Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

M2 - Pharm > Block 1 > Flashcards

Block 1 Flashcards

1
Q

pharmacology definition

A

biomedical science concerned w/study of drugs and their effects on life processes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

goal of pharmacology

A

understand mechanisms by which drugs interact w/biologic systems to enable rational use of effective agents in diagnosis & treatment of disease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

2 subdivisions of pharmacology

A
  1. pharmacokinetics
  2. pharmacodynamics
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Pharmacokinetics definition

A

study of actions of body on drug (ADME)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Pharmacodynamics definition

A

Study of actions of drug on body

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

4 domains of pharmacokinetics

A

ADME:

  • Absorption
  • Distribution
  • Metabolism (biotransformation)
  • Excretion
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

dose-response relationship

A

relationship btwn concentration of drug in tissue and magnitude of tissue’s response to drug

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Most drugs produce their effects by

A

bind to protein receptors in target tissues → activate signal transduction cascade

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Toxicology definition

A

study of poisons and organ toxicity; focuses on harmful effects of drugs & mechanisms by which these agents produce pathologic changes, disease, and death

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Pharmacotherapeutics definition

A

medical science concerned with the use of drugs in the treatment of disease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

clinical trials

A

Human studies used to determine efficacy & safety of drug therapy in human subjects

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Pharmacy definition

A

science & profession concerned w/preparation, storage, dispensation, proper use of drug products

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Pharmacognosy definition

A

study of drugs isolated from natural sources, including plants, microbes, animal tissues, and minerals

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Medicinal chemistry definition

A

branch of organic chemistry that specializes in design & chemical synthesis of drugs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Pharmaceutical chemistry / pharmaceutics definition

A

concerned w/formulation & chemical properties of pharmaceutical products, such as tablets, liquid solutions and suspensions, and aerosols

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

drug definition

A

natural product, chemical substance, or pharmaceutical preparation intended for administration to human or animal to diagnose or treat a disease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

types of drugs produced by body

A

hormones, neurotransmitters, or peptides

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

xenobiotic

A

synthetic or natural drug produced outside the body

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

poison

A

a drug that can kill

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

toxin

A

a drug that can kill and is produced by a living organism

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

alkaloid definition

A

contain nitrogen groups and produce an alkaline reaction in aqueous solution

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

alkaloid examples

A

morphine, cocaine, atropine, quinine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Antibiotics

A

drugs targeted to bacteria; isolated from numerous microorganisms, including Penicillium and Streptomyces species

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

structure-activity relationship

A

relationship btwn drug molecule, its target receptor, and resulting pharmacologic activity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

crude drug preparations

A

obtained from natural sources; can be made by drying or pulverizing plant or animal tissue (ex: opium), or extracting substances from a natural product (ex: coffee)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

pure drug compounds

A

isolated from natural sources or synthesized in lab (ex: morphine extract)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

pharmaceutical preparations

A

intended for administration to patients (ex: morphine solution)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

routes of drug administration

A
  • enteral
  • parenteral
  • systemic
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

types of drugs

A

natural, semi-synthetic, or synthetic

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

drugs regulated by

A

the FDA’s Center for Drug Evaluation and Research (CDER) – except biologics

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

CDER

A

FDA entity that regulates drugs (except biologics)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

Prescription drug

A

aka “legend drug;” considered potentially harmful if not used under supervision of licensed health care practitioner

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

biologics

A

complex mixtures that are not easily identified or characterized; incl. vaccines, recombinant therapeutic proteins, and gene therapy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

biologics regulated by

A

FDA’s Center for Biologics Evaluation and Research

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

CBER

A

FDA entity that regulates biologics

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

Controlled or scheduled drug

A

prescription drug whose use and distribution is tightly controlled b/c of abuse potential or risk

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

Classification of controlled drugs

A

Schedules CI, CII, CIII, CIV, and CV

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

Over-the-counter drugs

A

Do not require a prescription but still require FDA drug approval process

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

Behind-the-counter drugs

A

OTC drugs with restricted access (ex: sudafed)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

regulation of dietary supplements

A

FDA’s Center for Food Safety and Applied Nutrition

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

What to consider when Choosing a Drug for Your Patient

A

benefit vs risk

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

STEPS Approach to Evaluating and Comparing Drugs

A
  • S – Safety
  • T – Tolerance
  • E – Efficacy
  • P – Price
  • S – Simplicity
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

medication nonadherence

A

At least 50% of patients do this

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
44
Q

percentage of adults > 65 years old who take more than 5 drugs

A

42%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
45
Q

top 3 therapeutic classes of prescriptions

A
  1. antihypertensives
  2. mental health
  3. pain
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
46
Q

top 3 prescriptions (number prescribed)

A
  1. levothyroxine
  2. acetominophen/hydrocodone
  3. lisinopril
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
47
Q

how many phases of clinical testing

A

4

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
48
Q

Clinical Testing Phase 1

A

safety, PK, dose range, 20-80 subjects

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
49
Q

Clinical Testing Phase 2

A

test hypothesis of effectiveness, controlled trial, 100-300 subjects

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
50
Q

Clinical Testing Phase 3

A

randomized, blinded, placebo controlled trials for specific indications

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
51
Q

Clinical Testing Phase 4

A

post-marketing surveillance

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
52
Q

FDA Drug Development and Approval Process

A
  • Pre-clinical research (animals)
  • Investigational New Drug Application (IND)
  • Phases 1-3 of clinical testing New Drug Application (NDA) filed
  • FDA subcommittee review and approval
  • Phase 4 of clinical testing
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
53
Q

drug patent length

A

20 years; can be extended 5 years but total life of patent cannot go beyond 14 years after NDA approval

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
54
Q

chemical drug name

A

based on chemical structure

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
55
Q

generic drug name

A

public nonproprietary name; United States Adopted Names (USAN); Standards set by US Pharmacopeia (ex: sildenafil citrate)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
56
Q

trade drug name

A

exclusively owned by manufacturer (ex: Viagra)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
57
Q

most common formulation of drugs is for what kind of administration

A

oral

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
58
Q

most common preparations for oral administration

A

tablets and capsules

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
59
Q

benefits of tablets and capsules

A

suitable for mass production; stable and convenient to use; can be formulated to release drug immediately after ingestion or over a period of hours

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
60
Q

Variations in rate and extent of tablet disintegration and drug dissolution can give rise to

A

differences in the oral bioavailability of drugs from different tablet formulations

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
61
Q

drug in tablet must do what to reach circulation

A

dissolve in gastrointestinal fluids

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
62
Q

Enteric coatings

A
  • don’t disintegrate in gastric acid
  • break down in basic pH of intestines
  • protect drugs that would otherwise be destroyed by gastric acid
  • slow release & absorption when large dose given at one time (ex: fluoxetine)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
63
Q

two methods used to extend the release of a drug

A
  1. controlled diffusion
  2. controlled dissolution
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
64
Q

controlled diffusion

A

regulated by a rate-controlling membrane

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
65
Q

controlled dissolution

A

caused by inert polymers that gradually break down in body fluids

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
66
Q

osmotic pressure can be used for

A

sustained release – formulations contain osmotic agent that attracts gastrointestinal fluid at a constant rate, which then forces drug out of tablet thru small laser-drilled hole

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
67
Q

benefits / downsides of solutions and suspensions

A
  • convenient method for administering drugs to pts who can’t easily swallow pills or tablets
  • less convenient than solid dosage b/c liquid must be measured each time dose is given
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
68
Q

sterile solutions and suspensions be administered in these ways

A

parenterally: needle & syringe or IV infusion pump

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
69
Q

Transdermal administration

A
  • drug slowly released for absorption thru skin into circulation
  • most suitable for potent drugs w/lipid solubility (ex: fentanyl patch)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
70
Q

Aerosols

A
  • inhalation thru nose or mouth
  • particularly useful for respiratory disorders b/c of direct delivery
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
71
Q

Nasal sprays

A

type of aerosol used either for drugs that have a localized effect on the nasal mucosa or that are absorbed through the mucosa and exert an effect on another organ (ex: nasal butorphanol for pain)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
72
Q

types of enteral administration

A

sublingual, buccal, oral, rectal

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
73
Q

enteral administration definition

A

drug is absorbed from GI tract

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
74
Q

benefits of sublingual and buccal administration

A
  • enable rapid absorption of certain drugs
  • not affected by first-pass drug metabolism in liver (ex: nitroglycerin; hyosciamine)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
75
Q

oral administration definition

A

medication is swallowed, and drug is absorbed from stomach and small intestine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
76
Q

Per Os (PO)

A

oral administration

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
77
Q

benefits / disadvantages of oral administration

A
  • convenient, relatively safe, most economical
  • absorption can vary widely
  • some drugs inactivated by first-pass metabolism
  • not suitable for pts who are sedated, comatose, or experiencing nausea and vomiting
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
78
Q

benefits / disadvantages of rectal administration

A
  • useful when pts can’t take medications by mouth (nausea, vomiting)
  • can be administered for localized conditions like hemorrhoids
  • undergo relatively little first-pass metabolism
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
79
Q

Parenteral administration definition

A

administration w/needle and syringe or IV infusion pump

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
80
Q

most commonly used parenteral routes

A
  • intravenous
  • intramuscular
  • subcutaneous
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
81
Q

benefits / disadvantages of IV administration

A
  • bypasses absorption
  • greatest reliability and control over dose reaching systemic circulation
  • 100% bioavailability
  • preferred for drugs w/short T1/2
  • good for drugs that have to be carefully calibrated to physiologic response
  • dangerous b/c potential for serious toxicity from rapid administration
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
82
Q

intramuscular and subcutaneous administration suitable for these types of drug preparations

A

solutions and particle suspensions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
83
Q

intramuscular or subcutaneous absorbed faster?

A

intramuscular – greater circulation of blood to muscle

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
84
Q

solutions or suspensions absorbed faster?

A

Solutions are absorbed more rapidly than particle suspensions, so suspensions are often used to extend the duration of action of a drug over many hours or days.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
85
Q

Intrathecal administration

A
  • injection of drug thru thecal covering of spinal cord and into subarachnoid space
  • useful in administering antibiotics that don’t cross blood-brain barrier
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
86
Q

Epidural administration

A

targets analgesics into space above dural membranes of spinal cord

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
87
Q

intraarticular administration

A

parenteral route used for arthritis drugs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
88
Q

intradermal administration

A

parenteral route used for allergy tests

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
89
Q

insufflation / intranasal administration

A

parenteral route used for sinus medications

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
90
Q

transdermal patches

A
  • most use rate-controlling membrane to regulate diffusion
  • drug intended to reach circulation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
91
Q

benefits / disadvantages of transdermal administration

A
  • bypasses first-pass metabolism
  • reliable route for drugs effective at relatively low dosage and highly soluble in lipid membranes
  • controlled release possible
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
92
Q

Topical administration

A
  • application of drugs to the surface of the body to produce a localized effect
  • when applied over inflamed skin, can reach circulation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
93
Q

This route of drug administration is used with potent and lipophilic drugs in patch formulation and avoids first-pass metabolism

A

transdermal

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
94
Q

This route of administration does not have an absorption phase

A

intravenous

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
95
Q

Which parenteral route is used to administer drug suspensions that are slowly absorbed?

A

intramuscular

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
96
Q

An elderly patient has problems remembering to take her medication three times a day. Which one of the drug formulations might be particularly useful in this case?

A

extended-release

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
97
Q

Which form of a drug name is most likely known by patients from exposure to drug advertisements?

A

trade name

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
98
Q

These administration routes bypass first-pass metabolism / the hepatic portal vein

A
  • sublingual
  • buccal
  • rectal
  • transdermal
  • parenteral
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
99
Q

These administration routes bypass GI tract

A
  • intravenous
  • intramuscular
  • subcutaneous
  • transdermal
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
100
Q

mechanisms of absorption

A
  • Passive diffusion
  • Active transport
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
101
Q

passive diffusion

A
  • drug enters cell until intracellular conc = extracellular conc
  • rate depends on drug conc gradient
  • Most drugs absorbed by this method
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
102
Q

Most drugs absorbed by this method

A

passive diffusion

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
103
Q

active transport

A

drugs can enter cells against concentration gradient by linking to transport proteins

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
104
Q

function of Transport Proteins

A

Allow efficient transport of molecules across epithelial membranes in the intestine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
105
Q

OATP

A
  • organic anion transporting proteins
  • transporters that facilitate uptake
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
106
Q

P-glycoprotein (Pgp)

A
  • Efflux transporter that actively removes drugs from epithelial cells and prevents absorption
  • Essential mechanism to prevent toxin absorption
  • Can also lead to chemotherapeutic drug resistance
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
107
Q

essential mechanism to prevent toxin absorption

A

efflux transporters like Pgp

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
108
Q

form of drug that can cross lipid membranes

A

Only non-ionized form

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
109
Q

pKa value of a drug tells you this

A

pH value at which ½ of drug is in ionic form (i.e. ½ ionized & ½ non-ionized)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
110
Q

pKa and diffusion capability of weak acids

A
  • low pKa
  • diffuse across membranes at low pH
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
111
Q

pKa and diffusion capability of weak bases

A
  • high pKa
  • diffuse across membranes at high pH
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
112
Q

gastric acid pH

A

1.4

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
113
Q

plasma pH

A

7.4

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
114
Q

weak acids do what with protons?

A

donate them to form anions (A-)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
115
Q

weak bases do what with protons?

A

accept them to form cations (HB+)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
116
Q

non-ionized form of weak acid protonated or nonprotonated?

A

protonated (HA)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
117
Q

non-ionized form of weak base protonated or nonprotonated?

A

nonprotonated (B + H+)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
118
Q

Henderson-Hasselbach eqn

A
  • used to determine ionized:nonionized ratio
  • log (prot/nonprot) = pKa - pH
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
119
Q

Factors Affecting Oral Absorption

A
  • dosage formulations (coatings, controlled-release designs)
  • blood flow
  • gastric motility
  • first-pass effect
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
120
Q

Bioavailability (F)

A

fraction of drug that actually enters the systemic circulation in active form

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
121
Q

bioavailability = 100% for this kind of administration

A

parenteral

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
122
Q

First pass effect

A

drugs absorbed from GI tract are metabolized by liver before reaching systemic circulation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
123
Q

Drugs subject to first-pass effect have this kind of extraction rate and bioavailability

A
  • high hepatic extraction ratios
  • low oral bioavailability
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
124
Q

examples of drugs w/high (hepatic) extraction ratios

A
  • oral propanalol
  • morphine
  • meperidine
  • nitroglycerin
  • verapamil
  • lidocaine
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
125
Q

Factors Affecting Drug Distribution

A
  • Organ blood flow
  • plasma protein binding
  • lipid solubility
  • molecular size
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
126
Q

highly perfused organs that get faster drug distribution

A
  • Liver
  • kidney
  • heart
  • lungs
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
127
Q

less-perfused organs that get slower drug distribution

A
  • Skin
  • fat
  • bone
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
128
Q

drug bound to albumin is active or inactive?

A

inactive – only free drug is active and able to cross cell membranes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
129
Q

Lipid-soluble drugs distribute to a greater or lesser extent than polar and ionized molecules?

A

lipid-soluble have higher volume of distribution (Vd) and cross BBB

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
130
Q

apparent volume of distribution (Vd)

A

volume of fluid in which a drug would need to be dissolved to have the same concentration as in plasma

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
131
Q

can amount of drug in the body be directly measured?

A

no – usually measure the conc of drug in plasma

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
132
Q

Plasma concentration of drug depends on

A
  • dose of drug
  • extent of distribution into tissues
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
133
Q

Vd

A

Vd (L) = [amount in body or dose administered (mg)] / [plasma drug concentration after administration (mg/L)]

L = mg / (mg/L)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
134
Q

Plasma volume for 70 kg Individual

A
  • 2.8 L
  • 0.04 L/kg
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
135
Q

Extracellular fluid volume for 70 kg Individual

A

(ECF = Plasma + interstitial fluid)

  • 17.5 L
  • 0.25 L/kg
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
136
Q

Intracellular fluid volume for 70 kg Individual

A
  • 24.5 L
  • 0.35 L/kg
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
137
Q

Total body water volume for 70 kg Individual

A
  • 42 L
  • 0.6 L/kg
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
138
Q

High Vd indicates…

A

Drug highly distributed into tissues and fat

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
139
Q

Low Vd indicates…

A

Drug primarily in plasma

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
140
Q

Importance of Vd

A
  • Fundamental pharmacokinetic parameter for all drugs
  • Useful for calculating loading dose
  • Essential for determining elimination rate constant and T1/2
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
141
Q

loading dose

A
  • 1st dose of drug
  • necessary to reach therapeutic serum levels quickly for drugs w/long T½
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
142
Q

Calculate digoxin loading dose if

  • T½ = 2 days
  • Steady state plasma concentration desired (Cp) = 1.5 mcg/L
  • Vd = 7.3 L/kg
A
  • Vd = Dose / Cp
  • Dose = Vd x Cp
  • Dose = 7.3 L/kg x 70 kg x 1.5 mcg/L = 766.5 mcg or 0.75 mg
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
143
Q

Vd formula

A

Vd = Dose / Cp

or

Dose = Vd x Cp

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
144
Q

Drug Metabolism

A
  • activate OR inactivate compounds
  • transform compounds into easily excretable metabolites
  • 2 phases
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
145
Q

Drug Metabolism 1o locations

A
  • liver
  • intestinal cell lining
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
146
Q

Phase I of Drug Metabolism

A

Addition of small polar groups to drug structure by oxidation, reduction, or hydrolysis converts lipid-soluble drugs to more polar and water-soluble metabolites (active or inactive)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
147
Q

Phase II of Drug Metabolism

A

Formation of highly water-soluble conjugates to create inactive and easily-eliminated compound

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
148
Q

Cytochrome P450 Enzymes general characteristics & location

A
  • Responsible for most Phase I metabolism reactions
  • in all living organisms
  • primarily in liver, but also in intestine, lung, brain, and placenta
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
149
Q

Cytochrome P450 Enzymes structure

A
  • bound to membranes within a cell (cyto)
  • contain heme pigment (chrome and P)
  • absorb light at 450 nm when exposed to CO
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
150
Q

Cytochrome P450 Enzymes function

A
  • Essential for production of endogenous compounds like cholesterol, steroids, and prostacyclins
  • Necessary for detoxification of exogenous compounds like foreign chemicals and drugs
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
151
Q

Cytochrome P450 Enzyme Family

A
  • Over 50 distinct P450 enzymes in humans
  • Five (1A2, 2C9, 2C19, 2D6, 3A4) metabolize 90% of drugs
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
152
Q

Most drug interactions caused by this

A

changes in Cyt P450 metabolism

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
153
Q

Pro-drug

A
  • needs to be metabolized to become active
  • parent compound usually inactive
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
154
Q

When could pro-drug have little or no clinical effect?

A

when it depends on a P450 enzyme that isn’t functioning b/c:

  • in short supply (poor metabolizer)
  • inhibited by something else
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
155
Q

Examples of pro-drugs

A
  • Hydrocodone → hydromorphone (pain relief)
  • Tramadol (Ultram) → metabolite 33x more active (pain relief)
  • Enalapril → enalaprilat (HTN)
  • Vyvanse (lisdexamfetamine) → dextroamphetamine in gut (prevent intravenous abuse)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
156
Q

Examples of Active Metabolites of Old Drugs Developed as New Drugs

A
  • Zyrtec (cetirizine) from Atarax (hydroxyzine)
  • Allegra (fexofenadine) from Seldane (terfenadine)
  • Clarinex (desloratidine) from Claritin (loratidine)
  • Invega (paliperidone) from Risperdal (risperidone)
  • Pristiq (desvenlafaxine) from Effexor (venlafaxine)
  • Trilipix (fenofibric acid) from fenofibrate
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
157
Q

Biliary excretion

A
  • Conjugated drug metabolites and large molecular weight compounds
  • Drug may be reabsorbed by enterohepatic cycling
  • requires active center
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
158
Q

Renal excretion

A

Most drugs eliminated this way, either as parent compound or as inactive metabolite formed in liver

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
159
Q

Most drugs eliminated this way

A

renal excretion

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
160
Q

Glomerular filtration depends on

A

extent of protein binding

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
161
Q

3 methods of renal excretion

A
  1. Glomerular filtration
  2. Active tubular secretion
  3. Passive tubular reabsorption
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
162
Q

Passive tubular reabsorption depends on

A
  • lipid solubility
  • ionization
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
163
Q

Clearance (Cl) definition

A
  • Volume of plasma from which drug is eliminated per unit time (L/hr or ml/min)
  • Summation of clearance of drug metabolized by liver and excreted by kidney
  • Does not indicate how much drug is removed
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
164
Q

Clearance calculation

A

Elimination rate (mg/hr) = Clearance [Cl] (L/hr) x Plasma conc [Css] (mg/L)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
165
Q

Creatinine Clearance (ClCr)

A
  • allows estimation of GFR
  • need accurate estimate of renal function to dose drugs eliminated by kidney
  • most dosage adjustments for renally excreted drugs based on estimate of ClCr
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
166
Q

Creatinine

A
  • metabolic byproduct of muscle
  • constant rate of formation
  • elimination almost exclusively by GFR
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
167
Q

Formula name for estimating Creatinine Clearance

A
  • Cockroft and Gault formula widely used
  • Need to know sex, age, ideal body weight, and Scr
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
168
Q

Cockroft and Gault formula

A
  • ClCr = [(140 - age) x IBW in kg] / (Scr in mg/dl x 72)
  • multiply ClCr by 0.85 for women
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
169
Q

Zero-Order Elimination

A
  • aka capacity-limited or nonlinear elimination
  • Elimination rate constant and independent of plasma concentration
  • Cl inversely proportional to drug concentration (toxic levels can be reached quickly)
  • Very few drugs eliminated by this method
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
170
Q

Drugs eliminated by Zero-Order Elimination

A
  • phenytoin (Dilantin)
  • aspirin at high doses
  • ethanol
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
171
Q

First-Order Elimination

A
  • At normal doses, rate of drug elimination is proportional to plasma drug concentration
  • if drug concentration increases, so does clearance
  • most drugs eliminated by this method
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
172
Q

most drugs eliminated by this method

A

First Order Elimination

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
173
Q

Elimination Rate Constant (Ke)

A
  • a fraction of drug eliminated over a set period of time
  • ex: Ke = 0.25/hr → 25% of drug remaining in body is removed each hour
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
174
Q

Calculating Ke

A

Ke = Cl (L/hr) / Vd (L)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
175
Q

Mathematical Relationship btwn K and T½

A

T½ = 0.693 / k

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
176
Q

Relationship btwn Ke and Half-Life

A

T½ = 0.7 / Ke

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
177
Q

Relationship btwn Vd, Cl, and Half-Life

A

T½ = 0.7Vd / Cl

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
178
Q

Steady state

A

drug administration rate = elimination rate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
179
Q

time it takes for a drug to reach steady state is dependent on…

A

T½ of drug

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
180
Q

It takes about how many half-lives to reach steady state after starting drug (no loading dose)?

A

5

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
181
Q

It takes about how many half-lives for elimination of drug after last dose?

A

5

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
182
Q

Therapeutic Drug Monitoring

A
  • Usually for drugs with narrow therapeutic index
  • Drug needs to be at steady state, otherwise lab result may lead to dosage error
  • Depending on drug, may need peak level, trough level, or both
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
183
Q

Examples of Drugs Requiring Therapeutic Monitoring

A
  • Aminoglycoside antibiotics (Gentamicin, tobramycin, amikacin)
  • Clozapine (atypical antipsychotic)
  • Digoxin (antiarrhythmic)
  • Theophylline (bronchodilator)
  • Vancomycin (antibiotic)
  • Warfarin (anticoagulant)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
184
Q

Summarize the 5 important pharmacokinetic equations

A
  • Vd (L) = Drug in body (mg) / Plasma drug concentration or Cp (mg/L)
  • Loading Dose (mg) = Vd x Cp
  • Ke = Cl (L/hr) / Vd (L)
  • T½ = 0.7 / Ke
  • T½ = 0.7Vd / Cl
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
185
Q

what protein can lead to chemotherapeutic drug resistance

A

Pgp

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
186
Q

examples of Pgp inhibitors

A

amiodarone, erythromycin, propranolol

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
187
Q

acidic drugs generally bind to what in plasma?

A

albumin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
188
Q

basic drugs generally bind to what in plasma?

A

glycoproteins and β-globulins

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
189
Q

conjugation

A
  • attachment of polar groups
  • often allows for faster excretion
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
190
Q

microsomal P450 monooxygenase reaction requires what?

A
  • CYP (a hemoprotein)
  • NADPH-dependent CYP reductase
  • membrane lipids in which the system is embedded
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
191
Q

Most drug biotransformation is catalyzed by which three CYP families?

A
  • CYP1
  • CYP2
  • CYP3
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
192
Q

which CYP subfamily catalyzes more than half of all microsomal drug oxidations?

A

CYP3A

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
193
Q

polymorphism

A

individual variation in the genes coding for drug-metabolizing enzymes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
194
Q

examples of polymorphisms that affect drug metabolism

A
  • SA phenotype:
    • slow acetylators – reach toxicity of certain drugs faster
  • CYP2D6 and CYP2C19 differences:
    • altered enzymatic rxn rates (codeine; omeprazole)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
195
Q

enterohepatic cycling

A
  • drug excreted in bile
  • bile empties into intestines
  • fraction of drug may be reabsorbed into circulation and eventually return to liver
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
196
Q

biliary excretion eliminates substances from the body only to the extent that…

A

some of the excreted drug is not reabsorbed from the intestine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
197
Q

one-compartment model

A

drug undergoes absorption into blood according to rate constant Ka, and elimination from blood with rate constant Ke

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
198
Q

two-compartment model

A

drugs are absorbed into central compartment (blood), distributed from central compartment to peripheral compartment (the tissues), and eliminated back from central compartment

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
199
Q

how to accelerate rate of excretion of weak acid?

A
  • alkalinize urine via NaHCO3 administration
  • particularly useful for
    • aspirin overdose
    • salicylate overdose
    • phenobarbital overdose
    • 2,4-dichlorophenoxyacetic acid (herbicide) poisoning
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
200
Q

how to accelerate rate of excretion of weak base?

A
  • acidify urine
  • has been largely abandoned b/c does not significantly increase elimination of these drugs and poses serious risk of metabolic acidosis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
201
Q

when is manipulation of the urine pH worthwhile for accelerated excretion?

A

when drug is excreted to a large degree by kidneys

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
202
Q

Parameters of plasma drug concentration curve

A
  • maximum concentration (Cmax)
  • time needed to reach maximum (Tmax)
  • minimum effective concentration (MEC)
  • duration of action
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
203
Q

area under the curve (AUC)

A

measure of total amount of drug during time course

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
204
Q

formula to determine oral bioavailability of a particular drug

A

dividing the AUC of an orally administered dose of the drug (AUCoral) by the AUC of an IV-administered dose of the same drug (AUCIV)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
205
Q

Pharmaceutical factors that can affect bioavailability

A
  • rate and extent of tablet disintegration
  • drug dissolution
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
206
Q

Biologic factors that can affect bioavailability

A
  • food, which can sequester or inactivate a drug
  • gastric acid, which can inactivate a drug
  • gut and liver enzymes, which can metabolize a drug during absorption and first pass through the liver
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
207
Q

indication that drug has reached intracellular fluid?

A

Vd = total body water

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
208
Q

drugs w/renal clearance close to ClCr…

A

eliminated primarily by glomerular filtration, w/little tubular secretion or reabsorption

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
209
Q

drugs w/renal clearance higher than ClCr…

A

undergo tubular secretion

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
210
Q

drugs w/renal clearance lower than ClCr…

A

are highly bound to plasma proteins or undergo passive reabsorption from renal tubules

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
211
Q

hepatic clearance

A

usually determined by multiplying hepatic blood flow by arteriovenous drug concentration difference

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
212
Q

why is hepatic clearance difficult to determine?

A

hepatic drug elimination includes biotransformation and biliary excretion of parent compounds

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
213
Q

What does graph of first-order kinetics look like?

A
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
214
Q

Compare graphs of first-order and zero-order kinetics

A
215
Q

What does graph of Vd look like?

A
216
Q

How is plasma concentration affected by intermittent vs continuous administration?

A
  • intermittent will accumulate to a steady state at the same rate as a drug given continuously
  • but the plasma concentration will fluctuate as each dose is absorbed and eliminated
217
Q

maintenance dose

A

given to establish or maintain the desired steady-state plasma drug concentration

218
Q

what does graph of drug accumulation to steady state look like?

A
219
Q

In first-order kinetics, a drug’s half-life and clearance are constant as long as…

A

physiologic elimination processes are constant

220
Q

What does the graph of steady-state plasma drug concentration and dosage look like?

A
221
Q

What does the graph of steady-state plasma drug concentration and half-life look like?

A
222
Q

What does the graph of steady-state plasma drug concentration and intermittent vs continuous infusion look like?

A
223
Q

What does the graph of steady-state plasma drug concentrations after intermittent oral administration (affected by the rates of drug absorption, distribution, and elimination) look like?

A
224
Q

If food decreases the rate but not the extent of the absorption of a particular drug from the GI tract, then taking the drug with food will result in a smaller…

A

maximal plasma drug concentration

225
Q

If a drug exhibits first-order elimination, then the rate of elimination is proportional to…

A

the plasma drug concentration

226
Q

After a person ingests an overdose of an opioid analgesic, the plasma drug concentration is found to be 32 mg/L. How long will it take to reach a safe plasma concentration of 2 mg/L if the drug’s half-life is 6 hours?

A

24 hours. The half-life is the time required to reduce the plasma drug concentration 50%. In this case, it will take four drug half-lives, or 24 hours, to reduce the plasma level from 32 to 2 mg/L.

227
Q

What dose of a drug should be injected intravenously every 8 hours to obtain an average steady-state plasma drug concentration of 5 mg/L if the drug’s volume of distribution is 30 L and its clearance is 8 L/hr?

A

320 mg. The dose required to establish a target plasma drug concentration is calculated by multiplying the clearance by the target concentration and dosage interval. In this case, it is 5 mg/L × 8 L/hr × 8 hr = 320 mg.

228
Q

If a drug is is more ionized inside cells than in plasma, then its Vd will be…

A

greater.

When a drug is more ionized inside cells, the drug becomes sequestered in the cells and the Vd can become quite large. This is called ion trapping.

229
Q

ion trapping

A

When a drug is more ionized inside cells, the drug becomes sequestered in the cells and the volume of distribution can become quite large.

230
Q

Hierarchy of Evidence

A
  1. Randomized, double-blind, controlled studies (meta-analysis, Cochrane review)
  2. Randomized, controlled studies
  3. Cohort studies
  4. Case control studies
  5. Case series
  6. Case reports
  7. Ideas, editorials, opinions
  8. Animal research
  9. In vitro research
231
Q

Relative risk reduction (RRR) equation

A

RRR = (CER - EER) / CER

232
Q

Absolute risk reduction (ARR) equation

A

ARR = CER - EER

233
Q

Numbers needed to treat (NNT) equation

A

NNT = 100 / ARR

or NNT = 100 / (CER - EER)

234
Q

Numbers needed to harm (NNH) equation

A

NNH = 100 / ARI

or NNH = 100 / (EER - CER)

235
Q

Number needed to harm (NNH) definition

A

tells number of pts that must be treated for 1 to have a serious adverse rxn

236
Q

Numbers needed to treat (NNT) definition

A

A NNT of 20 means that you would need to treat 20 patients with drug M to prevent a migraine from recurring in 1 patient.

237
Q

Absolute risk increase (ARI) equation

A

ARI = (EER - CER)

238
Q

The CLASS Study

A

Study on GI Toxicity of Celecoxib vs NSAIDs

239
Q

the VIGOR Study

A

Study on GI Toxicity of Rofecoxib vs Naproxen

240
Q

benefits & drawbacks for RRR

A
  • Cannot discriminate large risks and benefits from small ones
  • Useful for marketing purposes
241
Q

benefits & drawbacks for NNT

A
  • Can estimate degree of benefit or risk
  • Easy method to use
  • Significant # depends on outcome, alternative treatments, risk, and cost
242
Q

P value

A
  • probability that observed result is due to chance
  • Usually findings are “statistically significant” if P < 5% (P<0.05)
243
Q

Confidence Interval (CI)

A
  • range of plausible results (precision)
  • Usually reported as 95% CI (range of true result in 95% of studies if repeated many times)
  • If 95% CI includes no difference between study groups, then P > 0.05
244
Q

Schedule I Controlled Drugs

A

have no currently accepted medical use in the United States, a lack of accepted safety for use under medical supervision, and a high potential for abuse.

245
Q

Examples of Schedule I Controlled Drugs

A

heroin, LSD, marijuana, peyote, methaqualone

246
Q

Schedule II Controlled Drugs

A

high potential for abuse which may lead to severe psychological or physical dependence

247
Q

Examples of Schedule II Controlled Drugs

A

hydromorphone, methadone, meperidine, oxycodone, fentanyl, morphine, opium, codeine

248
Q

Schedule III Controlled Drugs

A

potential for abuse less than substances in Schedules I or II and abuse may lead to moderate or low physical dependence or high psychological dependence

249
Q

Examples of Schedule III Controlled Drugs

A

Vicodin, Tylenol with Codeine

250
Q

Schedule IV Controlled Drugs

A

low potential for abuse relative to substances in Schedule III

251
Q

Examples of Schedule IV Controlled Drugs

A

alprazolam, carisoprodol, clonazepam, clorazepate, diazepam, lorazepam, midazolam, temazepam, and triazolam.

252
Q

Schedule V Controlled Drugs

A

low potential for abuse relative to substances listed in Schedule IV and consist primarily of preparations containing limited quantities of certain narcotics.

253
Q

Examples of Schedule V Controlled Drugs

A

cough preparations containing not more than 200 milligrams of codeine per 100 milliliters or per 100 grams (Robitussin AC®, Phenergan with Codeine®), and ezogabine

254
Q

Pt overdoses on adderall (amphetamine, weak base w/pKa 9.9). How do you minimize further GI absorption and enhance urinary excretion?

A

Acidify GI tract and urine

255
Q

2 types of drug action

A
  • receptor-mediated
  • non-receptor-mediated
256
Q

Receptors definition

A

Cell molecules, usually proteins, that initiate a series of biochemical events resulting in a physiological response when stimulated by an agonist

257
Q

Affinity

A

tendency of a drug to bind to a receptor

258
Q

Efficacy

A

ability of a drug to initiate effect by activating receptor once bound

259
Q

Agonist

A
  • Drug w/receptor affinity and efficacy
  • Can be full (maximal response) or partial (submaximal response)
260
Q

Antagonist

A
  • Drugs w/receptor affinity but no efficacy
  • Can be competitive (reversible) or non-competitive (irreversible)
261
Q

5 major transmembrane signaling mechanisms to bypass lipid membrane barrier

A
  1. Intracellular receptors for lipid soluble drugs
  2. Transmembrane enzyme receptors
  3. Transmembrane cytokine receptors
  4. Ligand-gated ion channels
  5. G Proteins and second messengers
262
Q

Intracellular receptors

A
  • MOA for lipid soluble drugs (steroid hormones, thyroid hormone, vitamin D)
  • Receptors on nucleus stimulate gene transcription via diffusion thru cell membrane
263
Q

Signaling MOA for steroid hormones, thyroid hormone, vitamin D

A

Intracellular receptors

264
Q

Transmembrane enzyme receptors

A
  • MOA of insulin & growth factors
  • Usually a tyrosine kinase that phosphorylates upon activation
265
Q

Signaling MOA of insulin

A

Transmembrane TK receptor

266
Q

Transmembrane cytokine receptors

A
  • MOA for regulators of growth and differentiation (growth hormone, erythropoetin, interferon)
  • Activate Janus-kinase enzymes which phosphorylate STAT molecules
267
Q

Signaling MOA for regulators of growth and differentiation

A

Transmembrane Janus-STAT cytokine receptors

268
Q

Ligand-gated ion channels

A
  • MOA of many drugs that mimic the action of natural NTs (Ach, 5-HT, GABA, glutamate)
  • Regulate ion flow thru channel by changing transmembrane electrical potential
269
Q

Signaling MOA of drugs that mimic NTs

A

Ligand-gated ion channels

270
Q

G Proteins and second messengers

A
  • MOA for many drugs, including sympathomimetics
  • Variety of G-protein subtypes determine 2nd messenger response
  • 3 separate components:
    • Serpentine cell-surface receptor
    • G protein on cytoplasmic side of membrane changes enzyme or ion channel activity
    • 2nd messenger (cAMP, PLC)
271
Q

3 components of G protein-second messenger signaling

A
  1. Serpentine cell-surface receptor
  2. G protein on cytoplasmic side of membrane that changes enzyme or ion channel activity
  3. 2nd messenger (cAMP, PLC)
272
Q

Signaling MOA for sympathomimetic drugs

A

G Proteins and second messengers

273
Q

What do intracellular signals look like?

A
274
Q

what does extracellular signaling look like?

A
275
Q

what does tyrosine kinase signaling look like?

A
276
Q

what does ion channel signaling look like?

A
277
Q

what does G protein signaling look like?

A
278
Q

Gs receptor for

A

ß-adrenergic amines, glucagon, histamine, serotonin, other hormones

279
Q

Gs signaling pathway

A

INcrease in ­Adenylyl Cyclase → INcrease in cAMP

280
Q

Gi receptor for

A

a2-adrenergic amines, muscarinic Ach, opioids, serotonin

281
Q

Gi signaling pathway

A

DEcrease in ­Adenylyl Cyclase → DEcrease in cAMP → open cardiac K+ channels → decrease in HR

282
Q

Golf receptor for

A

odorants (olfactory epithelium)

283
Q

Golf signaling pathway

A

INcrease in ­Adenylyl Cyclase → INcrease in cAMP

284
Q

Gq receptor for

A

muscarinic Ach, bombesin, serotonin

285
Q

Gq signaling pathway

A

Increase in PLC → Increase in IP3, DAG → increase in cytoplasmic Ca2+

286
Q

Gt receptor for

A

photons (rhodopsin & color opsins in retina)

287
Q

Gt signaling pathway

A

INcrease in cGMP phosphodiesterase → DEcrease in cGMP (phototransduction)

288
Q

4 Types of Drug AGonists

A
  1. Agonists of cell surface receptors
  2. Nuclear receptor agonists
  3. Enzyme activators
  4. Ion channel openers
289
Q

Examples of cell surface receptor agonists

A
  • Alpha-receptor agonists – epinephrine
  • Beta-receptor agonists – albuterol inhaler
  • Opioid analgesics – morphine and hydrocodone
  • NT agonists – levodopa for Parkinson’s
290
Q

Examples of Nuclear receptor agonists

A
  • Estrogens
  • Corticosteroids – prednisone
291
Q

Examples of enzyme activators

A

nitroglycerin

292
Q

Examples of ion channel openers

A
  • ethanol
  • benzodiazepines
293
Q

5 Types of Drug ANTagonists

A
  1. Antagonists of cell surface receptors
  2. Antagonists of nuclear receptors
  3. Enzyme inhibitors
  4. Ion channel blockers
  5. Neurotransmitter inhibitors
294
Q

Examples of cell surface receptor ANTagaonists

A

Beta-receptor antagonists (β-blockers) – atenolol

295
Q

Examples of nuclear receptor ANTagaonists

A

Estrogen receptor antagonists – tamoxifen for breast cancer

296
Q

Examples of enzyme inhibitors

A
  • ACE inhibitors for hypertension and heart failure
  • HMG-CoA Reductase inhibitors (statins) for hypercholesterolemia (remember: HMG-CoA reductase catalyzes a rxn early in the cholesterol synthesis pathway)
297
Q

Examples of ion channel blockers

A

Ca2+-channel blockers for hypertension and angina

298
Q

Examples of NT inhibitors

A

Selective serotonin reuptake inhibitors (SSRIs) for depression

299
Q

8 Types of Non-Receptor-Mediated Drug Mechanisms

A
  1. Enzyme action
  2. Chemical reaction
  3. Binding free molecules
  4. Nutrient supplementation
  5. Physical reactions
  6. Antigens
  7. Vaccines
  8. Antibiotics
300
Q

Equation for determining drug level at any time after administration

A

Cp = (Cp0)(e-<strong>ke</strong>t)

  • Cp = plasma conc at time t
  • Cp0 = initial plasma conc
301
Q

example of enzyme action drug mechanism

A

Streptokinase for thrombolysis after acute MI

302
Q

example of chemical reaction drug mechanism

A

antacids

303
Q

examples of binding free molecules drug mechanism

A
  • Drugs for heavy metal poisoning
  • monoclonal antibodies
304
Q

example of nutrient & supplementation drug mechanism

A

vitamins & minerals

305
Q

example of physical reaction drug mechanism

A

osmotic laxatives

306
Q

example of antigen drug mechanism

A

vaccines

307
Q

Potency

A

concentration of drug required to produce a particular effect

308
Q

Median effective dose (ED50)

A

Dose that produces 50% of maximal response

309
Q

Median lethal dose (LD50)

A

Dose that causes death in 50% of subjects

310
Q

Therapeutic Index (TI)

A
  • Ratio of LD50 to ED50
  • higher TI = safer drug
311
Q

A safer drug has a high or low TI?

A

High

312
Q

Dose-Response Relationship

A

Relationship btwn concentration of drug at receptor site and magnitude of response

313
Q

Graded dose-response curve

A

Tracks percent of maximum response vs dose

314
Q

Quantal dose-response curve

A

Tracks percent of subjects with response vs dose

315
Q

what does a graded dose-response graph look like?

A
316
Q

In this graded dose-response curve, which drugs are full agonists?

A

R and S

317
Q

In this graded dose-response curve, which drugs are partial agonists?

A

T

318
Q

For this graded dose-response curve, rank the drugs in order of potency.

A

R > S > T

319
Q

In this graded dose-response curve, what do X, Y, and Z represent?

A

X = agonist

Y = agonist w/competitive antagonist

Z = agonist w/noncompetitive antagonist

320
Q

In this graded dose-response curve, which letter represents agonist alone?

A

X

321
Q

In this graded dose-response curve, which letter represents agonist in presence of competitive antagonist?

A

Y

322
Q

In this graded dose-response curve, which letter represents agonist in presence of noncompetitive antagonist?

A

Z

323
Q

What does a quantal dose-response graph look like?

A
324
Q

What does another kind of quantal dose-response graph look like?

A
325
Q

What does TI look like on a graph?

A
326
Q

Tolerance

A

Same dose of drug given repeatedly loses its effect → Greater doses needed to provide previously obtained effect

327
Q

Tachyphylaxis

A

Acute tolerance – decrease in response after single exposure

Ex: Oxymetazolone (Afrin) for nasal congestion; ethanol

328
Q

Pharmacodynamic tolerance

A

downregulation of receptors (decreased synthesis)

ex: morphine

329
Q

Pharmacokinetic tolerance

A
  • *up**regulation of metabolic enzymes (increased synthesis)
    ex: Carbamazepine for seizure control
330
Q

2 types of enantiomer designations

A
  1. dextro- or levo- (rotation of polarized light R or L)
  2. rectus- or sinister- (molecular config)
331
Q

stereoisomers and enantiomers are

A

non-superimposable mirror images

332
Q

Isomerism effects on drug activity

A

Isomers can have/be:

  • identical efficacy and toxicity, but different potency
  • full pharm activity vs essentially inactive
    • ex: S-warfarin 5x more active than R-warfarin
  • both pharm active, but different therapeutic and toxic effects
  • metabolized by different pathways
    • ex: S-warfarin by CYP2C9 / R-warfarin by CYP1A2 and 3A4
333
Q

Examples of New Drugs Developed from Older Drug Isomer Mixtures

A
  • Escitalopram (Lexapro) for depression: S-isomer of citalopram (Celexa)
  • Levalbuterol (Xopenex) for asthma: R-isomer of albuterol
  • Esomeprazole (Nexium) for GERD/ulcers: S-isomer of omeprazole (Prilosec)
  • Levofloxacin (Levaquin) for bacterial infections: S-isomer of ofloxacin (Floxin)
  • Dexmethylphenidate (Focalin) for ADHD: D-isomer of methylphenidate (Ritalin)
  • Levocetirizine (Xyzal) for allergies: L-isomer of cetirizine (Zyrtec)
  • Dexlansoprazole (Kapidex) for GERD/ulcers: D-isomer of lansoprazole (Prevacid)
334
Q

Factors that can cause variability in drug response

A
  • Behavior (compliance)
  • Body weight
  • Body surface area
  • Age
  • Gender
  • Health status
  • Placebo effect
  • Genetics
335
Q

Pharmacogenetics

A

study of the genetic basis for variation in drug response

336
Q

Pharmacogenomics

A

use of tools to assess multigenic determinants of drug response

337
Q

polymorphic alleles

A

code for various amounts of protein resulting in various phenotypes

338
Q

Genetic variations (alleles) exist for which Cytochrome P450 enzymes?

A
  • 1A2
  • 2C9
  • 2C19
  • 2D6
339
Q

wild type allele

A

most common

340
Q

variant allele

A

usually codes for reduced or no enzyme activity

341
Q

extensive metabolizer

A

normal metabolizer homozygous for wild type allele

342
Q

intermediate metabolizer

A

heterozygous for wild type and variant allele

343
Q

poor metabolizer

A

homozygous for variant alleles

344
Q

ultrarapid metabolizer

A

multiple copies of wild type allele

345
Q

types of adverse drug reactions (ADRs)

A
  • Allergic (hypersensitivity reactions)
  • Toxic
  • Ideosyncratic
  • Alterations of biological or metabolic systems
346
Q

partial agonist

A

produces submaximal response

347
Q

Autonomic

A

“automatic” – regulated by brain stem

348
Q

Somatic

A

voluntary – skeletal muscle innervation activated by motor cortex

349
Q

Primary NTs in autonomic and somatic nervous systems:

A
  • Acetylcholine
  • Norepinephrine
  • Epinephrine – from adrenal gland
350
Q

Steps in Synaptic Transmission

A
  1. NT synthesis
  2. Cell Depolarization
  3. Activation of Ca2+ channel
  4. Fusion of vesicle with membrane, NT release
  5. NT binds to ion channel receptor or G protein-coupled receptors
  6. NT degraded by enzyme
  7. NT Reuptake
  8. Enzyme termination of signal
351
Q

Neurotransmitter Receptors

A

Molecule on neuron or other cell surface that accepts NT and activates a specific response

352
Q

Most autonomic drugs do what?

A

activate or block receptors

353
Q

direct acting drugs

A

activate or block receptors; most autonomic drugs

354
Q

Acetylcholine receptors are

A

cholinergic

355
Q

location of muscarinic Ach receptors

A

neuroeffector junctions

356
Q

location of nicotinic Ach receptors

A

all autonomic ganglia and somatic neuromuscular junctions

357
Q

Norepinephrine and epinephrine receptors are

A

adrenergic

358
Q

types of adrenergic receptors

A

α-adrenergic receptors
β-adrenergic receptors

359
Q

parasympathetic ganglion location relative to target

A

ganglion very close to target

360
Q

sympathetic ganglion location relative to target

A

ganglion far from target

361
Q

preganglionic sympathetic neurons release what NT at what kind of receptor?

A

Ach, nicotinic

362
Q

postganglionic sympathetic neurons release what NT at what kind of receptor?

A

NE or EPI, adrenergic

363
Q

preganglionic parasympathetic neurons release what NT at what kind of receptor?

A

Ach, nicotinic

364
Q

postganglionic parasympathetic neurons release what NT at what kind of receptor?

A

Ach, muscarinic

365
Q

somatic neurons release what NT at what kind of receptor?

A

Ach, nicotinic

366
Q

adrenal gland releases what NT?

A

Epi

367
Q

SNS organization

A
  • Nerves arise from thoracic and lumbar regions of spinal cord
  • Ganglia adjacent to spinal cord
  • Discharges as unit producing diffuse activation of target organs
368
Q

principal post-ganglionic neurotransmitter released by SNS neurons

A

NE

369
Q

SNS produces what kind of response

A

fight or flight

370
Q

PNS organization

A
  • Nerves arise from cranial and sacral region of spinal cord
  • Ganglia in organ systems, not spinal cord
  • Can discretely activate target tissues
371
Q

principal postganglionic neurotransmitter released by PNS neurons

A

Ach

372
Q

PNS produces what response

A

rest and digest (smooth mm contraction)

373
Q

Baroreceptor Reflex

A
  • Stretch receptors in aortic arch and carotid sinus activated with increased arterial pressure
  • brainstem vasomotor center receives impulse
  • Vagal/PNS response causes decreased HR
374
Q

Drugs affecting blood pressure can stimulate what reflex?

A

Baroreceptor – cause reflex bradycardia or reflex tachycardia

375
Q

types & locations of Cholinergic Receptors

A
  • Muscarinic – at neuroeffector junctions
  • Nicotinic – at all autonomic ganglia
376
Q

Types & locations of muscarinic receptors

A
  • M1 – CNS and autonomic ganglia
  • M2 – cardiac muscle
  • M3 – smooth muscle and glandular tissue
  • M4 and M5 – CNS
377
Q

nicotinic receptor actions

A
  • At (all) autonomic ganglia – leads to postganglionic NT release at neuroeffector junctions
  • At somatic neuromuscular junctions leads to skeletal mm contraction
378
Q

examples of Cholinergic Response at Muscarinic Receptors

A
  • Heart SA node - bradycardia
  • Heart AV node - slow conduction
  • blood vessels - vasodilation
  • GI tract - increased tone & secretions, sphincter relaxation
  • Eye iris - miosis
  • Eye ciliary mm - accommodation/contraction
  • urinary bladder - detrusor contraction, sphincter relaxation
  • lungs - bronchoconstriction, increase in secretions
  • exocrine glands - increase in tears, sweat, saliva
379
Q

examples of Cholinergic Response at Nicotinic Receptors

A
  • ganglia - SNS & PNS responses
  • adrenal medulla - EPI & NE release
  • skeletal mm - end plate depolarization
380
Q

Classification of Cholinergic Receptor Agonists

A
  • Direct-acting
  • Indirect-acting
    • Reversible
    • Irreversible
381
Q

Classification of Cholinergic Receptor Antagonists

A
  • muscarinic
  • nicotinic
382
Q

Direct-acting cholinergic receptor agonists

A
  • Directly stimulate cholinergic receptors
    • Choline esters
    • Plant alkaloids
383
Q

Indirect-acting cholinergic receptor agonists

A

Increase Ach at synapse by inhibiting acetylcholinesterase

  • Reversible
  • Irreversible
384
Q

Direct-acting choline esters

A
  • Ach: no therapeutic use
  • Methacholine: muscarinic, longer duration
  • carbachol: predom nicotinic
  • bethanechol: predom muscarinic
385
Q

Ach as direct-acting agent

A
  • choline ester w/no therapeutic use
  • nonselective
  • short duration
386
Q

Methacholine

A
  • direct-acting cholinergic (muscarinic)
  • longer duration
  • asthma stress test
387
Q

Carbachol

A
  • direct-acting cholinergic (nicotinic)
  • topical agent for glaucoma
388
Q

Bethanechol

A
  • direct-acting cholinergic (muscarinic)
  • used to stimulate bladder or GI tract w/o cardiac effects
389
Q

Muscarine

A
  • direct-acting plant alkaloid cholinergic
  • from poisonous mushrooms
390
Q

Nicotine

A
  • direct-acting plant alkaloid cholinergic
  • from tobacco
  • oral, nasal, or transdermal to assist in smoking cessation
391
Q

Pilocarpine

A
  • direct-acting plant alkaloid cholinergic (muscarinic – M1)
  • from small shrub
  • topical agent for glaucoma
  • oral agent for xerostomia (dry mouth)
392
Q

Therapeutic Uses for Direct-Acting Cholinergic Agonists

A

Relatively few primary uses

393
Q

Cevimeline (Evoxac)

A
  • synthetic direct-acting cholinergic agonist for xerostomia and xerophthalmia
  • use after radiation treatment or for pts with Sjögren’s syndrome
394
Q

Primary Open Angle Glaucoma

A
  • Elevated IO pressure due to narrowing of anterior chamber angle and decrease in aqueous humor outflow
  • Can result in irreversible optic nerve damage
395
Q

2 Topical Drug Tx Goals for Primary Open Angle Glaucoma

A
  • Increase aqueous humor outflow

OR

  • Decrease aqueous humor production
396
Q

Drugs to Increase aqueous humor outflow

A
  • Muscarinic receptor agonists
  • Prostaglandin analogs
397
Q

Drugs to Decrease aqueous humor production

A
  • α2-receptor agonists
  • β-receptor antagonists
  • Carbonic anhydrous inhibitors
398
Q

Pilocarpine mechanism in eye

A
  • direct-acting M1 agonist
    • Contracts ciliary muscle
    • Miosis
    • Thickens lens
  • Causes near vision
399
Q

Atropine mechanism in eye

A
  • M1 antagonist
    • Relaxes ciliary muscle
    • Mydriasis
    • Thinner lens
  • Causes far vision
400
Q

Neostigmine

A
  • Reversible Cholinesterase Inhibitor
  • Quaternary amine – poor penetration of CNS
401
Q

Edrophonium (Tensilon)

A
  • Reversible Cholinesterase Inhibitor
  • Neostigmine analog with shorter duration of action
  • Dx Myasthenia Gravis
402
Q

Physostigmine

A
  • Reversible Cholinesterase Inhibitor
  • Alkaloid from alabar bean
  • Tertiary amine – can penetrate CNS
403
Q

Myasthenia gravis

A
  • autoimmune disease
  • antibodies to nicotinic receptors in skeletal mm → severe muscle weakness
  • Dx: Edrophonium
  • Tx: Neostigmine, Pyridostigmine (cholinesterase inhibitors)
404
Q

Rx myasthenia gravis

A

Neostigmine, Pyridostigmine

  • Quaternary amines – do NOT cross BBB
  • Antidote for neuromuscular blockers such as d-tubocurarine

Contraindications:

  • Intestinal or bladder obstruction
  • Asthma
405
Q

Neostigmine & pyridostigmine

A
  • Tx myasthenia gravis
  • Quaternary amines → do not cross BB barrier
  • Antidote for neuromuscular blockers (d-tubocurarine)
  • Contraindications:
    • Intestinal or bladder obstruction
    • Asthma
406
Q

diseases associated w/decreased Ach production in brain

A

Dementia and Alzheimer’s Disease

407
Q

Reversible Cholinesterase Inhibitors for Alzheimer’s Disease

A
  • Donepezil (Aricept) – once daily
  • Galantamine (Rizatidine)
  • Rivastigmine (Exelon)
    • These easily cross BBB
    • Higher doses can cause typical cholinergic adverse effects (GI and bladder fx)
408
Q

Examples of Irreversible cholinesterase inhibitors

A
  • Organophosphates – pesticides, sarin
  • Malathion – Inactivated by hydrolysis in mammals and birds, but not insects
409
Q

Signs & Symptoms of Organophosphate Toxicity

A
  • Muscarinic: bradycardia, hypotension, salivation, sweating, lacrimation, miosis
  • Nicotinic: mm fibrillation, fasciculation, paralysis
  • CNS: confusion, ataxia, coma, respiratory paralysis
410
Q

Organophosphate Toxicity Acronym

A
  • S – salivation
  • L – lacrimation
  • U – urination
  • D – diarrhea
  • G – gastric
  • E - emptying
411
Q

Examples of Muscarinic receptor antagonists

A
  • Belladonna alkaloids
  • Semisynthetic and synthetic antagonists
412
Q

Examples of Nicotinic receptor antagonists

A
  • Ganglionic blocking agents
  • Neuromuscular blocking agents
    • Nondepolarizing
    • Depolarizing
413
Q

Most common of the cholinergic drugs

A
  • Anticholinergic drugs aka muscarinic receptor antagonists
  • Most are competitive antagonists (reversibly bind to same site as Ach)
414
Q

Atropine

A
  • muscarinic antagonist
  • belladonna alkaloid
  • widely distributed
  • T1/2 = 2 hours
  • eye effect > 72 hours
  • blocks M1, M2, and M3
415
Q

Scopolamine

A
  • muscarinic antagonist
  • greater CNS effects than atropine
416
Q

Expected Response to Anticholinergic Agents

A
  • Eye mydriasis, paralysis of accommodation
  • Sweating blocked, increased body temp
  • Drying effect on secretions generally
  • Bronchodilation, reduced secretions
  • Increased HR
  • Decreased GI motility
  • Bladder atonia, urinary retention
417
Q

Atropa belladonna

A
  • Nightshade
  • Source of belladonna alkaloids (atropine)
418
Q

Belladonna Alkaloids

A
  • Atropine (IV)
  • Hyoscyamine: L-isomer of atropine
  • Scopolamine (Transderm Scop)
419
Q

Hyoscyamine complications

A

GI spasms

420
Q

Toxicity profile for belladonna alkaloids

A
  • Dry mouth
  • blurred vision
  • tachycardia
  • palpitations
  • urinary retention
  • delirium
  • hallucinations
421
Q

Relative contraindications for belladonna alkaloids

A
  • Glaucoma
  • prostatic hyperplasia
  • dementia
  • delirium
422
Q

Examples of Synthetic and Semisynthetic Muscarinic Receptor Antagonists

A
  • Ipratropium (Atrovent) and tiotropium (Spiriva): Inhaled agents for asthma and COPD
  • Dicyclomine (Bentyl): For irritable bowel disease
  • Tropicamide (Mydriacyl): Topical agent to facilitate eye exams (short T ½)
  • Benztropine (Cogentin): For drug-induced Parkinsonian (extrapyramidal) symptoms from antagonism of dopamine receptors
423
Q

Drugs used for overactive bladder

A
  • Oxybutinin (Ditropan)
  • Tolterodine (Detrol)
  • Solifenacin (VESIcare)
424
Q

drugs that antagonize muscarinic receptors to some degree, even though this is not their primary mechanism of action

A
  • 1st generation sedating antihistamines – diphenhydramine
  • Antidepressants – amitriptyline
  • Antipsychotics – olanzapine
  • Muscle relaxants – carisoprodol
425
Q

Anticholinergic risk scale examples

A
  • 3 points:
    • Chlorpheniramine
    • Diphenhydramine
  • 2 points:
    • Loratidine
  • 1 point:
    • Carbidopa-levodopa
426
Q

Anticholinergic risk scale

A
  • ranks medications for anticholinergic potential on a 3-point scale
    • 0 – no or low risk
    • 3 – high anticholinergic potential
  • ARS score for a patient is the sum of points for his or her # of medications.
427
Q

Ganglionic blocking agents

A
  • Block nicotinic receptors at ganglia
  • Only useful for research b/c block all autonomic outflow – potential toxicity
428
Q

Neuromuscular blocking agents

A
  • Inhibit neurotransmission at skeletal neuromuscular junction (nicotinic antagonists)
  • Cause mm weakness and paralysis
429
Q

Majority of available nicotinic blocking agents use this mechanism

A

nondepolarizing

  • presynaptically by preventing NT release (Botulinum)
  • postsynaptically by blocking receptor (tubocurarine)
430
Q

Nondepolarizing Neuromuscular Blocking Agents

A
  • Competitive Ach antagonists
  • Highly polar and only given IV or IM
  • Prototypical drug: d-tubocurarine
  • Used for muscle relaxation during surgical procedures
431
Q

d-tubocurarine

A
  • prototypical nondepolarizing Neuromuscular Blocking Agent
  • First isolated from arrow poisons
  • Not used b/c more adverse effects than newer agents
432
Q

nondepolarizing Neuromuscular Blocking Agent mechanism of mm relaxation

A

Competitive Ach anatagonist:

  • first paralyzes small, rapidly moving muscles
  • then paralyzes larger limb mm
  • finally paralyzes mm necessary for breathing
433
Q

Only Depolarizing Neuromuscular Blocking Agent

A

Succinylcholine

434
Q

Succinylcholine

A
  • Only depolarizing Neuromuscular Blocking Agent
  • Binds to nicotinic receptor, causes persistent depolarization → sustained mm paralysis
  • 5-10min duration
  • Commonly used in ER setting
  • No pharmacologic antidote exists
  • Can cause clinically significant hyperkalemia
435
Q

what are the catecholamines?

A
  • Epinephrine
  • Norepinephrine
  • Dopamine
436
Q

what do the catecholamines do?

A

Endogenous adrenergic receptor agonists

437
Q

how are catecholamines metabolized and taken up?

A
  • Rapidly metabolized by:
    • Monoamine oxidase (MAO)
    • Catechol-O-methyltransferase (COMT)
  • Taken up into presynaptic nerves by
    • NET transporter
    • DAT transporter
438
Q

how are catecholamines administered as drugs?

A

Parenterally

  • Inactive by oral route
439
Q

rate-limiting step of catecholamine synthesis

A

tyrosine → DOPA

by tyrosine hydroxylase

440
Q

steps in catecholamine synthesis

A
441
Q

α2 receptor located where in synapse?

A

pre-synaptic

442
Q

α1 receptors location and action

A
  • smooth muscle
  • contraction/vasoconstriction
443
Q

α2 receptors location and action

A
  • mostly SNS postganglionic neurons
  • feedback inhibition of NT release (inhibitory autoreceptor)
  • Clonidine
444
Q

β1 receptors location and action

A
  • Cardiac tissue
  • Increase HR, contraction force, conduction speed
  • (1 heart)
445
Q

what receptor does clonidine act on? stopping suddenly can cause what?

A
  • α2
  • stopping → hypertensive crisis
446
Q

β2 receptors location and action

A
  • lungs
  • bronchodilation
    • be careful giving β2 blockers to asthmatic!
  • also smooth mm relaxation
  • (2 lungs)
447
Q

β3 receptors location and action

A
  • fat cells
  • activation of lipolysis
448
Q

autonomic drug that can be used to help organophosphate poisoning

A

atropine – blocks Ach receptors, which helps b/c organophosphates are Ach-esterase inhibitors (→ increased Ach)

449
Q

D1 receptors location and action

A
  • smooth muscle
  • dilation of renal blood vessels
450
Q

D2 receptors location and action

A
  • nerve endings
  • Modulation of NT release in CNS
451
Q

Adrenergic Receptor Agonist Classification

A
  • Direct-acting
  • Indirect-acting
  • Mixed-acting
452
Q

Adrenergic Receptor Antagonist Classification

A
  • Nonselective α-blockers
  • α1-blockers
  • Nonselective β-blockers
  • β1-blockers
  • α- and β-antagonists
453
Q

sympathomimetic drugs

A

Adrenergic Receptor Agonists

454
Q

Direct-acting adrenergic receptor agonists action

A
  • Bind to and activate adrenergic receptors
  • May be selective or non-selective for α and β receptors
  • Catecholamines & Non-catecholamines
455
Q

duration of action of catecholamines as Direct-acting Adrenergic Receptor agonists

A

short – metabolized rapidly by endogenous enzymes MAO and COMT

456
Q

characteristics of Non-Catecholamines as Direct-acting Adrenergic Receptor agonists

A
  • not metabolized by MAO and COMT
  • can be given orally
  • longer duration of action
457
Q

Indirect-acting Adrenergic Receptor agonist action & mechanism

A

Increase NE concentration at synapse by several different mechanisms

458
Q

Mixed-acting adrenergic receptor agonist action

A

Combination of direc and indirect action

  • bind to receptors
  • increase NE conc at synapse
459
Q

Epinephrine as Adrenergic Drug

A
  • Direct-Acting Nonselective (α + β) Adrenergic Agonist
  • Endogenous catecholamine given IV or SC
  • Low doses: β effects predominate
  • High doses: α1 effects predominate
  • Uses: anaphylactic shock, cardiac arrest, topical vasoconstriction
  • Adverse effects: tremor, palpitations, headache, arrhythmias
460
Q

Norepinephrine as adrenergic drug

A
  • Direct-Acting Nonselective Adrenergic Agonist
  • Endogenous catecholamine given IV
  • Receptor affinity: α1 = α2 ; β1 >> β2
  • Greater peripheral vascular resistance (PVR) than EPI
  • Uses: hypotension
  • Adverse effects: similar to EPI
461
Q

Isoproterenol

A
  • Direct-Acting β-Adrenergic Agonist
  • Synthetic catecholamine given IV
  • Uses: potent vasodilator & inotropic agent
  • Adverse effects: tachycardia, arrhythmias
462
Q

what do the effects of catecholamine drugs on the CV system look like?

A
463
Q

Dobutamine

A
  • β1-agonist
  • Synthetic catecholamine given IV
  • Uses: acute heart failure – potent inotropic agent
  • Adverse effects: HTN, tachycardia
464
Q

diphenhydramine, a 1st-gen sedating antihistamine, can exacerbate what condition?

A

Alzheimer’s / Dementia – b/c has anticholinergic properties and Ach is decreased in these conditions

465
Q

examples of β2-agonists

A
  • Albuterol
  • Levalbuterol (Xopenex)
  • Salmeterol (Serevent)
  • Terbutaline
466
Q

Albuterol

A
  • β2-agonist
  • Inhaled: bronchodilation for asthma and COPD
467
Q

Levalbuterol (Xopenex)

A
  • β2-agonist
  • Inhaled: bronchodilation for asthma and COPD
468
Q

Salmeterol (Serevent)

A
  • β2-agonist
  • Inhaled: bronchodilation for asthma and COPD
469
Q

Terbutaline

A
  • β2-agonist
  • PO – bronchodilation for asthma (but more systemic effects)
  • IV – relaxation of uterus in late pregnancy to delay premature labor
470
Q

Examples of Selective α1-adrenergic agonists

A
  • Phenylephrine
  • Oxymetazoline (Afrin)
471
Q

Phenylephrine

A
  • α1-agonist
  • Vasoconstriction w/increased vascular resistance and BP
  • IV – for hypotension and shock
  • PO – popular OTC decongestant
472
Q

Oxymetazoline (Afrin)

A
  • α1-agonist
  • Nasal decongestant
  • Causes acute rebound congestion (tachyphylaxis) if used for more than several days
473
Q

Examples of Selective α2-adrenergic agonists

A
  • Clonidine
  • α -methyldopa
474
Q

Clonidine

A
  • α2-agonist
  • Centrally-acting anti-HTN agent
  • Also used for attenuating substance withdrawal symptoms
  • Given orally or as transdermal patch
475
Q

α-methyldopa

A
  • α2-agonist
  • Centrally acting anti-HTN
  • Useful during pregnancy
476
Q

Examples of Indirect Acting Adrenergic Agonists

A
  • Amphetamine and methamphetamine
  • Ephedrin
  • Methylphenidate (Ritalin)
  • Cocaine
  • Tyramine
477
Q

Amphetamine and methamphetamine

A
  • Indirect Adrenergic Agonists
  • Stimulate NE & dopamine release
  • Very lipid soluble and easily enter CNS
  • Stimulant effects on mood/alertness, heart
  • Appetite depressant
  • Peripheral vasoconstriction
478
Q

Methylphenidate (Ritalin)

A
  • Indirect-Acting Adrenergic Agonist
  • Amphetamine derivative with similar action
479
Q

Cocaine

A
  • Indirect-Acting Adrenergic Agonist
  • Inhibits NE, dopamine, 5-HT reuptake – blocks NET and DAT transporters (like antidepressants)
  • Peripheral vasocontriction
  • Cardiac stimulant
  • Effects like amphetamine but shorter acting and more intense
  • Also has local anesthetic effects (used in ocular surgery)
480
Q

what does the mechanism of action of amphetamines look like?

A
481
Q

what does the mechanism of action of cocaine look like?

A
482
Q

Tyramine

A
  • Indirect-Acting Adrenergic Agonist
  • Increases NE release
  • Naturally occurring amine found in fermented products (cheese, sausage, beer); red wine, bananas, avocados, canned meats, yeast supplements
  • Levels can increase if foods taken w/MAO inhibitors (used for depression)
  • Can cause hypertensive crisis w/MAO inhibitors
483
Q

Examples of Mixed Acting Adrenergic Agonists

A
  • Dopamine
  • Ephedrine
  • Pseudoephedrine (Sudafed)
484
Q

Dopamine as adrenergic drug

A
  • Mixed-Acting Adrenergic Agonist
  • Endogenous catecholamine given IV
  • Dose-related activation of D, β1 , α1 receptors; NE release
  • Low doses: D receptor → increases renal blood flow
  • Medium dose: D + β1 receptors activated
  • High doses: D + β1 + α1 receptors activated
  • Uses: cardiogenic shock, acute renal failure
  • Adverse effects: similar to NE at high doses
485
Q

Ephedrine

A
  • Mixed-Acting Adrenergic Agonist
  • Natural product found in ma-huang
  • α + β receptor agonist, plus enhances NE release
  • High doses: similar effects to EPI
  • In 2006, sale of ephedrine-containing dietary supplements was prohibited in the US
486
Q

sale of dietary supplements containing what drug is prohibited in the U.S.? what does it do?

A

ephedrine – mixed α + β receptor agonist that also enhances NE release

487
Q

Pseudoephedrine (Sudafed)

A
  • Mixed-Acting Adrenergic Agonist
  • Popular OTC decongestant
    • also 1o ingredient for illegal meth manufacture
    • Most non-restricted OTC brands now contain phenylephrine (PE)
  • Avoid in pts w/HTN or cardiomyopathy
488
Q

Types of Adrenergic Receptor Antagonists

A
  • Nonselective α-blockers
  • Selective α1-blockers
  • Nonselective β-blockers
  • Selective β1-blockers
  • α- + β-adrenergic antagonists
489
Q

Examples of Nonselective α-Blockers

A
  • Phenoxybenzamine
  • Phentolamine
490
Q

Phenoxybenzamine

A
  • Nonselective α-Blocker (α1 > α2)
  • Non-competitive antagonist
  • Irreversible receptor blockade – lasts 4 days
  • Use: catecholamine excess (ex: pheochromocytoma)
  • Adverse effects: postural hypotension, reflex tachycardia
491
Q

Phentolamine

A
  • Nonselective α-Blocker
  • Competitive antagonist
  • Uses:
    • Pheochromocytoma
    • Reversal of ischemia from extravasation or injection of adrenergic agonists (EPI)
  • Adverse effects: same as phenoxybenzamine
492
Q

Examples of Selective α1-Blockers

A
  • Prazosin (prototype drug)
  • Terazosin (Hytrin)
  • Doxazosin (Cardura)
  • Tamsulosin (Flomax)
493
Q

Prazosin; Terazosin (Hytrin); Doxazosin (Cardura)

A
  • α1-Blockers
  • Relax smooth mm in vessels, bladder neck, prostate
  • Uses:
    • BPH
    • 3rd line for HTN (b/c increased morbidity compared to others)
  • Adverse effects:
    • 1st dose syncope – must use small doses and have pt lie down
    • Reflex tachycardia
494
Q

Tamsulosin (Flomax)

A
  • α1-Blocker – specifically prostate α1A receptor
  • Causes less vasodilation than other α1-blockers
  • Use: decreasing urinary obstruction from BPH
  • Little effect on BP at normal doses
495
Q

Examples of Nonselective β-Blockers

A
  • Propranolol
  • Nadolol (Corgard)
  • Timolol
  • Pindolol
496
Q

Propanolol

A
  • prototype nonselective β-Blocker
  • Highest lipid solubility – more CNS penetration
  • High 1st pass effect: oral dose >> IV dose
  • Negative inotropic and chronotropic effect
  • Bronchoconstriction and decreased glycogenolysis
  • Uses: HTN, arrhythmias, angina, migraine headache, essential tremor
  • Adverse effects/cautions: bradycardia, insomnia, heart failure, asthma, diabetes
497
Q

Nadolol (Corgard)

A
  • Nonselective β-Blocker
  • Low lipophilicity - fewer CNS adverse effects than propranolol
  • Renal excretion
  • Long T ½
498
Q

Timolol

A
  • Nonselective β-Blocker
  • Used primarily as topical agent for glaucoma
499
Q

Pindolol

A
  • Nonselective β-Blocker
  • Also partial β-agonist
  • Intrinsic sympathomimetic activity – causes less bradycardia
500
Q

Examples of Selective β1-Blockers

A
  • Metoprolol
  • Atenolol
  • Bisoprolol (Zebeta)
  • Esmolol (IV only)
  • Acebutolol
501
Q

Metoprolol

A
  • Prototype β1-Blocker
    • aka cardioselective β-blocker
    • Selectivity lost w/higher doses!
  • Use: HTN (higher doses), heart failure (lower doses), angina
  • Safer for asthma & diabetes than nonselective β-blockers but still must use caution
  • T ½ = 3 to 8 hrs dep. on CYP 2D6 phenotype
502
Q

Atenolol

A
  • β1-Blocker
  • Low lipophilicity - fewer CNS adverse effects than propranolol
  • Renal excretion
  • Long T ½
503
Q

Bisoprolol (Zebeta)

A
  • β1-Blocker
  • Moderate lipophilicity
504
Q

Esmolol

A
  • β1-Blocker
  • IV only
505
Q

Acebutolol

A
  • β1-Blocker
  • also partial β1-agonist
  • Intrinsic sympathomimetic activity
506
Q

Examples of α- and β-Adrenergic Blockers

A
  • Labetalol
  • Carvedilol (Coreg)
507
Q

Labetalol

A
  • α- and β-Blocker
  • Receptor affinity: β1 = β2 ; α1 > α2
  • More pronounced vasodilation than other β-blockers due to α1 blockade
  • Given IV, PO
  • Same cautions as nonselective β-blockers
  • Useful for rapid BP reduction
508
Q

Carvedilol (Coreg)

A
  • α- and β-Blocker
  • Receptor affinity: β1 = β2 ; α1 > α2
  • More pronounced vasodilation than other β-blockers due to α1 blockade
  • Given IV, PO
  • Same cautions as nonselective β-blockers
  • Useful for heart failure
509
Q

Criteria to consider in Choosing β-Blockers

A
  • Receptor selectivity
    • Note selectivity tends to be lost at higher doses
  • Lipid solubility
    • If too high, can have CNS adverse effects
  • Half-life
    • Determines doses per day
  • Elimination route (renal vs liver)
510
Q

This route of administration has the fastest absorption

A

inhalation

511
Q

narrow therapeutic index means

A

small margin between sub-therapeutic, therapeutic, and toxic drug concentrations

512
Q

Increasing the dose of a particular drug decreases its clearance. What kind of elimination does this drug undergo?

A

Zero-order

513
Q

Increasing the dose of a particular drug increases its clearance. What kind of elimination does this drug undergo?

A

First-order

514
Q

M1 receptor locations

A

CNS and autonomic ganglia

515
Q

M2 receptor locations

A

cardiac muscle

516
Q

M3 receptor locations

A

smooth muscle and glandular tissue

517
Q

M4 and M5 receptor locations

A

CNS

518
Q

Tensilon Test

A

Edrophonium used for Dx Myasthenia Gravis

519
Q

what drug can increase renal blood flow at low doses and what receptor does it work on?

A

Dopamine stimulating D1 receptor

520
Q

which adrenergic agonist could cause reflex bradycardia?

A

NE

521
Q

which adrenergic agonist causes a widening of pulse pressure?

A

EPI – increase in systolic + decrease in diastolic

522
Q

drug safe for Rx HTN in pregnancy

A
  • Methyldopa
  • Labetolol
523
Q

potential side effects of alpha-1 blockers

A
  • 1st dose syncope
  • reflex tachycardia (b/c Rx HTN also)
524
Q

drugs w/variable T1/2 based on CYP 2D6 phenotype

A
  • metoprolol
525
Q

beta-blocker w/highest lipid solubility

A

propanolol

526
Q

contraindications for beta-blockers

A
  • asthma
  • diabetes
527
Q

beta-blocker safer to give to pt w/asthma or diabetes

A

selective beta-1 blockers

528
Q

two mechanisms for treating glaucoma

A
  • increase aqueous humor outflow
  • decrease aqueous humor production
529
Q

types of drugs that increase aqueous humor outflow

A
  • muscarinic agonists
  • prostaglandin analogs
530
Q

types of drugs that decrease aqueous humor production

A
  • alpha-2 agonists
  • beta-blockers
531
Q

describe graph of cardiovascular effects of catecholamines

A
532
Q

Antidote for neuromuscular blockers

A

effects of d-tubocurarine, for example, can be treated with cholinesterase inhibitors like neostigmine and pyridostigmine

533
Q

Atropine Man

A
  • Can’t see (mydriasis, decreased lacrimation, ciliary mm relaxation)
  • Can’t pee (detrusor relaxation, int sphincter contraction)
  • Can’t spit (decreased salivation)
  • Can’t sh*t (decreased GI motility)
  • Toxicity: Hot (decreased sweating) and Delirious

M2 - Pharm (10 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions