nPharm textbook

Question 1

C2-ideal drug properties

Answer 1

Convenient route of administration, probably taken by mouth * Established dosage
* Immediate onset of action
* Produces a single desired biological action
* Produces no unwanted effects
* Convenient duration of action
* Dosage unaffected by loss of kidney or liver function or by disease state * Improves quality of life
* Prolongs patient survival

Question 2

C2-Homeostasis

Answer 2

Homeostasis is the tendency of a cell, tissue, or the body not to respond to drugs but instead maintain the internal environment by adjusting physiological processes. Before a medication can produce a response, it often must overcome homeostatic mechanisms.

Question 3

C2-Dose réponse

Answer 3

Drug effects depend on the amount of drug administered. If the dose is below that needed to produce a measurable biological effect, no response is observed; therefore, any effects of the drug are insufficient to overcome homeostatic capabilities.
If an adequate dose is administered, there will be a measurable biological response. With an even higher dose, we may see a greater response. At some point, however, we will be unwilling to increase the dosage further, either because we have already achieved a desired or maximum response or because we are concerned about producing additional responses that might harm the patient.

Question 4

C 2- Dose–Response Curves

Answer 4

Simply stated, the higher the concentration of a drug at its site of action, the more the drug will bind to its receptor and the greater the response will be. With a greater number of drug molecules in the vicinity, more are likely to interact with the receptor.

Question 5

C2- concentration/receptors occupied.

Answer 5

It is simplest to think that drug responses are directly related to the fraction of receptors that are occupied, or bound, by a drug. For example, 50% of the maximum response occurs at a blood level or concentration at which a drug occupies 50% of its receptors. But depending on the number of receptors in a tissue and the ability of drug binding to produce a change in the receptor conformation, far fewer receptors (less than 10%) may be needed to produce a maximum effect.

Question 6

c2 -Types of Drug Responses

Answer 6

There are two basic types of drug responses: quantal and graded. These responses differ in how they are measured and how they dictate dosing decisions to achieve the desired effect.

Question 7

Grades drug responses

Answer 7

Graded responses are biological effects that can be measured continually up to the maximum responding capacity of the biological system (Box 2-2). Most drug responses are graded. For example, changes in blood pressure are measured in millimeters of mercury (mm Hg), and patients may experience small or large changes in blood pressure following treatment with drugs. Graded responses are easier to manage clinically because we can see how each patient responds to a particular dose of medication and, if appropriate, alter the dosage to achieve a greater or lesser response.

Question 8

Drug responses - Quantal

Answer 8

Quantal effects are responses that may or may not occur (Box 2-3). For example, seizures either occur or they do not. The same is true for pregnancy, sleep, and death. If we designate a response as either occurring or absent, it is a quantal response. Prediction of drug dosages or blood levels that produce quantal effects is much more reliable for a population of patients than for an individual patient.

Question 9

grades responses

Answer 9

• Blood pressure
• Heart rate
• Diuresis
• Bronchodilation
• Forced expiratory volume in 1 second (FEV1) * Pain (scale 1–10)
• Coma score

Question 10

Quantal Responses

Answer 10

Convulsions * Pregnancy
* Rash
* Sleep
* Death

Question 11

dose response curve

Answer 11

Pharmacologists show the relationship between dosage or concentration and drug effect using graphs of the dose–response relationship, or dose–response curve. Graphs of drug responses will show the response on the vertical axis and the concentration or dose on the horizontal axis. And for statistical reasons, because drug dosages extend over a large range, the horizontal axis is logarithmic. This means that the graph covers a larger dosage range and that numbers are distributed along the axis so that moving a certain distance right or left represents multiplying or dividing the dosage or blood level concentration by a fixed amount. Most dosage changes in patients are doubled or halved—a “logarithmic” adjustment.

Question 12

Potency of a drug

Answer 12

Potency is the expression of how much drug is needed to produce a biological response (Fig. 2-1). Potency describes the difference in concentration or dosage of different drugs required to produce a similar effect. Drugs that are more potent require a lower dosage or concentration to produce the same response as a higher dosage or concentration of a less-potent drug. For example, compare doses of nonprescription drugs that relieve headache: 200 mg ibuprofen, 325 mg aspirin, and 50 mg ketoprofen. Because ketoprofen requires the lowest dose, it has the highest potency. Drugs that differ in potency differ in their horizontal position on the dose–response curve.

Question 13

Drug Efficacy

Answer 13

Efficacy expresses the ability of a drug to produce a maximum effect at any dosage. Efficacy is the expression of the maximum effect a drug can produce. For example, consider the treatment of pain. Many drugs will relieve mild pain. No matter how high we increase the dosage, drugs that work well for mild to moderate pain are usually ineffective for treating more severe pain
Drugs with high efficacy can produce greater effects than lower-efficacy drugs.

Question 14

Intrinsic activity

Answer 14

Intrinsic activity is very similar to efficacy in that it represents the ability of a drug to produce a large response. Intrinsic activity, however, is used to describe the ability of a drug to produce a response once it has occupied specific receptors. Some drugs produce the maximum receptor stimulation once they occupy receptors; their response is limited by how many drug molecules occupy receptor sites. Other drugs with lower intrinsic activity can occupy the same number of receptors but will produce a lesser response. Drugs can also occupy receptors and produce no receptor stimulation; they merely block the action of neurotransmitters or other drug

Question 15

Drug selectivity

Answer 15

effect vs side effects , patient dependent
The most reasonable way to express selectivity is as a ratio of the dose or concentration producing the undesired effect to the dose or concentration producing the desired effect. This is the same as determining how many times the therapeutic dosage needs to be increased to produce the undesired effect. A medication that produces the desired response at a dose of one tablet and does not produce undesirable effects unless five tablets are administered has a selectivity ratio of 5. That is not a bad drug. But many drugs produce significant undesired effects at or slightly above the therapeutic dosage.

Question 16

treatment of choice

Answer 16

A medication that has high selectivity and produces only the desired effects clearly would be the treatment of choice. There are problems, however, with consistently expressing selectivity based on desired and undesired effects. Medications often have more than one effect and might be used for any of their effects, so sometimes a particular effect is desired and sometimes it is undesired. Diphenhydramine can be a very beneficial drug that is used as an antipruritic, an antihistamine for allergies, an anticholinergic that dries secretions, and as a sleeping aid that produces drowsiness. Desired and undesired effects can differ for each patient, and if we compare dosages, there are several selectivity ratios.

Question 17

therapeutic index

Answer 17

The therapeutic index is a special ratio describing drug selectivity. It is the ratio of the lethal dose to the therapeutic dose of a drug. There are some limitations to the therapeutic index: It uses death, a very unacceptable adverse effect, and it uses data from animal studies. But the therapeutic index provides a fixed comparison for drug safety. The therapeutic index of drugs on the market is, of course, always greater than 1; a therapeutic index of less than 1 means that the drug kills before it cures. The therapeutic index ranges from 2 for some drugs (cancer chemotherapy, lithium carbonate) to 6,000 for others (penicillin in nonallergic patients).

Question 18

Placebo effect

Answer 18

The placebo effect is a pharmacological effect that is not caused by the active ingredient.
Dose–effect relationships in the real world do not start at zero response; they start at the response associated with the placebo effect. The level of response increases as the dose increases but rarely reaches 100%. Instead, the risk of toxicity will limit the maximum dosage, or another drug will be used if there has not been a satisfactory effect.

Question 19

Brand name

Answer 19

New drugs are patented to protect the innovator company for a period during which only it can manufacture the drug. New drugs are given a generic name that anyone can use to market the drug, but innovator companies will create a brand name that only they can use to market their drug.

Question 20

brand vs generic

Answer 20

Because brand-name and generic preparations contain the same active ingredient, the body treats the two exactly the same. Differences between branded and generic preparations can occur in the inactive ingredients of the tablet or capsule, such as coloring or filler materials.
Generic products are supposed to provide patients with the same dosage as brand-name products. Differences between branded and generic formulations result from variations in the time it takes for the formulations to break apart in the stomach and dissolve before absorption. There are always differences in the speed, or rate, of absorption.

Question 21

receptors-drug response

Answer 21

lmost all drugs act through receptors. Receptors are the large molecules, usually proteins, that interact with and mediate the action of drugs. Receptors are important because they determine the relationship between dose and effect, the selectivity of drugs, and the actions of pharmacological antagonists.

Question 22

receptors

Answer 22

Pharmacologists tend to organize drug activity based on the receptors through which individual drugs act.
Chemical energy from the drug–receptor interaction is used to change the receptor in some way that alters physiological processes to produce cellular changes that result in a measurable response.
Because chemical interactions determine the activity of a drug at a particular receptor type, changes in chemical structure result in changes in pharmacological activity.

Question 23

drug targets

Answer 23

enzymes, ion channels, cell surface receptors, nuclear hormone receptors, transporters, and DNA. In each case, chemical interactions take place between drug and receptor molecules.

Question 24

Ion Channel Receptors

Answer 24

Ion channel receptors transmit signals across the cell membrane by increasing the flow of ions and altering the electrical potential or separation of charged ions across the membrane.
Ion channel receptors can produce responses with rapid onset and short duration.
nicotinic receptors is responsible for muscle contraction.
i.e sodium to enter and potassium to leave the cell

Ion channel receptors include receptors for ACh (nicotinic), gamma- aminobutyric acid (GABA), and excitatory amino acids (glycine, aspartate, glutamate, etc.).

Question 25

types of receptors

Answer 25

ion channel coupled to g-proteins Transmembrane Receptors

Question 26

Receptors Coupled to G Proteins

Answer 26

Several guanine nucleotide regulatory proteins (or G proteins) are present in cell membranes. G proteins share a similar structure in which seven regions of protein span the cell membrane to create a pocket (in which drugs can bind) and end with a receptor “tail” inside the cell ( Activation of receptors then produces intracellular changes in the binding of the G-protein receptor to other proteins that control response through other molecules called second messengers. this receptor superfamily includes a large number of receptors that recognize different drugs and activate or inhibit different second messengers.

Question 27

Transmembrane Receptors

Answer 27

Transmembrane receptors consist of an extracellular hormone-binding domain and an intracellular enzyme domain that phosphorylates the amino acid tyrosine. When an active hormone binds to the extracellular binding site, the receptor conformation changes and two receptors bind to each other, activating the enzyme and sustaining the effect (Fig. 2-5). Different receptors catalyze the phosphorylation of tyrosine residues on various downstream signaling proteins. The protein tyrosine kinase includes receptors for insulin, epidermal growth factor, and platelet-derived growth factor.

Question 28

Intracellular Receptors Regulating Gene Expression

Answer 28

Lipid-soluble hormones can pass through the cell membrane and bind to intracellular receptors. The receptor then moves to the nucleus, where it controls the transcription of genes by binding to specific DNA sequences (Fig. 2-6). Hormone receptors of this type include corticosteroids, mineralocorticoids, sex steroids, vitamin D, and thyroid hormones; these produce more sustained responses.

Question 29

enzymes

Answer 29

Enzymes are biological molecules that encourage specific chemical reactions in the body. For example, the enzyme acetylcholinesterase breaks a chemical bond in ACh to terminate its action and produce acetic acid and choline Antibiotics are frequently inhibitors of enzymes essential for bacteria to remain alive.

Question 30

Drug Action at Receptors

Answer 30

Drugs can do three basic things once they bind to a receptor. Agonists, or full agonists, are drugs that produce receptor stimulation and a conformational change every time they bind.

Question 31

Full agonists

Answer 31

Full agonists do not need all of the available receptors to produce a maximum response. Some agonists can produce their maximum response by binding to less than 10% of the available receptors. The receptors that are left over and not needed for a response are called spare receptors.

Question 32

antagonists

Answer 32

Antagonists are drugs that occupy receptors without stimulating them. Antagonists occupy a receptor site and prevent other molecules, such as agonists, from occupying the same site and producing a response. Antagonists produce no direct response. The response we see following administration of antagonists results from their inhibiting receptor stimulation by agonists. For example, beta blockers such as propranolol and atenolol act as antagonists at the beta-adrenoceptor. he effect of antagonists depends on the background receptor activity that it can block. ntagonists produce a shift in the concentration–effect relationship for agonists acting at that same specific receptor as the antagonist; they make agonists for the same receptor appear less potent. The effect of an antagonist depends on its blood levels and its affinity for the receptor. Most antagonists in clinical use are competitive reversible antagonists, and it is possible to overcome the antagonist effects with higher concentrations of the competing agonist

Question 33

adrenergic activity

Answer 33

Adrenergic nerve activity can raise heart rate, and patients with high heart rates

Question 34

partial agonists

Answer 34

Partial agonists are drugs that have properties between those of full agonists and antagonists. Partial agonists bind to receptors but when they occupy the receptor sites, they stimulate only some of the receptors so they can act as part agonist and part antagonist. This is sometimes called intrinsic activity. Partial agonists would require all of the available receptors to produce their full response, and the maximum response for a partial agonist is less than that for a full agonist. he beta blockers acebutolol, penbutolol, and pindolol are partial agonists. Administration of these drugs can block the effects of adrenergic nerves on heart rate, but partial agonist activity keeps heart rate from falling too low, as might occur following administration of a pure beta-adrenoceptor antagonist. Because the maximum response to partial agonists depends on the number of receptors, an increase in receptor number will increase the response to partial agonists.

Question 35

Disease States and Receptors

Answer 35

Disease states or drug treatment can selectively alter the number of receptors in various tissues throughout the body. For example, hyperthyroidism upregulates, or increases, the number of beta-adrenoceptors, making hyperthyroid patients more likely to have hypertension and a rapid heart rate. Treatment with some agonist drugs can cause the receptors to downregulate, or decrease, in response to receptor stimulation; this can limit the duration over which the drug can be clinically useful. Treatment with some antagonist drugs can cause receptors to upregulate in response to the decrease in receptor stimulation, which can produce rebound effects if the antagonist is abruptly withdrawn.

Question 36

Nonreceptor Mechanisms

Answer 36

Not all drugs act through receptors. General anesthetics, sodium bicarbonate (which neutralizes stomach acid), and chelating agents (which bind to and remove metal ions in the blood) are some examples of drugs with actions are based on their physicochemical properties rather than interaction with receptors.