Intro to Pharmacotherapeutics Flashcards
Nursing responsibilities regarding drugs
a. provide maximum benefit with minimum harm
b. anticipate and respond to drug responses
c. patient’s advocate (and education)
d. last line of defense against medication errors
Patient Care Applications
a. pre-administration assessment (i.e. allergies, toxic effects)
b. dosage and administration
c. evaluate/promote therapeutic effects (i.e. non-pharm strategies alongside meds)
d. minimizing side effects
e. minimizing adverse drug interactions
f. making prn decisions
g. managing toxicities
Patient Education Applications
a. drug name and therapeutic category
b. dose, schedule, route, duration
c. how to store drug
d. expected therapeutic response and onset
e. non-drug measures to enhance response
f. side effects, symptoms and how to manage
g. drug and food interactions
pharmacology
study of drugs and their interaction with living systems
clinical pharmacology
study of drugs in humans
pharmacotherapeutics
use of drugs to diagnose, prevent or treat disease or prevent pregnancy
the medical use of drugs
Properties of an ideal drug
a. effectiveness: demonstrated in clinical trials
b. safety: all drugs can produce toxic effects
c. selectivity: elicit only the intended response (no drug is 100% selective, all have potential side effects)
d. reversible action
e. predictability
f. ease of administration
g. freedom from drug interactions
h. low cost
i. stability
Intensity of drug response is determined by
- Administration - route, dose
- Pharmacokinetics (PK) - what the body does to drug
- Pharmacodrynamics (PD) - what the drug does to body
Phamacokinetics (what body does)
ADME
absorption (GI tract, IV, IM, subcu)
distribution
metabolism (liver)
excretion (kidneys)
3 ways for drugs to cross cell membrane
- Direct penetration - drug must have some degree of lipid solubility
- Channels and pores
- Transport systems - may or may not use ATP energy
Absorption
= movement from site of administration into blood
= rate of absorption determines onset of effects
= amount absorbed determines intensity of effect
(bioavailability)
Bioavailability
amount of drug reaching systemic circulation from site of administration
Factors that affect drug absorption
a. rate of dissolution (how fast it can dissolve to cross membrane)
b. surface area
c. blood flow (i.e. to gut)
d. lipid solubility
e. pH effects (neutral state > charged molecules)
Intravenous administration
= drug reaches systemic circulation instantly and completely, no absorption
Advantages:
- rapid onset
- irritant drugs can be given
- large fluid volumes can be used
- control
Disadvantages:
- not reversible (antidote)
- infection
- high cost, inconvenient
- fluid overload
- embolism
Intramuscular/Subcutaneous administration
= no significant barriers to absorption
= absorption pattern determined by drug solubility in water and blood flow
Advantages:
- used for poorly soluble drugs (prolonged or delayed effect, sustained exposure)
- depot preparations
Disadvantages:
- discomfort
- inconvenient
Oral administration
Barriers to absorption
- epithelial cells lining GI tract
- most drugs pass freely through capillary wall
Absorption pattern determined by:
- solubility and stability of drug
- gastric and intestinal pH
- gastric emptying
- presence of food
- co-administration of other drugs
- coatings on drug
Advantages:
- easy, convenient, many dosage forms
- inexpensive and safe
Disadvantages:
- variability
- inactivation (first pass effect)
- patient requirements (swallowing)
- local irritation (upset stomach)
First Pass Effect (pharmacokinetics)
= drugs absorbed from GI tract are carried directly to liver, “first pass through liver”
= liver metabolizes drug, large amount may be inactivated and thus reducing therapeutic effects
= a determinant of oral bioavailability
Other routes of drug administration
a. topical
b. transdermal
c. sublingual
d. inhalational
e. vaginal
f. rectal
g. direct site injection
Distribution
= movement of drugs throughout the body
= factors affecting distribution: blood flow to tissue, drugs exit vasculature, ability of drug to enter cells (lipid solubility and transport systems)
Blood-brain barrier
the blood-brain barrier is unique in that it has tight junctions
- if it is lipid soluble, it can penetrate the cell membrane
- if it is ionized or polar, it may enter using existing transport systems
Protein binding of drugs
= albumin is a main protein for drugs to bound to
= when drugs bind to albumin, it cannot easily exit vasculature, only free drugs exit
Metabolism
= the enzymatic alteration of drug structure, aka biotransformation
= drug metabolism leads to drug inactivation, activation, increased therapeutic action or increased toxicity
= mostly occurs in liver
Cytochrome P450 (CYP450) enzymes
= family of hepatic enzymes
= expression can be induced or inhibited by drugs, infections, foods, alcohol, smoking, genetic polymorphism
basis for many drug drug interactions
Prodrug
= a compound which is administered in a pharmacologically inactive form and undergoes metabolic conversion to an active form
= usually done to improve bioavailability of a poorly absorbed drug
i.e. valacyclovir is a prodrug of acyclovir
Excretion
= the removal of drugs from the body
= biliary (liver) or urinary (kidney)
= occurs via urine, bile, sweat, saliva, expired air or breast milk
Renal drug excretion
a. glomerular filtration
b. passive tubular reabsorption
c. active tubular secretion
*renal dysfunction can increase drug effects and duration, influences decision on what drugs are safe
Minimum Effective Concentration (MEC)
the plasma drug level below which therapeutic effects will not occur
Toxic concentration
the plasma level at which toxic effects begin to appear
Therapeutic range
plasma level at which therapeutic effects occur without any toxic effects
Half-life (t1/2)
= time required for the amount of drug in the body to decrease by 50%
= drug dosing interval depends on t1/2
= half life is usually a constant but may be influenced by patient-specific factors such as renal function and genetics
= applies to most but not all drugs
Plateau phase
= a steady state phase, usually takes 4-5 half life’s to reach this plateau, prevents fluctuation of concentration
Loading dose
large initial dose to reach the therapeutic range more quickly
quickly produces drug level equivalent to plateau
Maintenance dose
a smaller dose given to remain in the plateau stage once it is reached
Dose-response relationship
= the higher the drug concentration, the greater the response
= at a certain point, the response maxes out, more will not produce more therapeutic effect, but maybe more side effects
Efficacy
some drugs will never reach the same maximal efficacy no matter how much is given
determined by how well drugs bind to receptors
Potency
amount of drug needed to reach the same level of maximal efficacy
Drug-Receptor Interactions
D+R»_space; DR complex»_space; Response
= receptor activity is regulated by endogenous molecules
= drugs either mimic or block actions of endogenous molecules
Agonist
drugs that mimic the body’s own regulatory molecules
i.e. insulin, dobutamine
Antagonist
drugs that block the actions of endogenous regulators
i.e. antihistamines, naloxone
Receptor affinity
strength of attraction between drug and receptor
- reflected in drug potency
Intrinsic activity
ability of drug to activate the receptor when bound
- reflected in maximal efficacy
Therapeutic Index (TI)
measure of drug safety: TI = LD50/ED50
LD50: dose that is expected to be lethal to 50% of a population
ED50: dose required to produce a defined therapeutic response in 50% of a population
larger TI = safer drug
Drug drug interaction
an interaction where the effectiveness or toxicity of one or more drugs is altered
Consequences of DDI
a. intensified effects (therapeutic or side effects)
b. reduced effects (therapeutic or side effects
c. unique effects
Mechanism of DDI
a. direct chemical or physical interactions (most common when combining drugs in solution)
b. pharmacokinetic interactions
c. pharmacodynamic interactions
PK Interactions: Absorption
usually results in decreased drug absorption
i.e. calcium binds tetracycline»_space; decreased absorption
laxatives increase gut motility»_space; decrease absorption
PK Interactions: Metabolism
most important and complex source of DI
enzyme induction vs inhibition
- certain drugs can change the induction and inhibition of enzymes, which change its ability to metabolize another drug
Common CYP450 Inducers
Barbiturates Rifampin Carbamazepine Phenytoin Corticosteroids
Common CYP450 Inhibitors
Macrolide antibiotics Paroxetine Fluoxetine Fluroquinolone antibiotics Azole antifungals Grapefruit
PK Interactions: Excretion
interactions may affect drug filtration, secretion or reabsorption by kidney tubules
i.e. diuretics - reduce reabsorption by kidney tubules
Pharmacodynamic Interactions
occurs when two drugs act on same receptors or physiologic systems
occurs when drugs with additive or antagonistic effects are combined
- antagonistic effects (antidotes, naloxone for narcotic OD)
- additive therapeutic effects (antihypertensive drug combinations, cancer chemotherapy, aspirin and warfarin)
- additive side effects (antihistamine and CNS depressant»_space; increased sedation)
- indirect effects (diuretics»_space; decreased K+»_space; increased digoxin effect)
DDI: Clinical Significance
= not all DIs are clinically significant or cause adverse effects
= DIs may be prescribed and may be desirable for their beneficial effects
= most clinically significant DIs occur for drugs with narrow TI
Common Narrow TI Drugs
digoxin (Lanoxin) phenytoin (Dilantin) theophylline (TheoDur) warfarin (Coumadin) cimetidine (Tagamet) cyclosporine (Neoral) tacrolimus (Prograf, Advagraf) lithium (Carbolith) carbamazepine (Tegretol)
Drug-Food Interactions
= food may increase, decrease or have no effect on drug absorption
= may alter bioavailability of a drug from a modified release dosage form
i.e. grapefruit juice
Adverse Drug Reaction (ADR)
a noxious, unintended, undesired effect that occurs at normal drug doses
a. side effect - secondary drug effect occurring at normal doses
b. idiosyncratic reaction - uncommon drug response due to genetic predisposition
c. allergic reaction - due to an immune response, independent of dose (less than 10% of ADRs are allergies!)
Adverse drug event
injury resulting from use of a drug
includes ADRs, medication errors and overdoses
Identifying an ADR
- did symptoms start soon after drug first given?
- did symptoms stop when drug discontinued?
- did symptoms reappear when drug re-challenged?
- is there another explanation for the symptoms? (underlying condition, DDI)
Nurse’s Role in identifying and preventing ADRs
a. be familiar with most common ADRs before administering
b. suspect ADR with a change in patient condition not associated with therapeutic response
c. medication history is valuable! distinguish allergy from intolerance
d. monitor relevant changes (liver FTs, serum creatinine, CBC)
