DHE122 Chapter#3

• Drugs may act on biologic systems to accomplish a desired effect, but they lack absolute specificity
•    They can act on many different organs or tissues
•    This is the reason for undesirable or adverse drug reactions
• No drug is free from producing some adverse effects in a certain number of patients

are clinically desirable actions

are clinically undesirable reactionsNot desired, potentially harmful, and occurs at usual therapeutic doses

• an extension of the pharmacologic effect resulting from a drug’s effect on the target organs
• The amount of the desired effect is excessive

• a dose-related reaction that is not part of the desired therapeutic outcome
• Drowsiness related to antihistamine use

a genetically related abnormal drug response

• hypersensitive response following previously exposure to drug. not dose related
• Neither predictable nor dose related
• Interferes with natural defense mechanisms
•    The drug reduces body’s ability to fight infection

• An extension of therapeutic effect caused by the overreaction of a sensitive patient or by a dose that is too large for that patient.
• Occasionally, this may result from liver or kidney disease

• Nontherapeutic action of the drug:Reactions can occur at usual doses
• Appear more often at higher doses
• A reduction in dose = reduction in adverse reactions

• The relationship between drugs and congenital abnormalities has been recognized since the middle of the twentieth century
• “Although more information is now available about the safety of drugs in pregnant women, sufficient information is still lacking”
• The U.S. Food and Drug Administration (FDA) has attempted to address concerns about the lack of adequate knowledge of drugs by defining five FDA pregnancy categories
• They are A, B, C, D, and X (from least to most risky)

• characterized by local tissue irritation
• Injectable drugs produce irritation, pain, and tissue necrosis at the site of injection
• Topically agents produce irritation at the site of application
• PO drugs can produce gastrointestinal upset such as nausea

• A drug interaction can occur when the effect of one drug is altered by another drug:
• Interactions may result in
• Toxicity
• Lack of efficacy
• or produce beneficial effects
• The more often the drug is taken the more likely drug interactions occur.

• Occurs when the immune system of an individual responds to the drug administered or applied
• The drug must act as an antigen, stimulates antibody production in a previously sensitized patient
• Neither dose dependent nor predictable
• Drug allergy can be divided into four types of reactions, depending on the type of antibody produced or the cell mediating the reaction

• Mediated by immunoglobulin E (IgE) antibodies
• When a drug antigen binds to IgE antibody, histamine, leukotriene, and prostaglandins are released, producing vasodilation, edema, and inflammation
• The targets of this reaction are
• Bronchioles, resulting in anaphylactic shock
• Respiratory system, resulting in rhinitis and asthma
• Skin, resulting in urticaria and dermatitis
• Because these reactions can occur quickly after drug exposure, they are known as immediate hypersensitivity reactionsAnaphylaxis is an acute, life-threatening allergic reaction characterized by hypotension, bronchospasm, laryngeal edema, and cardiac arrhythmias

• Complement-dependent reactions involving either immunoglobulin G (IgG) or immunoglobulin M (IgM) antibodies
• The antigen-antibody complex is fixed to a circulating red blood cell, resulting in lysis
• Examples are penicillin-induced hemolytic anemia and methyldopa-induced autoimmune hemolytic anemia

• Mediated by IgG antibodies
• The drug antigen-antibody complex fixes complement and deposits in the vascular endothelium
• Manifested as serum sickness; includes urticarial skin eruptions, arthralgia – joint pain, arthritis, lymphadenopathy, and fever
• Can be caused by penicillins and sulfonamides

• Mediated by sensitized T lymphocytes and macrophages
• When the cells contact the antigen, an inflammatory reaction is produced by lymphokines, neutrophils, and macrophages
• An example is contact dermatitis caused by topical application of drugs

• A drug’s effect on the body’s defense mechanisms can result in an adverse reaction
• Long-term administration of corticosteroids results in decreased resistance to infection

• Evaluations of the toxic effects of drugs are based on experiments performed with lower animals and clinical trials conducted in humans
• Animal experiments can often elicit adverse reactions that could occur in humans, but drug reactions in animals do not always predict reactions in humans

is the dose the kills 50% of experimental animals

is the dose required to produce a specified intensity of effect in 50% of the animals

is the therapeutic index (TI) of a drug

then toxicity is more likely

then the drug will be safer

therapeutically useful drug

activator

inhibitor

molecule that plays role in regulatory system

drugs that interact with other drugs

drugs synthesized in the body

norepinephrine and epinephrine

epinephrine

• Parasympathetic
• acetylcholinesterase

• ◦Parasympathetic autonomic nervous system (PANS)
• ◦Sympathetic autonomic nervous system (SANS)

◦Vasoconstrictors and drugs used to increase salivary flow

◦Anticholinergics produce xerostomia

many of the body systems i.e regulation of blood pressure, heart rate, gastrointestinal (GI) tract motility, salivary gland secretions, and bronchial smooth muscle

neuron and target tissues

afferent (sensory) fibers, central integrating areas, and efferent motor preganglionic and postganglionic fibers

Between postganglionic nerves and effector tissues

acetylcholine

• acetylcholine
• It is also termed cholinergic
• Because the postsynaptic tissue responds to muscarine, it is called muscarinic

ACh acetylcholine

• ( NE) norepinephrine
• adrenergic