Autonomic Drugs

ANS- controls cardiac sm and glands - parasympathetic, sweat glands, and Ach transmitter
SNS- skeletal muscle and voluntary movement - Ganglionic transmission- transmits symp and PS impulses
from preganglionic neurons to nicotinic (N) receptors of
ANS ANS
Sympathetic: - NM transmission- causes influx of Ca after bound to
- Catabolic nicotinic R receptors
- Expends energy - Central- Ach in brain, mainly M receptors
- Fight or flight- under stress
- Increases hr, dilates bronchi, decreases secretions Sympathomimetics (mimic NE and E)
parasympathetic: - Direct sympathomimetics
- Anabolic - Indirect or mixed
- Conserves energy - Centrally acting
- System at rest - Peripheral presynaptic anti- adrenergics
- Decreases HR and stimulates GI fnx - Adrenergic agonists

Norepinephrine Cholinomimetics- increase Ach

- Binds to postsynaptic adrenergic receptors - Direct cholinergic agonists
- A1, a2,b1,b2 second messenger - Cholinesterase inhibitors

Epinephrine- released from adrenals during stress. Agonist at Others: cholinergic antagonists, muscarinic antagonists, nmj
sympathetic receptor blockers, local anesthetics
Acetylcholine
Class Drug Receptor Effect Indication notes
Direct Epinephrine α+β Vascular (α1) vasoconstrix Shock Act directly on adrenergic
Sympathomimetics- Cardiac (β1) increase heart rate and Endogenous NT of receptors
catecholamines contractility postsynaptic SNS Short duration of action
Pulmonary (β2) bronchodilator and Degraded by COMT and MA
decreased secretions( α) Treat
Metabolic effects (β2) glycogenolysis and Asthma cardiac arrest shoc
gluconeogenesis anaphylaxis
Norepinephrine α > β1 >>β2 Similar to Epi but has little effect on β2 Shock
Intense vasocontrix leading to Increase in Endogenous NT of
MAP postsynaptic SNS
Vasoconstrix can cause reflex bradycardia
despite β1 fx

NET effect:
↑PVR,↑ MAP ↓HR
Dopamine D1 receptors Vasc effects – low dose constrix arterioles in Shock
(Precursor to NE) and brain and kidney, higher dose contrix all
Β1 vessels
Cardiac β1 ↑contractility, HR SBP
Direct Phenylephrine α (pure Intense vasoconstrix and increased MAP Nasal /ophthalmic Not degraded by COMT or
sympathomimetics- agonist) Decreased HR (reflex brady) decongestants MAO therefore longer actin
non catecholamines Vasopressor for Majority are bronchodilato
Shock
Salbutamol β2 Bronchial vasodilation bronchodilator
(ventolin) Few cardiac effect bc β2 specific
A little tachy bc of β1

Indirect Amphetamine Acts on β + α Release of NE and other stored catechols Narcolepsy Summary:
Sympathomimetics Vasoconstrix and increased MAP (α) ADD, misuse... indirect cause NE release b
Increased myocardial contrax (β) do not bind to adrenergic
Wakefulness decreased appetite receptors directly
 Euphoria mixed displace NE from
terminals and bind to
Undesirable fx: hypertension, cerebral adrenergic receptors
hemorhage, coma, confusion, anxiety,
tremor, hallucinations
Mixed Ephedrine (stored a + β2 Vasoconstrix (α1) increased MAP Hypotension
Sympathomimetics catecholamines No change in HR Narcolepsy
released) Nasal congestion
Less CNS tox than
amphetamine
Adrenergic Clonidine α2 agonist Binding to postynapt α2- inhibits Hypertension, and Decrease preganglionic
Blockers- Central Sympathetic neurons in the brain eyedrops sympathetic outflow from
Acting α 2 found on presynaptic nerve where they brain, resulting in decrease
inhibit NE release BP

Unwanted fx-
Orthostatic hypertension and sedation

Adrenergic Phentolamine α 1 and α 2 Vasodilation HTN w Rapid onset, short half-life

antagonists antagonism pheochromocytoma
(competitive) Unwantex fx- tachy, arrhythmias, prolonged Cocaine induced
hypotension HTN
Labetalol α 1, β1 β2 Decreased BP w/o reflex tachy HTN Oral absorbed w peak level
competitive at 1-2 hr, extensive first pas
antagonist Undesired fx- hypotension IV peak 5 min

Metoprolol β1 Decreased ionotropy and chronotropy as Angina IV onset 20 min

antagonist well as O2 demand MI CYP 2D6 metabolism
Less bronchospasm HTN

Sidefx- lower toxicity vs. Propranolol

Tamsulosin α1 Vasodilation in SM of prostate and urethra/ BPH
antagonist bladder neck Renal colic
Cholinomimetics- Acetylcholine M M1 – stomach- acid secretion
cholinergic agonists (muscarinic) M1 CNS- neurotransmission - Carbachol – M3 eye- glaucoma
mediate PNS M2- SA node- bradycardia - Methacoline (M2) lung- dx for bronchi
and CNS M2- atria- decreased contrax airway hyperreactivity
N (nicotinic) M2- AV node- slows condux - Bethanechol (M2)- induce bladder
found in M2 – lung- bronchoconstrix evacuation
ganglia and M2- bladder- relax sphincter - Pilocarpine (M3 glands)- glaucoma, cystic
NMJ M2 penis- erection fibrosis sweat test
M3- eye- miosis - Nicotine (N CNS) smoking cessation
N- skeletal- contrax
N- CNS- neurotransmission
Cholinomimetics- Physostigmine Carbamyl Cholinesterase inhibition- competes w Ach Reverse toxic CNS PK- absorbed w/in minutes
Cholinesterase for binding site of acetylcholine esterase effects for IM IV preps- lasts 1-2h
inhibitors Binds w enzyme and leaves Ach to rx w
(prevent the receptors- reversibly
degradation of Ach
and increase the Malathion Organophosphorus None- pesticide Pk- lipid soluble, absorbed
amt of Ach for M Binds to Acetylcholinesterase so cannot thru skin, mucosa, GI
and N receptors) degrade Ach
Longer acting than carbamyls – can be wks
or permanent
Edrophonium Competitive mech
Inhibits destrx of Ach
Test for myasthenia Gravis
Distinguishes MG from cholinergic crisis
Neostigmine Reverses NM blockade after anesthesia
Pyridostigmine Treatment of MG
Reversal of NM blockade
Cholinergic Atropine Blocks muscarinic action of cholinergic Preanesthetic to
Antagonists, agonist prevent resp
muscarinic -decreased saliva and broch secretions secretions
antagonist -decreased sweating Bradycardia
-pupil dilation Peptic ulcers
- tachycardia Bladder spasms
- inhibits voiding Organophosphate
 - decreases GI motility poisoning antidote
Neuromuscular Succinylcholine Depolarizing NMB Ideal for rapid IV onset- 30-60s, lasts 3-
Blockers Floods N receptor w Ach and inhibits a intubation 5mins
(depolarizing vs non response on N. Contraindications-
depolarizing) Muscle remains depolarized, ca enters cell, burn, hyperkalemia,
therefore no contraction. myophathies,
malignant
hyperthermia,
increased ICP or IOP
Vecuronium Nondepolarizing NMB Intubation Onset- 3-5min, duration 25
Competes w Ach at N receptors 40min

Local Anesthetic Liducaine Inhibits nerve conduction via sodium Anesthesia Onset <1.5min
channel blockade- prevents action potential Arrhythmias
Toxic- oral numbness,hypotention, tinnitus
Cardiovascular Drugs

Cardiovascular disease: - ASA

Hypertension - Nitroglycerine
Angina - Beta blockers
Myocardial infarction - Calcium channel blockers
Heart failure - Other antiplatelets
Arrhythmias - Heparin
- IIb/IIIa inhibitors
Anti hypertensives Heart failure
- Diuretics - Diuretics
- Calcium channel blockers - ACE inhibitors
- Vasodilators - Beta blockers
o Ace inhibitors - Nitroglycerine
o Angiotensin II antagonists - Digoxin
o Direct vasodilators
Anti- Anginals: Arrythmias
-sinoatrial node paces the heart by depolarizing atrium
- impulses reach the AV node and transmit conduction to His- Therapeutic goals for heart failure
purkinje system - Reduce workload
- interruption causes arrhythmias - Improve myocardial contractility

Antiarrhythmatics
Class 1- Na channel blockers
- 1a slow conduction and prolong refractory period
- 1b- no generalizations
- 1c- slow conduction velocity most effectively
Class 2- adrenergic antagonists (beta-blockers)
Class 3 prolong repolarization (K channel blockers)
Class 4 calcium channel blockers

Therapeutic goal for Anti hypertensives

- Reduce volume overload
- Block adrenergic receptors in heart
- Dilate bvs

Therapeutic goal of anti-anginals

- Reduce work of heart and improve cardiac circulation
- Reperfuse ischemic tissue

Class Drug Receptor Effect Indication Other

Diuretics Thiazide Inhibit Na and Cl Reduce BP and edema by increasing urine HTN All diuretics enhance
(Chlorothiazide) reabsorption in distal output water and Na excretion
tubule
Loop (Furosemide) Inhibit CL Reduce BP and edema by increasing urine Heart failure
reabsorption in the output HTN
thick ascending loop
 of henle
K-sparing Increase excretion of Reduce BP and edema by increasing urine HTN
(spironolactone) Na and decrease K output Heart failure
secretion in
collecting tubule
Beta Blockers Atenolol, Bisoprolol, Block β1 Good starting therapy Hypertension PK- long half life allows
Metoprolol Reduce HR and myocardial work Angina for overdose, poor
 inotropy penetration into brain
chronotropy so few CNS fx

Propranolol Block both β1 β2 Bronchoconstriction as well Hypertension Good CNS penetration

 inotropy Angina so more side fx
chronotropy Heart Failure
Bronchoconstrx CNS side effects
Contra: asthma
Angiotensin Catopril, lisinopril, Inhibits Ang II synth vasodilation Suppress synthesis of ang II HTN Can cause renal dysfxn
converting enzyme enalapril, ramipril natriuresis (suppress aldosterone) Heart failure
inhibitors
(ACE inhibitors) Side fx- hypotention dizziness HA cough CONTRA-
pregnancy
Angiotensin II Losartan, valsartan, Ang II Receptor Vasodilation HTN DI- phenobarb reduces
antagonists irbesartan, blocker CONTRA- levels
candesartan SE: dizziness hypotention pregnancy
Direct Nitroprusside NO induces cGMP Stimulates phosphorylation cascade and HTN crisis Pk
Vasodilators relaxes SM Metabolized to Cyanice
and
SE- severe HTN and CN tox cyanmethemoglobin

Calcium Channel Diltiazem, Verapamil Block Ca into muscle Vasodilation - prevents contraction of BVs HTN Dihydropiridine vs non-
Blockers Nifepidine cells of BVs Bradycardia- blocks Ca efflux to myocytes dihydropiridine
Anti-anginals Aspirin Inhibits Prevents formation of thromboxane A2 Angina Halflife- 15mins
cyclooxygenase and PGs. Decreases platelet aggregation MI risk decreased
in angina pts DI- increased risk of
bleeding w anticoags
 GI ulcers w EtOH
Nitroglycerine Dilates large arteries to increase blood to Angina Immediate onset- peak
heart MI level 1-2min
Reduces preload (decreased venous tone) Contra- sildenafil IV peak- 2min duration
3-5min
Transdermal peak- 30-
60min duration 1 day
Antiplatelet Clopidogrel Inhibits ADP Blocks platelet aggregation Antiplatelet Given PO- metabolized
to active drug
Eptifibatide, Blocks fibrinogen Blocks platelet aggregation Given IV only
Tirofiban, Abciximab and vWf to
glycoprotein IIb/IIIa
receptor on platelet
surface
Heparin Binds to Inhibits activated clotting factors (factor Angina Low MW heparins used
antithrombin III Xa) MI Dalteparin, enoxaparin,
DVT fondaparinux
SE: risk of bleeding w other anticoags PE
Thrombolytics Streptokinase Activation of plasminogen to plasmin IV clotbuster All given IV
TPA Plasmin digest fibrin and fibrinogen
Alteplase forming products

SE: risk of bleeding

Heart failure Digoxin Inhibits Na/K ATPase Net intracellular CA Afib PO/IV 36 hr halflife
pump Increase CO CHF 75% absorbed in GI trac
Inhibits Ca/Na Large Vd
exchange SE: dig toxicity

Antiarrythmatics Class Ia Na channel blocker Slow conduction and prolong refractory Arrhythmias
Quinidine period- little effect on SA node
procainamide Depresses automaticity
Prolong QRS and QT
Class Ib Na Channel blocker Depresses automaticity of ectopic foci Vtach, Vfib, WPW
Lidocaine May shorten QT
Class Ic Na channel blocker Reduces automaticity of sA node and Afib
Flecainaide, ectopic foci
propafenone Reduces conduction velocity
Prolongs QRS and QT
10% of population metabolizes drug
Class II Beta blocker
Propranolol, esmolol
Class III K blocker Reduces k efflux and reduces SA Vfib, VTach, WPW DI increases serum
Amiodarone automaticity as well as condux velocity levels of digoxin and
warfarin
SE- corneal deposits, thyroid disease,
pulmonary fibrosis, photosensitivity
Class IV Ca channel blockers Reduces Ca entry into cells Afib
Verapamil Reduces SA node automaticity MAT
Adenosine Decreases conduction velocity, prolongs SVT PK: IV form has halflife
*unclassified* refractory period, decreases automaticity <30 seconds

SE: feeling of doom

Dexamethasone,
Betamethasone
indomethacin