Antiadrenergic Drugs (Exam 1)

Question 1

Antiadrenergics

Answer 1

• Compound that inhibits the effects of exogenous catecholamines or adrenergic agonists
• Also includes Adrenergic blocking agents/drugs that deplete catecholamines (epi/NE/dopamine)
• Adrenergic alpha and beta blockers

Question 2

Sympatholytic

Answer 2

Compound that inhibits the response due to sympathetic nerve stimulation on alpha or beta receptors

Question 3

Adrenergic antagonists

Answer 3

Agents that inhibit or reverse the effects of NE and epinephrine (alpha and beta antagonists)

Question 4

-osin

Answer 4

Alpha antagonist

Question 5

-lol

Answer 5

Beta antagonist

Question 6

Mixed Antagonists

Answer 6

labetalol (Trandate)

carvedilol (Coreg)

Receptor Affinity: ß₁=ß₂ ; a1>a2

Question 7

doxazosin (Cardura)

prazosin (Minipress)

terazosin (Hytrin)

Answer 7

alpha₁ selective antagonists

-direct relaxation of arterioles and veins

*Peripheral vascular disease and pheochromocytoma (Adrenal gland tumor)

High incidence of orthostatic/postural hypotension

Question 8

afluzosin (Uroxatral)

*doxazosin (Cardura)

*prazosin (Minipress)

silodosin (Rapalfo)

tamsulosin (Flomax)

*terazosin (Hytrin)

Answer 8

• Benign Prostatic Hyperplasia
• Blockade of alpha_1a receptor in prostate = smooth muscle relaxation in bladder neck and prostate (increasing urine flow)

*Note doxazosin, prazosin, and terazosin are also used to manage hypertension

Question 9

What should you think when you see B₂? How about B₁?

Answer 9

B₂ think lungs

B₁ think heart

Question 10

What are some of the major therapeutic adrenergic antagonists used for hypertension? What’s an important not to add on beta blockers in general?

Answer 10

Note: beta blockers in general are old medications and FDA-approved indications do not necessarily reflect current practice

Question 11

What is the drug of choice for a hypertensive emergency (historically used for a cocaine overdose)? Why?

Answer 11

IV labetalol (Trandate)

• ß₁ = ß₂ and alpha blockade (antagonist)
• No unopposed alpha unlike other beta-blockers

Question 12

How do certain beta blockers indicated for hypertension control act? (3)

Answer 12

• Decrease:
  1) Heart rate
  2) Renin release (BP decrease)
  3) Myocardial contractility and cardiac output (block epinephrine)

Question 13

What are certain beta blockers with an established mortality benefit for systolic heart failure? (reduced ejection fraction)

Answer 13

Question 14

Which beta blockers have intrinsic sympathomimetic activity? What are these contraindicated for?

Answer 14

acebutolol (Sectral)

penbutalol (Levatol)

pindolol (Visken)

-Mycocardial infarction or angina

Question 15

Which beta blockers have been shown to improve mortality, prevent cardiac remodeling/arrythmias, and reduce angina in patients with ischemic heart disease or recent MI?

Answer 15

Question 16

Which beta blocker is a class 3 K⁺ channel blocker and also considered an anti-arrythmic?

Answer 16

sotalol (Betapace)

Question 17

How can beta blockers be used for rate control in the treatment of supraventricular arrythmias such as atrial fibrillation?

Answer 17

Because they block conduction through AV node via ß₁ blockade

*metoprolol (Lopressor/Toprol) is the most common for a-fib

Question 18

What are specific examples of beta blockers used for glaucoma and what is their mechanism of action?

Answer 18

They decrease aqueous humor production by the ciliary body to decrease introcular pressure

*eye drop form

Question 19

What are some miscellaneous uses of propranolol (Inderal) due to certain special properties?

Answer 19

Special properties: very lipophilic & penetrates the BBB; membrane stabilizing effects, which inhibits action potentials across membranes acting like a local anesthetic

-Migraine prophylaxis

-Essential (benign) tremor

Thyrotoxicosis

Antipsychotic-induced akathisia (movement disorder)

Off-labels: stage fright

Question 20

What are some of the side effects of beta blockers?

Answer 20

• Bradycardia and heart block
• Bronchospasm
• Disturbance in glucose metabolism
• CNS
• Sexual

Question 21

Which is worse for bronchospasm: selective or non-selective beta blockers?

Answer 21

Non-selective are worse (best to use a ß₂-specific antagonist)

-At high doses, ALL beta blockers become non-selective

Question 22

How can you tell if someone on beta-blockers is hypogycemic (or becoming hypoglycemic)?

Answer 22

They will have excessive sweating and and mood changes still; however, other signs and symptoms are inhibited

Question 23

What are some of the CNS side effects of beta blockers?

Answer 23

Fatigue, drowsiness, depression, sleep disturbance, and nightmares

*Dependent on lipid solubility

Question 24

What are the low lipid soluble beta blockers?

Answer 24

acebutolol, atenolol, betaxolol, bisoprolol, esmolol, nadolol, and timolol

Question 25

What are the medium lipid-soluble beta blockers?

Answer 25

**Labetalol**, **metoprolol**, and **pindolol**

Question 26

What are the high lipid soluble beta-blockers?

Answer 26

**Carvedilol**, **nebivolol**, and **propranolol**

Question 27

Phentolamine (OraVerse)

Answer 27

**Nonselective alpha blocker** - _Vasodilation_ around area of injection - Used for _reversal of soft tissue anesthesia_ **\*Side effect is marked orthostatic hypotension**

Question 28

phenoxybenzamine (Dibenzyline)

Answer 28

**Non-selective Alpha blocker** - Long acting and irreversible - Blocks both pre- and post-synaptic receptors causing vasodilation (Pheochromocytoma sweating and hypertension) **\*Side effect is marked orthostatic hypotension**

Question 29

Ergot Alkaloids effects

Answer 29

- Produced by a fungus that infects rye/other grains - Gangrene of extremities, hallucinations, delirium, uterine stimulation/miscarriage Affects alpha adrenergic receptors (coonstriction) seratonergic and dopaminergic receptors (hallucinations)

Question 30

ergonovine (Ergotrate)

Answer 30

Control of postpartum/postlabortal hemhorrage ## Footnote **Alpha and seratonin agonist**

Question 31

methylergonovine (Methergine)

Answer 31

Used to induce uterine contraction and to control bleeding Seratonin agonist

Question 32

bromocriptine (Cycloset, Parlodel)

Answer 32

treatment of Parkinson's disease (**dopamie agonist**)

Question 33

ergotamine/dihydroergotamine

Answer 33

Migraine treatment (**_alpha vasoconstriction_** and _stimulation_ of **_serotonin receptors_**) \*Often combined with _caffeine_ in formulations to facilitate absorption

Question 34

What is the toxicity of ergot alkaloids for: - Acute use - Chronic use - Overdose

Answer 34

Acute use: GI disturbances (diarrhea/nausea/vomit) Chronic use: gangrene of nose, finger, and ears due to severe vasoconstriction and prolonged vasospasm OD: muscle contraction, hallucination, delirium, and convulsion

Question 35

What is a contraindication to Ergot Alkaloid use?

Answer 35

**Obstructive vascular disease** and **collagen diseases** (can cause connective tissue proliferation)

Question 36

How many serotonin receptors have been cloned? What are the most common?

Answer 36

14 Most common: * **5-HT1** * ​Brain * **5-HT₂** * _{​Brain and peripheral tissue​} * 5-HT3 * ​Chemoreceptive and vomiting centers in CNS/periph. sensory and enteric nerves

Question 37

What are the effects of seratonin on the CV system?

Answer 37

Contraction of smooth muscles Constricts most vascular beds

Question 38

What are the effects of seratonin on blood platelets? Small intestine? CNS?

Answer 38

- Enhances platelet aggregation - Increased intestinal motility - Mood changes/cognition/sexual behavior/learning/memory/sleep/appetite/perception of pain/depression/anxiety

Question 39

5-HT_1B/1D Receptor agonists

Answer 39

**Triptans** ## Footnote -Used to treat migraines by _preventing vasodilation_ Stimulation of these receptors ( presynaptic trigeminal nerve endings) **inhibits the release of vasodilating peptide** (Calcitonin gene related peptide/***_CGRP_***) Contraindications: coronary/cerebral vasospasm; coronary artery disease or stroke

Question 40

sumatriptan (Imitrex)

Answer 40

**Selective Seratonin 5-HT_1B/D agonist** **migraine treatment**

Question 41

When are selective serotonin receptor agonists especially toxic?

Answer 41

When they are used in comnination with anti-depressants that increase serotonin levels! This can lead to **Serotonin Syndrome**

Question 42

Seratonin Syndrome Management - Mild - Moderate - Life Threatening

Answer 42

Mild: Observe 6 hours and **Benzodiazepines (sedative)** Moderate: Admit to hospital/heart monitoring/Cyproheptadine Life Threatening: ICU; **Esmolol** (IV ß₁ agonist)

Question 43

Symptoms of Serotonin Syndrome - Mild - Moderate - Life Threatening

Answer 43

Mild: pupils dilated (mydriasis), shivering, sweating, and mild tachycardia Moderate: Altered mental status, autonomic hyperactivity, and neuromuscular abnormalities Life threatening: delirium, hypertension, hyperthermia, muscle rigidity, and tachycardia

Question 44

CGRP Antagonists

Answer 44

Migraine specific and monoclonal antibodies (-mab suffix) 1. _Fremanezumab_: **attaches to CGRP receptor** 2. _Galcanezumab_: **attaches to CGRP receptor** 3. _Erenumab_: **blocks CGRP receptor**

Question 45

How many half lives before a medication's effect is gone?

Answer 45

4-5

Question 46

If drug A has a therapeutic index of 3 and drug B has a therapeutic index of 50, which would be the greatest safety concern?

Answer 46

Drug A (drug b is safer)

Question 47

Which agency regulates safety and efficacy of drugs?

Answer 47

FDA

Question 48

Which route of administration works the fastest?

Question 49

Will a drug bound to plasma-protein have activity?

Question 50

What are the parts of kinetics of drugs (pharmacokinetics)?

Answer 50

ADME Absorption, Distribution, Metabolism, Elimination