General Pharmacology, part 2 Pharmaco-dynamics & Medication Administration

1. General Pharmacology, part 2Pharmaco-dynamics &Medication Administration • F ‘08 • P. Andrews

2. Pharmacodynamics • Most drugs bind to a receptor • Protein molecules • Can be stimulated/inhibited by chemicals • Each receptor’s name generally corresponds to the drug that stimulates it • Affinity • Force of attraction between a drug and a receptor • Different drugs may bond to same receptor site, but strength of bond may vary – binding site’s shape determines receptivity to chemicals

3. Drug’s pharmacodynamics involves its efficacy • Generally, drugs either stimulate or inhibit the cell’s normal actions. • Efficacy and affinity not directly related • Drug A causes a stronger response than drug B • Drug B binds to the receptor site more strongly than drug A

4. When drug binds to receptor, chemical change occurs • Drugs • Interact with receptor and result in desired effect • Interact with receptor and cause release/production of a second compound

5. Giving medications safely • Know: • Indications • Contraindications • Precautions • Practice proper technique • Observe & document • Take careful drug histories

6. Remember the 6 rights of medication administration! • Right • Person • Drug • Dose • Time • Route • Documentation • And - refusal

7. So…. What happens anyway?

8. Cells talk to each other • Three distinct languages • Nervous system • neurotransmitters • Endocrine system • hormones • Immune system • cytokines

9. In disease, all systems are affected • The three systems can’t exist without each other • The actions of one impact the actions of the others • I.e., stress (nervous system) disrupts endocrine system which may respond with glucocorticoid production = suppressed immune response

10. Drugs have class

11. Drug Class Examples • Nitroglycerin • Body system: “Cardiac drug” • Action of the agent: “Anti-anginal” • Mechanism of action: “Vasodilator” • Indications for nitroglycerin • Cardiac chest pain • Pulmonary edema • Hypertensive crisis • Which drug class best describes this drug?

12. Another way to classify drugs • Mechanism of Action • Drugs in each category work on similar sites in the body and will have similar specific effects/side effects • Beta blockers: metoprolol • ACE inhibitors: lisinopril • Alpha blockers: prazosin • Calcium-channel blockers: verapamil • Example: beta blocker actions and impacts • Suppress the actions of the sympathetic nervous system • Prehospital administration of epinephrine may not produce as dramatic effects with a patient taking a drug in this class

13. Prehospital example: Hyperglycemics • Dextrose 50% and glucagon • Both will raise blood glucose • Mechanism of action • Glucagon: hormone that works in the liver to convert stored chains of carbohydrate to glucose • Dextrose 50%: ready-made simple sugar that is ready to enter into the cell • Which drug is considered first-line for hypoglycemia? Why? • What are some limitations for glucagon in the presence of severe hypoglycemia?

14. Distribution • Some drugs bind to proteins in blood and remain for prolonged period • Therapeutic effects due to unbound portion of drug in blood • Drug bound to plasma proteins can’t cross membranes • Changing blood pH can affect protein-binding action of drug. • TCA’s are strongly bound to plasma proteins.

15. Drugs bind to proteins • Albumen is one of the chief proteins in the blood available for binding with drugs. • When a pt. Is malnourished, albumen is low. • What significance does this have re; drug therapy?

16. The blood – brain barrier • Tight junctions of capillary endothelieal cells in CNS form a barrier • Only non-protein-bound, highly lipid-soluble drugs can enter CNS • Placental barrier similar

17. Other deposits • Fatty tissue serves as drug reservoir • Bones and teeth can accumulate drugs that bind to calcium • Ie., tetracycline

18. Ok, you’ve given the drug – now what?

19. Biotransformation • Drugs are metabolized – broken down into metabolites • Transforms drug into more or less active metabolite • Make drug more water soluble to facilitate elimination • Protein-bound drugs are not available for biotransformation

20. Biotransformation, cont. • Occurs in liver primarily • Also occurs in kidney, lung, GI tract • First-pass effect • Some drugs can’t be given orally

21. What alters drug response? • Age • Body mass • Sex • Environmental • Time of administration • Pathologic state • Genetic factors • Psychological factors

22. Drugs that change physical properties • Osmotrol • Drugs that chemically bind with other substances • Isopropyl alcohol – denatures proteins on surface of bacterial cells • Drugs alter a normal metabolic pathway • Anticancer, antiviral drugs

23. Response to drug administration • We must carefully weight risk vs benefit! • Allergic reaction • Hypersensitivity • Idiosyncrasy • Effect unique to person; not expected • Tolerence • Decreased response to drug after repeated administration

24. It’s all about the cell….

25. Brain sends out the response via nerve paths • Nerve moves the response: depolarization • Depolarization stimulates norepinephrine sacks • Sacks move to the end of the nerve and dump out their contents 2 3

26. Norepinephrine travels across the synapse • Attaches to a receptor on the organ, organ responds to the signal • Norepineprhine detaches and is deactivated • 2 options: destroy it or move it back into its sack 5 2 3 4

27. Now, how do we get rid of the drug?

28. Elimination • Most drugs excreted in urine • Some in feces or air • Glomerular filtration • A function of glomerular filtration pressure (BP and kidney blood flow) • Active transport system; requires ATP • Tubular secretion • Urine pH affects reabsorption in renal tubules

29. Elimination, cont. • Some drugs and metabolites are eliminated in expired air • Breathalyzer • Feces, sweat, saliva, breast milk

30. Ok, so how do they get in our system?

31. Drug Routes • Enteral • Oral (PO) • Orogastric/Nasogastric (OG/NG) • Sublingual (SL) • Buccal • Rectal (PR)

32. Intravenous (IV) Endotracheal (ET) Intraosseous (IO) Umbilical Intramuscular (IM) Subcutaneous (SC, SQ, SubQ) Inhalation/ Nebulized Topical Transdermal Nasal Instillation Intradermal Drug routes, cont. Parenteral

33. Drug forms • Liquid: (solute - solvent) - Solution • Tinctures: drug extracted chemically with alcohol. • Suspensions - liquid preparations don’t remain mixed • Spirits: Volatile chemicals dissolved in alcohol • Gaseous – Oxygen, Nitrous Oxide

34. Emulsions: oily substance mixed with a solvent that won’t dissolve it. (oil and vinegar). • Elixirs: Drug in an alcohol solvent. (Nyquil) • Syrups: Drug dissolved in sugar and water (cough syrup). • Solids: capsule, tablet, lozenge, powder • Topical use: ointment, paste, cream, aerosol

35. Other stuff you should know

36. Drug storage • Properties may be altered by environment. • Temperature • Light • Moisture • Shelf-life

37. Drug response relationship • Plasma level profiles • Length of onset, duration, termination of action, minimum effective concentration and toxic levels • Onset of action • A medication reaches it’s minimum effective concentration • Minimum effective concentration • Level of drug needed to cause a given effect

38. Duration of action • How long the drug remains above it’s minimum effective concentration • Termination of action • Time from when a drug drops below minimum effective concentration until it’s eliminated • Therapeutic index • Ratio of a drug’s lethal dose for 50% of population to its effective dose for 50% of population • Half-life • Time the body takes to clear one half of the drug

39. Cross tolerence • Tolerence for a drug that develops after administration of a different drug • Tachyphylaxis • Rapidly occuring tolerance to a drug • Decongestants, bronchodilators • Cumulative effect • Increased effectiveness when a drug is given in several doses

40. Drug dependence • Pt becomes accustomed to drug; will suffer withdrawal symptoms • Drug interaction • Effects of one drug alters response to another drug • Drug antagonism • Effects of one drug blocks response to another drug • Summation • Additive effect; two drugs that both have same effect are given together

41. Second messenger • Calcium or cyclic adenosine monophosphate (cAMP) • Most common second messenger • Activates other enzymes; cascading • Number of receptor sites on target cell constantly changes • Receptor proteins destroyed during function • Reactivated or remanufactured • Down regulation • Binding of a drug or hormone that causes number of receptors to decrease

42. Synergism • Two drugs that have the same effect are given together and produce a response greater than the sum of their individual responses • Potentiation • One drug enhances the effect of another • Interference • One drug affects the pharmacology of another drug

43. Summary