DHE122 Exam#1

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

• 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 reactions
• Not 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 genetically related abnormal drug response

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

• hypersensitive response following previously exposure to drug.
• Neither predictable nor dose related
• Interferes with natural defense mechanisms
• The drug reduces body’s ability to fight infection

• Amount of drug needed to produce an effect.
• Some drugs are strong and only require a small amount to reach the desired effect.

• Maximum intensity produced by the drug.
• If more of the drug is introduced into the system it will result in adverse reaction, i.e overdose

• are chemicals responsible for transporting a wide variety of messages across the synapse
• Chemical signaling involves release of neurotransmitters and local substances and hormone secretion
• Neurotransmitters talk to the nerve and tell it what to do.

The study of how a drug enters the body, circulates within the body, is changed by the body, and leaves the body

Absorption Distribution Metabolism Excretion

• Lipid-soluble substances move across the lipoprotein membrane by a passive transfer process called simple diffusion
• Water-soluble molecules small enough to pass through membrane pores may be carried through pores by bulk flow of water
• No active energy is needed

Certain substances are transported across cell membranes by processes more complex than simple diffusion or filtration

• is a process by which a substance is transported against a concentration or electrochemical gradient.
• Energy required.

• Effect of ionization
• Weak acids
• Weak bases
• Oral absorption
• Absorption from injection site

drug acts on a variety of receptors

“margin of safety”- relationship between a drug’s desired therapeutic effects and its adverse effects

drug has an affinity for a receptor and stimulates it (activator)

drug’s ability to initiate a response after binding to a receptor

interferes with the agonist by binding to the receptor but displays little or no intrinsic activity(inhibitor)

competes with agonist for receptor sites

binds to receptor sites and blocks the effects of the agonist

molecule that plays role in regulatory system

drugs that interact with other drugs

drugs synthesized in the body

norepinephrine and epinephrine

epinephrine

requires no energy

requires energy

cell engulfing drug particles

liver metabolism before the drug enters circulation

time it takes half the drug to be elimina

rate of distribution equals the rate of excretion

two drugs with similar effects are administered

two drugs that produce the same effect are given together and one enhances the effect of the other

combined response of two drugs is less powerful than the response of either drug alone

alters the rate and amount absorbed from the GI tract; inhibits metabolism (e.g., grapefruit)

decreased response to a drug over time

physical or psychological need for a drug

• Easiest, convenient, least expensive
• Drugs made from proteins inactivated by gastric juices – i.e. insulin
• Blood levels not as predictable as other routes, iv.
• Oral drugs pass through hepatic (Liver) system know as first pass effect.
• This can inactivate some drugs.
• Drugs with high first pass effect require larger oral doses in order to be effective. i.e. morphine (capsules, liquids, tablets) *Periostal for chronic periodontitis

enteral rapid drug response low dose must be given *Testosterone

enteral rapid drug response low dose must be given *Nitroglycerin tablets for angina

Drug is absorbed from the gut Oral, sublingual, buccal, rectal

• All other drug routes except enteral
• Drugs not absorbed via gut
• Intravenous, intramuscular, intrathecal, intradermal, and subcutaneous

• Subgingival Placement of medicaments into the gingival crevice
• Atridox, Arestin
• Anesthetic gel

• most rapid response,
• absorption phase is bypassed,
• best for emergencies,
• drug recall injected directly into blood stream once injected drug cannot be retrieved

provides sustained effect, massaging increases absorption. *Meperidine (Demerol)severe pain Hep B vaccine

• insulin and local anesthesia, great for administering protein products rapid drug response.
• Doses must be in small volume dental anesthetic; insulin

injected into epidermis – TB only small volumes can be injected

rapid delivery, i.e – albuterol, nitrous

great in emergency situation when patient is unconscious, vomiting

• intravascular
• intramuscular
• intradermal
• inhalation
• rectal
• subcutaneous

cannot give large amounts of dose not a rapid response *DentiPatch, nitroglycerin, nicotine patch

• localized effect on skin treats localized areas
• Local anesthetic

• The process by which drug molecules are transferred from the site of administration to the circulating blood
• Requires the drug to pass through biologic membranes

• Physicochemical factors
• The site of absorption, which is determined by the route of administration
• The drug’s solubility

more basic, the drug can more easily penetrate tissues

more acidic, the drug cannot easily penetrate tissues

increases (and the pH decreases), and the effect of local anesthetics decreases

• the form that exerts the pharmacologic effect
• Only the free drug can pass across cell membranes

reservoir for the drug

site of action in the body. The manner in which a drug is distributed in the body will determine how rapidly it produces the desired response, the duration of that response, and, in some cases, whether a response will occur at all

a study of interaction of chemical substances with living systems including cells, tissues, and organisms.

Substances or chemical agents that affect biologic or living systems.

Amount of drug needed to produce an effect. Some drugs are strong and only require a small amount to reach the desired effect.

Maximum intensity produced by the drug. If more of the drug is introduced into the system it will result in adverse reaction, i.e overdose

• Study of drug movement throughout the body, including:
•    – how a drug is absorbed, distributed, metabolized, and excreted by the body
•    –Can be passive or active

Action of a drug on a specific target organ, tissue including:

–mechanism of action

–receptor interactions

–dose-response relationship

– therapeutic and toxic reactions.

• Depends on route of administration, lipid drugs pass blood brain barrier
• –Absorption depends on drug solubility, circulation, drug pH – infection, temperature at site, total surface area
• – when drugs enter body largest absorption occurs in small intestines

• –How drug leaves the blood stream and enters the body system
• –Drug enters body – distributed to the liver. Liver metabolizes the drug – breaks it down
• –Drug leaves and goes to the body/organs

• drug is eliminated (excreted) by the kidneys
• – Fat soluble drugs not excreted in urine, must be metabolized by liver
• – drugs can also be excreted by: sweat, tears, saliva, crevicular fluid
• –Major route of excretion of fluoride in body is KIDNEYS/URINE

• scientific study of poisons, industrial pollutants, and the undesirable effects of drugs on living cells, tissues, and organisms. 
• –poison is any substance detrimental to health, leading to incapacitation, illness, or death.

• 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 use of many medications; many elderly are taking more than one drug.

–Set standards and guidelines to protect the public from drug misuse

• Food and Drug Administration (FDA).
• Before a new drug is introduced into the general population must be approved by the FDA

• –Drug Facts
•    –Required on all OTC drug package labels
•    –Help consumer understand how to use product

–Refers to the chemical makeup of the drug and defines the unique chemical structure that is listed in the United States Adopted Names (USAN) designations.

• – written in small letters
• –United States Adopted Names (USAN) designations (e.g., ibuprofen (generic), Advil(brand)

• your book calls Trade name
• Registered trademark belonging to a particular drug manufacturer (e.g., Advil).
• –Always in capital letter
• Patent lasts for 17 years.

before meals

morning

twice a day

capsule

dispense

as needed

every

every day

hour

at bedtime

every hour

every 8 hours

4 times a day

after meals

afternoon

at once

write on label

3 times a day

orally (by mouth)

prescription (recipe)

a sufficient quantity

tablet

drops

right eye

left eye

no refills

milliliters

–Require a prescription to be dispensed

• –OTC
• –Do not require a prescription

Not filled at pharmacy. Highest abuse Heroin, hashish

Must have prescription. No refills. High Abuse. Cocaine, morphine, methamphetamine.

• Written oral prescription.
• No refill more than 5 times within 6 months.
• Moderate abuse. Tylenol with codeine, Vicodin, anabolic steroids.

• Written or oral prescription.
• No refill more than 5 times within 6 months.
• Low abuse. Valium, Xanax.

• No Prescription or OTC.
• Lowest abused.
• Cough medicines that contain codeine.

• 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

yield the inactive metabolites choline and acetic acid

Fight or flight: stress

• rest and digest:
• peace.

• ANS: part of drug names, will mimic the action that is in front
• mimicking, enhancing or amplifying action

• ANS: blocking, impairing or otherwise interfering drugs
• block or decrease the word that is in front