Respiratory Pharmacology Week 1

1. Respiratory PharmacologyWeek 1

2. HOMEWORK/Reading • Read RAU’s Pharmacology • Ch. 1-3 • Do workbook chapters for each

3. Objectives • Syllabus and Course Outline • Discuss what Pharmacology is • Process of naming Drugs • Abbreviations and Symbols • Routes of Administration

4. Pharmacology • The study of substances that interact with living systems through chemical processes • Especially by binding to regulatory molecules and activating or inhibiting normal body processes • Basically manipulating normal human chemical mechanisms for a desired effect

5. Pharmacology • We will focus on respiratory therapy drugs, but must first learn basic general terms and regulatory systems • Medical pharmacology is the science of substances used to prevent, diagnose and treat disease

6. Toxicology • Not covered in this class, but must be able to differentiate between pharmacology and toxicology which is: • The branch of pharmacology that studies the harmful effects of chemicals on living systems

7. Drug • Any substance that interacts with a molecule or protein that plays a regulatory role in living systems. • Includes oxygen and other therapeutic gases along with our inhaled aerosolized medications.

8. Definitions • Endogenous: Substances made inside body • Exogenous: substances made outside the body • Hormones: are endogenous drugs • Toxin: poisons of biologic origin

9. Definitions • Receptors: Specific molecule, usually a protein, that interacts with a specific chemical that then causes a change in the specific molecule, causing a change in regulatory function • Lock that a key fits into; ex: • Lock receptor and epinephrine the key to opening the lock

10. Definitions • Agonist: any drug that binds to a receptor and activates the receptor • Drug that fits into a receptor, will then activate and a chemical reaction occurs within the cell. When agonist leaves the binding site it deactivates the receptor.

11. Definitions • Antagonist: any drug that binds to a receptor and prevents the activation of the receptor • Can be called competitive antagonist; competes with the agonist for binding site.

12. Definitions • Chemical Antagonist: binds directly with an agonist, instead of the receptor site, to prevent the agonist from reaching the receptor. Ex: Heparin

13. Definitions • Absorbed: drug must be able to absorb into the body to work • Delivery: Must be able to get to intended site to work; gut, intestines, liver, blood…then to site of action • Elimination: drugs must be eliminated at a reasonable rate. Affected by kidney or liver problems

14. Terminology • Names of a drug • Chemical name • Generic name (assigned by US Pharmacopoeia) • Proprietary name

15. Drug Name • The chemical name is assigned according to rules of nomenclature of chemical compounds • The brand name is always capitalized and is selected by the manufacturer. • The generic name refers to a common established name irrespective of its manufacturer.

16. Example • The chemical name for albuterol sulfate (albuterol sulfate inhalation solution) is α1 [(tert-butylamino) methyl]-4-hydroxy-m-xylene-α, α'-diol sulfate (2:1) (salt), and its established chemical structure is as follows:

17. Chemical Name- not responsible for knowing • Code name- not responsible for knowing • Generic Name/Official name: Zafirlukast • Trade/Brand: Accolate (manufactures chosen name)

18. Sources of drugs • Animal • Thyroid hormone, insulin, pancreatic disease • Plant • Khellin, atropine, digitalis, reserpine, eucalyptus oil, pine, anise • Mineral • Copper sulfate, magnesium sulfate, mineral oil

19. FDA • When a drug is approved by the Food and Drug Administration (FDA—the government agency responsible for ensuring that drugs marketed in the United States are safe and effective), it is given a generic (official) name and a trade (proprietary or brand) name. The trade name is developed by the company requesting approval for the drug and identifies it as the exclusive property of that company. • When a drug is under patent protection, the company markets it under its trade name. When the drug is off-patent (no longer protected by patent), the company may market its product under either the generic name or trade name. Other companies that file for approval to market the off-patent drug must use the same generic name but can create their own trade name. As a result, the same generic drug may be sold under either the generic name or one of many trade names.

20. Terminology • General terms • Action (mode of action, intended drug effect) • Side effect (not intended effect, nausea/tachycardia…) • Half life time required for concentration of a drug in the body to decrease by 50%. Half-life also represents the time necessary to reach steady state or to decline from steady state after a change

21. Terminology • General terms • Tolerance decrease in susceptibility to the effects of a drug due to its continued administration. • Tachyphylaxisrapid decrease in response to a drug after administration of a few doses. Initial drug response cannot be restored by an increase in dose • Potentiation The action of a substance, at a dose that does not itself have an adverse action, in enhancing the effect of another substance

22. Terminology • General terms • Synergism the interaction of elements that when combined produce a total effect that is greater than the sum of the individual elements, contributions, etc. • Agonist is a chemical that binds to a receptor of a cell and triggers a response by that cell. Agonists often mimic the action of a naturally occurring substance. Whereas an agonist causes an action, an antagonist blocks the action of the agonist and an inverse agonist causes an action opposite to that of the agonist. • Antagonist: blocks reaction of a agonist

23. Terminology • Anticholinergic actions • inhibition of parasympathetic response manifested by dry mouth, decreased peristalsis, constipation, blurred vision, and urinary retention. • Bioavailability • fraction of active drug that reaches its action sites after administration by any route. Following an IV dose, bioavailability is 100%; however, such factors as first-pass effect, enterohepatic cycling, and biotransformation reduce bioavailability of an orally administered drug. • cholinergic response • stimulation of the parasympathetic response manifested by diaphoresis, salivation, abdominal cramps, diarrhea, nausea, bronchoconstriction and vomiting

24. Phases of Action • Pharmaceutical phase • Refers to method by which a drug is administered and the form in which it is administered

26. Routes of Administration • Intravenous (IV) (RT will never give IV drugs, most common route of systemic meds) • Inhaled (Aerosol) RT route of administration • Intramuscular (IM) (includes diabetes meds, vaccines, boosters…) • Subcutaneous (SubQ) (Xylocain administration, numbing agent)

27. Routes of Administration • Sublingual • Rectal • Oral (most common route outside of hospital) • Topical

28. Pharmacokinetic Phase • Describes the time course and disposition of a drug in the body based upon absorption, distribution, metabolism, and elimination and the effects and routes of excretion of the metabolites of the drug

29. Pharmacokinetic Phase • Ionized drugs have minimal side effects generally; non-ionized drugs have greater side effects

30. Ionized vs. Nonionized • Ionized • Some drugs are made up of several elements combined to make the drug which has no charge (neither plus or minus). If these drugs can be ionized, they can split into two parts. One of the parts carries a plus charge (+) while the other part has a negative charge (-). A simple example is table salt or sodium chloride (NaCl) which can become ionized in water. NaCl is an inorganic compound. NaCl = Na+ + Cl- [the pluses and minuses should be positioned higher like the number for a footnote]Nonionized • Other types of drugs such as organic compounds don't ionize. The molecules in their structures are stuck together in such a way that they do not separate into parts. An example of a nonionized compound is benzene.

31. Pharmacodynamic Phase • Describes the mechanism of action of a drug (how it actually works in the patients body) • Effects are caused by combining a drug with a matching receptor

32. Neurotransmission • Neuron: basic cell of the nervous system, provide instant method of cellular communication • Don’t confuse nerve with neuron, nerve is a collection of neuron axon fibers • The signals in nerves can run both ways • Efferent (out) • Afferent (in)

33. Neurotransmission • Hormones such as epinephrine and AcH are stored in packets in the neuron; action potential causes these stored transmitters to release into organs, muscles… • AcH: made by mitochondria as part of energy transfer (Kreb cycle) along with lecithin that contains choline. • AcH is in the neuromuscular junction. Voluntary muscle movement, stimulated at nicotinic receptors to cause muscle contraction

34. Neurotransmission • Myasthenia Gravis antibodies block the nicotinic receptors in the neuromuscular junction from getting AcH. • AcH is also used by the autonomic nervous system in the control of • Parasympathetic smooth muscle movement (lungs, heart). The receptor here is called muscarinic

35. Neurotransmission • AcH also found in the CNS, and affect brain and spinal cord transmissions. • Catecholamines (Dopamine, norepinephrine, epinephrine): • Made from the amino acid tyrosine. Located in the autonomic nervous system signals sympathetic smooth muscle movement and organ is epinephrine and norepinephrine. The receptors are alpha and beta

36. Neurotransmission • AcH esterase breaks down AcH in the synapse. (cholinesterase) • So, if we block AcH esterase, we end up with more AcH in the synapse • MG patients are on cholinesterase inhibitors

37. Second messenger activation • drugs cause a reaction once it attaches to a receptor site, or blocks a receptor site. • Second messenger activation allows complex chemical reactions to occur • Drugs that affect smooth muscle use 2nd messengers

38. Second messenger activation • When a neurotransmitter attaches to a receptor it then activates a G protein within the cell. • This then stimulates a enzyme called adenylyl cyclase to actively convert ATP to cAMP • ATP is energy source that makes cAMP; increase cAMP activates many different regulatory proteins

39. Second messenger activation • cAMP regulates calcium within the bronchial smooth muscle cells to cause bronchodilation • Cyclic AMP is made from ATP and is a second messenger. • Phoshodiesterase (PDE) removes cAMP • Phosphodiesterase is inhibited by caffeine (Xanthines)

40. Second messenger activation • Caffeine can increase cAMP • Weak bronchodilator • Second messenger drugs such as all of those we use as RT’s have gradual and long lasting effects. As opposed to drugs which work directly through ion channels.

41. Neurotransmission • Epinephrine used by the sympathetic nervous system. • Also in the CNS

42. Review of basic Pharm • http://www.youtube.com/watch?v=OawHxPiGBio

43. Neurotransmitter • http://www.youtube.com/watch?v=haNoq8UbSyc • http://www.youtube.com/watch?v=X0Iz2FTSe2M

44. Agonist/Antagonists • http://www.youtube.com/watch?v=oD12QHE-4WY&feature=related