pharmacology exam 1

FDA

• part of the US department of health and human services (HHS) that is responsible for how new drugs are researched and brought onto market

• grants approval for marketed drugs and sets standards for quality control in drug manufacturing plants

• regulates the trade practices of drug companies and determines which can be sold by perscription or OTC

• prohibits the false advertising of foods, non prescription (OTC) drugs, and cosmetics

DEA

• part of the department of justice

• regulates the manufacture and distribution of substances that have a potential for abuse, including opioids (narcotics), stimulants, and sedatives

• administers the controlled substances act of 1970

FTC

• how things are marketed (truth-not falsely advertising

seuqence of drug development

1. drug discovery

2. animal testing (preclinical trials to determine acute and chronic toxicity)

3. clinical trials (Phase I-IV)

4. FDA approval

phase I of clinical studies

• small and then increasing doses are administered to a limited number of healthy human volunteers

• determines biologic effects, metabolism, safe dose range in humans, and toxic effects of the drug

phase II of clinical studies

• larger groups of humans are given the drug

• adverse reactions are reported to the FDA

phase III of clinical studies

• clinical evaluation involving a large number of patients who have the condition for which the drug is indicated takes place

• safety and efficacy must be demonstrated

• dosage is determined

phase IV of clinical studies

• post marketing surveillance

• toxicity that occurs in patients taking the drug after it is released is recorded

clinical evaluation of a drug

• animal studies begin my measuring both acute and chronic toxicity

• process if the preclinical phase and lasts about 3 years

• in total takes almost 12 years and $350 million the the time a drug is synthesized in the laboratory to its availability on the pharmacy shelves

Harrison Narcotic Act

• 1914

• federal control of narcotics

• established regulations governing the use of opium, opiates, and cocaine

pure food, drug, and cosmetic act

• 1952

• made certain drugs required to be sold by prescription only

controlled substances act

• 1970

• replaced Harrison narcotic act and sets current requirements and standards for writing prescriptions

Omnibus budget reconciliation act (OBRA)

• OBRA

• pharmacists must provide patient counseling and a prospective drug utilization review (DUR) for Medicaid patients

schedule I controlled substances

• heroin

• LSD

• hallucinogens

• no accepted medical use

schedule II controlled substances

• Oxycodone

• morphine

• amphetamine

• secobarbital

• hydrocodone immediate-release  with acetaminophen

• ibuprofen hydrocodone extended-release

• written prescription with providers signature only, no refills, some states allow for the electronic prescribing

schedule III controlled substances

• Codeine (Tylenol 3), buprenorphine (Suboxone), anabolic steroids

• prescriptions may be faxed or sent electronically to the pathway, no more than five prescription refills in 6 months

schedule IV controlled substances

• Diazepam (Valium), tramadol (Ultram)

• prescriptions may be faxed or sent electronically to pathway, no more than five prescriptions in 6 months

schedule V controlled substances

• some codeine-containing cough syrups

• can be bought over the counter in some states

generic name

• “official” nonproprietary name

• ex ibuprofen

trade (brand) name

• always capitalized and registered trademark intended for easy recognition and marketing purposes

• ex Motrin

chemical name

• determined by the chemical structure of the compound

• code name based on chemical structure

• typically used while medication is still undergoing research or being investigated

one

• each drug only has _ generic name(s) but may have several trade names (brand names)

drug name categories

• chemical name

• trade name (brand name such as Motrin, Advil so it is always capital)

• generic name (official nonproprietary name - ibuprofen)

labeled use

• indicated that the FDA has approved the drug for specific use

off label use

• is use outside the stated FDA indications

• manufacturer CANNOT mention to practitioner, patient, nor marketing

characterization of drug action

• dose-response curve

  • log dose effect curve

• potency

• efficacy

potency of drug

• the amount of a drug required to produce an effect

• more of a less _ drug is needed to produced a desired effect equivalent to that of a more _drug

• review proper dose of each drug before prescribed

efficacy

• the maximum intensity of effect or response that can be produced by a drug

• aka the maximum effect a drug can produce

• administering more drug will NOT increase effect but WILL increase the probability of an adverse reaction

not

• efficacy and potency of a drug are _ related

therapeutic index

• ratio of median lethal dose (LD) to median effective dose (ED)

• the greater (wider) the index, the safer the drug is when preventing overdose

• = LD50 / ED50

lethal dose (LD50)

• is the dose that causes death in 50% of test animal

effective dose (ED50)

• is the dose required to produce the desired clinical effect in 50% of test animals

pharmacokinetics

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

• membrane composed of

  • lipids

  • proteins

  • carbohydrates

• physiochemical properties of drug that influence membrane crossing

• modes of drug transfer across membrane

physiochemical properties of drugs that influence membrane crossing

• lipid solubility

• degrees of ionization

• molecular size and shape

absorption

• Process by which drug molecules are transferred from site of administration to the circulating blood.

• Influenced by the following factors

  • Physicochemical factors

  • Site of absorption, determined by route of administration

  • Drug’s solubility. Drugs in solution absorbed more rapidly

factors that affect drug absorption and clinical pharmacokinetics

• presence of infection

• dose form

• drug solubility

• blood flow at injection site

disruption

• tablet coating or capsule shell

• is the passage of drugs into various body fluid compartments such as plasma, interstitial fluids, and intracellular fluids

• manner determines how rapidly it produces desired response, duration of response, and in some cases if any response is elicited

• drugs move to various sites of the body including site of action and areas where no action is desired

disintegration

• tablet or capsule contents break apart

dispersion

concentrated drug particles spread through stomach and intestines

dissolution

• drug dissolved in gastrointestinal fluid

oral absorption of drug

• absorption takes place primarily in GI tract

• rate of absorption dependent upon dose form

• disruption, disintegration, dispersion, and dissolution necessary for tablet or capsule

• a drug in solution skips these steps and usually has a quicker onset of action

absorption from injection site

• Dependent on the solubility of the drug

  • Lower water solubility slower absorption

• Dependent on blood flow at site

• Affected by dosage form

  • Drugs in suspension absorbed more slowly

  • Drugs in solution absorbed more quickly

    • Suspension: Solute does not completely dissolve

    • Solution: Solute completely dissolves in solvent

• Drugs that are least soluble will have longest duration of action

distribution of drug is determined by

• size of organ

• blood flow to the organ

• solubility of the drug

• plasma-protein binding capacity

• presence of certain barriers (blood brain, placenta)

distribution by plasma

• Biologic activity of drug is related to concentration of the free, or unbound, drug in the plasma

• drugs bound reversibly to plasma proteins

  • albumin

  • globulin

• Drug bound to plasma protein does not contribute to intensity of drug action. It is considered a storage site. Only unbound, free portion, of the drug is active

• If a more highly bound drug administered it can displace the first bound drug increasing it's effect

blood brain barrier

• For a drug to enter the CNS must cross

• Related to the drug's lipid solubility and degree of ionization

• to diffuse transcellularly, the drug must cross the endothelial and basement membrane cells

• Must be highly lipid-soluble

placenta

• drugs cross by simple diffusion in accordance with their lipid solubility

• Most drugs pass easily across the barrier

• Therefore, when drugs administered to pregnant mom, they are also administered to the fetus.

drug metabolism

• also known as biotransformation, is the body’s way of changing a drug so that it can be more easily excreted by the kidneys

• many drugs undergo metabolism in the liver

  • active to inactive

  • inactive to active

  • active to active

first pass effect

• When drugs are administered orally, are absorbed through intestines, and then pass through the hepatic portal circulation, which can inactivate some drugs. The drug passes through the liver first, then it circulates systemically. The amount of metabolization varies. 

• Drugs with a high first pass effect require a larger oral to parenteral dose ratio.

half life

• The time it takes for the concentration of a drug to fall to one-half (50%) of its original blood level

• It takes 4-5 half-lives for a drug to be considered eliminated from the body because 3%-6% remains after 4 or 5 half-lives

• Conversely it takes 4-5 half-lives of repeated dosing for a drug level to build up to a steady state.

• Steady state the point at which the rate of drug input equals the rate of drug elimination. 

steady state

the point at which the rate of drug input equals the rate of drug elimination.

cytochrome p-450 induction and inhibition

• A microsomal enzyme system

  • Can be induced to speed up drug metabolism

  • Can be inhibited to reduce or slow down drug metabolism

• Divided into isoenzymes

  • Induction (decreases drug levels)

  • Inhibition (increases drug levels)

 

induction

• stimulates production of microsomal enzymes for a certain drug, thus decreasing that drugs effectiveness

• decreases drug levels by increasing metabolism

inhibition

• Slow or block metabolism of certain drugs. Blood levels and action of the drugs metabolized by these enzymes are increased

• increase drug levels by decreasing metabolism

enterohepatic circulation

• Most drugs absorbed by intestines, distributed through serum, pass to specific and non-specific sites of action, arrive in liver, are metabolized, and excreted by the KIDNEYS

• With enterohepatic circulation all of these steps are the same UNTIL the drug is metabolized. The metabolite is secreted by the bile into the intestines. The metabolite is broken down by enzymes which release the drug, then reabsorbed, and process repeats losing a small amount of drug each time

major excretory organs

• kidney

• liver

• lungs

adverse effects

• clinically undesirable reactions

• Undesirable response to drug; potentially harmful; occurs at usual therapeutic doses

toxic reaction

• excessive desire reaction

• predictable

• dose-related

• acts on target organs

• extensions of pharmacologic effects

side effect

• dose related, not part of desired therapeutic outcome

• predictable

• acts on non target organs

idiosyncratic reaction

• genetically related abnormal response

drug allergy

• immunologic response resulting in rash or anaphylaxis

clinical manifestation of adverse reactions

• Exaggerated effect on target tissues

• Effect on nontarget tissue

• Teratogenic effect

• Local effect

• Drug interactions

• Hypersensitivity

• Idiosyncrasy

• Interference with natural defense mechanisms

factors that affect drug metabolism

• impaired liver function (liver disease)

• Hepatic portal circulation (kidney disease)

• Drugs and environmental substances

• Inhibitors of cytochrome P450

factors affecting drug action

• Liver disease

• Kidney disease

• Age

• Body weight

• Genetics

• Drug interactions

teratogens

• are agents that cause congenital malformations and development abnormalities if introduced during gestation

drugs safe to use during pregnancy

• penicillin

• erythromycin

• acetaminophen

• local anesthetic lidocaine

drugs contraindication during pregnancy

• tetracycline

• nonsteroidal antinflammatory agents

• benzodiazepines

• metrodiazole

hypersensitivity reactions

• allergic reactions

• occurs when the immune system of a patient responds to the drug administered

• neither dose dependent nor predictable

type I hypersensitivity reaction

• immediate hypersensitivity: anaphylaxis

• IgE (histamine) mediated

• anaphtlactic shock, rhinitis, asthma, urticaria, dermatitis, hypotension, bronchospams, laryngeal edema, cardiac arrythmias

type II hypersensitivity reactions

• cytotoxic/cytolytic

• complement-dependent reactions involving either immunoglobulin G (IgG) or immunoglobulin M (IgM) antibodies

• onset is within hours or a couple of days

type III hypersensitivity reaction

• arthus, immune complex, serum sickness

• usually mediated by IgG antibodies

• develop 4-10 days after exposure, and can become chronic if continued exposure to antigen

• manifested as serum sickness, urticarial skin eruptions, arthralgia, arthritis, lymphadenopathy, and fever

type IV hypersensivity reactions

• delayed hypersensitivity

• reactions are mediated by sensitized T lymphocytes and macrophages

• time of onset is 2-3 days

• contact dermatitis caused by topical drug, poison ivy, metal allergies

autonomic nervous system anatomy

• sympathetic autonomic nervous system (SANS - fight or flight)

• parasympathetic autonomic nervous system (PANS- rest and digest)

• both consist of

  • consists of afferent (sensory) fibers (whats happening)

  • central integrating areas (lets coordinate info)

  • efferent (peripheral) motor preganglionic fibers (what is happening)

  • postganglionic motor fibers (heres what needs to happen)

sympathetic autonomic nervous system anatomy

• Thoracic (T1) to lumbar (L2)

• Adrenal medulla (kidneys)

  • Epinephrine

  • Norepinephrine (NE)

• Preganglionic fibers exit spinal column and join sympathetic chain on either side of vertebral column

• Forms multiple synaptic connections with post ganglionic cell bodies

• Produces a more diffuse effect

parasympathetic autonomic nervous system anatomy

• (head and butt)

• cell bodies in the CNS give rise to preganglionic fibers

• cranial nerves

  • III oculomotor nerve

  • VII facial nerve

  • IX glossopharyngeal nerve

  • X vagus nerve

• sacral (S2-S4) segments of spinal cord

• preganglionic fibers extend almost to innervated organ

PANs and SANs relationship

• The divisions of the ANS tend to act in opposite directions

  • PANS is concerned with conservation of body processes

  • SANS is designed for emergencies (fight-or-flight response)

• Almost all body tissues are innervated by the ANS, with many parts receiving both parasympathetic and sympathetic innervation

autonomic nervous system

• is part of the peripheral nervous system and regulates involuntary body functions including

  • heart rate, blood pressure, breathing, digestion, salivation, pupil size, and sweating

• automatic modulating system for many bodily functions

• help maintain homeostasis (stable internal environments) in which the body is always trying to achieve

sympathetic nervous system

• prepares the body for stress

  • increases heart rate

  • dilates pupils (mydriasis)

  • decreased salivation (transforms it to thicker, viscous saliva)

  • inhibits digestion

  • dilates bronchi

• norepinephrine is the neurotransmitter released from post ganglionic nerve

• short preganglionic nerve

parasympathetic nervous system

• maintains normal body functions and promotes recovery

  • conserves energy

  • decreases heart rate

  • constricts pupils

  • increases salivation (copious watery saliva)

  • stimulates digestion

  • constricts bronchi

• releases the acetylcholine neurotransmitter at both pre and postganglionic fibers

adrenergic receptors (sympathetic system)

• Alpha-1 (a1)

• Beta- 1 (B1)

• Beta- 2 (B2)

Alpha-1 adrenergic receptor

• stimulation results in smooth muscle excitation or contraction causing vasoconstriction

• located in skin and skeletal muscle

  • vasoconstriction

  • increased blood pressure

  • pupil dilation

Beta-1 adrenergic receptors

• located in the heart

  • increases heart rate

  • increased cardiac output overall

• excitation causes stimulation of the heart muscle

Beta- 2 adrenergic receptors

• stimulation results in smooth muscle relaxation

• located in lungs and skeletal muscle

  • bronchodilation

  • vasodilation

cholinergic (parasympathomimetic) agents

• mimics parasympathetic system by directly acting like acetylcholine at receptor sites

• used for xerostomia and sjogren syndrome to increase salivation and sweating, can also be used to treat glaucoma by contricting pupils

• examples: Choline derivatives and Pilocarpine (Salagen)

• Indirect acting: Causes increase in amount of acetylcholine indirectly

  • Inhibits acetylcholinesterase (AChE)

• overall increase in Ach and causes a mimicked effect of parasympathetic ANS

cholinergic agents adverse effects

• S = salivation (excessive)

• L = lacrimation

• U = urination

• D = defecation

• Large doses = Neuromuscular paralysis

• excessive salivation, sweating, bradycardia, and bronchoconstriction!

toxic doses can result in mental confusion

Pralidoxime and atropine used to treat OD of cholinesterase inhibitors

eye pharmacological effects of cholinergic (parasympathomimetic) agents

• Miosis (pupil constriction) cause cycloplegia-paralysis of ciliary muscles and loss of visual accommodation.

• Decrease intraocular pressure (treat glaucoma- resting)

parasympathomimetic medications

• pilocarpine

• cevimeline

contraindications of cholinergic (parasympathomimetic) agents

• Bronchial asthma

• Hyperthyroidism

• GI or urinary tract obstruction

• Severe cardiac disease

• Myasthenia gravis treated with neostigmine

• Peptic ulcer

anticholinergic (parasympatholytic) agents

• Cholinergic blocking agents that prevent acetylcholine action at postganglionic parasympathetic nerve endings

  • examples include atropine and scopalamine

• Block acetylcholine action on smooth muscle, glandular tissue, and the heart which mimic effects of sympathetic ANS

• Antimuscarinic agents (block muscarinic receptors)

• may impose dry mouth, increased heart rate, and reduced secretions

• patients may have increased caries risk and require xerostomia management

anticholinergic (parasympatholytic) medications

• atropine

• scopolamine

adverse effects of anticholinergic (parasympatholytic) agents

• Xerostomia

• Blurred vision

• Photophobia

• Tachycardia

• Fever

• Urinary and gastrointestinal stasis

• Hyperpyrexia and hot, dry, flushed skin caused by lack of sweating

• Anticholinergic Toxicity>Signs of CNS excitation

  • Delirium, hallucinations, convulsions, respiratory depression.

contraindications of anticholinergic (parasympatholytic) agents

• Glaucoma- angle closure (narrow angle)

• Prostatic hypertrophy

• Intestinal obstruction

• Urinary obstruction or retention

• Cardiovascular disease- agents block the vagus nerve, resulting in tachycardia

primary uses of anticholinergic (parasympatholytic) agents

• Preoperative medication

  • Reduce saliva and bronchial mucus

  • Prevent cardiac slowing from general anesthesia

• Treatment of GI disorders

• Ophthalmologic examination

• Reduction of Parkinson-like movements

  • Only used occasionally today

• Motion sickness

  • Transdermal patch

mixed acting adrenergic drug

• (ex. Ephedrine)

• can either directly stimulate the receptor, or release endogenous NE

indirect acting adrenergic drug

• (ex. Amphetamine)

• release endogenous NE to produce a response

direct acting adrenergic drug

• NE, epi, isoproterenol act directly on the receptor site by stimulating the receptor

catecholamine enzymes responsible for epinephrine and NE metabolism

• monoamine oxidase (MAO - sits inside nerve endings on outer layer of mitochondria)

• catechol-o-methyltransferase (COMT - floats freely in cytoplasm)

Mydriasis

pupil dilation

termination of action of adrenergic drugs

• NE is primarily terminated by reuptake into presynaptic nerve terminal

• 2 enzyme systems involved in metabolism of NE and epinephrine

  • Mono-amine Oxidase (MAO)

  • Catechol-O-methyltransferase (COMT)

dental hygiene considerations for adrenergic (sympathomimetic) agents

• Take BP and pulse

• Take detailed medication/health histories

• Lower doses of a vasoconstrictor

adrenergic (sympathomimetic) agents

• play important role in the treatment of anaphylaxis and asthma

• are added to local anesthetics as vasoconstrictors to prolong action

• produce CNS excitation, increase the force and strength of contraction in heart, vasoconstriction, increased blood pressure, mydriasis, relaxation of the bronchial smooth musce (treatment for asthma), mucous secreting cells of submandibular and sublingual glands are stimulated to release small amonuts of thick, biscous saliva