Lesson 3- HISTAMINE, ANTIHISTAMINES, DRUGS FOR LIPID DISORDERS, OVERVIEW OF THE NERVOUS SYSTEM AND ADRENERGIC AGENTS AND SHOCK

What are autocoids?

Circulating or locally acting hormone-like substances that are responsible for causing the inflammatory response

what are the functions of histamine (3)?

1. Inflammation

2. Allergic reactions

3. Wakefulness

what are the functions of angiotensins? (2)

1. Vasoconstriction

2. Sodium retention

what are the functions of leukotrienes? (3)

1. Bronchoconstriction

2. Mucus production

3. Airway edema

What are the functions of prostaglandins? (5)

1. Vasodilation

2. Bronchoconstriction

3. Platelet aggregation

4. Dysmenorrhea

5. Pain

And more…

What are the functions of serotonin? (5)

1. Vasoconstriction

2. GI motility

3. Eating

4. Compulsive behaviors

5. Depression

What are the actions of the histamine 1 (H1) receptor sites? (5)

1. Vasodilator of arterioles and venules (skin flushing, warmth)

2. Increases capillary permeability (edema)

3. Bronchoconstriction and mucus production = dyspnea

4. Activates sensory nerves in skin (itching, pain)

5. Neurotransmitter in CNS

   1. Wakeful center

   2. Memory

   3. Modulates other neurotransmitters —> energy regulation, endocrine homeostasis, suppression of seizures

What is the action of the histamine 2 (H2) receptor sites?

causes secretion of gastric acid HCl in the stomach

How do allergic responses work?

exposure to allergens cause antibody production

Antibodies bind to mast cells and basophils

On the SECOND exposure to the allergen histamine is released from the mast cells and basophils and begins the reaction

What is anaphylaxis? How does it differ from a standard allergic reaction?

severe allergic reactions that results from the release of histamine and other mediators such as leukotrienes which lead to angioedema

They cannot be treated with antihistamines due to the leukotrienes causing the most severe symptoms

How do first generation antihistamines work?

They are able to cross the blood-brain-barrier which leads to CNS depression (drowsiness, slowed reactions) and overdose can cause seizures

what are some examples of first generation antihistamines?

• Brompheniramine (Dimetapp)

• Diphenhydramine (Benadryl)

• Chlorpheniramine (Chlor-Trimeton)

• Promethazine (Phenergan)

• Hydroxyzine (Vistaril)

How do second generation antihistamines work?

non lipid soluble and do not cross blood-brain-barrier and therefore are non-sedating

what are some examples of second generation antihistamines?

• Cetirizine (Zyrtec)

• Fexofenadin (Allegra)

• Loratadine (Claritin, Travist)

• Desloratadine (Clarinex)

what are some examples of H2 blockers?

• ranitidine (Zantac)

• cimetidine (Tagamet)

• famotidine (Pepcid)

• nizatidine (Axid)

what are some indications for antihistamines? (6)

• mild allergy

• Adjunct in severe allergies

• Motion sickness

• Vertigo/dizziness

• Insomnia

• Common cold/sinusitis

what are some adverse effects of antihistamines?

• Sedation

• Confusion, incoordination and fatigue (particularly in the elderly

• Respiratory depression (do not administer promethazine to children under 2 years of age)

• Alcohol and other CNS depressants intensify the sedation

• GI effects – nausea, vomiting, loss of appetite, diarrhea or constipation (minimal effect if drug is given with food)

• ANTICHOLINERGIC effect

  • Atropine-like effects

    • Decrease in GI motility and secretions (dry mouth, constipation)

    • Cardiac dysrhythmias

  • Males may have the inability to urinate

What should the level of cholesterol be?

less than 200mg/dL

what is the function of cholesterol in the body? (2)

1. Making certain hormones

2. Make bile salts for fat digestion

What are very low density lipoproteins (VLDL) responsible for?

delivering triglycerides and other substances to adipose tissue and muscle

Eventually used as fuel by the tissues

what are low density lipoproteins (LDL) responsible for?

LOUSY CHOLESTEROL or L= want it Low

Contains the majority of the cholesterol in the blood that is used by body cells

Can accumulate in the bloodstream and contribute to atherosclerosis

what are high density lipoproteins (HDL) responsible for?

HEALTHY CHOLESTEROL or H = want it High

Carries cholesterol back to the liver for destruction

Increases with exercise

what are triglycerides?

combines with proteins to make lipoproteins

what should the total cholesterol be?

less than 200 mg/dL

Less than 180 is ideal

what are some non-pharmacological ways for managing high cholesterol levels? (4)

1. Limit saturated fats in the diet- eat good cholesterols

2. Control body weight

3. Exercise regularly

4. Smoking cessation

What do the “statins” or HMG-CoA reductase inhibitors do?

Lower LDL and total cholesterol

Some lower triglycerides

Some raise HDL

what are some adverse reactions of the statins?

• myopathy

• Rhabdomyolysis

• Hepatotoxicity

• Pregnancy category X- do not give if pregnant

are drug interactions a concern for the statins?

YES- there are lots of

Big one is grapefruit or grapefruit juice

Is there one specific way the statins should be administered?

no, each one is different

what is niacin/nicotinic acid? What is special about it?

A B vitamin that reduces LDL and TG levels while increasing HDL

No longer used to lower cholesterol because therapeutic doses for lowering cholesterol would be in toxic ranges for the body

what are the adverse reactions to taking niacin/nicotinic acid? (3)

• intense flushing

• GI upset

• Liver damage

How do bile acid sequestrants work?

normal process = bile acids are excreted by liver into the intestines to assist in digestion and then the bile acids are reabsorbed back into the liver for reuse

Drug = drug binds and eventually excretes bile acids from the GI tract

what are some examples of bile acid sequestrants?

• Cholestyramine (Questran)

• Colesevelam (Welchol)

• Colestipol (Colestid)

What are some adverse reactions associated with bile acid sequestrants?

GI PROBS ← b/c drug is not absorbed it’s actions are contained to the GI tract

• constipation

• Bloating

• Indigestion

• Decreased absorption of fat and fat soluble vitamins (A, D, E, K)

Are there drug interactions for bile acids sequestrants? How does it impact how we give the med?

YES- lots of interactions can occur

Espesh with meds like digoxin, warfarin, thiazide diuretics, and some antibiotics

Therefore, bile acid sequestrants are preferred for YOUNGER patients or those who don’t require the above medications (which usually increase with age)

How does the fibric acid drug work?

activate lipoprotein lipase that breaks down triglycerides and allows them to be eliminated from the blood

what is the therapeutic effect of fibric acid drugs? How do you identify them?

lower triglycerides and VLDL

“Fenofibr-“

what are some adverse reactions to fibric acid drugs?

should be taken with meals to avoid GI disorders- GERD, diarrhea, abdominal discomfort, N/V

What are some contraindications for fibric acid drugs? Including drug interactions

• liver disease

• Gall bladder disease

• Pancreatitis

• Oral anticoagulants

• Statins

• Insulin

• Some oral antidiabetic drug

what are some examples of the omega-3 fatty acid esters?

Espanova

Lovaza

Icoaspent

(Prescription drugs)

What is the main adverse reaction to the omega 3 fatty acid esters?

diarrhea

What are the indications for omega-3 fatty acids in fish oil? What is the name of omega-3 fatty acids in fish oil? (1)

Reducing risk of CAD and stroke

American heart association recommends to servings of oily fish weekly

Called lovaza

What is the primary neurotransmitter of the sympathetic nervous system?

norepinephrine

What is the primary neurotransmitter of the parasympathetic nervous system?

acetylcholine

What are the adrenergic receptors? (5)

1. Alpha 1

2. Alpha 2

3. Beta 1

4. Beta 2

5. Beta 3

What do alpha-1 receptors do when stimulated? (4)

ORGAN RECEPTORS ← pressor effect

1. Constricts veins and many arterioles (skin and organs)

   1. Increases BP

   2. Increases organ blood flow

   3. Stops skin from bleeding

   4. Nasal decongestant

   5. Slows absorption of anesthesia

2. Mydriasis (dilates pupils) and contracts iris of eye

3. Causes ejaculation

4. Contracts bladder and prostatic capsule

What do the alpha-2 receptors do when stimulated? (1- 2 strengths + 3 more)

NERVE RECEPTORS

1. Peripheral neurons cause mild vasodilation

2. Central neurons cause potent vasodilation (blocks SNS outflow)

decreases sympathetic outflow- slows NE release from nerves and inhibits the release of NE from adrenergic nerves

• lowers BP

• Relieves pain

• Decreases insulin secretion

What do the beta-1 receptors do when stimulated? (2)

1 = 1 HEART

1. Increases heart rate and contraction → increases cardiac output

2. Releases renin

What do the beta-2 receptors do when stimulated? (2)

2 = 2 LUNGS

1. Dilate bronchi

2. Dilate blood vessels

3. Release glucose from liver

4. Relaxes uterus

5. Relaxes ciliary muscle that suspends lens of the eye

What do the beta-3 receptors do when stimulated? (2)

1. Breakdown fat AKA increases free fatty acids

2. Relaxes bladder (detrusor muscle)

3. Increases the production of heat in the body (thermogenesis)

What is an agonist?

a stimulator

What is an antagonist?

Blocker

What is responsible for breaking down norepinephrine? (2)

1. COMT enzyme in synapse

2. MAO in blood stream

what happens if a drug stops the break-down enzyme of norepinephrine? (2- #2 has 4 subcategories)

1. More neurotransmitter is present in the synapse

2. A more adrenergic action

   1. BP climbs

   2. HR is faster

   3. Breathing is faster

   4. Etc.

What is the usefulness of drugs that inhibit the break down of norepinephrine? (2)

• prolong adrenergic action

• Little practical reaction → can cause serious adverse reactions

What is shock?

inability of the circulatory system to send adequate amount of oxygen and nutrients to body cells

what are the types of shock? (5)

1. Anaphylactic

2. Cardiogenic

3. Hypovolemic

4. Neurogenic

5. Septic

What is the treatment for anaphylactic shock?

epinephrine- rescue med that triggers the adrenergic system

What is the treatment for cardiogenic shock?

treat the cause/disorder

what is the treatment for hypovolemic shock?

increase blood volume

what is the treatment for neurogenic shock?

Treat the cause of spinal shock, emotional distress

Counteract the offending drug

what is the treatment for septic shock?

antibiotics

what are the components of basic shock treatment that are used to treat all kinds of shock? (3)

1. Basic Life Support (BLS) and Advanced Life Support (ALS)- maintain oxygenation and HR

2. Maintain blood volume- Administer IV fluids or blood

3. Maintain blood pressure- dopamine and inotropic agents (epinephrine, norepinephrine, dobutamine, digoxin)

what are adrenergic drugs or agonists?

these drugs may stimulate one or more of the adrenergic receptor sites. Norepinephrine and epinephrine have strong stimulate of all the receptor sites. Other adrenergic agonists stimulate one or more of the receptor sites.

What is the overall function alpha-1 agonists?

vasoconstrictors → increase BP

what are some examples of alpha-1 agonists?

• midodrine

• Phenylephrine

• Oxymetazoline

What is the overall function alpha-2 agonists?

decrease vasoconstriction ← lower BP

what are some examples of alpha-2 agonists?

• clonidine

• Methyldopa

what is the drug that is a beta 1 and beta 2 agonist? what does it do?

Isoproterenol- bronchodilation and increases HR

What is the overall function beta-1 agonists?

heart

what are some examples of beta-1 agonists?

• Dobutamine - increases hearts contractions (an inotropic agent)

• Dopamine – increases heart rate (low dose dilates renal arteries & high doses will up the BP)

What is the overall function beta-2 agonists?

dilates the bronchial tree of lung

what are some examples of beta-2 agonists?

Salmeterol

Olodaterol

Levalbuterol

Indacaterol

Metaproterenol

Terbutaline -also used to stop uterine contratictions (relaxes the uterus)

What are some examples of beta 3 agonists?

• Mirabegron – treats overactive bladder

• Droxidopa – treats neurogenic orthostatic hypotension