6 - Sympathetic Drugs

a. Methyl phenidate

1. A drug for ADHD

   a. Methyl phenidate

   b. morphine

   c. cocaine

   d. atropine

d. Beta 3 receptor

2. Mirabegron activates

   a. Alpha 1 receptor

   b. beta 1 receptor

   c. Alpha 2 receptor

   d. Beta 3 receptor

a. Vasoconstriction

3. activation of alpha 1 receptor causes

   a. Vasoconstriction

   b. miosis

   c. increased salivation

   d. smooth muscle relaxation

b. Silodosin

4. which of the ff is a selective alpha-1 receptor blocker?

   a. Prazosin

   b. Silodosin

   c. Doxazosin

   d. Terazosin

a. epinephrine

5. Catecholamine of choice for anaphylaxis

   a. epinephrine

   b. Norepinephrine

   c. Isoproterenol

   d. dobutamine

• Pre-ganglionic: Acetylcholine

• Post-ganglionic: NE

Sympathetic drugs neurotransmitter:

Adrenergic Receptor

Sympathetic drugs receptor:

Reverse DUMBELS

Sympathetic drugs Response:

Phenylalanine Hydroxylase

Enzyme for the conversion of Phenylalanine → L-Tyrosine

Tyrosine Hydroxylase

Enzyme for the conversion of L-Tyrosine → Levodopa

DOPA Decarboxylase

Enzyme for the conversion of Levodopa → Dopamine

Dopamine-Beta Hydroxylase Enzyme

Enzyme for the conversion of Dopamine → Norepinephrine

Phenylethanolamine N-methyltransferase (PNMT)

Enzyme for the conversion of Norepinephrine → Epinephrine

MAO Enzyme

Enzyme that is involved in oxidation process for NE degradation or conversion of NE → inactive form

COMT

Enzyme that is involved in methylation process for NE degradation or conversion of NE → inactive form

NET

NE goes back to neuron for NE reuptake via

RESERPINE

NE Vesicular storage blocker

BRETYLIUM

NE release via exocytosis blocker

TCA, Cocaine

NET blocker

Alpha-1

A receptor that binds w/ Gq

Muscle Contraction

• Blood Vessels: Vasoconstriction

• Eyes: Mydriasis

• Bladder: Contraction

• Salivary Gland: decrease secretion

• Gq → Phospholipase C → ↑ Cal

• Results:

Vasoconstriction

activation of alpha 1 receptor in blood vessel results in:

Mydriasis

activation of alpha 1 receptor in eyes results in:

Viscid saliva or decrease of secretion

activation of alpha 1 receptor in salivary gland results in:

• Post Ganglionic:  NE release (HTN)

• Pancreas:  Insulin ( Glucose)

• Eyes:  Humor Secretion (Anti-glaucoma)

• Gi → blocks Adenyl Cyclase → decrease cAMP

• Results:

Inhibition of NE release

activation of alpha 2 receptor in post-ganglionic results in:*

Inhibition of Insulin release

activation of alpha 2 receptor in pancreas results in:

Inhibition of aqueous humor secretion

activation of alpha 2 receptor in eyes results in:

Increase glucose

Inhibition of Insulin release means __ glucose

Beta (1,2,3)

Receptors that is coupled w/ Gs

Increase of cAMP

stimulation of adenyl cyclase means ___ cAMP

Alpha-2

A receptor that is coupled w/ Gi

decrease cAMP

Blocking adenyl cyclase means ___ cAMP

Heart

Location of Beta 1 receptor

Lungs, Uterus

Location of Beta 2 receptor

Adipose Tissue, Bladder

Location of Beta 3 receptor

Chronotropy

Activation of beta 1 receptor in heart results in:

Bronchodilation

Activation of beta 2 receptor in lungs results in:

Uterus relaxation (Tocolytic)

Activation of beta 2 receptor in uterus results in:

Increase Lipolysis

Activation of beta 3 receptor in adipose tissue results in:

Urinary Retention

Activation of beta 3 receptor in bladder results in:

Mirabegron

A drug that promotes beta 3 receptor and tx for over productive bladder

D1

A dopamine receptor that mediates vascular smooth muscles

Kidney Failure

Activation of D1 receptor helps people w/

Gs

Dopamine 1 is coupled w/

Gi

Dopamine 2 is coupled w/

D2

A dopamine receptor that neurotransmitter release

Direct-Acting Adrenoceptor Agonist

MOA: activates adrenoceptors

• Epinephrine

• Norepinephrine

• Dopamine

Endogenous Catecholamines:

Adrenaline

Epinephrine is known as

Epinephrine

DOC for Anaphylactic shock

alpha1 = alpha2 & beta1 = beta2

Epinephrine has a great activity in what receptors?

Noradrenaline

Norepinephrine is also known as

a1=a2; b1>b2

Norepinephrine has a great activity in what receptors?

Norepinephrine

• DOC for Septic Shock

• Used for shock if the dobutamine is unsuccessful

Dopamine

• Dose> b1> alpha

• Tx: Shock + Hypotension

• Adjunct Therapy for Hypovolemic Shock

• Dobutamine

• Isoproterenol

Exogenous Catecholamines

Dobutamine

• B1>b2>alpha

• Tx: Shock + No Hypotension

• DOC: Cardiogenic Shock

Isoproterenol

• B1=b2>alpha

• Treatment of refractory bradycardia and AV block if other treatments fail

Hypotension and Bronchoconstriction

Anaphylactic shock is the cause of:

massive vasodilation

Septic shock is the cause of

Epinephrine

• Tx of of px with *bleeding conditions and to increase the DOA of local anesthetics that promotes Hemostasis

• Tx for Ventricular Fibrillation & Cardiac Arrest

Phenylephrine

• alpha-1 agonist

• Uses:  Nasal Congestant, Orthostatic Hypotension, Mydriasis (Retinal Exam)

Midodrine

• alpha-1 agonist2

• orthostatic hypotension, especially for infants or induced by psychotropic agents

• Short-Acting: RELIVER

• Long-Acting: CONTROLLER

Beta-2-Agonists:

SABA

Tx: Acute Asthma

Albuterol/Salbutamol, Levalbuterol, Terbutaline

Examples of Short-Acting

Terbutaline

a SABA that is also used for as a tocolytic agent

LABA

Chronic Asthma

Reliever

SABA acts as a

Controller

LABA acts as a

Salmeterol, Ormoterol

examples of Long-Acting

• Oxymetazoline

• Apraclonidine, Brimonidine

• Clonidine, Dexmedetomidine

Imidazoline Drugs:

Oxymetazoline

• (+) alpha-1

• Topical Decongestant

• Reco: 3-5 days only to avoid S/E

Rhinitis Medicamentosa (Rebound Congestion)

S/E of Oxymetazoline if you drink it for more than 5 days

Apraclonidine, Brimonidine

• (+) Ocular alpha-2

• Anti-glaucoma

Clonidine

• (+) alpha-2

• Lipophilic

• Induce Sedation

• For ADHD (not the DOC)

• Anti-HPN

• Tx for Opioid Independence

Dexmedetomidine

• (+) alpha-2

• Lipophilic

• Induce Sedation

• Analgesic + Sedative effect

• Adv: No respiratory depression

Indirect-Acting Adrenoceptor Agonist

MOA: blocks NE reuptake & NE displacers

• Amphetamine

• Methyl Phenidate

• Modafinil

Displacers adrenoceptor agonist:

Amphetamine

• Drug of abuse

• Tx: Nacrolepsy

Methyl Phenidate

DOC for ADHD

Modafinil

Psycho stimulation (promotes mood brightening effect, memory enhancer)

• Cocaine

• TCA’s, SNRI

Examples of Reuptake Inhibitors

Cocaine

1st local anesthetics

Mixed-Acting Adrenoceptor Agonist

(+)  alpha & beta receptors

Ephedrine

• Obtained from: Ma Huang

  • Nasal decongestant & Anti-asthma

Ma Huang

Ephedrine is obtained from

Norephedrine

• similar to phenylpropanolamine

• Nasal decongestant

• High risk of Cerebral Haemorrhage in young females (because of phenylpropanolamine)

Phenoxybenzamine, Phentolamine

A Tx for Pheochomocytoma

Phenoxybenzamine

tx for pheochomocytoma a nonselective irreversible alpha blocker

Phentolamine

tx for pheochomocytoma that is a selective reversible alpha-blocker

Phentolamine

• Reverses the effect of Epinephrine

• Result: vasodilation

Adranoceptor Antagonist

• MOA: blocks adrenoceptor

• Response: DUMBELS

• §  Reflex Tachycardia

• §  Dizziness

• §  Head ache

• §  Nasal Congestion

Alpha Blockers can cause

Prazosin, Doxazosin, Terazosin

• Tx for HPN + BPH

• Blocks alpha-1 receptor

  -   BV: vasoconstriction

  -   Smooth muscle: Urinary Bladder, Prostate

• S/E: FIRST DOSE PHENOMENON

FIRST DOSE PHENOMENON

Prazosin, Doxazosin, Terazosin’s S/E

Siladosin, Tamsulosin, Alfuzosin

• Blocks alpha-1A receptor

• Adv: less hypotension, dizziness, sedation

• Tx of BPH only

Non-Selective – beta blockers

• Tx for HPN w/ out Asthma

• Blocks Beta 1: decrease cardial activity

• Blocks Beta 2: Bronchoconstriction (dangerous to people w/ asthma

• Propanolol

• Timolol

• Pindolol

• Nadolol

Ex of Non-Selective – beta blockers