pharmacology test 1

situations in which parenteral administration may b easier

situations in which parenteral administration may b easier

• Emergencies that require rapid onset of drug action.

• Situations in which plasma drug levels must be tightly controlled. (Because of variable absorption, oral administration does not permit tight control of drug levels.)

• Treatment with drugs that would be destroyed by gastric acidity, digestive enzymes, or hepatic enzymes if given orally (e.g., insulin, penicillin G, nitroglycerin).

• Treatment with drugs that would cause severe local injury if administered by mouth (e.g., certain anticancer agents).

• Treating a systemic disorder with drugs that cannot cross membranes (e.g., quaternary ammonium compounds).

• Treating conditions for which the prolonged effects of a depot preparation might be desirable.

• Treating patients who cannot or will not take drugs orally.

chemical equivilance

preparations contain same amount of identical chemical compound (drug)

bioavailability

preparations equal in bioavailabilty if absorb at same rate to same extent.

is possible for two drugs of same formulation to b chemically equivalent but not equal in bioavailability

six possible therapeutic consequences of drug metabolism

• Accelerated renal excretion of drugs

• Drug inactivation

• Increased therapeutic action

• Activation of “prodrugs”

• Increased toxicity

• Decreased toxicity

water content in body weight of an adult

50-60% body weight

water content in body weight of OLDER adults

40-50% in older adults

water weight content in body of infants

70-80%

water weight content variables

varies with gender, men have more bc have more lean body mass

body mass

age

extracellular fluid includes

• intravascular (plasma in veins)

• interstitial (everything not in blood or cells)

fluid compartment n total body mass female

45% solids

55% fluids

fluid compartment total body mass male

40% solids

60% fluids

of the fluids compartment how much is intracellular and extracellular?

2/3 is ICF

1/3 is ECF

thereforre in a male, 40% of body mass is intracellular and 20% in extracellualr

percentages of interstitial and plasma in extracelllular fluid

80% interstitial

20% plasma

electrolytes

substances whose ions dissociate into ions (charged particles) when placed in water

International standard is millimoles per liter

U.S uses milliequivalent (mEq)

cations are charged

positively

anions are charged

negatively

what are the prevalent electrolytes in intracellular fluid?

cation: K+

anion: PO4 -3

KIN = K IN cell

what are the prevalent electrolytes in extracellular fluid ?

cation: Na+

amion: Cl-

mechanisms controlling fluid and electrolyte movement

• diffusion

• facilitated diffusion

  • active tranport

• osmosis

• hydrostatic pressure

• oncotic pressure

osmosis

movement of water between two compartments by a membrane permeable to water but not to solute

water moves from low solute to high solute []

no energy

MILKSHAKE EXAMPLE- milkshake by adding more milk (water)

osmotic pressure

amount of pressure required to STOP osmotic flow of water

determined by concentration of solutes in a solution bc it is the pull that sucks H2O BACK IN, more solutes = more osmosis into where solutes are

oncotic pressure

osmotic pressure in the body

osmotic pressure exerted by colloids in solution

ALBUMIN is a major colloid

hydrostatic pressure

force within a fluid compartment

major force that pushes water out of vascular system at capillary level

pushes H2O out of plasma

fluid movement in capillaries determined by

• capillary hydrostatic pressure

• plasma oncotic pressure

• interstitial hydrostatic pressure

• interstitial oncotic pressure

plasma to interstitial fluid shift results in edema if

• there is an increase in hydrostatic pressure (more push into the tissues)

• increase in plasma (venous) oncotic pressure (less fluid is pushed into tissues)

• increase of interstitial oncotic pressure water is pulled into tissues

***** ask if this is correct during office hours

interstitial fluid goes to plasma if…

there’s an increase in plasma osmotic/oncotic pressure

compression stockings decrease peripheral edema

CAUSES OF EDEMA increased capillary volume

plasma → interstitial

• increased capillary volume

• heart failure

  • blood backs up in legs, ankles, feet bc heart is not pumping as well, also cause fluid in lungs (pulmonary edema)

• kidney disease

  • kidneys cant get rid of excess fluid in body

• premenstrual sodium retention

• pregnancy

• thiazolidinediones such as Pioglitazone and rosiglitazone, (diabetes medication that increases vascular permeability in adipose tissues and increased fluid reabsorption in the nephron)

increased capillary permeability causes edema in

• allergic reactions

• tissue injury

• trauma

edema caused by decreased colloidal osmotic pressure (less pressure sucking back in) in

• increased loss of plasma protein as in a protein losing kidney disease, extensive burns

• decreaed production of plasma protiens as in liver disease and starvation/malnutrition

venous obstructions causes of edema

• liver disease w portal vein obstruction

• acute pulmonary edema

• venous thrombosis (thrombophlebitis)

• decreased arterial resisitance

• calcium channel blocking drug response

fluid spacing - first spacing

normal distrubution of fluid in ICF and ECF

fluid spacing - second spacing

means an abnormal accumulation of interstitial fluid in body (edema)

fluid spacing - third spacing

*problem

fluid accumulation in a part of the body where it is not easily exchanged with ECF, therefore hard to get rid of

places such as interstitial, pleural, pericardial, abdominal cavity

hypothalmic reguation of water

• osmoreceptors in HYPOTHALAMUS sennse flid deficit or increase

• stimulate thirst response

• result in inc. free water and dec. plasma osmolality

pituitary water regulation

• under control of hypthalmus

  • posterior pituatary releases ADH

ADH release is stimulated by

• stress, nausea, nicotine, surgery, anesthetic agents, lung tumors, intrathoracic conditions, mechanical ventilation, morphine

ADH is a vasopressin meaning

• its an antidiuretic (LESS pee)

• causes DCT to be more permeable to water so water is reabsorbed

• less pee when dehydrated to retain fluid

adrenal cortical regulation

adrenal gland releases hormones to regulate water and electrolytes

mineralcorticoids released

• aldosterone

  • retains salt, water follows salt

    • SALt S= sodium, Al = aldosterone

what stimulates aldosterone?

stress and physical trauma → ant. pituitary rel. ACTH → stimulates adrenal glands to release aldosterone

high serum K+

low serum Na+

serum = blood - cellular component and clotting factors

low renal perfusion/low plasma volume → inc. renin secretion → inc. plasma angiotensin II → inc. adlosterone secretion

results in inc Na+ resabsorption and decreased K+ excretion

how does kidney regulate fluid and electrolyte balance

• adjust urine volume

  • selective reabsorption of water and electrolytes

  • renal tubules are sites of action of ADH and aldosterone

cardiac regulation of fluid and elctrolytes

DECREASE EVERYTHING

• natriuretic peptides are antagonists to the RAAS

  • produced by cardiomyocytes in response to atrial pressure

  • suppress secretion of aldosterone, renin, and ADH to decrease blood volume and pressure

insensible water loss

lungs and skin to regulate body temp

400-800ml/ day is lost

no electrolytes lost

gerontologic considerations

structural changes in kidney decreases ability to conserve water

hormonal changes lead to decrease in ADH and ANP

loss of subcutaneous tissue leads to increased loss of moisture

reduced thirst mechanism may result in reduced fluid intake

nurse must assess for these changes and implement treatment accordingly

hypovalemia

• fluid volume deficit

• abnormal losses of body fluids

• patient could go into shock

• nurse should monitor

  • HR, RR, BP

What kind of patients are at risk for FVD? (fluid vol. deficit)

trauma

surgery

vomiting

diarrhea

burns

ascites

thiracentesis

paracentesis

diuretics

diseaes w polyuria

during FVD does HR increase or decrease? why?

heart rate increases because the volume decreases so it is trying to have the same cardiac output by making up for decreased stroke volume

it is also trying to perfuse body better by pumping faster w less blood

CO = SV x HR

during FVD does BP increase or decrease? why

decreases because a decreased volume causes decreased pressure

cool extremeties in FVD are a sign of shock, why?

lack of perfusion

FVD causes flattened neck/peripheral veins, why?

theres a drop of blood pressure, causes veins to shrinks

what happens to LOC during FVD?

loc decreases

urinary output during FVD

decreases

has a specific gravity/ concentration of >1.025

pat. loses weight

fluid volume excess clinical manifestations

HR decreases but has a bounding pulse

Bp increases

lungs sound wet and crackles

rate of resp. increases

UOP increases

spec. gravity = <1.010

weight increase

nursing hypothesis during hypovolemia

• excess Fv, the risk for imbalanced FV

• risk for impaired skin integrity

• disturbed body image

• Potential complications: pulmonary edema

nursing management cues for hypervolemia

• I & Os (inputs and outputs)

• monitor cardiovascular changes

• asses respiratory changes

• daily weights

• skin assessment

• mental status

hypervolemia

excessive intake of fluids, abnormal retention of fluids (heart failure or kidney failure), or interstitial → plasma fluid shift

treatment: remove fluid without changing electrolyte composition or osmolality of ECF (diuretics, fluid restrictions)

pharmacodynamics

study of what drugs do to the body and how they do it

therapeutic objective and pharmacodynamics

educating patients about their medications

making PRN decisions

evaluating patients for drug responses (both beneficial and harmful)

collaborating with physicians about drug therapy

dose response relationships

determines min amount of drug we can use and max response it can illicit

how much we need to inc the dosage to produce the desired inc in response

efficacy vs potency

efficacy = effect more efficacy means more effect, higher degree of pain relief

potency = strength, abiltiy to kill you ex: smaller dose of morphine has same effect as higher dose of meperidine so morphine is more potent

receptor

any functional macromolecule in acell which a drug binds to produce its effects

• incl. enzymes, proteins, ribosomes etc

typically reserved for bodys own receptors for hormones, nuerotransmitters, regulatory molecules

important properties of receptors

receptors are normal points of control of physiological proesses

under physiologic conditions receptor function is regulated by molecules supplied by the body

drugs can only mimic or block the bodys own regulatory molecules

drugs CANNOT give cells new functions

drugs produce therapeutic effects by helping body use its preexisting capabilities

in theory, should be possible to synthesize drugs that can alter the rate of any biologic process for which receptors exist

what are the 4 primary receptor families

• cell membrane embedded enzymes

• ligand gates ion channels

• G protein couples receptor systems

• transcripton factors (change DNA of cell)

which one of the 4 receptor-drug responses to activation will be delayed?

*******

the more selective a drug is,

the fewer side effects it will produce

receptors make selectively possible

each type of receptor participates in the regulation of just a few processes

lock and key mechanism

does not garuntee safety

body has receptors for each:

nuerotransmitter

hormone

all other molecules in the body used to regulate the physiologic processes

modified occupancy theory

affinity- strength of interaction

intrinsic activity - ability of drug to activate a receptor upon binding

agonists

molecules that activate receptors

endogenous regualtors (produced naturally in body) also considred agonists

have both affinity and high intrinsic activity

can make processes go “slower or faster”

ex: dobutamine mimics norepinephrine at cardiac receptors

antagonists

produce their effects by preventing receptors activation by endogenous regulatory molecules and drugs

affinity but no intrinsic activity

have no effects on their own recpetor functions

block a response or precipitate a less than typical response

can be competitive or noncompetitive

**if there is no agonist present an antaonsit will have no observable effect

generic drug names

not capitalized

name given by those who developed drug

fda makes sure new generic drugs are of therpudic equivalence to brand names

oral drugs

• tablet, capsule,powder, liquid form

• powder drugs are taken through mouth and absorbed through lungs

• enteric coated drugs r xtended release

parenteral drugs

INJECTED

intravenously (IV)

subcutaneous

intramuscularly

intravenous absorption and onset

complete and immediate

complete

subcutaneous absorption and onset

rapid absorption if highly water soluble and good circulatory flow, slow if not

variable onset

topic/transdermal drugs

through skin eyes, ears, nose rectum, vagina, ears, lungs

deliver a constant amount of drugs over an extended amount of time

pharmacokinetics

administration

distrubution

metabolism

excretion

competitive antagonists

you give in increasingly high doses will decrease the typical response by an agonist but will rarely completely block it

compete with agonists for receptor binding

bind REVERSIBLY to receptors

EQUAL AFFINITY: receptor occupied by whichever agent is present in the highest concentration

noncompetitive antagonists

block an agonists access for receptor sites

bind irreversibly, but impact not permanent bc cells are constantly breaking down “old” receptors and synthesizing new ones

reduce maximal response that an agonist can elicit (bc they have fewer available receptors due blocking)

given in high enough doses completely block the typical response caused by an agonist

partial agonists

there are agonists that have only moderate intrinsic (ability to mind) activity

max effect that a partial agonist can produce is less that that of a full agonist

can act as antagonist or agonists

expected pharmacologic action

the action a drug exerts in the body

provider chooses drugs for clients treatment plan based on this

ex: antibiotics or anti infectives have the ability to kill/inhibit reproduction of bacteria so they’re for clients who have an infcetion

regulation of receptor sensitivity

# of receptors on cell surface and sensitivity to agonists can change in response to

• continuous activation

• continuous inhibition

continuous exposure to an agonist causes

desensitized or refractory

down regulation ***

continuous exposaure to an antagonist

hypersensitive

drug responses that DO NOT involve receptors

simple physical or chemical interaction with other small molecules

examples of receptorless drugs

• antacids, antiseptics, saline laxitives, chelating agents

******

clinical implications of interpatient variability

• inital dose of a drug is necessarily an approximation

• sbsequennt doses must be fine tuned based on patients response

  • ED50 in pat. may need to be increased or decreased after the patient response is evaluated

therapeudic index

measure of a drugs safety

ratio of drugs LD50 (avg lethal dose to 50% of animals treated) to its ED50

latger/higher therapeutic index, the safer the drug

the smaller/lower the index, the less safe the drug

when teaching a patient who has a gastric ulkcer about cimetidine (a histamine H2 antagonist) therapy the nurse should incluide which information about antagonists ?

A. antagonist causes a chemical reaction in the stomach

B. an antagonist activates receptors in the stomach lining

C. an antagonist prevents receptor activation in the stomach

D. an antagonist improves receptor sensitivity in the stomach

drug-drug interactions

• interactions can occur whenever a patient takes more than one drug

• some interactions are intended and desired, some aren’t

• patients frequently take more than one drug

  • multiple drugs to treat one disorder

  • multiple disorders requiring different drugs

  • otc medications, caffeine, nicotine, alcohol and so on

  • who is most likely to be prescribed multiple medications ? geriatric patients ??

consequences of drug to drug interactions

• intensification of effects

  • increased therapeutic effects (sulbactam and ampicillin)

  • increased adverse effects (aspirin and warfarin)

• reduction of effects

  • inhibitory: interactions that result in reduced drug effects

  • reduced therapeutic effects

  • propranolol and albuterol

  • reduced adverse effects

    • naloxone treats morphine OD

• creation of a unique response

  • alcohol w/ disulfiram (antibuse)

drugs can interact through what four basic mechanisms?

1. direct chemical or physical interaction

2. Pharmacokinetic interaction

3. pharmacodynamic interaction

4. combined toxicity

direct chemical or physical interaction

• never combine drugs in the same container without establishing compatibility

• most common in intravenous solution

  • precipitate: do not *****

pharmacokinetic interactions

• altered absorption

• altered distribution

• altered renal excretion

• altered metabolism

• cytochrome P450 (CYP) group of enzymes

  • inducers: carbamapazine, phenoytoin, phenobarbital alcohol

  • inhibitors: azmoles, isoniazid, oral contraceptives, amiodarone

  *******

pharmacokinetic interations that alter absorptions

elevated gastric pH

laxatives

drugs that depress peristalsis

drugs that induce vomiting

adsorbent drugs

drugs that reduce regional blood flow

pharmacokinetic interactions that alter distribution

• competition for protein binding (think ab phenotyin/Dilantin)

  • alteration of extracellular pH

pharmacokinetic interactions that alter renal excretion

drugs can alter

• filtration

• reabsorption

• active secretion

pharmacokinetic interations that alter metabolism

• most important and complex mechanism in which drugs interact

• cytochrome P450 (CYP) group of enzymes

  • inducing agents : phenobarbital

    • inc. rate of metabolism 2-3x over 7-10 days

    • resolve over 7-10 days after withdrawal

  • inhibition of CYP isoenzymes

    • usually undesired

interactions that involve P-glycoproteins (PGPs)

• transmembrane protein that transports a wide variety of drugs out of cells

• reduced or increased PGP

  • intestinal epithelium: affects absorption

  • placenta: affects drug export from placental cells to maternal blood

  • blood brain barrier: affects drug export from cells of brain cap. into blood

  • liver: affects drug export from liver to bile

  • kidney tubules: affects drug export from renal tubular cells into the urine

pharmacodynamic interactions

• at the SAME receptor :

  • are almost ALWAYS inhibitory

• at SEPARATE sites

  • may be potentiative (morphines and diazepam) (aspirin and warfarin shouldnt be taken tgt, potentiative side effects inc. risk of bleeding)

  • OR inhibitory (hydrochlorothiazide and spironolactone)

• combined toxicty

  • drugs with overlapping toxicities should not be used tgt

clinical signifigance of drug-drug interactions

• can signifigantlly affect outcome of therapy

• responses mat be increased or reduced

• the risk for adverse interaction DIRECTLY correlates to the amount of drugs pat. is taking

• esp. imprtant for drugs w low therapudic indexes

  • !!!! mant interactions are YET TO BE IDENTIFIED