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SIU SOM: CRR > pharmacology > Flashcards

pharmacology Flashcards

1
Q

enteral administration

A

entering the body by alimentary canal

oral, sublingual, buccal, rectal

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2
Q

paretnal administration

A

introduces drugs directly across the bodys barriers and into the systemic circulation or other vascular tissue
intravenous (most direct route), intramuscular, subcutaneous, intrathecal/intraventricular (directly into cerebrospinal fluid or intracranial ventricles), intraperitoneal, intraosseous (into bone marrow),

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3
Q

inhalation adminitration

A

breahting of the drug through the nose and into the bronchi and lungs

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4
Q

intranasal administration

A

aka transmucosal

administration directly into the nose

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5
Q

topical

A

direct application of a drug to the desired point of action (ex. to skin or eye)

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6
Q

transdermal

A

applied directly to the skin to achieve systemic effects

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7
Q

define absorption

A

movement of a molecule from its site of administration to the blood

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8
Q

what molecule characteristics affect a drugs ability to be absorbed

A

lipid solubility: more soluble = more likely to cross membrane
ionization state: charged are less like
molecular size: smaller more likely

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9
Q

how is lipid solubility tested in drugs

A

add drug to mixture of equal volumes of water and lipd and shake, let settle and separate
amount in lipid divided by the amount in water is the partition coefficient
higher the coefficient he more lipophilic the compound and more likely to cross membranes

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10
Q

weak acid dissociation equation

A

weak acid drug + water base conjugate acid + weak base drug anion/conjugate base

aka: HA + H2O H+ + A-

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11
Q

weak base dissociating equation

A

weak base drug + water acid conjugate base + weak base drug conjugate acid

aka: B + H2O BH+ + OH-

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12
Q

Kd

A

dissociation constant, at equilibrium at this point

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13
Q

pKa

A

negative log of dissociation constant

is equal to the pH when half of the molecules are non ionzed and half are ionized

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14
Q

how to find pKa from pKb

A

pKa + pKb = 14

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15
Q

henderson hasselbach equation

A

pH = pKa + Log (concentration of non-protonated species/concentration of protonated species)

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16
Q

in what environments do acidic compounds absorb well

A

acidic environments

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17
Q

in what environments do basic compounds absorb well

A

basic environments

ex. small intestine

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18
Q

describe ion trapping

A

when a molecule becomes ionized after crossing a membrane thus becoming trapped in its new environment

ex. weak acids are not ionized in stomach so can be absorbed into blood but then are ionized in the blood bc more basic than stomach

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19
Q

what facilitates restrictions of molecule permeability based on size

A

water filled pores - aquaporins

allow small molecules to cross the membrane along with water

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20
Q

Fick equation

A

Rate of diffusion = DRAdeltaC/deltaX

delta C: concentration gradient across membrane
R: lipid/H2O partition coefficient of the molecule
D: the diffusion coefficient
A: the area of the membrane through which the molecules must diffuse
X: the thickness of the membrane

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21
Q

advantages and disadvantages of oral administration

A

advantages: convenient, safe, economical, can be removed by emesis or activated charcoal
disadvantages: requires conscious and non-vomitting patient, slow onset, poor control of plasma level (bc GI tract absoprtion), drug must be potent and very lipid soluble, must survive first pass effect

more basic drugs are less able to be absorbed in stomach because

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22
Q

first pass efffect

A

once an orally administered drug is absorbed by the digestive system, it first enters the hepatic portal system. it is then carried through the portal vein into the liver

the liver metabolizes many drugs and may alter the concentration reaching the circulatory system. this “first pass” through the liver thus can greatly reduce the bioavailability

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23
Q

bioavailibility

A

fraction of administered drug that reaches the systemic circulation in a chemically unchanged form

calculated by: (AUC oral/AUC injected) x 100
AUC= area under curve in reference to plotting the plasma concentration of drug over time

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24
Q

factors that affect bioavailibility

A 
first pass hepatic metabolism
solubility of the drug
chemical stability (or instability)
nature of the drug formulation (ie. coatings, crystal structure, salt form, etc. )
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25
Q

bioequivalence

A

how drugs compare in terms of bioavailabilityand therefore time to achieve peak blood concentrations

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26
Q

factors affecting absorption of drugs from the gi tract

A

lipid solubility
drug concentration at absorbing surface
vascularity
surface area
GI tract disease
rate of movement of contents through GI (greater time means greater absorption)
food in GI tract (solid food delays gastric emptying which will delay absorption of drugs that are absorbed mainly from small intestine but not those absorbed from stomach)
enzymes, acid, bacteria, etc. in GI tract

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27
Q

factors affecting drug absorption regardless of route administration

A

physicochemical properties of the drug
vascularity of the area
concentration gradients
surface area

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28
Q

define pharmacokinetics

A

measurement and interpretation of changes in drugs concentrations over tiem in body regions in response to dosing
“what the body does to/with the drug”

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29
Q

pharmacodynamics

A

events consequent on interaction of the drug with its receptor or other primary site of action

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30
Q

describe the two-neuron pathway in the nervous system

A

preganglionic neuron (in CNS), axon, postganglionic neuron (in ganglion), axon, effector cell

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31
Q

two divisions of autonomic nervous system

A

sympathetic/thoracolumbar

parasympatheitc/craniosacral

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32
Q

autonomic effects of sympathetic vs parasympatheic stimulation on the heart (what receptors)

A

sympathetic: B1 receptor, increase HR, force, and conductionvelocity
parasympathetic: mus2 receptor, decrease HR, force, and conductance velocity

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33
Q

autonomic effects of sympathetic vs parasympathetic stimulation on the coronary blood vessels (what receptors)

A

sympathetic: alpha1 receptor: constriction, beta1 and 2: dilation
parasympathetic: mus: dialation

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34
Q

describe parasympathetic outflow w common neurotransmitters

A

CNS, preganglionic cholinergic axon, acetylcholine release in ganglion on postganglionic neuron, postganglionic cholinergic axon, acetylcholine release at neuroeffector junction on effector cell

*can produce NO instead of ACh

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35
Q

describe sympathetic outflow w common neurotransmitters

A

CNS, preganglionic cholinergic axon, acetylcholine release in ganglion on postganglionic neuron, postganglionic adrenergic axon, norepinephrine release at neuroeffector junction on effector cell

*postganglionic is cholinergic and produces ACh in sweat glands

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36
Q

epinephrine and alpha, beta adrenoceptor activation

A

epinephrine is generally classified as a mixed a-b agonist, it is primarily a b receptor agonist at low doses and an a receptor agonist at high doses
when first administered and at low doeses will only affect b receptors

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37
Q

isoproterenol and alpha, beta adrenoceptor activation

A

isoproterenol is virtually a pure b agonist

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38
Q

NE and alpha, beta adrenoceptor activation

A

NE is primarily an a agonist but does activate excitatory b receptors in the heart

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39
Q

parasympathetic innervation of the heart

A

vagus nerve stimulate release of ACh which increases K+permeability making it hyperpolarize–> decreased excitability

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40
Q

define chronotropy

A

rate

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41
Q

define dromotropy

A

conduction velocity

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42
Q

define inotropy

A

force of contraction

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43
Q

define lusitropy

A

time to relaxation

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44
Q

coronary artery regulation by alpha vs beta sympathetic stimulation

A

beta sympathetic stimulation by iso, epi, NE causes dilation (beta receptors dominate these vessels)

alpha stimulation by iso, epi, NE results in constriction

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45
Q

catecholamines on the heart

ex.

A

direct acting sympathomimetic amines

NE, Epi, Iso

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46
Q

clinical uses of epi

A

epi used to promote local vasoconstriction to delay absorption of anesthetics, local hemostatic to control bleeding, increase cardiac activity after cardiac arrest, treats allergic reactions: counteracts hypotension and cardiac irregularities and counter constriction of bronchiolar pathways

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47
Q

clinical uses of NE

A

pressor agent: blocks systemic hypotension in spinal anesthesia
prolongs action of inflitration anesthesia

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48
Q

clinical uses of iso

A

increases cardiac activity after cardiac arrest but can produce excessive tachy

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49
Q

nonselective B1-B2 agonists function and ex

A 
postitive intropic (contraction force) and chronotropic (rate) effects with some local vasodilation 
ex. isoproterenol
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50
Q

B1 selective agonists

ex

A

increases contractile force (inotropic) without great effects on HR (chronotropic) relatively cardioselective effects
ex. dobutamine

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51
Q

B2 selective agonists

A

selective for bronchodilation with less cardiac excitability

ex. arformoterol tartrate

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52
Q

effects of B1 receptor blockers

A

decrease HR, contractile force, cardiac output, and conduction veolcity

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53
Q

effect of B2 receptor blockers

A

inhibits sympathetic bronchodilator activity and results in bronchiolar contriction

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54
Q

nonselective B blockers

ex.

A

ex. propranolol
at rest = minimal decrease in HR, CF, and CO
suring increased sympathetic tone= blocking the affect of catecholamines so decrease in HR, CF, and CO which may cause a reflexive increase in BP via vasoconstriction if the effects are dramatic enough

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55
Q

b1 selective beta blockers

ex.

A

cardioselective
produce less bronchoconstriction than nonselective so these are given to patients with pulmonary difficulties
ex. metoprolol, atenolol, esmolol, nadolol

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56
Q

alpha receptor blockers

ex.

A

ex. prazosin, terazosin, doxazosin
decrease peripheral vascular resistance (lower bp)
useful for treating hypertension without effecting cardiac output, RBF, or GFR

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57
Q

muscarininc agonists

ex.

A

stimulate effects of ACh (parasympathetic response)
ex. direct (receptor agonists): pilocarpine, carbachol
indirect (inhibit AChE): neostigmine, physostigmine, organophosphates

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58
Q

muscanarinic antagonists

A

inhibit responses causes by stimulation parasympathetiv neurons
direct block of mus receptors (atropine, ipratropium)
atropine is used to block pNS effects on the heart leading to an increase in heart rate and therefore increases cardiac output

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59
Q

define parasympathomimetics

A

drugs that act either by directly stimulating the muscarinic receptor or by inhibiting the enxzyme acetylcholinesterase which hydrolyses the acetylcholine in the synapse

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60
Q

define parasympatholytics

A

drug that reduces the activity of the parasympathetic nervous system

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61
Q

define sympathomimetics

A

drug that stimulates the sympathetic nervous action

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62
Q

define sympatholytics

A

drug that opposes physiological results of sympathetic nervous

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63
Q

arrhythmia vs dysrrhythmia

A

arrhythmia: loss of rhythm without rhythm being re established
dysrrhythmia: defective rhythm, any abnormality in the rate, regularity or site of origin of the cardiac impulse, or a disruption in impulse conduction changing the normal sequence of atrial and ventricular activation

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64
Q

List the the classes and mechanisms of the antiarrhythmic drugs (according to Vaughan-Williams classification)

A 
Class I: sodium channel blockers
Class II: beta blockers
Class III: potassium channel blockers
Class IV: calcium channel blockers
Class V/non-classified: miscellaneous
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65
Q

Class I antiarrhymic drug mechanism

explain how they are state dependent

A

block sodium channels: slows rapid inward Na+ which slows the depolarization and decreases the maximal rate of depolarization with little or no effect on resting membrane potential

many of these drugs are “state dependent”, they bind more rapidly to open or inactivated channels than closed ones, they are often more likely to work on tissues frequently depolarizing (ie. during tachycardia)

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66
Q

explain the 3 groups of Class I antiarrhymic drugs

A

IA: intermediate block of AP duration, slow phase 0 depolarization, prolong action potential, and slow conduction

IB: shortest channel block, shorten phase 3 repolarization and decrease the duration of the action potential

IC: long channel block, slow phase 0 depolarization

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67
Q

theraputic uses for class I antiarrythmic drugs

A

abolish reentry by producing a bidirectional block inplace of a unidirectional block (mainly class IA)

slow tachyarrhythmias by increasing required stimulus to reach threshold

inhibit spontaneous diastolic depolarizations in cells that have abnormal automaticity (mainly class IA and flecainide)

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68
Q

examples in class IA, IB, and IC antiarrhythmic drugs

A

IA: procainamide
IB: lidocaine
IC: flecainide

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69
Q

class II antiarrhythmic drugs

A

beta blockers
block beta adrenergic receptors thereby inhibiting adenylyl cyclase and decrease PKA and intracellular calcium- has most effect when sympathetic tone
supress positive inotropic (contraction force) and chronotropic (rate) effects of catecholamines thus reduce rate and contractility of the heart

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70
Q

ex of class II antiarrhymic drugs

A

propranolol, metrolol, nadolol, atenolol

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71
Q

theraputic uses of class II antiarrhythmic drugs

A

effective in controling tachyarrhythmias associated with sympathoadrenal discharge by blocking hyperactivity of SNS

minimal effects at rest, more effects as sympathetic tone increase

*b1-selective antgonists/cardioselective b blockers are safer to administer to cardiac patients with pulmonary difficulties because they will not have the side effect of bronchoconstriction that non-selective have

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72
Q

class III antiarrhythmic drugs

A

K+ channel blockers
block potassium channels and prolong repolarization thereby increase effecctive refractory period, action potential depolarization, and prolong AV conduction, many depress phase 4 depolarization and automaticity

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73
Q

ex class III antiarrhythmic drugs

A

amiodarone (most commonly used antiarrythmic), sotalol

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74
Q

theraputic use of class III

A

treat supraventricular and/or ventricular tachyarrhythmias

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75
Q

class IV

A

calcium channel blockers
decrease slope of phase 4 action potential (especially in AV node), prolongs effective refractory period, slows conduction in tissues dependent on calcium currents (especially depresses AV node conduction)

predominent action is in AV node bc it has a lot of Ca ++ channels there and therefore reduces AV conduction

depresses normal and abnormal automaticity

76
Q

theraputic use class IV

A

control supraventricular arrhythmias that involve AV reentry and ectopic stimulation

77
Q

ex class IV

A

verapamil, dilitiazem

78
Q

digitoxin (class and mechanism)

A 
class V (miscellaneous)
increases intracellular calcium by affecting Na+/K+ pumps and Ca+ exchangers and increase contractile force
enhances PNS/cholinergic tone at nodal areas: decreases automaticity (can result in bradycardia)
predominant action at AV node (decreasing AV conduction)
79
Q

atropine (class and mechanism)

A 
class V
mus blocker
used during bradycardia or sinus arrest secondary to vagal discharge and accumulation of ACh
80
Q

epinephrine (class and mechanism)

A 
class V
can be used to restart the heart after cardiac arrest
increases heart rate in cases of sinus bradycardia associated with impaired sympathetic tone
81
Q

isoproterenol (class and mechanism)

A

increase heart rate in cases of sinus bradycardia associated with impaired sympathetic tone

82
Q

adenosine (class and mechansim)

A 
class V
adenosine receptors are prevalent on atrial myocytes and SA and AV nodes, when adenosine binds to these receptors it inhibits adenylyl cyclase resulting in decreased Ca++ and increased K+ resulting in decreased conduction velocity, prolonged refractory period and decreased AV node automaticity
83
Q

define volume of distribution (Vd)

A

volume of body fluid in which a drug appears to be dissolved, assuming uniform distribution

84
Q

TBW is what % of body weight

A

60% (about 40 L)

85
Q

extracellular water is what % of body weight

A

20% (about 12-14 L)

86
Q

whole blood volume and plasma volume are each what % of total body weight

A

whole blood volume = 8%

plasma= 4%

87
Q

Vd equation

A

Vd=Q/Cp
Vd= amount of drug in cells
Q= total drug in body
Cp= plasma drug concentration

88
Q

equation to find how much to increase dose for desired Vd

A

Q=Vd(C2-C1)

89
Q

mechanisms of blood brain barrier

A 
lack fenestrations (no leaky holes)
tight junctions (hold cells together tightly letting little through)
astrocytes (wrap around cells providing extra membrane layer)
P-glycoprotein transporters (transport molecules out of brain back into the blood)
90
Q

which drugs cross the blood-brain barrier well

A

highly lipophilic compounds

91
Q

mechanisms of blood-placental barrier

A

3 layers: epithelial layer, chorionic layer, endothelium of fetal capilaries

92
Q

which drugs cross the blood-placental barrier well

A

highly lipophilic although blood flow rate here is not high so even highly lipophilic drugs take a long time to cross

93
Q

mechanisms of drug-testicular barrier

A

tight junctions between sertoli cells

94
Q

which drugs bind best to albumin and which drugs bind best to alpha1-acid glycoprotein

A

albumin binds well with acidic and neutral drugs

alpha1-acid glycoprotein binds well to basic drugs

95
Q

OAT and OCT functions

A

OAT: organic anion transporters/acid transporters pump acidic compounds against their gradient into the lumen of tubules using ATP

OCT: organic cation transporter/base transporter transports basic compounds down their gradient

96
Q

does plasma protein binding affect drug excretion

A

no, tubular transit time is long enough that dissociation from plasma proteins can take place and as drug is excreted the equilibrium drives more proteins to become unbound

**however, transporters can become saturated which would effect excretion

97
Q

define theraputic index

A

ratio of toxic dose divided by therapeutic does
want this to be large
ex. warfarin has low therapeutic index

98
Q

thiopental

A

good for inducing anesthesia because high lipid:water partition coefficient so travels to the brain very quickly

99
Q

define biotransformation

A

metabolism of lipophillic drugs into more easily excreted hydrophillic compounds (making more polar and more water soluble)

100
Q

first pass effect

A

drugs entering through GI are carried to the liver first by portal circulation

101
Q

what organ has the highest density of drug metabolizing enzymes

A

liver

102
Q

detoxication reaction (liver)

A

when the liver acts upon compounds making them less active/toxic

103
Q

activation reaction (liver)

A

when liver acts upon compounds making them more active/toxic

104
Q

define prodrug

A

medication that is administered in an inactive or less than fully active form and then is converted to its active form through a normal metabolic process

105
Q

how can using a prodrug alter how a drug is absorbed/distributed

A

prodrug may be able to cross a a barrier that the drug may not be able to

106
Q

michaelis-menten kinetic equation for first and zero order kinetics

A

first order: V = (Vmax * concetration)/Km
zero order: V= (Vmax * concentration)/concentration

v= rate of metabolism
vmax= maximum rate at which reaction can occur
Km= substrate concentration that is required for the reaction to occur at .5 vmax
107
Q

what order kinetics are observed in drug metabolism at high and low doses

A

low doses: first order

high dose: zero order kinetics (bc enzymes saturated)

108
Q

first order kinetics

A

rate of metabolism is directly proportional to the concentration of free drug

a constant fraction of drug is metabolized per unit of time

ex. 50% every hour

109
Q

zero order kinetics

A

a constant amount of drug is metabolized per unit time

enzyme is saturated by free drug concentration thus the rate of metabolism remains constant over time

110
Q

phase I reactions

A

generally make compounds less active or less toxic and or more water soluble but can make them more toxic, may add or unmask existing polar functional group

reduction (add H+)
hydrolysis (lyse using H2O)
oxidation

111
Q

phase II reactions

A

generally conjugation reactions which make compounds more water soluble

112
Q

microsomal oxidation reactions

A

enzymes of the smooth ER

  1. cytochrome P450s (CYP)
  2. FAD-containing monooxygenase
113
Q

Cytochrome P450s (CYP) oxidation reactions

A

heme-containing enzymes which are generally in smooth ER

uses molecular oxygen to oxidize drug
CYP must be oxidized in order for O2 binding drug
NADH acts electron donor which is supplied by electron transport chain

114
Q

FAD-containing monooxygenase oxidation reactions

A

it is a flavoprotein
uses NADPH cofactor and FAD
competes with CYP450s for oxidation of amines

115
Q

aliphatic hydroxylation

A

add hydroxy group to aliphatic group (C’s and H’s)

116
Q

aromatic hydroxylation

A

adding hydroxide to aromatic group

117
Q

O-dealkylation

A

removing alkyl group (CH3) from oxygen leaving an OH

118
Q

N-oxidation

A

adding oxygen to nitrogen

119
Q

oxidative deamination

A

removing amine group and add double bond O via H20

120
Q

S-dealkylation

A

removing alyl group (CH3) from S

121
Q

sulfoxidation

A

adding oxygen to S

122
Q

desulfuration

A

remove S

123
Q

N-dealkylation

A

removes alkyl group (leaving polar NH)

124
Q

inducers of CYP450 enzymes

A

more quickly metabolize drugs

ex. phenobarbital, rifampin and carbamazepine, cruciferous vegetables, smoking

125
Q

inhibitors of CYP450 enzymes

A

less quickly metabolize drugs, may cause build up of drugs which would cause a higher response of drugs

ex. omeprazole, erythromycin, grapefruit juice, cumin

126
Q

rhabdomyolysis

A

can be caused by high plasma concentrations of HMG-CoA reductase inhibitors (lowers cholesterol production, statins)

increased muscle breakdown –> increased myoglobin –> kidney damage

127
Q

what CYP breaks down HMG-CoA reductase inhibitors

A

CYP3A4 (promotes cholesterol synthesis)

128
Q

effect of high CYP3A4

A

if CYP3A4 is high HMG-CoA inhibitors are broken down
HMG-CoA is therefore not broken down
therefore high levels

129
Q

nonmicrosomal oxidations

A

generally in cytosol or mitochondria

include oxidation (breakdown) of catecholamines, alcohol, and histamine

130
Q

MAO

A

breaks down catecholamines and serotonin

131
Q

inhibitors of MAO

A

inhibit breakdown of catecholamine and serotonin

can lead to build up of these neurotransmitters and increase their stimulation to the post synaptic neurons

132
Q

MAO-A preferentially deaminate what

A 
serotonin
melatonin
tyramine
epinephrine
norepinephrin
133
Q

MAO-B preferentially deaminate what

A

phenylethylamine

trace amines

134
Q

what may people on non-selective MAOIs or high doses of MAO-BIs need to restrict in their diet? why?

A

wine and aged cheese
they have high levels of tyramine which is normally broken down by MAO-A
high levels of tyramine can result in hypertensive crisis

135
Q

3 ways that alcohol is metabolized

A

microsomal ethanol oxidizing system (MEOS)
alcohol dehydrogenase (ADH) in cytosol Of stomach (most common pathway) producses acetaldehyde which enters mitochondria to be reduced to acetic acid via aldehyde dehydrogenase (ALDH)
catalase in the peroxisome

136
Q

disulfiram

A

inhibits aldehyde dehydrogenase
when drinking alcohol, aldehyde builds up and causes person to become ill very quickly
causes person to associate alcohol with sickness

137
Q

naltrexone

A

blocks m opiod receptor in brain thus decreasing ethanol-induced activation of the dopamine reward pathway
person will not have pleasurable effects of alcohol

138
Q

acamprosate

A

blocks ability of glutamate to cause excitatory activity in CNS so decreases cravings for alcohol

139
Q

glucuronic acid conjugation

A

glucuronic acid is a glucose derivative that is transfered to an acceptor molecule from UDP-glucuronic acid with the action of the enzyme UDP-glucuronosyl transferase

140
Q

functional groups that can undergo glucuronic acid conjugation

A

carboxyl (-COOH)
alcohol (-OH)
sulfhydryl (-SH)
amino groups (-NH2)

141
Q

ethyl glucuronide test (EGT)

A

small amount of ethanol is conjugated to glucuronic acid and can be detected in urine for up to 5 days or more after alcohol consumption
used in legal proceedings

142
Q

glucuronic acid conjugation in jaundice

A

UDP-glucuronosyl transferase is low so bilirubin is not conjugated with glucuronic acid for excretion
bilirubin builds up causes jaundice

143
Q

glutathione conjugation

A

catalyzed by glutathione S-transferase
glutathione group is conjugated to nitro group, hydroxylamines, or epoxides
these are then cleaved into cysteine derivatives which are acetylated forming mercapturic acid which is excreted in urine

144
Q

sulfate conjugation

A

sulfertransferase in liver takes sulfate group from PAPS and puts in on phenols, alcohols, and aromatic amines
acetaminophen undergoes this conjugation

145
Q

acetylation

A

N-acetyltransferase puts acetyl group from acetyl-CoA and is conjugated preferentially to amino acids

146
Q

glycine conjugation

A

in the mitochondria of liver cells acylCoA glycinetransferase puts amino acid glycine onto aromatic carboxylic acids
ex. salicyaltes (i.e. aspirin)

147
Q

methylation

A

methyltransferase puts methyl groups from S-adenosylmethionine onto S, N, and O groups

148
Q

list all phase I reactions

A

reduction
hydrolysis
oxidation: microsomal (CYP450 and FAD-containing monooxygenase) and non-microsomal (MAO, ADH, diamine oxidase)

149
Q

list all phase II reactions

A 
conjugation reactions
glucuronide conjugation
glutathione conjugation
acetylation
sulfate conjugation
glycine conjugation
methylation
150
Q

aspirin metabolism

A

salicylic acid group is active part of compound

the acetyl group aids in absorption and with crossing the blood-brain barrier

151
Q

what is the dosing technique in people with liver insufficiencies

A

dosage is adapted empirically base upon serum drug concentrations because they will not handle drugs the same

152
Q

drug elimination routes

A
  1. renal clearance (most common)
  2. biliary clearance
  3. intestine
  4. lung
  5. sweat
  6. tears
  7. milk
153
Q

enterohepatic cycling

A

increase time of drug in body by reabsorption in the intestine and return to systemic circulation

154
Q

why is there typically not back flow of of metabolized molecules back out of the lumen of the kidney

A

when metabolized they are made polar

155
Q

how does pH and altering urine pH aid in drug elimination

A

weak acids can be eliminated by alkalinization of the urine via bicarbonate treatment

elimination of weak bases may be enhanced by acidification of the urine via ammonium chloride treatment

156
Q

if creatinine clearance is 50% of the normal value what can renal elimination of a drug expected to be

A

renal elimination of a drug is expected to be affected the same way as creatinine clearance is, so in this case it would also be decreased to 50% of normal and the drug dosage should be adjusted accordingly

157
Q

3 factors that affect plasma drug concentrations

A
  1. rate at which drug is administered
  2. volume in which drug distributes
  3. drug clearance
158
Q

equation for total clearance

A

total clearance = Ke (Vd)

Ke= a constant used to represent the fraction of drug eliminated per unit of time

159
Q

4 most commonly used antihypertensice drugs

A

ACE inhibitors
AT1 antagonists
calcium channel antagonist
thiazide diuretic

160
Q

ACE inhibitor examples

A

captopril (short duration of action)

enalapril and lisinopril (longer durations of action)

161
Q

ACE inhibitors are more often used to treat what populations

A

younger or people of european origin who are more likely to have normal or high plasma renin

162
Q

ARB mechanism of action

A

block receptors of angiotensin II which inhibits vasoconstriction to occur

163
Q

ARB examples

A

losartan, candesartan, valsartan, and irbesartan

164
Q

ARBs are more often used to treat what populations

A

younger and people of european origin who are more likely to have normal or high plasma renin

165
Q

calcium channel antagonist examples

A

dihydropyridines (nifedipine, amlodipine) act preferentially on smooth muscle anda re used as casodilators but may cause tachy

verapamil: causes vasodilation but it also acts directly on heart producing negative chronotropic and inotropic effects
dilitiazem: works a little bit on vasodilation and a little bit on the heart

166
Q

calcium channel antagonists are more often used to treat which populations

A

older people or people of African origin who are more likely to have lower plasma renin

167
Q

HYZAAR

A

combination of losartan, potassium, and hyrochlorothiazide

168
Q

vaseretic

A

enalapril, maleate, and hydrochorothiazide

169
Q

renin inhibitor example

A

aliskiren

170
Q

alpha 1 antagonist mechanism of action

A

inhibit sympathetic vasoconstriction and cause vasodilation

171
Q

alpha 1 antagonists ex

A

doxazosin and terazosin

172
Q

phenoxybenzamine

A

non selective alpha receptor antagonist which binds irreversibly and produces a drop in blood pressure, only used for patients undergoing surgery to remove phaeochromocytoma (catecholamine secreting tumor) to prevent effects of sudden catecholamine when the tumor is disturbed

173
Q

metroprolol

A

beta receptor antagonist
useful in patients with other indication or beta blockade such as angina
low doses are combined with diuretic for example metoprolol and HCTZ are combined in Lopressor HCT

174
Q

aldosterone antagonist mechanism of action

A

normally aldosterone increases reabsorption of Na and H2O and the release of potassium in the kidneys which increases BP, useful when potassium sparing is desired

175
Q

aldosterone antagonist examples

A

spironolactone

176
Q

potassium channel activator mechanism of action

A

open KATP channels to hyperpolarize smooth muscles and switch off voltage dependent calcium channels, calcium levels drop resulting in vasodilation

177
Q

potassium channel activator ex

A

minocidil: very potent and long lasting, used as last resort

178
Q

endothelin receptor antagonist mechanism of action

A

block receptors of endothelin (normally causes vasoconstriction, synthesis stimulated by trauma or inflammatio) receptors: ETA, ETB
used mainly for pulmonary artery hypertension

179
Q

endothelin receptor antagonist ex

A

bosentan

180
Q

alpha methyldopa

A

safely used in pregnancy, decreases blood pressure as a sympatholytic without affecting renal function and is suitable for renal insufficient patients

181
Q

hydralazine

A

decreases BP by unknown mechanism acting mainly on arteries and arterioles
often accompanied by reflex tachy and increases CO, mainly used for short term treatment of severe hypertension during pregnancy

182
Q

Nitric Oxide treating hypertension, mechanism of action

A

activates guanylyl cyclase –> cGMP –> PKG, cyclic nucleotide phosphodiesterase, and ion channels –> inhibits calcium induced smooth muscle contraction

183
Q

nitric oxide donor example

A

nitroprusside

184
Q

neprilysin

A

neutral endopepridase that cleaves natriuretic peptides: ANP, BNP, CNP to produce vasodilation

185
Q

sacubitril

A 
inhibits neprilysin (normally cleaves natriuretic peptides- ANP, BNP, CNP) leading to increased levels of natriuretic peptides and the subsequent vasodilation 
neptrilysin also degrades angiotensin II therefore sacubitril increases angiotensin II

SIU SOM: CRR (15 decks)

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