If alpha antagonist is given before epinephrine administration, blood pressure will fall - this is called epinephrine reversal

Heart rate will increase because of reflex tachycardia as well as stimulation of B1 receptors 

A1 receptors

A1 receptors cause contraction of urethral sphincters and the prostate, so blockage facilitates flow

Miosis: blcokage of A1 effect on radial muscle - allows PS system to dominate

Nasal stuffiness

Gastrointestinal hypermotility

Sexual dysfunction (centrally mediated), dry mouth, dizziness, somnolenec, and headache

Irreversible 

Nonselective alpha antagonist

Reduces BP when sympathetic tone, such as in pheochromocytoma

Primary adverse effect: tachycardia because of reflex and blockage of A2 receptors

Hypertension resulting from pheochromocytoma, Raynaud's

Competitive antagonist nonselective alpha (A1 and A2)

Primary adverse effect is tachycardia because of blockade of presynaptic A2 and reflex mechanisms

Used in hypertensive emergencies

Short half life

Selective for A1 receptors, so less likely to cause tachycardia

Mild hypertension

A1 selective antagonists

Mild hypertension, BPH

A1 and D1 antagonist thought to predominate in the prostate

BPH

Large amounts of NE and E released - hypertension, headaches, tachycardia, and sweating

Phenoxybenzamine most commonly used before surgery; also used for inoperable tumors

B blockers might be needed, but only AFTER A1 antagonists to prevent unopposed vasoconstriction 

Agents like prazosin are used, but usually not used alone because other classes of drugs known to be efficacious in heart failure

Major side effect is orthostatic hypotension; palpitation can occur

Prazosin or phenoxybenzamine can be used to treat vasospasm in peripheral circulation (Raynaud's phenomenon)

Other agents like calcium channel blockers are preferred 

Behavior modifications should be tried first

Phentolamine used as a part of a mixture that is injected into penis to help erection

If injected orally, less of an effect, because thought to be a centrally mediated effect 

1. Suppression of renin

2. CNS effects

3. Inhibition of stimulatory action of NE on the heart 

Most widely used drugs to treat glaucoma

Reduce aqueous humor production in the eye

B blockers will block epi mediated glycogenolysis

Bad for diabetic patients because they would have impaired recovery from hypoglycemia, and their symptoms for hypoglycemia, like tachycardia and tremors, would be blocked

Non specific beta antagonists will increase VLDL, triglycerides, but decrease HDL, and not change LDL

HDL:LDL ratio is therefore lowered

Thought to be from inhibition of hormone sensitive lipase

Less likely to occur with beta antagonists that have intrinisic sympathomimetic activity and with B-1 selective antagonists 

Propranolol, pindolol, and metoprolol have membrane stabilizing activity 

Local anesthetic action through blockade of sodium channels; can also affect myocyte sodium channels

Can contribute to toxicity by prolonging QRS duration and impairing cardiac conduction 

Beta blockers with local anesthetic action would not be used in patients with glaucoma 

These agents cause less bradycardia, slight vasodilation, and minimal changes in lipids 

Pindolol and acebutolol

Can cause: dizziness, fatigue, depression, and sexual dysfunction 

Hydrophilic drugs like atenolol have fewer CNS effects 

Nonselective B blocker

Used for hypertension, angina, arrhythmias, migraine, thyroid toxicosis, and essential tremor

Lipid soluble and will readily enter the CNS - may have excessive somnolence and impaired cognition

Nonselective beta blocker

Has no membrane stabilizing activity

Widely used to treat glaucoma

Nonspecific B blocker

Same indictaions at propranolol, but very long half life

B1 selective antagonists

May be preferred in patients that experience bronchoconstriction after propranolol, or diabetes/lung disease

Still, selectivity for B1 receptors is not absolute 

Atenolol has low lipid solubility so CNS effects are diminished

Metoprolol is more lipid soluble, but still widely used for HT and other cardiac effects

Very short acting B1 antagonist

Ester linkage is cleaved by esterases in RBCs

Half life of 10 min - steady state concentrations can be achieved quickly

Drug is good for patients who are critically ill that need beta blocker therapy

Also usd for intraoperative and postoperative hypertension

B1 selective antagonist

Used in glaucoma; less likely to cause bronchoconstriction

B blocker with alpha 1 blocking activity

Used for hypertension and severe hypertension

Same adverse effects as alpha and beta blockers

Blocks beta receptors more effectively than alpha-1 receptors

One of the beta blockers used to treat CHF

Effectiveness in CHF may be attributable to attenuation of oxygen free radial action, and inhibition of vascular smooth muscle mitogenesis

Non-selective B blocker with intrinsic sympathomimetic activity

Less likely to cause bradycardia and changes in lipids, but clinical advantage is unclear, also will cause slight vasodilation

Indirect acting adrenergic antagonists

Will displace norepinephrine by entering through the reuptake system - chemical sympathectomy

Used for severe hypertension

Agents that block reuptake would inhibit its action

Inhibits vesicular transport system, so that NE cannot be taken up into vesicles

NE is degraded by monoamine oxidase in the cytoplasm

This agent would also deplete dopamine and serotonin, so can lead to depression 

Timolol, propranolol, and metoprolol

Should not be used in patients with contraindications like bradycadia or hypotension 

They will slow AV nodal conduction, so can be used for atrial flutter or fibrillation

Can be used in ventricular arrhthmias due to ectopic beats if due to excessive NE or E stimulation

often used in combo with other agents like diuretics or ACE inhibitors 

B blockers & ace inhibitors not as effective in african americans, but difference is eliminated if diuretic is also given 

- heart stimulation

- increase renin release from JG cells

- increase aqueous humor production in the eye

- enhance effect of parasympathetic stimulation of amylase secretion

Primarily to relax smooth muscle

Also will increase glycogen breakdown, and increase glucose synthesis

Modest increase in insulin secretion

Can also induce skeletal muscle tremors - probably an effect on contractile proteins mediated through cAMP

Leads to increased arterial resistance and decreased venous capacitance

Overstimulation can cause hemorrhage due to increased blood pressure

Stimulation of B1 receptors on heart will cause phosphorylation of A1 subunit of calcium channels --> increase inward flow of calcium

Cyclic AMP may also lead to phosphorlyation of troponin C, increasing sensitivity of contractile apparatus 

Overstimulation of these receptors can cause arrhythmias

MLCK is phosphorylated and inhibited

all beta receptors increase cAMP

A1 agonist will dilate eye - used in combinaton with muscarinic antagonists to dilate eye

A2 agonist will work on ciliary body to decrease aqueous humor secretion - used for glaucoma

B2 agonist relax ciliary muscle which allows aqueous humor to leave via uveosclearl pathway; sometimes used to treat glaucoma although not preferred agents

Stimulation of A1 receptors - contraction of urethral sphincters

Stimulation of B2 receptors - relaxation of detrusor muscle

Net effect is urinary retention

PS will cause increase in K and amylase secretion

A1 agonists will increase potassium watery secretion (small)

B1 agonist will enhance amylase secretion from PS system

Net effect is small thick amount of saliva

Alpha, beta, and dopamine receptors are present within the CNS

Sympathomimetic agents can enter the CNS and cause arousal, euphoria, and anorexia

A1 receptor agonist

Dilates eye, nasal decongestant, terminates episodes of paroxysmal atrial tachycarida by activating baroreceptor reflex

Treats hypotension

A2 agonist that acts centrally to decrease sympathetic outflow to decrease BP

Analogues are also used to treat glaucoma

Alpha 2 agonist

Converted to methylnorepinephrine centrally to decrease sympathetic outflow and decrease blood pressure

Activates primarily B1 receptors

Used to treat cardiogenic shock, low cardiac output

Primarily an inotrope 

Non-specific B agonist

Not the agent of choice for any application, but has been used for bronchospasm, heart block, and arrhythmias

Causes release of NE and also directly stimulates receptors 

Mild stimulatory effects

Component of herbal medication Ma Huang

Mixed acting sympathomimetic

Pseudoephedrine has been used as a decongestant; also been used in illicit manufacture of methamphetamine

Indirect acting sympathomimetic

Blocks reuptake of NE, dopamine in CNS

Profound stimulatory effect

Substrate for NE transporter, and will enter vesicles to displace NE which then exits presynaptic terminal via reversal of transporter

This drug and analogues are stimulants

They are used to treat attention deficit hyperactivity disorder, and narcolepsy

Indirect acting sympathomimetic

Rapidly metabolized by monoamine oxidase in the liver and GI tract

In presence of MAO inhibitors, can cause a hypertensive crisis by releasing large amounts of norepinephrine

Epinephrine has been used - would help redistribute blood flow to the heart

Isoproterenol would not be used because it would increase work of the heart

Will decrease volume of nasal secretions

Can cause rebound hyperemia when terminated

Local application with nasal sprays can cause ischemic changes in mucosa

Both tertiary amines so they can distribute to the CNS

Scopolamine is generally more sedating than atropine

Atropine first causes stimulation, followed by a sedating effect

High doses can cause confusion and/or hallucinations

Used for motion sickness

Major side effect is drowsiness

Administered as a patch

Fast, but short acting mydriatic agents

May be used in combination with an alpha adrenergic agonist

Quaternary amine that is administered through inhalation

Effective in use in COPD

Tiotropium is similar to ipratropium, but longer lasting

Management of overactive bladder with symptoms of increased urinary frequency, urgency, nocturia, and incontinence

Thought to have fewer side effects like dry mouth and blurred vision

Contraindicated for individuals with narrow angled glaucoma

anticholinergic

Relaxes intestinal smooth muscle

Used for irritable bowel syndrome

Low doses preferentially inhibit secretion, so this drug is used preoperatively to inhibt secretions

Prevention of excessive generalized sweating

Prevention of muscarinic side effects in patients receiving neostigmine to reverse neuromuscular block

Antihistamines

Antidepressants - tricyclics

Phenothiazine antipsychotics

First effective anti-hypertensive

Problems of poor absorbance and autonomic side effects

Can be used to improve GI absorption

Recent interest for use in Tourette syndrome

Can be injected directly into the eye to produce miosis after lens extraction

May also be used during diagnostic coronary angiography where intracoronary injection causes vasodilation 

Can be used to diagnose vasospastic angina where intracoronary injectino of ACh has direct effect on smooth muscle causing contraction

Used for wide angle glaucoma only when other cholinomimetics are no longer effective

Effective at nicotinic and muscarinics

Used post-op after abdominal surgery and postpartum to reduce bladder distension

Alternative to pilocarpine for promotion of salivation under conidtions of xerostomia

Activates primarily muscarinic receptors, is a tertiary amine

May be used as a miotic agent for wide angle glaucoma

narrow angle would use pilocarpine + physostigmine

Pilocarpine also administered orally to overcome xerostomia

Chronic use can result is decreased night vision and difficulty focusing on distant objects

Activates ganglionic nACh receptors, which is followed by receptor blockade from persistent depolarization

Thus, nicotine poisoning can cause tachycardia or bradycardia, hypertension or hypotension, depending on the dose and timing

Simple Competitive Inhibitor

Reversible

Quaternary - brief duration of action (1-5 minutes)

Used to test for myasthenia gravis: rapid IV administration will result in brief improvement of strength

Attaches to anionic site only

Tertiary amine used in treatment of wide angle glaucoma, sometimes together with pilocarpine

Facilitates efflux of aqueous humor 

Can enter CNS and reverse effects of atropine and other drugs with anti muscarinic properties

Adverse: Can facilitate cataract formation, decreased night vision

Quaternary amine having short duration of action (2-4 hours)

Drug of choice for use in paralytic loss of tone in GI tract and bladder

Often given to reverse neuromuscular block along with glycopyrrolate

Drug standard used for myasthenia gravis

Close congener of neostigmine

Used in myasthenia gravis; when effective - drug of choice owing to long duration of action

May be used as a pretreatment to reduce risk of mortality on exposure to nerve gases

Organophosphate - irreversible AChE inhibitor

Only clinically useful organophosphate

Used in glaucoma

Pro drug insecticide which once activated, undergoes 'detox' in mammals via plasma esterases

Potent insecticide 'pro-drug': metabolized by mixed-function oxygenases (more efficiently in insects) to paraoxon 

**responsible for most cases of poisoning and death**