Kaplan Pharmacology - Section 2 - Autonomic Pharmacology (2)

Front 1

Put organophosphates and competitive inhibitors of AChE on a lineweaver-burk plot.

Back 1

Front 2

What receptors antagonize each other in the heart?

Back 2

beta1 and M2

Front 3

What renin response would you see in a patient with a pheochromocytoma?

Back 3

Decreased due to alpha1 stimulation. Alpha-receptors are less sensitive to activators than beta, but at higher doses they become predominant.

("It's like a safety valve. If you already have plenty alpha1 response to increase BP you don't need RAAS engaged")

Front 4

Beta2 receptors are mostly not innervated. What neurotransmitter(s) cannot reach this receptor?

Back 4

NE. This is the receptor for E.

Front 5

Beta2 receptors are coupled to what intracellular protein?

Back 5

Gs, increasing cAMP.

Front 6

What is the effect of epinephrine on the liver?

Back 6

(1) Glycogenolysis
(2) Gluconeogenesis
(3) Lipolysis

Front 7

Insulin secretion is slightly enhanced by ______________.

Back 7

epinephrine

Front 8

What is the result of alpha2 stimulation and beta2 stimulation in the pancreas?

Back 8

Alpha2 - decreased
Beta2 - increased

Front 9

D1, just like beta2 will result in an increased intracellular __________.

Back 9

cAMP

Front 10

Why can dopamine bind to beta and alpha adrenergic receptors?

Back 10

Remember dopamine has a similar molecular structure to norepinephrine, only differing by an hydroxyl group.

Front 11

As you're titrating your patient with increasing dopamine dosages, what will happen?

Back 11

You will go from D1 stimulation to beta1 stimulation to alpha1 stimulation.

Front 12

What drug has a good clinical use in shock?

Back 12

Dopamine. It dilates coronaries and renal vasculature (maintaining GFR), it increases cardiac output (beta1) and can help maintain BP (alpha1).

Front 13

This is a D1 agonist used for severe HTN.

Back 13

Fenoldopam

Front 14

What BP tracing would you see with addition of phenylephrine?

Back 14

Front 15

Why should you think twice about administering phenylephrine systemically in a hypotensive patient?

Back 15

It does increase BP, but increases the risk for ischemia and reflex bradycardia.

Front 16

Mention two alpha1 agonists and their uses.

Back 16

(1) Phenylephrine: Nasal decongestant and ophthalmologic use (mydriasis w/o cycloplegia)
(2) Methoxamine: Paroxysmal atrial tachycardia because of vagal reflex
- Increased BP can cause a reflex bradycardia which slows down the heart.

Front 17

Alpha2 agonists are used clinically for what? How does it work?

Back 17

Mild to moderate HTN. It stimulates prejunctional receptors in the CNS to decrease sympathetic outflow.

Front 18

These two drugs are alpha 2 agonists.

Back 18

Clonidine and methyldopa

Front 19

How would a BP tracing look when administering beta agonists?

Back 19

Front 20

What is the drug that is a non-selective beta agonist?

Back 20

Isoproterenol (iso = the same). Works equally on beta 1 and beta 2.

Front 21

What is a clinical use of isoproterenol? What are side effects?

Back 21

(1) Bronchospasms (asthmatic; beta 2)
(2) Heart block (beta 1)
(3) Bradyarrhythmias (beta 1)

Side effects will be those of tachycardia; angina, arrhythmia and flushing (beta 2)

Front 22

What is Dobutamine? What is it useful for?

Back 22

beta-agonist. It is practically a beta 1 selective agonist, but with weak beta 2 agonistic properties.

Acute management of CHF.

Front 23

What drugs could be used in asthmatics?

Back 23

Selective beta2 agonists:
(1) Salmeterol
(2) Albuterol
(3) Terbutaline

Front 24

This beta agonist is used to prevent premature labor.

Back 24

Ritodrine, works on beta 2 (selective). It relaxes

Front 25

Compare salmeterol with albuterol and terbutaline.

Back 25

Salmeterol is slow acting, it is used for prophylaxis in asthmatics only.

Albuterol and terbutaline can be given in IV form to have an immediate effect in severe asthmatic attacks.

Front 26

What is a common complaint of anti-asthma drugs?

Back 26

Beta2 agonists works just like epinephrine. It causes vasodilation that may cause reflex tachycardia.

Front 27

What adrenergic receptors do NE work on? E?

Back 27

Everything except beta2 (not innervated). Epinephrine works on everything.

Front 28

How would NE appear on a tracing?

Back 28

Front 29

NE CAN NEVER ___________________________.

Back 29

LOWER BLOOD PRESSURE (no beta 2)

Front 30

How would E appear on a tracing? (increasing doses)

Back 30

Low doses: Primarily beta activity
Medium doses: Alpha1 is poking its nose in the pharmacology. It looks like a beta 1 agonist.
High dose: Alpha 1 predominates. BP increased. May see reflex bradycardia.

Front 31

What drug would look like medium dose epinephrine on a tracing?

Back 31

Dobutamine (beta 1).

Front 32

Is this E or NE?

Back 32

We don't know. If we were told, however, that the drug bronchodilates, it would be E.

Front 33

How do NE and E at high doses differ?

Back 33

NE: Alpha1, Beta1
E: Alpha1, Beta1, Beta2

Leaving out alpha2

Front 34

You have given too much epinephrine in a patient in shock. His BP is high and HR is progressively lower. What can be done?

Back 34

Alpha 1 blocker (this is epinephrine reversal)

Front 35

In too high doses E, we can reverse it by alpha-1 blockade by unmasking its beta-2 activity. How can we do the same with NE?

Back 35

We can't. NE can never reach beta 2 receptors (has not beta2 activity).

Front 36

What are uses of NE and E?

Back 36

(1) Cardiac arrest (beta1)
(2) Adjunct to local anesthetic (prevent absorption)
(3) Hypotension (alpha1, beta1)
(4) Anaphylaxis (only E)
(5) Asthma (only E)

Front 37

What are releasers?

Back 37

Drugs that displace NE from its mobile pool in the nerve terminal.

Front 38

Where are MAO-A enzymes found in the body?

Back 38

Anywhere (A for Anywhere)

Front 39

MAO-A inhibitors will prevent the metabolism of what exogenous compound? What happens?

Back 39

Tyramine from wine and cheese. Tyramine causes a massive release of NE from the mobile pool. Extreme alpha1 (BP), beta 1 (tachycardias). This is called a HTN crisis, it will kill the patient.

Front 40

A patient is on a MAO-A inhibitor. What must they avoid?

Back 40

(1) Tyramine
(2) Ephedrine
(3) Amphetamines

They are releasers.

Front 41

A consequence of chronic cocaine use?

Back 41

Dilated cardiomyopathy, potential for dying from MI or strokes.

Front 42

What should you worry about when you give tricyclics?

Back 42

Cardiotoxicity (it's a limiting side effect of these drugs)

Front 43

Alpha receptor antagonism may cause ____________ and __________.

Back 43

reflex tachycardia; salt and water retention

Front 44

What else should you add to an alpha antagonist in the drug regimen in the treatment of hypertension?

Back 44

Beta blocker (reflex tachycardia) and diuretic (RAAS may increase

Front 45

Major uses of alpha antagonists?

Back 45

(1) Hypertension
(2) Pheochromocytomas

Front 46

What is the drug of choice in a patient with pheochromocytoma? Explain your choice.

(1) Phentolamine
(2) Phenoxybenzamine

Back 46

Phenoxybenxamine. It is an irreversible inhibitor and works noncompetitively. Phentolamine is a competitive inhibitor. This is a bad choice due to the extreme doses we would need to out-compete epinephrine.

Front 47

How would you fit phenoxybenzamine and phentolamine in a graph with % TPR as a function of log dose of NE?

Back 47

Front 48

When would you give a beta blocker to a patient with a pheochromocytoma?

Back 48

After phenoxybenzamine. If you do it before, you allow all the E to bind only to alpha1.

Front 49

List these selective alpha 1 blockers.

Back 49

(1) Prazosin
(2) Doxazosin
(3) Terazosin
(4) Tamsulosin

Front 50

Alpha 1 selective blockers are used for what?

Back 50

(1) HTN
(2) Benign prostatic hyperplasia

Front 51

We use alpha 1 blockers in benign prostatic hyperplasia to allow for better voiding of the bladder. What can we do to actually decrease the size of the prostate?

Back 51

Finasteride (5 alpha reductase inhibitor)

Front 52

List alpha 2 blockers you know.

Back 52

(1) Yohimbine
(2) Mirtazapine

Front 53

What drug could you give a woman with anorexia and depression?

Back 53

Mirtazapine. Causes weight gain as well as treating depression by increasing NE in the brain.

Front 54

Beta1 blockade results in what?

Back 54

(1) Decreased HR, Decreased SV, Decreased CO
(2) Decreased Renin
(3) Decreased aqueous humor production

Front 55

What are clinical uses of beta1 antagonists?

Back 55

Heart: SVTs, Angina, MI
Kidney: HTN, CHF

Front 56

What is the rationale for use of beta blockers in HTN?

Back 56

BP = TPR x CO

Renin secretion is decreased, decreasing angiotensin II and reducing TPR. Cardiac output is also decreased.

Front 57

A beta blocker in overdose will cause?

Back 57

AV block. Could potentially stop the heart.

Front 58

How can you reverse a beta blocker overdose?

Back 58

Glucagon. It has positive inotropic and chronotropic effects on the heart that are G-protein linked to adenylyl cyclase.

Front 59

Don't use this drug in these groups of patients unless you really have to. Explain why.

Back 59

Beta blockers in asthmatics. Beta 2 blockade may precipitate bronchospasms.

Beta blockers may precipitate vasospasms in patients with vasospastic dx such as Raynauds or Prinzmetals angina.

Front 60

In prinzmetals angina you should not use? What could you use?

Back 60

Don't use beta blockers. Use Calcium channel blockers or nitrates.

Front 61

What can beta blockade result in other than bronchospasms in asthmatics and vasospasms in patients with vasospastic disorders?

Back 61

Metabolic effects upon fasting. We need E's effect on beta 2. It can decreased glycogenolysis, decrease gluconeogenesis. Result is hypoglycemia.

Front 62

What group of patients will be most affected by the metabolic side effects of beta 2 blockade?

Back 62

Diabetics.

Front 63

In what three groups of patients would you want to avoid using beta blockers?

Back 63

(1) Asthmatics
(2) Vasospastic dx
(3) Diabetics

Front 64

What do we really mean (in vivo) when saying that a drug is, for example, beta 1 selective?

Back 64

Beta 1 > Beta 2

It's a matter of dose.

Front 65

Memory help: How can we easily remember what beta blockers are beta1-selective drugs?

Back 65

If they start with letters A through M. From letters P and onwards you have beta non selective.

Front 66

What does it mean that a drug have ISA?

Back 66

Intrinsic Sympathomimetic Activity, it means that the drug has partial agonist activity (partial agonists have duality; by themselves they behave as agonists, in the presence of full agonists they behave as blockers)

Front 67

These two beta blockers that have ISA?

Back 67

(1) Acebutolol
(2) Pindolol

Front 68

What does it mean that certain beta blockers have a "ceiling" on their effect?

Back 68

It means that they might be less effective, but they are also far less toxic.

Front 69

List some properties of beta blockers with ISA.

Back 69

(1) Act as partial agonists
(2) Less bradycardia (beta1)
- Partial agonist activity
(3) Slight vasodilation or bronchodilation (beta2)
(4) Minimal change in plasma lipids (beta2)

Front 70

What beta blocker has ISA and is non-selective?

Back 70

Pindolol

Front 71

Blood lipids often increase with beta blockers. Why?

Back 71

Lipolysis is impaired particularly in the liver.

Front 72

These beta blockers have no issues with hyperlipidemia.

Back 72

(1) Acebutolol
(2) Pindolol

Front 73

Atenolol is ________-soluble and does not produce _________.

Back 73

water; sedation

Front 74

What beta blockers produce sedation?

Back 74

Acebutolol (+)
Metoprolol (+)
Pindolol (+)
Timolol (++)
Propranolol (+++)

Front 75

Patient has hx of angina. They are treating insomnia with benzodiazepines. Which beta blocker will be safer to use?

Back 75

Atenolol (no CNS depressant effect)

Front 76

General uses of beta-blockers?

Back 76

(1) Angina
(2) HTN
(3) Post-MI

Front 77

Some beta-blockers are classified as antiarrhythmics. What class are they?

Back 77

II

Front 78

What beta blockers are approved as antiarrhytmics?

Back 78

(1) Propranolol
(2) Acebutolol
(3) Esmolol

("APE")

Front 79

These beta-blockers are used in glaucoma.

Back 79

(1) Timolol
(2) Betaxolol

Front 80

Propranolol has some special uses since it penetrates the CNS. What is it?

Back 80

(1) Migraine
(2) Thyrotoxicosis
(3) Performance anxiety
(4) Essential tremor

Front 81

Propranolol is the only beta blocker that inhibits __________.

Back 81

deiodinase

Front 82

What is special about Labetalol and Carvedilol?

Back 82

They have combined alpha-1 and beta-blocking activity. Used in CHF.

Front 83

How can we easily remember that Labetalol and Carvedilol have combined alpha and beta action?

Back 83

They don't end in olol, but rather lol.

Front 84

This beta blocker is also a class III antiarrhythmic.

Back 84

Sotalol

Front 85

What is special about sotalol?

Back 85

It's a potassium channel blocker AND beta blocker. It has a use as antiarrhythmic (class III)

Front 86

Glaucoma comes in two flavors, what are they?

Back 86

(1) Open-angle glaucoma
(2) Closed-angle glaucoma

Front 87

What angle are we talking about in glaucoma?

Back 87

The angle between the iris and the cornea

Front 88

What is the problem in glaucoma and what happens?

Back 88

Increased intraocular pressure which compromises the vascular supply to the retina. With hypoxic damage (fragile neural tissue) we can get blindness.

Front 89

Describe open-angle glaucoma.

Back 89

Chronic condition with IOP due to decreased reabsorption of aqueous humor, leading to progressive (painless) visual loss and, if left untreated, blindness.

Front 90

Drug treatment of open-angle glaucoma?

Back 90

Drug treatment: Beta blockers to decrease the formation of fluid by ciliary epithelial cells and muscarinic activators to improve drainage through the canal of Schlemm. Muscarinic agonists to improve outflow. AChE inhibitors improve outflow.

Front 91

Describe closed-angle glaucoma.

Back 91

Acute (painful) or chronic (genetic) condition with increased IOP due to blockade of the canal of Schlemm. When it's acute it's a matter of hours for us to decrease intraocular pressure using powerful diuretics, otherwise blindness will be the result.

Front 92

What is latanoprost?

Back 92

Prostaglandin analogue that will open the canals of schlemm.

Front 93

Side effect of Latanoprost for glaucoma?

Back 93

Darkening of the iris

Front 94

Treatment of acute glaucoma attack?

Back 94

Diuretics. Mannitol and short term treatment with carbonic anhydrase inhibitors.

Front 95

_____________ (Miosis/Mydriasis) is a good idea in glaucoma.

Back 95

Miosis

Front 96

These drugs are contraindicated in treatment of glaucoma.

Back 96

(1) Alpha1 agonists
(2) Muscarinic blockers

Causes mydriasis. Can precipitate an acute attack in people with glaucoma and result in blindness.