pharm: adrenergic drugs

adrenergic agonists

• sympathomimetics - mimic sympathetic NS

• activate adrenergic receptors

direct receptor binding

• most common mechanism for drugs

• drugs bind to adrenergic receptors and mimic natural transmitters

other mechanism for drugs are

• promoting norepinephrine release

• inhibiting norepinephrine reuptake

• inhibiting norepinephrine inactivation (MAO inhibitior)

what’s special about ephedrine

ephedrine acts through both direct binding and promoting norepinephrine release

catecholamines

• cannot be swallowed, must be injection

• polar - cannot cross BBB

• has a brief effect - broken down quickly by MAO and COMT

noncatecholamines

• can be PO

• can cross BBB

• has a longer effect

when a1 receptors are stimulated in the blood vessels and mucous membranes….

• they all will constrict

• raises BP, stops bleeding, nasal decongestant

• will also trap anesthetic is blood vessels

adverse effects when a1 receptors are stimulated in the blood vessels

• hypertension

• bradychardia as a result of hypertension

when a1 receptors are stimulated in the eye….

• dilated pupils

which drugs hit the alpha 1 receptors

• epi

• norepinephrine

• dopamine

• ephedrine

• phenylephrine

when a2 receptors are stimulated …

they inhibit transmitter release in the presynaptic nerve terminals

• more significant in the CNS then in the PNS

• relieves severe pain

• reduces sympathetic outflow to the heart and blood vessels

when b1 receptors are stimulated in the heart….

• increases HR

• increase force of contraction

• increases AV conduction velocity

• improves blood flow and tissue perfusion

• good for shock, heart failure, cardiac arrest and hypotension

• may cause angina

when b1 receptors are stimulated in the kidney…

• stimulates release of renin to raise BP

what drugs activate Beta 1 receptors

• epi

• norepinephrine

• isoproterenol

• dopamine

• ephedrine

when b2 receptors are stimulated in the bronchi…

• bronchodilation

• releives asthma attacks

when b2 receptors are stimulated in the uterus …

• relaxes uterine muscle

• delays preterm labor

when b2 receptors are stimulated in the liver…

• glycogenolysis - may cause hyperglycemia

when b2 receptors are stimulated in the skeletal muscle…

• enhanced contraction

• may cause tremor

what drugs activate Beta 2 receptors

• epi

• isoproterenol

• ephedrine

• albuterol

what happens when dopamine receptors are activated

dilated blood vessels in kidneys, improving renal blood flow

what is the only drug that hits dopamine receptors

dopamine

norepinephrine: what receptors? indications? catecholamine or noncatecholamine

• activates a1, a2, and b1, but NOT b2 receptors

• has no effect on lungs or glycemia

• only indications are hypotension and cardiac arrest

• catecholamine - cannot be PO

isoproterenol

• only activates b1 and b2 receptors

• the first beta selective agent used clinically

dopamine: at what doses does it act on certain receptors? and what is is used to treat?

• at low doses - acts on dopamine receptors only (renin release)

• at moderate doses - acts on beta 1 and dopamine receptors

• at high doses - acts on alpha 1, beta 1 and dopamine receptors

• treats shock - dilation of renal blood vessels

phenylephrine uses (4) and what receptor?

• alpa 1 agonist

• nasal spray for decongestion

• parental injection to raise BP

• eyedrops can dilate pupil

• used with local anesthetics to delay absorption

albuterol

• only activates beta 2 receptor

• used over isoproterenol, so cardiac isn’t effected

• opens airways

ephedrine MOA, receptors and uses

• both direct acting and indirect acting (stimulates release of norepinephrine)

• acts on a1, a2, b1 and b2 receptors

• uses are limited bc it is not selective

Adrenergic Antagonists

Cause direct blockade of adrenergic receptors

which adrenergic blocker reduces hypertension

alpha 1 antagonist

• causes vasodilation in blood vessels

• decrease of blood return to the heart

• cardiac output decreases

• reduced arterial pressure

how do alpha 1 antagonists treat benign prostatic hyperplasia

reduces contraction of smooth muscle in the prostatic capsule and bladder neck

pheochromocytoma

• catecholamine (adrenaline like chemicals) secreting tumor

• causes hypertension by activation of alpha 1 receptors

treatment of pheochromocytoma

if inoperable - alpha 1 antagonists to suppress hypertension

raynauds disease

peripheral vascular disease characterized by vasoconstriction in the toes and fingers

• treated with alpha 1 antagonist - prevents alpha mediated vasoconstriction

adverse effects of alpha 1 antagonists (5)

• orthostatic hypotension

• reflex tachycardia

• nasal congestion

• inhibition of ejaculation

• sodium retention and increased blood volume

prazosin

• a1 antagonist (selective )

• dilates blood vessels

• relaxes bladder muscle and prostatic capsule (helps in BPH)

• approved for hypertension

selective vs nonselective alpha antagonsist blockers

selective - block alpha 1 receptors

nonselective - block both alpha 1 and alpha 2 receptors (phentalomine and phenoxybenzamine)

terazosin

• selective alpha antagonist (a1)

• approved for hypertension and BPH

Tamulosin

• selective (a1) antagonist

• used for BPH

• off label used for chronic prostatitis and lower UTI symptoms

phentalomine

• competitive nonselective alpha antagonist

• used for dx and treatment of pheochromocytoma

Phenoxybenzamine

• Noncompetitive alpha 1 and alpha 2 antagonist

• Receptor blockade is not reversible

• Approved only for pheochromocytoma

therapeutic actions of beta blockers (10)

• angina - reduces cardiac workload to meet oxygen demands

• hypertension

• cardiac dysrryhtmia

• MI

• heart failure

• hyperthyroidism

• migrane prevention

• stage fright

• pheochromocytoma

• glaucoma

adverse effects of beta1 blockers (selective)

• metoprolol

• bradycardia

• reduced cardiac output

• precipitation of heart failure

• AV heart block - delays conduction

• rebound cardiac excitation

adverse effects of beta 2 blocker (nonselective)

• propanolol

• bronchoconstriction - contraindicated in asthmatics

• hypoglycemia from inhibition of glycogenolysis - contraindicated in diabetics

indirect acting antiadrenergic agents

prevents activation of peripheral adrenergic receptors, but do not involve direct interaction.

• centrally acting a2 agonists

• adrenergic neuron-blocking agents

centrally acting alpha 2 agonists

• works in brain

• stimulates alpha 2 receptors, decreasing release of norepinephrine

• reduces firing of sympathetic nuerons

• used for hypertension

• clonidine and methyldopa

how does clonidine reduce hypertension

• reduces sympathetic outflow - promotes vasodilation

• results in bradycardia and decreased cardiac output

methyldopa

• causes alpha 2 activation but as a precursor

• it has to be converted to methylnorepinephrine (this is the a2 agonist)

• lowers BP by causing vasodilation