. Rodriguez
VISUALIZATION TIME! Get a scratch paper. And try to create a concept map for the whole cholinergic
Pharmacology by following the table you completed above. Use this as your go-to notes when you
review Dr. Rodriguez ADRENERGIC PHARMACOLOGY A. CATECHOLAMINE SYNTHESIS
NOREPINEPHRINE • Primary transmitter at the sympathetic postganglionic neuron effector cell
synapses in most tissues o EXCEPTIONS: § Accrine sweat glands (uses ACh) § Vasodilator sympathetic
fibers in skeletal muscle • It is the immediate precursor of epinephrine STEP 1 – SYNTHESIS •
Tyrosine is hydroxylated by tyrosine hydroxylase to DOPA o Rate-limiting step o Inhibitor: Metyrosine
• DOPA is decarboxylated to dopamine • Dopamine is hydroxylated to norepinephrine STEP 2 –
STORAGE • Norepinephrine and dopamine are transported into vesicles o Inactivated by monoamine
oxidase in the cytoplasm o Monoamine oxidase inhibitors (MAOi) increase stores of NE and
dopamine • Inhibitor: Reserpine o The transfer of DOPA into vesicles is BLOCKED by the drug o STEP
3 – RELEASE • entry of calcium -> calcium interacts with SNARE proteins (VAMPs and SNAPs) ->
vesicle fuses with membrane o Inhibited by: Guanethidine o Promoted by: Amphetamines and
Tyramine * Release of NE via these agents is calcium INDEPENDENT. STEP 4 – TERMINATION •
diffusion and reuptake via NET and DAT in synaptic cleft o inhibited by Cocaine and TCAs •
metabolized by MAO and COMT into metanephrines and VMA o inhibited by MAOi and COMTi
Remember earlier, we asked you to remember the inhibitors for cholinergic NT synthesis. Now notice
the inhibitors for the adrenergic nervous system. Can you try to fill out the table below in order to
synthesize the idea? Dr. Rodriguez Adapted from Katzung BG. Pharmacology Board Exam Review
STEPS INHIBITORS CHOLINERGIC ADRENERGIC Synthesis A F Storage B G Release C H Termination
Metabolism D I Reuptake E J Answer: A. Hemicholinium. B. Vesamicol C. Botulinum D. Neostigmine.
E. None F. Metyrosine G. Reserpine H. Guanethidine I. MAOis, and COMTs, J. Cocaine and TCA Dr.
Rodriguez B. ADRENERGIC RECEPTORS Receptor Location G 2nd Msgr Function Alpha 1 (ɑ1) Effector
tissues, Smooth muscle, Glands Gq ↑IP3, DAG ↑Ca2+, causes contraction, secretion Alpha 2 (ɑ2)
Nerve endings, Smooth muscle Gi ¯cAMP ¯transmitter release, causes contraction Beta 1 (β1) Cardiac
muscle, JG apparatus Gs ↑cAMP ↑heart rate, force ↑renin release TOPNOTCH MEDICAL BOARD
PREP PHARMACOLOGY MAIN HANDOUT BY DR. YNS PEREYRA-BORLONGAN, MD-MBA For inquiries
visit www.topnotchboardprep.com.ph or https://www.facebook.com/topnotchmedicalboardprep/
This handout is only valid for October 2022 PLE batch. This will be rendered obsolete for the next
batch since we update our handouts regularly. TOPNOTCH MEDICAL BOARD PREP PHARMACOLOGY
MAIN DIGITAL HANDOUT BY MARIA YNA PEREYRYA-BORLONGAN, MD-MBA Page 14 of 95 For
inquiries visit www.topnotchboardprep.com.ph or
https://www.facebook.com/topnotchmedicalboardprep/ This handout is only valid for the October
2022 PLE batch. This will be rendered obsolete for the next batch since we update our handouts
regularly. Receptor Location G 2nd Msgr Function Beta 2 (β2) Smooth muscle, Liver, Heart Gs ↑cAMP
Relax smooth muscle ↑glycogenolysis ↑heart rate, force Beta 3 (β3) Adipose cells Gs ↑cAMP
↑lipolysis Dopamine 1 (D1) Smooth muscle Gs ↑cAMP Relax renal vascular smooth muscle C.
SYMPATHOMIMETICS (ADRENERGIC AGONISTS) Adapted from Katzung and Trevor’s Pharmacology
Examination and Board Review. 12th ed. 2019 Section guide: This section will be divided into: Non-
selective agonists, followed by the selective agonists for each for the adrenergic receptors in the
table above. Dr. Rodriguez MOA OF SYMPATHOMIMETICS • Direct activation of adrenoceptors o a1:
vasoconstriction, increases BP, increase pulmonary vascular resistance o b1: increased HR,
conduction and contractility of heart o b2: bronchodilation in lungs o D1: vasodilation in splanchnic
and renal blood vessels o These can be divided into non-selective and selective agonist. • INDIRECT
activation by increasing concentration of available catecholamines in the synapse o Release of stored
catecholamines (amphetamine & tyramine) o Inhibition of reuptake (cocaine & TCA) NON-SELECTIVE
ADRENERGIC AGONIST ENDOGENOUS CATECHOLAMINES Endogenous catecholamines are the
neurotransmitters found in the sympathetic nervous system. Endogenous, meaning ginawa sila ng
katawan. And they have action on all the receptors of the SNS – alpha, beta, dopamine. Dr.
Rodriguez, Im Epinephrine MOA β 1 = β 2 > Alpha Uses • Anaphylaxis, Cardiac arrest, Hemostasis •
Added to local anesthetics to decrease systemic absorption (increases duration of action) • Severe
asthma/COPD SE Hypertension, arrhythmia, stroke, MI, pulmonary edema, Hyperglycemia,
Tachycardia, Mydriasis Norepinephrine MOA a > b1 >> b2 almost negligible Uses • First line: Septic
shock • Shock • Cardiogenic shock SE Extreme vasospasm, tissue necrosis, excessive increase in BP,
arrhythmia, MI, ischemia → decreased organ perfusion, reflex bradycardia, metabolic acidosis (due
to decreased tissue blood flow) Dopamine MOA D1, ⍺1, ⍺2, β1, β3 agonist Dose-dependent actions:
Low dose: D1 Mod dose: β1 Higher dose: ⍺1 Uses • First line: Septic shock especial if with renal
shutdown • Cardiogenic shock • Acute heart failure (especially if with accompanied severe
hypotension SE Cardiovascular disturbance, arrhythmia Try to answer the following important points
(all the answers are in the tables above) 1. Has negligible B2 effect: ___________ 2. First line for
anaphylaxis: ___________ 3. First line for septic shock ___________ 4. First line for shock with renal
failure: ___________ Kindly take note also that all the ENDOGENOUS neurotransmitters are all non-
selective. Take a look at the heading of each in the table. Dr. Rodriguez, Im DOPAMINE: DOSE
DEPENDENT ACTIONS • LOW DOSE (0.5 to 3 mcg/kg/min) o Stimulates D1 and D2 receptors o
Leading to vasodilation, decreased arterial blood pressure and increased renal and splanchnic blood
flow (natriuresis and diuresis will occur) • MEDIUM DOSE (3-10 mcg/kg/min) o Stimulates β1
receptors (high chronotropy and contractility) o Results in increased cardiac output • HIGH DOSE
(>10 mcg/kg/min) o Stimulates α1 receptors o Leads to arterial and venous vasoconstriction,
increased systemic vascular resistance, increased blood pressure o Reflex bradycardia may be seen at
this point CLINICAL APPLICATIONS OF SYMPATHOMIMETICS CLINICAL CONDITION DESIRED
PARAMETER SYMPATHOMIMETIC OF CHOICE Acute heart failure Septic chock Increased cardiac
output b1 & D1 agonists Hemostasis Decongestion Spinal shock Vasoconstriction Temporary
maintenance of BP a1 agonist Bronchospasm Premature labor Bronchodilation Uterine smooth
muscle relaxation b2 .agonist Hypertension Glaucoma Decrease BP a2 agonist BETA NON-SELECTIVE
Isoproterenol MOA β1, β2 β3 agonist Uses • Asthma (as adjunct to B2 agonist) • Drug for sustained
increases in HR (during pacemaker insertion for bradydysrhythmia) SE Cardiovascular disturbance,
arrhythmia Okay at this point, we are still under Adrenergic AGONISTS. But we just finished non-
selective AGONISTS. Review, when you hear Non-selective adrenergic agonist, what drugs should
come to mind again? ____________ That’s right, the endogenous catecholamines NE, E, D. Now we
move on to SELECTIVE Adrenergic Agonists (i.e. Alpha Agonist and Beta Agonists) Dr. Rodriguez, Im
SELECTIVE ADRENERGIC AGONISTS ALPHA-1 AGONIST Phenylephrine, Pseudoephedrine, (-ZOLINES)
Oxymetazoline, Tetrahydrozoline, Naphazoline Xylometazoline, Midodrine Uses • Decongestant •
Mydriatic, Neurogenic hypotension, drug-induced hypotension, orthostatic hypotension SE •
Rebound nasal congestion (Rhinitis medicamentosa) • Hypertension, stroke, MI, Piloerection, urinary
retention, reflex bradycardia. • Ocular administration causes mydriasis WITHOUT cycloplegia; also
used intranasally to produce local vasoconstriction as a decongestant. • 1st trimester: avoid
Pseudoephedrine because it may be associated with possible risk of gastroschisis • Midodrine:
treatment of orthostatic hypotension • High doses may cause Alpha-1 agonist overdose o DOC:
Phentolamine (adrenergic blocker)
