Term
The study of biochemical & physiologic effects of drugs & the molecular mechanisms by which those effects are produced
|
|
Definition
|
|
Term
The relationship between the size of administered dose & intensity of response to drug
|
|
Definition
| Dose-Response Relationship |
|
|
Term
| The dose-response relationship determines what? |
|
Definition
• Minimum amt of drug to use
• Maximum response elicited
• How much increase is needed to produce desired increase in response
|
|
|
Term
| What are the Phases of Dose Response? |
|
Definition
Phase 1: Doses are too low to elicit a clinical response
Phase 2: The response is graded on a graph
Phase 3: Higher doses do not cause much response but can cause toxicity and SE
|
|
|
Term
How effective a drug at a given dose is at eliciting a desired response
|
|
Definition
|
|
Term
Largest effect a drug can produce
|
|
Definition
|
|
Term
Amount of drug (ex: mg) needed to elicit a response
|
|
Definition
|
|
Term
A more potent drug is _________ more therapeutically effective
|
|
Definition
|
|
Term
What’s more important, potency or efficacy?
|
|
Definition
|
|
Term
| What are the characteristics of drug receptors? |
|
Definition
• Control normal body processes
• Normally controlled by endogenous substances
• Drug binding to receptors is reversible
|
|
|
Term
|
Definition
|
|
Term
| Drugs either ________________ or __________________ on drug receptors. |
|
Definition
• Mimic endogenous substances (agonists)
• Block action of endogenous substances (antagonists)
|
|
|
Term
Drugs (and their endogenous counterparts) exert their action by binding to a functional __________ in or on a cell (receptor)
|
|
Definition
|
|
Term
| When competing with endogenous molecule drug may bind to ________________. |
|
Definition
| several different receptors besides intended site |
|
|
Term
Intensity of drug response is proportional to the __________________.
|
|
Definition
| number of receptors occupied by the drug |
|
|
Term
| Max response is when _________________. |
|
Definition
all receptors are occupied
|
|
|
Term
The ________________ Theory assumes all drugs binding to a receptor have same abilities to bind & elicit response
|
|
Definition
|
|
Term
Simple theory + explanation of how 2 drugs on same receptor have different abilities
|
|
Definition
| Modified Occupancy Theory |
|
|
Term
Strength of attraction between drug & receptor
|
|
Definition
|
|
Term
Ability of drug to activate receptor after binding
|
|
Definition
|
|
Term
High affinity = ________ attraction = ______ concentration to elicit response = ________ potency
|
|
Definition
|
|
Term
Low affinity = _____ attraction = ______ concentration to elicit response = ______ potency
|
|
Definition
|
|
Term
High intrinsic activity = __________ receptor activity = ______ efficacy
|
|
Definition
|
|
Term
Low intrinsic activity = ______ receptor activity = _____ efficacy
|
|
Definition
|
|
Term
What are the characteristics of agonists?
|
|
Definition
• Activate receptors
• Mimic endogenous substance
• May bind to different receptors at different doses
• Has both affinity & high intrinsic activity
|
|
|
Term
| What are the characteristics of antagonists? |
|
Definition
• Block actions of endogenous substance or other drugs
• Have affinity but don’t have intrinsic activity
• Pharmacological effect results from blocking post receptor responses
• No agonist = no pharmacological effect
|
|
|
Term
| What are the characteristics of partial agonists? |
|
Definition
• Has moderate intrinsic activity
• Maximal effect is lower than that of full agonist
• Act as both agonist & antagonist
• Elicit small response & also blocks other agonists
• Administered alone = small response
• Administered in large doses w/another drug = occupies receptors = blocks full agonist from binding to receptor = lower response
|
|
|
Term
Receptor sensitivity ______ constant
|
|
Definition
|
|
Term
Number of receptors on cell ______ constant
|
|
Definition
|
|
Term
Drugs may be selective to a receptor but produce ______________.
|
|
Definition
|
|
Term
| A receptor may be responsible for several ___________. |
|
Definition
|
|
Term
| Continuous exposure to agonists can cause __________. |
|
Definition
• Cell to be less responsive (desensitized or refractory) - AKA down regulation
• Liver to produce more metabolizing enzymes
|
|
|
Term
Down regulation can happen ________ or _______.
|
|
Definition
|
|
Term
| Continuous exposure to antagonist can cause ____________. |
|
Definition
• Receptor to become more responsive
(AKA hypersensitive or supersensitive)
• More receptors to be synthesized
|
|
|
Term
What drugs act thru physical/chemical interactions instead of receptors?
|
|
Definition
Antacids
Antiseptics
Laxatives
Chelating agents |
|
|
Term
| When more than one drug is taken by a patient, there is a risk that the drugs will conflict with each other by altering ______________. |
|
Definition
|
|
Term
There is a _______ relationship between the number of drugs taken and the risk for a serious interaction.
|
|
Definition
|
|
Term
The average 65-year-old takes ________ medications and has about a ___% risk for one or more drug-drug interactions.
|
|
Definition
|
|
Term
| What are the possible drug interactions? |
|
Definition
• Intensification of effects (potentiation)
• Reduction of effects (inhibition)
• The drug combination may elicit a response not seen with either drug alone
|
|
|
Term
The four basic mechanisms of drug-drug interactions are:
|
|
Definition
1. Direct interaction by way of physical contact or chemical reaction
2. Pharmacokinetic interactions (affecting ADME)
3. Pharmacodynamic interactions
4. Combined toxicity
|
|
|
Term
| What are the pharmacokinetic drug interactions regarding absorption? |
|
Definition
• Changes in gastric or intestinal pH
• Changes in peristalsis
• Vomiting
• Drugs that absorb or bind other drugs
• Anti-infectives that kill intestinal bacteria
• Drugs that reduce regional blood flow
|
|
|
Term
| What are the pharmacokinetic drug interactions regarding distribution? |
|
Definition
Competition for protein binding sites
Alteration of extracellular pH
|
|
|
Term
| What are the pharmacokinetic drug interactions regarding metabolism? |
|
Definition
Some drugs have the potential to compete with other drugs for enzymes (primarily CYP)
|
|
|
Term
| Increased synthesis of certain CYP enzymes (enzyme inducers) _________ metabolism. |
|
Definition
|
|
Term
| Decreased activity of certain CYP enzymes (enzyme inhibitors) _________ metabolism. |
|
Definition
|
|
Term
| Enzyme induction ________ the rate of biotransformation of inducing drug & other drugs using the enzyme as much as ____x normal rate |
|
Definition
|
|
Term
Some drugs and toxins increase the levels of, or _______, certain CYPs
|
|
Definition
|
|
Term
It may take _________ days of exposure before the full effects of enzyme induction appear.
|
|
Definition
|
|
Term
It takes as long as _________ days after withdrawal of the inducer for the CYPs to return to previous levels of activity.
|
|
Definition
|
|
Term
| What are some examples of enzyme inducers? |
|
Definition
• Cigarette/marijuana smoke and chewing tobacco
• Passive smoke
• Alcohol (chronic use, consumption of 1 to 3 drinks/day)
• Compounds in charcoal-broiled food
• St. John's wort
• Phenobarbital
• Phenytoin (Dilantin)
• Rifampin
|
|
|
Term
What can enzyme inhibition cause?
|
|
Definition
Decreased activation of prodrugs
Accumulation of parent drug to toxic levels
|
|
|
Term
What are some examples of enzyme inhibitors?
|
|
Definition
• Alcohol (binge drinking or long-term intake of more than 3 drinks/day)
• Anabolic steroids
• Some antidepressants (SSRIs)
• Some antibiotics
• Antifungal drugs
• Some cardiac drugs
• Acid reducers
• Grapefruit juice
|
|
|
Term
Drugs that __________ renal blood flow directly or indirectly by __________ cardiac output can reduce glomerular filtration of drugs.
|
|
Definition
|
|
Term
Drugs that alter ________ can affect passive tubular reabsorption.
|
|
Definition
|
|
Term
| Two drugs that compete for ___________ can decrease the excretion of one or both drugs |
|
Definition
|
|
Term
Drugs can interact when they bind to __________ if they alter the same physiologic process.
|
|
Definition
|
|
Term
| Drug interactions at the same site are almost always ______________. |
|
Definition
|
|
Term
If unusual s/s develop, suspect ____________.
|
|
Definition
|
|
Term
| How can you minimize drug interactions? |
|
Definition
Reduce number of drugs taken
ASSESS!!!!
Thorough drug history
Lab values
Give with/without food as ordered
Be familiar with drugs & consequences
|
|
|
Term
Adequate _____________ is essential for optimal PO drug absorption
|
|
Definition
|
|
Term
| How can protein and calorie malnutrition affect absorption? |
|
Definition
| Reduce the villous absorptive surface area of the intestine thereby decreasing the absorption of drugs, vitamins, and minerals |
|
|
Term
Food usually ___________ rate of absorption
|
|
Definition
|
|
Term
Food occasionally __________ extent of absorption
|
|
Definition
|
|
Term
| Taking a medication with food can affect drug bioavailability in what ways? |
|
Definition
• Food can alter drug absorption by affecting the gastric emptying time and the intestinal residence time.
• Food can increase the bioavailability of drugs with a high extraction ratio (ER).
• Constituents in food can bind to medications to create an insoluble complex or reduce drug absorption |
|
|
Term
| Meals high in simple sugar & fluids & low in fat = __________ gastric emptying |
|
Definition
|
|
Term
Drugs that need to be absorbed in stomach or drugs requiring a slow rate of intestinal absorption will not have enough time for absorption in ______________.
|
|
Definition
| increased gastric emptying |
|
|
Term
| In a patient with increased gastic emptying, drugs that can be inactivated in stomach will have ___________ bioavailability. |
|
Definition
|
|
Term
_________ will compete with drugs for binding sites on plasma protein.
|
|
Definition
|
|
Term
| Drugs & Nutrient interactions can cause _________. |
|
Definition
|
|
Term
Some vitamins must be ___________ to exert action.
|
|
Definition
|
|
Term
| Some drugs can induce the enzymes that convert vitamins into inactive metabolites causing __________. |
|
Definition
|
|
Term
Some CYPs induced by BBQ & cruciferous veggies (cabbage, broccoli, etc)
may cause _______ steady state of some drugs.
|
|
Definition
|
|
Term
Some CYPs inhibited by grapefruit can last up to _____ days after eating/drinking it.
|
|
Definition
|
|
Term
2 or more cups of grapefruit juice regularly will have great impact on ___________.
|
|
Definition
|
|
Term
| In what foods is Tyramine found in? |
|
Definition
Aged cheese & meats
Overripe figs
Large amount of bananas
Soy sauce
Red wines
Yeast extracts |
|
|
Term
Avoid Tyramine with _________.
|
|
Definition
|
|
Term
| What considerations should be made concerning Food & Drug Toxicity? |
|
Definition
• Potassium-sparing drugs – avoid potassium supplements
• CNS stimulants – avoid caffeine
• Lithium – maintain consistent sodium intake
• Aluminum antacids (Maalox) + citrus = excessive aluminum absorption
|
|
|
Term
Any noxious, unintended, undesired effect that occurs at normal drug doses
|
|
Definition
|
|
Term
| When are adverse drug reactions most common? |
|
Definition
Age extremes
Severe illness
Multiple drug therapy
|
|
|
Term
| What are the characteristics of side effects? |
|
Definition
Nearly unavoidable secondary drug effect
Are predictible
Intensity is dose dependent
Can develop immediately or after long use |
|
|
Term
What are the characteristics of toxicity?
|
|
Definition
• ADR caused by excessive dosing
• Can also be any severe ADR regardless of dose
|
|
|
Term
The intensity of an allergic response is determined by ____________, not dose of drug.
|
|
Definition
| degree of sensitization of immune system |
|
|
Term
Immune response caused by prior sensitization of immune system.
|
|
Definition
|
|
Term
Uncommon response resulting from genetic predisposition
|
|
Definition
|
|
Term
Produced by physician or drugs and are nearly identical to idiopathic diseases.
|
|
Definition
|
|
Term
| Organ Specific Toxicity occurs in what organs? |
|
Definition
Kidneys
Liver
Lungs
Heart
Inner ear
|
|
|
Term
__________ must be monitored if on Hepatotoxic drugs
|
|
Definition
|
|
Term
| What are the s/s of liver injury? |
|
Definition
Jaundice
dark urine
light stools
n/v
malise
abd pain
anorexia
|
|
|
Term
QT interval is time required for ventricles to _________ after each contraction
|
|
Definition
|
|
Term
QT Prolongation can lead to __________, which can be fatal.
|
|
Definition
|
|
Term
| QT interval drugs should be used cautiously in what patients? |
|
Definition
Elderly
Bradycardia
Heart failure
Congenital QT prolongation
Low potassium or magnesium
Women
|
|
|
Term
| What can be asked when trying to identify ADRs? |
|
Definition
When did s/s appear
Did resolve when drug stopped
Reappear if drug restarted
Can s/s be attributed to illness
Other drugs to blame
|
|
|
Term
About ____% of new drugs have SERIOUS ADRs not revealed in Phase II or III trials
|
|
Definition
|
|
Term
Report ADRs to _________ even if no absolute proof that drug was to blame
|
|
Definition
|
|
Term
| What are the signs/symptoms of a drug reaction? |
|
Definition
Rash
Uticaria (Hives)
Fever
Diarrhea
Nausea
Vomiting
Anaphylactic reaction |
|
|
Term
Decreased responsiveness to a drug as a result of repeated drug administration
|
|
Definition
|
|
Term
___________ is result of adaptive process occurring in response to chronic activation of receptor
|
|
Definition
| Pharmacodymanic Tolerance |
|
|
Term
| In Pharmacodymanic Tolerance, the MEC is __________. |
|
Definition
|
|
Term
____________ Results from accelerated drug metabolism b/c some drugs induce synthesis of metabolizing enzymes.
|
|
Definition
|
|
Term
| In Metabolic Tolerance, the MEC __________. |
|
Definition
|
|
Term
Reduction in drug responsiveness brought on by repeated dosing over a short time
|
|
Definition
|
|
Term
| What is an example of a drug that causes Tachyphylaxis? |
|
Definition
|
|
Term
Ability of the drug to reach the systemic circulation from its site of administration
|
|
Definition
|
|
Term
| study of how genes affect individual drug responses |
|
Definition
|
|
Term
Quinidine causes ___________ QT-interval prolongation in women than in men.
|
|
Definition
|
|
Term
Certain opioid analgesics are much more effective in __________. women or men?
|
|
Definition
|
|
Term
| Alcohol is metabolized more slowly by __________. |
|
Definition
|
|
Term
Digoxin may increase mortality in _______ but have no effect on mortality of _______.
|
|
Definition
|
|
Term
Starvation reduces protein binding of drugs, which __________ levels of free drugs
|
|
Definition
|
|
Term
What factors alter distribution in the elderly?
|
|
Definition
Increased % of body fat
Decreased % of lean body mass
Decreased total body water
Reduced concentration of serum albumin
|
|
|
Term
What factors slow the rate of hepatic metabolism in the elderly?
|
|
Definition
Reduced hepatic blood flow
Reduced liver mass
Decreased enzyme activity
|
|
|
Term
Excretion progressively declines beginning in ___________.
|
|
Definition
|
|
Term
___________________ is THE most important cause of adverse reactions in elderly!!!
|
|
Definition
| Drug accumulation secondary to reduced renal excretion |
|
|
Term
| What factors slow the rate of excretion in the elderly? |
|
Definition
Reduced renal blood flow
Reduced glomerular filtration rate
Decreased active tubular secretion
Decreased number of nephrons
|
|
|
Term
Adverse drug reactions are ____ times more common in the elderly than in young adults
|
|
Definition
|
|
Term
Adverse drug reactions accounts for ___% of hospital admissions among elderly
|
|
Definition
|
|
Term
| Adverse drug reactions account for ___% of all medication related deaths in the elderly. |
|
Definition
|
|
Term
Up to ___% of the elderly don’t take meds as prescribed for various reasons
|
|
Definition
|
|
Term
Most adverse drug reactions in the elderly are ____________.
|
|
Definition
|
|
Term
| What are the high risk drugs in the elderly? |
|
Definition
• Analgesics
• Antidepressants
• 1st generation antihistamines
• Antihypertensives
• Sedatives/hypnotics (Barbiturates, benzodiazepines)
• Incontinence meds
• Muscle relaxants |
|
|
Term
The elderly are predisposed to ADRs due to what factors?
|
|
Definition
• Lower serum albumin levels
• Drug accumulation r/t reduced renal function
• Polypharmacy
• Greater severity of illness
• Multiple pathologies
• Greater use of drugs with low TI
• Increased individual variation
• Inadequate supervision of long-term therapy
• Poor adherence
|
|
|
