In smooth muscle and cardiac muscle

Gs

Increase cAMP -> downstream phosphorylation -> promote calcium inflow and reuptake -> increased contraction, rate of relaxation, and pacemaker activity

(positive inotropic and chronotropic effects)

Gi

Decrease cAMP --> promote contraction

Postsynaptic CNS adenoreceptors

Platelets

Adrenergic and cholinergic nerve terminals

Some vascular smooth muscle

Fat cells

Gq

Increase Ca --> contraction

Affects alpha 1, alpha 2, beta 1, and beta 2

Used for anaphylactic shock (alpha, beta)

Acute asthma attacks (beta)

Prolong action of local anesthetics (alpha)

Topical hemostatic agent (alpha)

Cardiac arrest (alpha)

Side effects, esp in hyperthyroid or patients on beta blockers: hypertension, arrhythmia, angina, necrosis

Catecholamine

alpha 1 = alpha 2, beta 1 >> beta 2

Uncommon use for pressor effects

Catecholamine

Beta 1 = beta 2 >>> alpha

Uncommonly used for bronchodilation (Beta 2 agonists are a better pick)

Used for heart stimulation in bradycardia or heart block

Catecholamine

Beta 1 > Beta 2 >>> alpha

Positive iontropic effects

Some chrontropic effects

Used in acute congestive heart failure

Catecholamine

D1=D2 >> beta 1 >> alpha

D1 response = vasodilation of renal, mesenteric, and coronary beds

Dose dependent.  Small dose -> D1 response, larger alpha effect

May cause vasoconstriction -> ischemia of peripheral tissues

Norepinephrine

Isoproterenol

Dobutamine

Dopamine

All produce tolerance over time

Chronic use in heart failure may worsen outcome

Phenyleprhine

Clonidine

Albuterol

Ritodrine

Direct-acting noncatecholamine

Alpha 1 > alpha 2 >>> beta

Vasoconstrictive effects

Used to treat hypotension and shock

Used as topical nasal decongestant

Topical opthalmic treatment causes myadriasis

Direct acting noncatecholamine

Alpha 2 > alpha 1 >>>> Beta

Penetrates CNS

Inhibits sympathetic output 

Causes hypotension, bradycardia, sedation

Used in hypertension, to diminish cravings in narcotic, alcohol, and nicotine withdrawal

Albuterol

Ritodrine

Direct acting noncatecholamine

Beta 2 > beta 1 >>> alpha

Used for bronchodilation in asthma, COPD

Inhalant prep to minimize systemic effects

Sometimes used to stop preterm labor by relaxing uterus (better drugs for this)

Amphetamine

Methylphenidate

Cocaine

Tyramine

Amphetamine

Methylphenidate

Indirect acting noncatecholamine

Enters CNS to cause release of catecholamines (incl. DA)

CNS effects: mood elevation, increased alertness, decreased appetite

Peripheral effects: NE-like

Used for narcolepsy, weight loss, ADD

Indirect acting noncatecholamine

Causes vasoconstriction and local anesthesia

Abuse side effects = hypertensive response

Indirect acting noncatecholamine

Found in food

When MAO inhibitor present, promotes norepi release, causing NE-like hypertensive response

Ephedrine and pseudoephedrine

Some CNS penetration -> mild stimulant

Orally available

Excreted unchanged

Long duration of action

Used in cold meds for nasal decongestion

Block alpha 1 and alpha 2

Predominant effect = vasodilation

Can cause reflex tachycardia by decreased alpha 2 feedback inhibition

Increased cardiac output blunts hypotensive response

Adverse effects: orthostatic hypotension, nasal stuffiness, tachycardia

Example: phenoxybenzamine, phenotlamine

Nonspecific alpha blocker

Requires bioactivation (lag in onset)

Covalent

Irreversible (24+ hour duration)

Used to treat pheochromocytoma

Nonspecific alpha blocker

Competitive - short duration of action

Used for:

Short term treatment of pheochromocytoma

Iatrogenic alpha-agonist reversal

Hypertensive crisis (from clonidine withdrawal, or tyramine + MAOI interaction)

Specific for alpha 1 receptor

Decrease BP with less reflex stimulation of heart rate

Decreases preload and afterload

Used to treat hypertension or promote urine flow 

First dose causes orthostatic hypotension, then tolerance develops

Example: prazosin, terazosin, tamsulosin

Prazosin

Terazosin

Alpha 1 blockers

For treatment of hypertension and BPH

First dose produces orthostatic hypotension before tolerance kicks in

Alpha 1 blocker

Some selectivity for alpha 1A receptors

Promotes urine flow in BPH with little effect on BP

Structurally similar to catecholamines

Ring + tail motif

1. Decrease heart rate and contractility.  

Short term: decrease CO, increase PVR (Beta 2 block)

Long term: Decrease myocardial O2 consumption

2. Decrease hypertension (no effect if normal)

3. Antagonism of bronchodilation via beta2s (bad for COPD, asthma)

4. Decrease aqueous humor production from ciliary epithelium

5. Blocks glucose metabolization (beta 2 antagonism of glycogenolysis)

6. Slow lipolysis -> increases VLDL, lowers HDL

Angina

Hypertension

Supraventricular arrhythmia

Ventricular arrhythmia

Myocardial infarction

Hyperthyroidism/thyroid storm

Migraine

Heart failure

Heart failure

Bradycardia

COPD/asthma

Angina, sudden death if in withdrawal

Blunt recovery from hypoglycemia

Adverse plasma lipoprotein profile

CNS effects - sleep disturbance, depression

Heart - increases force/rate of contractions

Juxtaglomerular cells - stimulates renin release

Found in most vascular smooth muscle

Pupillary dilator muscle

Pilomotor smooth muscle

Prostate

Respiratory, uterine, vascular smooth muscle

Skeletal muscle

Liver