Exam 1 Flashcards
1
Q
Schedule I
A
- highest potential for abuse
- NO accepted medical use in US or lacks safety for use in tx in US
- eg) heroin, marijuana
2
Q
Schedule II
A
- high potential for abuse
- HAS a currently accepted medical use
- abuse may lead to severe psychological or physical dependence
- eg opiates (morphine, oxycodone, methadone), amphetamines (ritalin, adderall), cocaine
3
Q
Schedule IV
A
- currently accepted medical use in US
- abuse may lead to limited physical or psychological dependencies relative to III
- benzos
4
Q
Schedule III
A
- less abuse potential than I or II
- accepted medical use
- abuse may lead to moderate/low physical dependence or high psychological dependence
5
Q
Schedule V
A
- low potential for abuse
- some can be sold in limited amounts without rx
6
Q
Where to look for Drug Information
A
lexi-comp, MICROMEDEX, package, URI pharm library
7
Q
Where do drugs come from (4)?
A
-plants/natural products, synthetic, semi-synthetic, human pool
8
Q
Drug Testing Phases (7)
A
- compound discovery/”bench”
- animal phase
- Human phase I, II, III
- FDA approval with patent
- human phase IV (post-marketing phase)
9
Q
Human Phase I
A
- determine effects, safe dosage, pharmacokinetics
- small number (<1 year
10
Q
Human Phase II
A
- assess drugs effectiveness in treating a specific disease/disorder
- limited number (200-300) with target disorder
- 2 years
11
Q
Human phase III
A
- assess safety and effectiveness in larger pt population
- large number (1000-3000)
- double/single blinding, placebo controls
- 3 years
12
Q
Human phase IV (post-marketing phase)
A
- monitor any problems after NDA approval
- general pt population
- indefinite
13
Q
Pharmacotherapeutics
A
-area of pharm that refers to use of specific drugs to prevent, treat, or diagnose a disease
14
Q
Pharmacokinetics
A
-how body deals with drugs in terms of absorption, distribution, metabolism, excretion
15
Q
Pharmacodynamics
A
- what the drug does to the body
- biochemical and physiological effects and mechanism of action
16
Q
Enteral methods
A
-oral, sublingual/buccal, rectal
17
Q
Parenteral methods
A
-inhalation, injection, topical, transdermal
18
Q
Drug Absorption
A
entrance of drug into bloodstream
19
Q
Drug factors affecting absorption (5)
A
-dosage form, drug water solubility, drug lipid solubility, drug particle size, drug concentration
20
Q
Physiologic factors affecting absorption
A
-biologic/cell membranes, body “compartments”, cell membrane phospholipid bilayer
21
Q
Lipid Bilayer
A
- hydrophilic tails, hydrophobic tails
- SMALL, UNCHARGED particles will pass
- small/charged and large/uncharged will not
22
Q
Bioavailability
A
percentage of administered dose that is absorbed into systemic circulation
23
Q
Factors affecting bioavailability (5)
A
- how administered
- where administered
- drug properties
- properties of the environment
- additional barriers
24
Q
ADME
A
Absorption
Distribution
Metabolism
Excretion
25
Distribution
-after drug gains access to bloodstream, it is distributed to the organ/tissues of the body
26
Factors affecting Drug distribution (4)
- tissue permeability
- blood flow
- binding to plasma proteins
- binding to subcellular components
27
BBB
- additional lipid barrier that protects the brain by restricting the passage of electrolytes and similar water soluble substances
- drugs must have a certain degree of lipid solubility to penetrate
28
Most likely to penetrate BBB?
- small, uncharged, lipophilic
| - eg) heroin, alcohol, benzo, meth
29
Plasma protein binding
- plasma proteins (esp albumin) assist in transport of hormones and vitamins
- only the UNBOUND portion of the drug is able to exert pharmacologic activity. remainder will continue to circulate
- 80% of most drugs will bind at some level
30
Blood Flow
- diff parts of body receive diff amounts of blood
| - liver, kidney, heart, and brain have largest blood supply, therefore exposed to largest amount of drug
31
Volume of Distribution (Vd)
- Vd = amount administered / plasma concentration
- not physical volume, refers to size of compartment necessary to account for total amount of the drug in the body if it were present throughout in the same concentration found in plasma
32
Drugs that are activated with metabolism are called ______.
Pro-drugs
33
Kidney prefers ___ , _____ molecules
ionized, water soluble
34
Biotransformation
chemical aleration of drugs and foreign compounds in the body (phase I)
35
DMMS function
takes lipid-soluble drugs and prepares for excretion via renal system
36
First-pass effect
- drugs taken orally are absorbed through GI tract into portal circulation. Drug goes to liver BEFORE body. many drugs are inactivated by liver
- if drug is significantly metabolized, can reduce amount of active drug that reaches circulation
37
enzyme induction
when used repetitively, some drugs may increase enzyme activity. This may lead to faster metabolism of the drug and shorter duration of action (eg barbituates)
38
enzyme inhibition
will slow metabolism of all other drugs metabolized by the enzyme system and increase duration and intensity of drug
39
common pathways of drug excretion
-kidney/renal, liver/hepatic, lungs/pulmonary
40
Clearance (CL)
- ability of the body to remove drug from blood or plasma
- expressed as volume per unit time (eg ml/min)
- amount of drug removed depends on plasma concentration as well as clearance
41
entero-hepatic recirculation
- drug secreted into bile, may go into feces
| - some drugs reabsorbed, process may be repeated
42
periodic measurements of plasma levels can help establish ________ for the drug
therapeutic range
43
plasma half-life (t 1/2)
time required for the plasma concentration of a given drug to fall to 1/2 its original level
-dependent on CL and Vd
44
Why is establishing half-life important?
kidney and liver disease
45
Loading dose
- try to get the person into therapeutic range quickly
- many drugs require loading dose to do this effectively
- a large initial dose of a substance or series of such doses given to rapidly achieve a therapeutic concentration in the body
46
Maintenance Dose
- the amount of drug required to keep a desired mean steady-state concentration in the tissues
- usually drop from loading dose to maintenance dose
47
Median Effective Dose (ED50)
-dose required to produce a specific therapeutic response in 50% of a group of patients
48
Median Lethal Dose (LD50)
-the dose that causes lethality in 50% of a group of animals
49
Therapeutic Index (TI)
TI = LD50/ED50
50
Potency
- measure of strength
| - more potent drug requires lower dose to produce same effect as a higher dose of the second drug
51
Maximal Efficacy
-point at which there is no further increase in response even if dosage continues to be increased
52
Factors that influence drug response
-age, height, weight, gender, body fat, genetics, emotional state, placebo effect, presence of disease, patient compliance
53
Pregnancy and drugs
- fetus is exposed to drugs taken during pregnancy
- placenta is NOT a drug barrier
- harmful drugs = teratogens
54
Passive exposure
-drugs passed from breast milk to infant
55
Difference in Pediatric populations
-thinner skin, less skeletal muscle, higher % body water, lower body fat, higher percentage of unbound drug due to reduced plasma protein levels
56
Physiology of Aging
--decreased CO --> decreased blood flow
-reduced gastric acid secretion, motility, and intestinal absorption
-lean body mass and total body water decrease, % body fat increases
-decreased renal blood flow
-increased bioavailability of oral drugs
= reduced rate of metabolism, increase in duration of drug action
57
SNS origin
T1-L2/3
58
PSNS origin
Midbrain, medulla, sacral spinal cord
59
Autonomic Ganglia
contain synapses between pre- and post-ganglionic neurons
60
ACh
- in ALL autonomic ganglia
| - in effector junction of PSNS
61
ACh synthesized in the _____ from ____ and ____ by _____
in the NEURON from ACETYL CoA and CHOLINE, by CHOLINE ACETYLTRANSFERASE
*one step synthesis, synthesized as needed, choline reabsorbed. not used as a drug
62
ACh broken down in the ____ or ______ by ______
in the GANGLIONIC JUNCTION or NEURO-EFFECTOR JUNCTION by ACETYLCHOLINE ESTERASE
63
NE is the neurotransmitter at _______
NEUROEFFECTOR JUNCTION OF SNS
64
NE belongs to group of endogenous chemicals called ______, which also include ____ and _____
CATECHOLAMINES which include EPINEPHRINE and DOPAMINE
65
NE is re-uptaken by the ______, a process mediated by pre-synaptic _______.
PRE-SYNAPTIC FIBER, mediated by A2 RECEPTORS (receptor gives signal to decrease NE synthesis = feedback inhibitor)
66
Other mechanisms of inactivation of NE (2)
- breakdown by monoamine oxidase (MAO)
| - breakdown by catechol-O-methyltransferase (COMT)
67
M receptors -- location
-at neuro-effector junction of PSNS
68
N receptors -- location (2)
-autonomic ganglia (SNS and PSNS) and neuro-muscular junction
69
A1
arteriolar smooth muscles --> vasoconstriction
70
A2
pre-ganglionic synapse and in CNS
| -activation leads to decrease in SNS flow from CNS (decreased NE production)
71
Parasympathomimetics
mimic effects of PSNS nerve stimulation
72
Direct acting parasympathomimetics
=muscarinic receptor agonists
- stimulation of M receptors at neuro-effector junction with little or no N receptor stimulation
- eg) metacholine, carbachol, bethanchol, pilocarpine
73
Indirect Acting parasympathomimetics
=prolong action of endogenous ACH by inhibiting ACh esterase (prevent breakdown of ACh)
- Carbamates eg) -stigmines
- all are REVERSIBLE inhibtors of esterase -used for same reasons as direct acting, also -- myasthenia gravis, paralytic ileus, dementia (aricept)
74
Irreversible ACh esterase inhibitors
- insecticides, nerve gas
- NO therapeutic use
- intoxication sx increased secretions, tremors, respiratory collapse
- atropine, pralidoxime given to counteract
75
Toxic reactions to muscarinic agonists
- treated with atropine sulfate
| - epinephrine can help overcome cardiovascular or bronchoconstrictor response
76
Parasympatholytics: Muscarinic Receptor Antagonists
- competitive blocking of M receptors at neuro-effector sites on smooth muscle, cardiac muscle, gland cells, and in CNS
- little effect on ACh at N receptors
- given when poisoned by agonists to stimulate heart, bronchodilators
77
M Antagonists - heart
increased heart rate by blocking vagal nerve effects on M2 receptors on SA nodal pacemaker
78
M Antagonists - vessels
- only work with choline esters
| - block vasodilation
79
M Antagonists - respiratory
- induce bronchodilation
| - inhibit secretions of nose, pharynx, and bronchii thus drying mucous membrane of the respiratory tract
80
M Antagonists - GI
- ihibit GI motility and secretions
| - inhibit gastric acis secretion
81
M Antagonists - Urinary
-decrease tone and amplitude of contractions of ureter and bladder
82
M Antagonists - Sweat glands
- inhibition of sweating, skin becomes hot and dry
| - high doses may raise body temp
83
M Antagonists - CNS (atropine and scopolamine)
- only effect if drug crosses BBB
- Atropine at higher doses (>10mg) causes central excitation, leading to restlessness, hallucinations, delerium. followed by CNS depression - drowsiness, anemia, fatigue
- Scopolamine - therapeutic doses case SN depression - drowsiness, anemia, fatigure
84
M Antagonist - eye
mydriasis and cycloplegia
85
M Antagonist - Principal Use
-bronchodilator in COPD, asthma (atrovent)
86
Sympathomimetic Agents
- direct stimulation of adrenergic receptors
| - endogenous ones: NE, E, dopamine
87
E - cardiac
-through B1, stimulates heart
88
E - respiratory
-through B2 - bronchodilate
89
Rapid intravenous injection of E can cause
cerebral hemorrhage from sharp rise in BP
| -also, tremor, palpation, anxiety, restlessness
90
E - therapeutic uses
- rapid relief of hypersensitivity reactions including anaphylaxis
- restore cardiac rhythym in pt with cardiac arrest
91
NE - effects
- more powerful activator of A1 than E, but much weaker activator of B2
- increases BP much more than E (E doesn't affect BP due to balance of A1/B2)
- not useful as bronchodilator
92
A1 major effect
vasoconstriction
93
A2 major effect
decreased SNS activity
94
B1 major effect
stimulate heart
95
B2 major effect
vasodilation, bronchodilation
96
NE -- clinical use
limited, can be used for hypotension
97
Dopamine - effects
- central NT and can act as agonist on its own receptor
- Low doses: D1 receptors in renal, coronary, mesenteric beds can lead to vasodilation
- High doses: stimulates cardiac B2 - stim heart
98
Dopamine - therapeutic uses
- severe CHF
| - dilates renal arteres, increased renal perfusion, increased urine output (= decreased fluid retention)
99
B-Agonists - non selective
- Isopretrenol, Isuprel
- increased cardiac output (contractility, HR) and dilation of muscle and mesenteric arteries
- used in emergencies to stimulate HR in pt with bradycardia or heart block
100
B2 selective Agonists
-asthma
101
B2 selective agonists - short acting
- rapid onset of action (15 min) and short duration (4-6 hours)
- albuterol, terbutaline
102
B2 selective agonists - long acting
-duration up to 12 hours (salmeterol)
103
A1 selective agonists
- nasal decongestants in pt with allergic rhinitis - constriction of blood vessels in nasal tissues
- chronic use bad - lost efficacy, worse sx
104
A2 selective agonists
- clonidine*
| - stimulates a2 receptors in CNS -- decreased CNS sympathetic outflow = tx of HTN
105
Miscellanious Adrenergic Agonists
- dexedrine, ritalin
- CNS stimulant - release NE in CNS
- ADHD
106
Beta-blockers main functions (3) and Alpha-blocker main function (1)
Bblocker -- arrythmia, CHF, HTN
| Ablocker -- HTN
107
A-adrenoceptor blockers
- *Phentolamines and Tolazoline are non-selective reversible a-blockers
- Phentolamine used in short term to control HTN in pts with pheocromocytoma (tumor of adrenal glands)
- Tolazoline used to treat persistent pulmonary HTN in newborns
108
A1 Selective Blockers
- blocking of a1 receptors in vascular smooth muscles of arterioles and veins = decreased peripheral resistance
- less tachycardia than with non-selective a blockers
- caution with hypotension
- Used for treatment of primary systemic hypertension
109
A1 Selective Blockers - adverse effects
- first-dose phenomenon = marked postural hypotension and syncope 60-90 mins after first dose
- because of vasodilating effect, can promote water retention
110
B Blockers - heart
-blocking of B1 leads to slowing of HR and decreased contractility
111
B blockers - pulm
little effect in normal ppl
| -in pt with asthma or COPD, can lead to life-threatening bronchoconstriction
112
B Blockers - peripheral vascular resistance
- blocking of B2 in arteriolar smooth muscle can lead to increase in vascular resistance
- long term effect of B1 blocker in HTN pt with high circulating renin levels is a reduction in peripheral vascular resistance
113
Non-Selective B-blockers
- reversibly block both B1/B2 with no selectivity
| * *Propranolol - angina pectoris, arrthymia, HTN, prevent reinfarction, prevent vascular headache
114
B1 selective blockers
- higher selectivity to B1
| - HTN, CHF, angina, MI
115
B1 selective blockers - adverse effects
- in pt w AV conduction defects, can cause life-threatening bradyarrythmias
- abrupt discontinuation can exacerbate angina, increase risk of MI
116
B2 selective blockers -- adverse effects
-can worsen bronchoconstriction in asthmatic pt
| B1 selective or nonselective produce less bronchoconstriction
