ANS Con't - Adrenergic Agonists

Question 1

What are Adrenergic Agonists?

Answer 1

• Stimulators (SYMPATHOMIMETIC) Mimic action of
norepinephrine, dopamine & epinephrine
• Can be selective or non-selective (of site, receptor subtype, tissue location)
• Almost all are at least partially non-selective (majority of side-effects

Question 2

What are the uses of Adrenergic Agonists?

Answer 2

• HEMODYNAMIC compromise (shock, depressed cardiac rhythm)
• BRONCHOSPASMS (asthma)
• Nasal and sinus CONGESTION
• Often used in EMERGENCY situations

Question 3

What is the prototype of Adrenergic Agonists?

Answer 3

• EPINEPHRINE: Also called ADRENALINE.
• Stimulates both alpha and beta receptors
• EMERGENCY drug: asthma, cardiac arrest, anaphylaxis
• Give PARENTALLY: GI tract enzymes destroy the drug.

Question 4

Describe Epinephrine & what it’s used for

Answer 4

• Non-selective agonist. Used for
– Severe, acute bronchospasm
– Anaphylactic shock (type 1 hypersensitivity)
– Cardiac arrest (heart injection)
– Adjunct to anasthetic (why?)
Works fast, but short-acting

Question 5

What are Epinephrines side effects?

Answer 5

•Stimulant effects on brain (anxiety, paranoia, headache, tremor)
• Hypertension-induced hemorrhage • Cardiac Arrythmia
• Hyperglycemia in diabetic

Question 6

What are other non-selective agonists?

Answer 6

norephinephrine & pseudoephedrine

Question 7

Norepinephrine:

Answer 7

Primarily used to treat shock (increases blood pressure)

Question 8

What is shock?

Answer 8

massive drop in BP (faint b/c too much O2 in blood –> hyperventilate)

Question 9

Pseudoephedrine:

Answer 9

Nasal decongestant

Question 10

Describe brain-targeted non-selective Adrenergic Agonists

Answer 10

• Critical role of NE and dopamine in mood and motor control-Imp for depression, anxiety, Parkinson’s Disease
• Adrenergic Agonists (sympathomimetics) –like any drug-must cross the BBB to effect brain
• Many side effects come from undesired peripheral SNS activation

Question 11

List brain-targeted non-selective Sympathomimetics

Answer 11

• Cocaine
• Amphetamines
• Anti-Parkinsons Disease
• Anti-depressants 1
• Anti-depressants 2

Question 12

Describe the brain-targeted Non-selective sympathomimetics: COCAINE

Answer 12

Inhibits the reuptake of serotonin, norepinephrine, and dopamine. Non- selective for receptor subtype and organ.
Peripheral activation causes side effects (HR, sweating, Hypertension, etc)

(medically used to stop bleeding locally & its a v. powerful anaesthetic even though its a stimulant)

(euphoric, energetic etc.)

Question 13

What is the difference b/t cocaine & meth?

Answer 13

meth leaks it out so lasts longer (effect is much longer)

(*check to add more)

Question 14

Describe the brain-targeted Non-selective sympathomimetics: AMPHETAMINES

Answer 14

Inhibits uptake and increases NT release (including serotonin and NE)
• Very potent effects in CNS and periphery- • Crystal Meth, RITALIN, MDMA (ecstasy)

Question 15

Ectasy…the love drug?

Answer 15

makes you feel closer & more romantic
- take viagra with it (anti-stimulant)

Question 16

Describe the brain-targeted Non-selective sympathomimetics: ANTI-PARKINSONS DISEASE

Answer 16

Monoamine Oxidase Inhibitor (MAOi) Example:
SELEGILINE (used with LEVADOPA)

Question 17

What are side-effects of drugs for Anti-Parkinsons Disease
Monoamine Oxidase Inhibitor (MAOi) Example:
Selegiline (used with Levadopa)

Answer 17

Dry mouth
Constipation
Tachycardia

Question 18

Describe the brain-targeted Non-selective sympathomimetics: ANTI-DEPRESSANTS 1

Answer 18

Monoamine Oxidase Inhibitor
• Example: PHENELZINE

Question 19

What are side effects (among others) of Anti-depressants 1
Monoamine Oxidase Inhibitor
• Example: Phenelzine

Answer 19

Dry mouth, constipation, urinary retention, mydriasis, hyperthermia, sweating, hypertension,

(act of SNS)

Question 20

Describe the brain-targeted Non-selective sympathomimetics: ANTI-DEPRESSANTS 2

Answer 20

Tricyclic Antidepressants (TCA)
• Example: Amytriptyline

Question 21

What are the Contraindications of brain-targeted Non-selective sympathomimetics: ANTI-DEPRESSANTS 2

Answer 21

Urinary retention
Pregnancy
Myocardial infarction
Congestive heart failure

Question 22

Describe Selective sympathomimetics

Answer 22

• Even if selective, almost always some “leaky” effect on other receptor types
▪ alpha1, beta1, beta2 Recall that alpha2 receptors inhibit sympathetic response, so activating alpha2 is not sympathomimetic

Question 23

Describe Peripheral sympathomimetics a1 agonist

Answer 23

• PRIMARY function of a1 is vasoconstriction, so drugs will be usually geared to this:
– Nasal decongestant- reduces blood flow, thus fluid release
– Increases peripheral resistance, thus increasing blood pressure (trauma, bleeding, shock)
– Example PHENYLEPHRINE

Question 24

What are side effects of a1 activation?

Answer 24

STIMULANT EFFECTS! Cocaine, nicotine,
caffeine, meth all stimulate adrenergic – Sweats, manic behavior, anxiety, paranoia – Increased thinking speed and reflexes
(any stimulant will increase IQ for time you’re on it (state-dependent))

Others:
Weight loss, hyperglycemia, impotence, hypertension, GI effects, exacerbation of prostatic urinary inhibition, bradycardia (hypertensive response)

Question 25

Describe B1 agonists

Answer 25

• Beta 1 activation causes: • Increases: Heart rate, Force of contraction, Velocity of conduction in AV node – DOBUTAMINE: Increases – cardiac output- used in – congestive heart failure

Question 26

Describe B2 agonists

Answer 26

2 activation causes: – Bronchial dilation, Relaxation of uterine muscle,Vasodilation,Glycogenolysis – Almost exclusively found as inhalers – Bronchial dilation: • SHORT ACTING: ALBUTEROL (SALBUTAMOL, VENTOLIN)-asthma, COPD (may increase death in COPD) • LONG ACTING- SALMETEROL Works 12 hr vs 2 hr for albutarol – Other use- IV inhibition of preterm labor

Question 27

a1 primarily causes _______. So, agonists __________

Answer 27

vasoconstrictor raise blood pressure and decrease local blood flow (PHENYLEPHRINE)

Question 28

B1 primarily ___________, so use to _______

Answer 28

stimulates the heart increase cardiac activity (DOBUTAMINE)

Question 29

B2 primarily causes _________, so use for _________

Answer 29

bronchodilation asthma & COPD (Salmeterol)

Question 30

What do Anti-Adrenergic Drugs do?

Answer 30

• INHIBIT OR BLOCK the effects of sympathetic nerve stimulation. • Not naturally occurring: SYNTHETIC drugs • Most block (ANTAGONIST action) alpha 1, beta 1 and beta 2 receptors • Alpha 2 agonists are adrenergic antagonists

Question 31

Alpha2-Adrenergic agonists are....

Answer 31

adrenergic antagonists a2 agonists treat HTN. • Despite being an AGONIST, produce BLOCKING OF RELEASE OF SYMPATHETIC neurotransmitter. • INHIBIT RELEASE of norepinephrine in CNS • Lower blood pressure • CLONIDINE

Question 32

Describe a1 antagonists

Answer 32

Remember- a1 causes vasoconstriction and constriction of prostate neck • Thus inhibition would.... • Treat hypertension: PRAZOSIN, DOXASIN- Competitive blockers of a1, causing decreased blood pressure (stronger & faster than clonidine) • Treat prostatic hypertrophy and vasospastic (urinary) problems- TAMSULOSIN (more selective for a1A receptors on prostate) • IN CONGESTIVE HEART FAILURE - Causes decreased preload and afterload by decreasing peripheral resistance (vasodilation) – Means the heart has less resistance to contract against, leading to increased cardiac output, decreased pulmonary congestion- PRAZOSIN – So we can use one drug to ACTIVATE a SNS receptor subtype found on the heart (B1), to increase cardiac output, and a different drug to INHIBIT a SNS receptor subtype found on peripheral vessels (a1) to decrease peripheral resistance, to treat the same condition

Question 33

What are side effects to blocking a1 receptors?

Answer 33

Early on, causes massive orthostatic hypotension (fainting when standing - v. rapid drop in BP), so start with low doses • Vertigo • Sexual dysfunction • Reflex Tachycardia (b/c of drop in BP) • “floppy Iris Syndrome”

Question 34

What are Beta Blockers?

Answer 34

Used to treat rapid pulse arrhythmias, hypertension, MI, other heart problems • DECREASE CONTRACTILITY, cardiac output, heart rate and blood pressure. • REDUCE OXYGEN DEMAND on the heart. • SLOW CONDUCTION through the AV node, slow the ventricular response (therefore, slow the heart) (to reduce heart activity) (when you have heart probs like this, you may also have changes in BP)

Question 35

What are the generations of B-blockers?

Answer 35

• 1st generation- Non selective (B1 and B2) - block heart & lungs • 2nd generation- Cardioselective (B1) - selective to heart • 3rd generation- Partially selective (with a1 inhibition)

Question 36

Describe nonselective beta blockers. & what they cause

Answer 36

block both beta 1 (heart) and beta 2 (lung) receptors.- Example PROPRANOLOL • Can cause BRONCHOSPASMS: not for use with asthma (side effect on lungs)

Question 37

1st generation-Non-selective beta blocker - PROPANOLOL

Answer 37

– Decreases cardiac output – Reflex peripheral vasoconstriction (slow decrease in hypertension) – Bronchoconstriction (danger to asthmatics and COPD) – Decreased glycogenolysis and glucagon secretion-this amplifies the effect of insulin on hypoglycemia.

Question 38

What are propanolol uses?

Answer 38

• Reduced hypertension through decreased cardiac output, decreased renin and decreased peripheral resistance (long term) • Angina and Myocardial infarction from reduced oxygen demands • Blocks the effect of hyperthyroidism on adrenergic system

Question 39

Other non-specific beta blockers:

Answer 39

TIMOLOL- Used for glaocoma by decreasing production of aqeous humor and intraocular pressure

Question 40

Describe a typical response to stress

Answer 40

1. During stressful situation, brain tells adrenal glands to produce adrenaline 2. Adrenaline flows through blood vessels to heart 3. Adrenaline enters heart's cells through receptors 4. Heart rates goes up, producing fight-or-flight rxns

Question 41

Describe how beta-blockers short-circuit stress

Answer 41

1. Beta-blockers enter the bloodstream through gastro-intestinal tract 2. Beta-blockers prevent adrenaline from attaching to the receptors on the heart's cells 3. Heart rate stays normal; fight-or-flight rxns do not occur

Question 42

Describe 2nd generation- B1 specific blockers

Answer 42

• These are developed to specifically avoid the BRONCHOCONSTRICTION of B2 receptors • Used to treat hypertension- reduced pulmonary, vascular, and blood glucose effects • Especially good for diabetic hypertensive patients (very common co-morbidity- DIABETIC OBESE HYPERTENSION) • Example: ATENALOL

Question 43

Describe 3rd generation. Partial B1 receptor blockage (with examples described)

Answer 43

• Reduction in a receptor leads to reduced peripheral resistance, less load on heart • CARVEDILOL: Higher affinity for b1 and b2, so reduces HR significantly and may exacerbate asthma • LABETALOL: Higher affinity for a1, so reduce BP w/o large effect on resting HR. Used for pre-eclampsia and emergency

Question 44

B2 specific antagonists?

Answer 44

?