11 04 2014 Adrenergic Agonists and Antagonists Flashcards Preview

Cardiology M2 > 11 04 2014 Adrenergic Agonists and Antagonists > Flashcards

Flashcards in 11 04 2014 Adrenergic Agonists and Antagonists Deck (38):
1

Name of drugs that mimic SNS response vs. drugs that go against SNS response

Agonists: Sympathomimetics, adrenomimetics

Antagonists: Sympatholytics

2

Epinephrine

Adrenergic Agonist

alpha 1 = alpha 2 , Beta 1= B2

3

Norepinephrine

Adrenergic Agonist

Alpha 1= alpha 2; Beta 1>>>> B2

Used (uncommonly) for pressor effects

4

Isoproterenol

Adrenergic Agonist

Beta 1 = Beta 2 >>>>> alpha

Used mostly for heart stimulation in bradycardia or heart block (direct and reflex from beta 2 effects)

5

Dobutamine

Adrenergic Agonist

Beta 1 > Beta 2 >>>>>>> alpha

(+) inotropic effects more prominent than (+) chronotropic effects ( HR)
- used in congestive heart failure

6

Dopamine

Adrenergic Agonist

D1 = D2 >>>>> beta 1>> alpha

Vasodilation of renal, mesenteric, and coronary beds
* dose dependent. If go too high you can cause severe vasoconstriction = ischemia of peripheral tissues

Use: heart stimulation with positive effects on renal output

7

Who are the catecholamines

Epinephrine, Norepinephrine, Isoproterenol, Dobutamine, Dopamine

All work directly on receptor

8

Who are the direct noncatecholamines?

Phenylephrine
Clonidine
Albuterol, ritodrine

9

Phenylephrine

Noncatecholamine-- Direct

Alpha 1 > Alpha 2 >>>> Beta

Vasoconstrictive effects used to treat hypo tensions, shock

nasal decongestion (topical), ophthalmic effect (topical) - mydriasis (dilation of pupil)

10

Clonidine

Noncatecholamine-- Direct

Alpha 2 > alpha 1 >>>>>> Beta

Penetrates CNS, inhibits SNS output
= Hypotension, bradycardia, sedation

Used in hypertension

Also used in deminish craving in narcotic, alcohol, and nicotine withdrawal

11

Albuterol, ritodrine

Noncatecholamine-- Direct

Beta 2 >> Beta 1 >>>>>> alpha

- Asthma, COPD for bronchodilation
- Inhalers minimize systemic effects
- uterine muscle relaxant to delay preterm labor (benefits?)

12

Who are the Noncatecholamine-- Indirect ??

Amphetamine, methylphenidate
Tyramine (when MAO inhibitor present)
Cocaine

( alpha and beta, typically like NE)

13

Who are the mixed Noncatecholamines

Ephedrine
Pseudeoephedrine

(indirect plus direct alpha and beta)

14

Therapeutic uses of Epinephrine

1. Anaphylactic shock ( bronchioconstriction, hypotensions and vasucular collapse, angioedema) ( via alpha and beta)

2. Acute asthmatic attacks (not really anymore because of beta -2 specific agonists)

3. Prolonged action of local anesthetics (alpha)

4. Topical hemostatic agent (alpha)

5. Cardiac arrest ( alpha -- increase diastolic pressure)

15

Adverse effects of Epinephrine

** DO NOT USE ON HYPERTHYROID PATIENTS because increase in thyroid hormone increases epinephrine receptors = crisis

1. Marked HYPERTENSION
2. Arrhythmias
3. Angina
4. Necrosis following extravasiation

16

Amphetamine, methylphenidate

Noncatecholamine, indirect (alpha and beta, typically like NE)

Readily enters CNS, releasess catecholamines (including DA)

CNS: elevates mood, alterness, suppresses appetite

used in narcolepsy, weight loss, and ADHD

17

Cocaine

Noncatecholamine, indirect (alpha and beta, typically like NE)

Vasoconstrictive
Local anesthetic
Abuse side effects--> hypertensive response

18

Tyramine

Noncatecholamine, indirect (alpha and beta, typically like NE)

Found in FOOD: cured meats, smoked fish, cheese

produces NE-like Hypertensive crisis if paired with MAO inhibitor.
- inhibits VMAT on vesicle membrane in pre-synaptic cell and NET at cell membrane of presynaptic cell reverses--> into synapse

19

Ephedrine, pseudoephedrine

Noncatecholamine, mixed

Orally available, excreted unchanged (kidneys), long duration of action, some CNS penetration, mild stimulant

Used as nasal decongestant, bronchodilator (cold medications)

20

Pharmacology of non-specific alpha blockers (antagonists)

Alpha 1 and alpha 2 targeted

Predominant effect = vasodilation
- reflex tachycardia because alpha 2 receptors mediate a negative feedback role and
-hypotensive response is blunted by increased CO.
BP = CO x PVR

21

What are some of non-specific alpha blockers Adverse effects?

orthostatic hypotension, nasal stuffiness, tachycardia

22

Phenoxybenzamine

nonspecific alpha blocker

-requires bioactivation (lag in onset)
-Covalent, irreversible modification

used for treatment of pheochromocytoma (tumor of the medulla = increase in catecholamine synthesis ex. NE)

23

Phentolamine

Nonspecific (alpha 1 + alpha 2) blocker

used for short term treatment of phenochormocytoma because shorter duration and for hypertensive crisis.

-alpha agonist reversal for hypertensive crisis

24

Alpha 1 blockers Pharmacology

Decrease blood pressure with less reflex stimulation of heart rate

Decreases preload and after load

Used to treat hypertension, relaxes smooth muscle in prostate, urethra, and bladder neck
= promotes urine flow (benign prostatic hyperplasia)

25

Prazosin, terazosin

Alpha 1 blockers

used for hypertension and BPH

26

Tamsulosin

Primarily alpha 1 blocker, but is somewhat selective for alpha 2 as well
- promote urine flow in BPH with little effects on blood pressure.

27

Effects of beta blockers?

1. CV: decrease HR and contractility
- short term = decrease CO, increase Peripheral resistance
-long term: peripheral resistance normalizes, decrease myocardial O2 consumption

2. BP --no effects on blood pressure if normal but will decrease hypertension in hypertensive patients

3. LUNGS-- Bronchoconstriction (antagonism of B2) Dangerous in COPD and asthma

4. EYE-- Decreases aqueous humor production from ciliary epithelium

5. METABOLIC: blocks glucose mobilization ( B2 antagonism); slows lipolysis, increases vLDL, and lowers HDL (mechanism unclear)

28

Pharmacokinetics of Beta blockers

- well absorbed orally
- bioavailbity -- 1st pass metabolism and clearance dependent on agent

-lasts for hours, exception is Esmolol (10 min half-life) - used IV

- partial agonist activity

29

Therapeutic uses of beta blockers

1. Angina
2. Hypertension
3. Supraventricular and ventricular arrythmias
4. Myocardial infarction
5. Hyperthyroidism
6. glaucoma
7. Neurological: migraine; tremor
8. heart failure

30

Adverse effects/ constraints of beta blockers

1. Heart Failure -- acute treatment
2. Bradycardia
3. COPD and asthma
4. Abrupt withdrawal = angina, sudden death
5. Blunt recovery from hypoglycemia (also mask symptoms of concern in insulin-dependent diabetics)
6. Adverse plasma lipoprotien profiles
7. CNS : sleep disturbances, depression

31

Propanol

Beta-blocker
no selectivity
no intrinsic sympathomimetic activity (partial agonist)

- membrane stabilizing activity ( local anesthetic properties)
- High lipid solubility

* Prototypic agent

32

Esmolol

Beta 1 selectivity

- no intrinsic sympathomimetic activity
- no membrane stabilizing activity
-low lipid solubility
- half-life = 10 min, IV administration

33

Acebutolol

Beta 1 selectivity

- intrinsic sympathomimetic activity
-membrane stabilizing activity
-low lipid solubility

34

Carvedilol

No selectivity
- no intrinsic sympathomimetic activity
- no membrane stabilizing activity
-lipid solubility unknown
* SOME alpha 1 blockage

35

Pindolol

No selectivity

- intrinsic sympathomimetic activity
-membrane stabilizing activity
-moderate lipid solubility

36

Atenolol

Beta 1 selective

- no intrinsic sympathomimetic activity
- no membrane stabilizing activity
-low lipid solubility

37

Timolol

No selectivity beta antagonist

- no intrinsic sympathomimetic activity
- no membrane stabilizing activity
-moderate lipid solubility

38

Who are the beta 1 selective beta blockers?

Esmolol, Acebutolol, and atenolol

Metoprolol, Bisoprolol, Nebivolol