1. Summation and Potentiation25
Two common types of “agonistic” drug interactions are : 1. Summation: When two drugs with similar mechanisms are given together, they typically produce additive effects. 2. Potentiation or synergism : if the effect of two drugs exceeds the sum of their individual effects.
Potentiation requires that the drugs act at different receptors or effector systems.
Example of potentiation would be the increase in beneficial effects noted in the treatment of AIDS by combination therapy with AZT (a nucleoside analog that inhibits HIV reverse transcriptase) and a protease inhibitor (protease activity is important for viral replication).

2. Receptor Theory
1)Receptors largely determine the quantitative relations between dose or concentration of drug and pharmacologic effects 2)Receptors are responsible for selectivity of drug action 3)Receptors mediate the actions of pharmacologic agonists & antagonists

3. The first step in drug action on specific receptors is the formation of a reversible drug-receptor complex, the reactions being governed by the Law of Mass Action
Where [D] = concentration of free drug; [DR] = the concentration of bound drug; [RT] = the total concentration of receptors; kd = the equilibrium dissociation constant and represents the concentration of free drug at which half- maximal binding is observed

4. Relationship of binding to effect
The binding of a drug to its receptor initiates events that ultimately lead to a measurable biologic respons
The magnitude of response is proportional to the amount of receptors bound/occupied according to the following equation:
E = Emax × [D]
[D] + EC50
Where [E] = is the effect observed at concentration [D], Emax is the maximal response that can be produced by the drug; and EC50 is the concentration of drug that produces 50% of maximal effect

5. Drug receptor interaction
The tendency of the a drug to bind to its receptor is governed by its affinity.
The equilibrium dissociation constant (kd) [k-1/k+1] characterizes the receptor affinity for binding the drug in a reciprocal fashion i.e. a high affinity means a small kd
The ability of a drug , once bound, to activate a receptor and generate response is denoted by its efficacy: a drug with high efficacy eliciting, at some concentration, a full response

8. G-Proteins coupled receptors (GPCRs)
GPCRs are comprised of a single polypeptide chain that has seven membrane-spanning transmembrane) regions
GPCRs couple to a family of heterotrimeric GTP-binding regulatory proteins termed G proteins signal transducers)
The G protein heterotrimer is composed of three subunits: α, β, and γ

9. The activated G-protein changes the activity of an effector (E) element, usually an enzyme or ion channel.
This effector then changes the concentration of the intracellular second messenger.

10. Pharmacodynamics
When the drug blocks a receptor, it is known as antagonist and therefore blocks the action of the endogenous transmitter (i.e. it will prevent the natural chemical from acting on the receptor).However, as most drug binding is reversible, there will be competition between the drug and the natural stimulus to the receptor.
The forces that attract the drug to its receptor are termed chemical bonds and they are : (a)hydrogen bond (b) ionic bond (c) covalent bond (d) Vander waals force.
Covalent bond is the strongest bond and the drug-receptor complex is usually irreversible.

11. Pharmacodynamics K1 K3 D+R DR Biological effect K2
Where D = Drug, R= receptor DR= Drug receptor complex (affinity)
K1 = association constant
K2 = dissociation constant
K3 = intrinsic activity

12. When first messengers like neurotransmitters, hormones, and most of drugs bind with their specific receptors, the drug receptor complex is formed which subsequently causes the synthesis and release of another intracellular regulatory molecule termed as second messengers e.g. cyclic AMP, calcium, cyclic GMP, inositol triphosphate (IP3), diacylglycerol and calmodulin which in turn produce subcellular or molecular mechanism of drug action

13. Basics of Drug Action
Desired action – the expected response of a medication
Side effects –known and frequently experienced, expected reaction to drug.
Adverse reaction –unexpected, unpredictable reactions that are not related too usual effects of a normal dose of the drug.

14. Therapeutic Threshold
Therapeutic Action
The intended action of a drug given in an appropriate medical setting
Therapeutic Threshold
The minimum amount of a drug that is required to cause the desired response
Therapeutic Index
The difference between the therapeutic threshold and the amount of the drug considered to be toxic
Often referred to as Safe and Effective range

15. Potentiation Refractory Synergism
The enhancement of a drug’s effect by another drug
Eg. promethazine may enhance the effect of morphine; also alcohol and barbiturates
Refractory
The failure of a patient to respond as expected to a certain medication
Synergism
The combined action of 2 or more drugs that is greater than the sum of the 2 drugs acting independently

16. Hypersensitivity Idiosyncrasy Indication
A reaction to a drug that is more profound than expected and which often results in an exaggerated immune response
Idiosyncrasy
A reaction to a drug that is significantly different from what is expected
Indication
The medical condition for which the drug has proven therapeutic value

17. Important Pharmacological Terms
Antagonism
The opposition between 2 or more medications ex. narcotics and Naloxone
Bolus
A single, often large dose of a drug. Often the initial dose
Cumulative action
An increased effect caused by multiple doses of the same drug. Caused by buildup in the blood.

18. Tolerance Untoward Effect
The decreased sensitivity or response to a drug that occurs after repeated doses
Increased doses are required to achieve the desired effect
Tolerance
A side effect of a drug that is harmful to the patient
Untoward Effect

19. Pharmacotherapeutics
Depends on:
Severity
Urgency
Prognosis of patient’s condition
Is defined as the use of drugs to treat diseases.

23. Routes of Drug Administration

24. 1: Enteral Medications
Administered directly into the G.I.T. through the oral, nasogastric (NG) or rectal routes
Advantages:
Convenience for nurse & patient
Most medications are available in oral route
Inexpensive to make oral preparations
Can be removed by gastric lavage or make to vomit
2/5/2019

25. Disadvantages
cannot be administered to very nauseated/vomiting or unconscious persons
some loose their effectiveness if mixed with gastric secretions
onset of action may vary due to changes in absorption in the GIT
2/5/2019

26. Forms of Oral Medication
Capsules-are gelatin containers that hold powder or liquid medicine.
Elixirs- clear liquids made up of drugs dissolved in alcohol & water with coloring & flavoring agents added.
Emulsions-are solutions that have small droplets of water & medication dispersed in oil, or oil & medication dispersed in water.
2/5/2019

27. Forms of Oral Medication
Lozenges- are medicines mixed with a hard sugar base to produce a small, hard preparation of various shapes & sizes.
Suspensions- are liquids with/solid, insoluble drug particles dispersed throughout.

28. Forms of Oral Medication
Syrups-are liquids w/ a high sugar content designed to disguise the bitter taste of a drug. Pediatric use.
Tablets-dried, powdered drugs compressed into small shapes.

29. 2.Parenteral Administration
Reasons:
When the patient cannot take an oral medication
When the medication must be given quickly
When medication might be destroyed by gastric enzymes
When medication must be given at a controlled rate
When the medication is not available in an enteral form.
2/5/2019

30. Parenteral Medications
INTRAMUSCULAR – 90 °
Provides faster medication absorption because of muscle’s greater vascularity
SUBCUTANEOUS- 45 °
Placing medications in the loose connective tissue under the dermis
INTRADERMAL- 15 °
2/5/2019

31. Other Routes of Administration
Topical administration – skin
Cleanse
Soften
Disinfect
Lubricate
E.g. clotrimazole –cream dermatophytosis
atropine- eye-dilate the pupil
Transdermal route - nitroglycerin (skin patch) systemic vasodilation in angina

32. Other Routes of Administration
Inhalation – provides rapid delivery of drugs to a large area of mucus membranes & tissues of the respiratory system.
Anesthesia
Bronchodilators
Intranasal – desmopressin for diabetes insipidus
Calcitonin- a peptide hormone for tx of osteoporosis
2/5/2019

33. Other Routes of Administration
Intrathecal injection- introduction of hypodermic needle into the subarachnoid space for the purpose of instilling a material for diffusion throughout the spinal fluid.
Intraventricular- space into the ventricle
Both gains access to the CSF e.g. amphotericin B –in meningitis
2/5/2019

34. Rational dosage design
Is based on the assumption that there is a target concentration that will pro duce the desired therapeutic effect
The intensity of a drug's effect is related to its concentration above a minimum effective concentration, whereas the duration of this effect reflects the length of time the drug level is above this value
By considering drug’s PKs, it is possible to individualize the dose regimen to achieve the target concentration