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MDTI > Pharmacology > Flashcards

Pharmacology Flashcards

1
Q

Glucocorticoid

A
  • endogenous steroid hormone produced and released by adrenal gland
  • exogenous analogs are used anti-inflammatories and immunsuppressives
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2
Q

3 classes of corticosteroids, their roles, and their endogenous sources

A
  1. mineralocorticoids - Zona glomerulosa
    • salt/water retention
  2. glucocorticoids - Zona Fasiculata
    • immunity and metabolism
  3. androgens/estrogens- Zona Reticularis
    • sexual function
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3
Q

Endogenous regulation of glucocorticoid production

A
  • HPA: CRF–> Ant. Pit. –> ACTH–> corticosteroids
  • negative feedback from glucocorticoids and ACTH
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4
Q

Negative effects of glucocorticoids

A
  • Metabolic: gluconeogenesis, lipolysis, lipgenesis
  • Catabolic: protein catabolism, wasting, osteoporosis
  • Other: Na homeostasis, behavior
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5
Q

Anti-inflammatory effects of glucocorticoids

A
  1. decrease T cell production of IFN gamma
  2. reduce macrophage production of Il1 and TNFalpha
  3. reduce mast cell production of histamine, NO, prostaglandins
  4. inhibition of PLA2
  5. decrease mRNA Cox
  6. decrease IL2,3
  7. decrease antibodies
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6
Q

Immunosuppressive effects of glucocorticoids

A
  1. cell mediated immunity
  2. reduced proliferation of lymphocytes, neutrophils, and monocytes
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7
Q

Glucocorticoid Receptor and 4 domains

A
  • intranuclear steroid hormone receptor family
  • 4 functional domains
    1. ligand binding domain-gr interaction with chaperones Hsp90 and Hsp56
    2. DNA binding domain-binds to DNA GRE response element within promoter of target gene
    3. C terminal AF2-ligand dependent transactivation domain; interacts with co activator or cosuppressor proteins that optimize receptor induced gene transcription; recruited to ligand receptor complex after steroid binds GR
    4. N terminal AF1- ligand dependent transactivation domain; constitutive interaction with receptor complex
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8
Q

Ligand-binding domain of glucocorticoid receptor binds to

A

chaperone proteins Hsp 90 and 56

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9
Q

DNA binding domain of glucocorticoid receptor binds to

A

glucocorticoid response element (GRE) on promoter in DNA of specific gene

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10
Q

C-terminal AF2 of glucocorticoid receptor binds to

A

coactivator/cosuppressor proteins that optimize receptor induced gene transcription

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11
Q

N-terminal AF1 of glucocorticoid receptor binds to

A

constitutively to transcription machinery of the cell

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12
Q

Glucocorticoid MOA

A
  1. GR/Hsp resides in cytoplasm in a ligand friendly complex
  2. binds to hormone in the cell and dissociates from chaperone
  3. steroid receptor complex translocates to the nucleus and binds target gene
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13
Q

Lipocortin effect

A

when gene bound by glucocorticoid –> increased expression of lipocortin –> downregulates PLA2 –> decreased synthesis of PGs and leukotrienes

*gc can also inhibit IL6/8

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14
Q

Factors optimized in synthetic production of glucocorticoids

A
  1. limit salt-retaining properties (a la mineralocorticoids which are endogenous)
  2. improve anti-inflammatory response (via double bonds, 3 keto and oh groups)
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15
Q

Glucocorticoid-physiological doses

A
  • replacement therapy to treat adrenal insufficiency (mimic physiology)
  • need to maintain negative feedback loop –> otherwise disrupt homeostasis (e.g. interrupt growth and development in kids)
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16
Q

Glucocorticoid-supra physiological doses

A
  • anti-inflammatory effect
  • immunosuppressive
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17
Q

Glucocorticoid toxicities

A
  • HPA suppression–> no endogenous cortisol
  • electrolyte imbalance (Na retention/K excretion)
  • Infection from immunosuppression
  • Osteoporosis from inhibition of osteoblast activity
  • Hyperglycemia
  • Cataracts
  • Growth retardation
  • Behavioral changes
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18
Q

Sudden withdrawal of therapeutic glucocorticoids can lead to acute adrenal insufficiency because of reduced endogenous cortisol production called

A

Addisonian crisis

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19
Q

Immunosuppressives-indications

A
  1. organ/tissue transplant
  2. treatment of autoimmune diseases
  3. treatment of inflammatory conditions like asthma
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20
Q

Immunosuppression most effective in

A

prophylaxis: primary/initial steps prior to immunologic memory

  1. antigen presentation
  2. cell proliferation
  3. lymphokine synthesis & differentiation *immunosuppressants don’t have a uniform effect on all steps of immune response *prophylaxis is key
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21
Q

Stages of immunosuppression

A
  • Induction - T cell depletion and prevention of activation
  • Maintenance - prevention of T cell activation/cytokine production
  • Treatment of Rejection or Disease Flare
  • Tapering
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22
Q

Key risks during immunosuppression

A
  1. Infection
    • donor-derived opportunistic
    • worsening of pre-existing conditions
  2. Malignancy
    • donor derived pre-existing
    • de novo
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23
Q

of medications needed for immunosuppression

A
  • 3 rejection
  • 3 infection
  • 3-5 non-immune and metabolic regulators (e.g. statins)
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24
Q

IFN gamma, IL 2 and TNF alpha are produced by

A

Th1 –> cellular response

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25
Q

Il4, 5, and 13 are produced by

A

Th2 cells –> B cell/humoral response

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26
Q

IL 17, 21, and 23 are produced by

A

Th17 –> can mediate steroid resistant rejection

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27
Q

IL10 and TGF beta are produced by

A

Treg cells

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28
Q

Three signal model

A
  1. MHC vs TCR
  2. B7 vs. CD28
  3. IL2 vs CD25/IL2R
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29
Q

Anti-CTLA4 Ig (against CD80/86)

A
  • Belatacept –> blocks B7 which allows CTLA4 to bind to CD28 –> anergy/apoptosis
  • compare to Ipilimumab –> binds to CTLA4 –> constitutively on
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30
Q

Anti-CD25 Ig

A

Basiliximab: targets CD25 chain in IL2 receptor on t-cell (induction but not rejection)

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31
Q

Polyclonals used in immunosuppression

A
  1. equine anti-thymocyte globulin (eATG)
  2. rabbit (rATG)
  • bind to t-cells –>deplete circulating lymphocytes –> use for induction and rejection
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32
Q

Challenges to using polyclonals

A
  1. mass production
  2. toxicity/serum sickness
  3. immunosuppression (profound)
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33
Q
A
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34
Q

Which kinds of patients do we give belatacept to?

A

EBV+

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35
Q

Toxicities and risk of Belatacept

A
  • PTLD
  • anemial, hypertension, UTI, GI, fever
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36
Q

MOA of calcineurin inhibitors

A
  1. bind to immunophyllin (c-proteins)
  2. drug-protein complex binds to calcineurin phosphatase
  3. prevents dephosphorylation and translocation of nuclear factor of activated T cells
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37
Q

What does the calcineurin inhibitor tacrolimus bind to?

A

FK binding protein 12

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38
Q

What does the calcineurin inhibitor cyclosporine bind to?

A

cyclophillin

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39
Q

Common toxicities of calcineurin

A
  1. nephrotoxicity
  2. hyperglycemia
  3. hypertention
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40
Q

Neurotoxicity is associated with which calcineurin inhibitor?

A

tacrolimus

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41
Q

Gingival hyperplasia is associated with which calcineurin inhibitor?

A

cyclosporine

  • hypertension/hyperlipidemia/hyperuricemia too
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42
Q

What class of drugs do we not want to administer with calcineurin inhibitors and mTOR inhibitors?

A

CYP3A-related drugs

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43
Q

MOA of mTOR inhibitors

A
  1. bind to FKBP
  2. inhibits mTOR
  3. decrease cytokine dependent cell proliferation of T-cells
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44
Q

Common toxicities of mTOR inhibitors

A

leukopenia, thrombocytopenia, wound healing impairment, pneumonitis, peripheral edema

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45
Q

2 important mTOR inhibitors

A

tacrolimus and everolimus

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46
Q

3 drugs that prevent lymphocyte proliferation

A
  1. Azathioprine –>blocks de novo and salvage purine –> S phase arrest
  2. Mycophenolic mofetil –> blocks de novo purine synthesis –> S phase arrest
  3. Methotrexate –> DHFR blocker-pyrimidine –> S phase arrest
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47
Q

What drug should we prescribe with azathioprine (low dose)

A

Allopurinol –> blocks xanthine oxidase –> need less azathioprine (which is broken down by xo)

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48
Q

Common toxicities of DNA blockers

A

leukopenia, anemia, thrombocytopenia, liver dysfunction, lung disease, skin cancer, GI

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49
Q

What drugs do we use for induction therapy?

A
  1. Basilixumab
  2. rATG/eATG
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50
Q

What drugs do we use for maintenance immunosuppression?

A
  1. corticosteroids
  2. calcineurin inhibitor
  3. mTOR inhibitors
  4. belatacept
  5. azathioprine/mmf/mpa
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51
Q

What drugs do we use to manage acute rejection?

A
  1. high dose pulse steroids
  2. rATG, eATG
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52
Q

Drug

A

chemical entity that affects living protoplasm

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53
Q

medicine

A

chemical entity used to treat, cure, prevent, and diagnose disease

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54
Q

Pharmacokinetics

A

what happens to a drug when given to a patient

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55
Q

Pharmacodynamics

A

the body’s response to a given drug

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56
Q

Routes of administration

A
  • Enteral- oral, rectal, sublingual
  • Parenteral- IV, IM, SubQ
  • Other- transdermal, topical, inhalation, intranasal
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57
Q

Key advantages and disadvantages of oral administration

A
  • Advantages: ease, cost, outpatient
  • Disadvantages: complicated, variable response, gastric pH, food, first pass effect, biotransformattion
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58
Q

First pass effect

A
  • concentration of a drug is greatly reduced before it reaches the systemic circulation
  • the fraction of lost drug during the process of absorption w/biotransformation–> hepatic/gut wall
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59
Q

Key advantages and disadvantages of rectal administration

A
  • Advantages: ease, outpatient, cost, tolerability
  • Disadvantages: some first pass effect, slightly complicated/variable response, hepatic biotransformation
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60
Q

Key advantages and disadvantages of sublingual administration

A
  • Advantages: ease, outpatient, no first pass
  • Disadvantages: cost, taste, limited formulations
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61
Q

Which modes of administration avoid the first pass effect?

A

Sublingual, Parenteral, Transdermal, Topical, Inhalation, Intranasal

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62
Q

Key advantages and disadvantages of IV administration

A
  • Advantages: no first pass, control of dose, rapid onset
  • Disadvantages: invasive, cost, overdose, inpatient
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63
Q

Key advantages and disadvantages of IM administration

A
  • Advantages: no first pass, fast onset aqueous/slow response non aqueous
  • Disadvantages: pain, cost, supervision
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64
Q

Key advantages and disadvantages of SubQ administration

A
  • Advantages: no first pass,aqueous fast onset, slow sustained (nonaqueous)
  • Disadvantages: invasive, cost, supervision
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65
Q

What factor determines absorption of transdermal drugs?

A

Lipid solubility

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66
Q

What is a limiting factor in inhalation-based administration?

A

molecular size of drug

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67
Q

What mode of administration guarantees 100% bioavailability?

A

IV

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68
Q

What does the HH equation tells us about drug delivery?

A

what proportion of drug is uncharged at a given pH –> how much of drug will be absorbed

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69
Q

Bioavailability

A

Proportion of drug that reaches systemic circulation in an unchanged form:

[AUC]/AUCiv * 100

70
Q

Distribution

A

process by which drug reversibly leaves blood stream and enters interstitium and/or cells of tissues

71
Q

3 body compartments

A
  1. plasma
  2. interstial fluid volume
  3. intracellular fluid volume

+bone, adipose, fetus

72
Q

4L

A

Plasma

73
Q

14L

A

ECF = plasma + IF

74
Q

42L

A

Total body water = Plasma + IF + ICF

75
Q

Factors affecting drug distribution

A
  1. blood flow
  2. capillary permeability
  3. hydrophobicity
  4. binding to plasma proteins
76
Q

If Vd is small and drug is displaced from binding site on plasma protein

A

concentration in plasma is high and high risk of toxicity

77
Q

If Vd is large and drug is displaced from plasma proteins

A

drug can distribute to other compartments and risk of toxicity is lower

78
Q

Volume of Distribution Vd

A

hypothetical volume of fluid into which a drug is disseminated

Vd = bioavailable dose/concentration in plasma @ t= 0 (L/kg)

79
Q

Large molecular weight drugs can be found in ________ because _________.

A
  1. plasma
  2. too big to pass to IF or bound to PP
80
Q

Low molecular weight hydrophilic drugs can be found in ________ because _________.

A
  1. ECF
  2. can move to IF and stay in solution
81
Q

Low molecular weight lipophilic drugs can be found in ________ because _________.

A
  1. total body water
  2. can move through cell membranes and slit junctions
82
Q

Receptor bound drugs can be found in ________.

A

Tissues

83
Q

Biotransformation purpose

A
  • method of inactivating drug in order to excrete
  • can be used to activate prodrugs
  • occurs primarily in liver
84
Q

Main locations of biotransformation enzymes

A
  1. extrahepatic microsomal enzymes: oxidation, conjugation
  2. hepatic microsomal enzymes
  3. hepatic non-microsomal enzymes: acetylation, sulfation, GSH, dehydrogenase, hydrolysis, ox/red
85
Q

Phase 1 metabolism

A

oxidation involving cyt P450

86
Q

Phase 2 metabolism

A
  • coupling of an endogenous substrate to a drug or its Phase 1 metabolite
  • can come before, with, not at all, or after Phase 1
87
Q

Which CYP is implicated in metabolism of many drugs?

A
  • CYP3A4 –> oxidation of drugs
  • altered activity in GI tract an change bioavailability of drug
  • differences between people can generate different metabolizing profiles
88
Q

2 drugs that can increase metabolic function of CYP3A4

A

Rifampin, St. John’s Wort

89
Q

How does increased metabolism effect efficacy of a drug

A

Decreased

90
Q

1 substance that reduces CYP3A4 activity

A

Grapefruit juice –> increased absorption –> prolonged effect and/or toxicity

91
Q

Which CYPs are responsible for the major differences in drug metabolism between people

A
  • 2D6
  • 2C19
92
Q

Which ethnocultural groups tend to overexpress CYP2D6, resulting in high metabolism of drugs?

A

Ethiopians, Saudi Arabians

93
Q

3 consequences of altered drug metabolism

A
  1. reduced = toxicity, death
  2. increased = loss of efficacy
  3. drug-drug interactions
94
Q

Are prodrugs or metabolites easier to clear? Why?

A

metabolites; they are more polar

95
Q

Modes of drug excretion

A
  1. bile
  2. urine
  3. air
  4. sweat
  5. saliva
96
Q

Processes implicated in renal excretion

A
  1. glomerular filtration (if bound to PP, won’t work)
  2. active tubular secretion (competitive inhibition can prevent this)
  3. passive tubular reabsorption (nonionized lipids)
97
Q

Amount of drug excreted renally is the sum of

A

amount filtered and secreted minus amount reabsorbed

98
Q

Elimination

A

process by which body terminates drug action: metabolism/biotransformation (liver, muscle) + excretion(kidney)

99
Q

Clearance

A
  • rate of elimination
  • proportional to concentration of drug = 1st order kinetics
  • elimination is not saturable
100
Q

For which drugs is elimination saturable (capacity limited elimination)

A

Alcohol, phenytoin = 0 order kinetics

101
Q

Half Life

A
  • time required to eliminate half drug in body or reduce plasma concentration by 505
  • useful only in 1st order kinetics
102
Q

How long does it take to reach steady state?

A

4-5 half lives of a 1st order drug b/c

rate of elimination = rate of administration

103
Q

time to reach steady state is independent of

A
  • dose
  • frequency of administration
104
Q

steady state concentration is dependent on

A
  • drug dose/time
  • elimination half life
105
Q

continuous infusion reaches steady state faster/slower/same rate as intermittent drug administration

A

same rate but with more fluctuation of plasma level

106
Q

Loading dose

A

used to rapidly achieve a therapeutic plasma concentration –> then maintenance dose to sustain steady state

107
Q

Which age groups have higher volumes of distribution for water-soluble drugs?

A

Neonates and infants because of incomplete BBB

108
Q

Which age groups have higher volumes of distribution for fat soluble drugs?

A

elderly//lower Vd for water-soluble

109
Q

Full agonist

A

drug that if given in sufficient quantity to saturate receptor pool binds to receptor and induces Ra form at large %

110
Q

Partial agonist

A

has intermediate affinity for Ra/Ri and generates partial response

111
Q

Antagonists

A

have equal affinity for Ri/Ra and maintain same level of constitutive activity as receptor on its own

112
Q

Inverse agonists

A

have higher affinity for Ri and reduce constitutive activity

113
Q

Potency

A

concentration of drug required to achieve EC50

114
Q

Efficacy

A

magnitude of drug’s action at Emax

115
Q

The dose response relationship and selectivity of drug action are dependent on

A

receptors

116
Q

5 transmembrane signaling mechanisms

A
  1. GPCR
  2. ion channel
  3. steroid receptor
  4. cytokine receptor
  5. RTK
117
Q

Gs

A

epinephrine –> B1 adrenergic receptor –> adenylyl cyclase –> camp

118
Q

Gi

A

ACh –> M2 muscarinic receptor –> reduce adylyl cyclase activity

119
Q

Gq

A

binding –> PLC –> PIP3 formation –> IP3–>Ca2+ release

120
Q

Histamine receptor effect

A

bronchioles: Gq –> H1 receptor –> Ca2+ –> constrict
vessels: Gs –> B2 receptor –> cAMP –> dilation

121
Q

Platelet receptor effect

A

TxA2: Gq –> TP –> Ca2+ –> aggregation

PGI2: Gs –> cAMP –> relaxation

122
Q

Importance of receptor subtypes

A

subtle differences in structure and anatomic distribution can provide unique points of pharmacological attack –> therapeutic leverage

123
Q

GPCR desensitization occurs via

A

Barrestin recruitment to phosphorylated GPCR carboxyl tail

124
Q

Two types of dose response curves

A
  • graded
  • quantal: all or nothing
125
Q

4 types of antagonism

A
  1. competitive - same receptor//reversible
  2. noncompetitive-different receptors on same pathway
  3. chemical-drug drug binding
  4. physical-different receptors with opposite effects
126
Q

Therapeutic index formula

A

LD50/ED50

127
Q

Safety Index

A

LD1/ED99

128
Q

ACH, muscarine, and pilocarpine are agonists for

A

muscarinic cholinergic receptors

129
Q

ACH and nicotine are agonists for

A

nicotinic cholinergic receptors

130
Q

Norepinephrine and epinephrine are agonists for

A

Alpha 1 adrenergic receptors

131
Q

Epinephrine is an agonist for

A

Beta 1 adrenergic receptors

132
Q

Atropine and scopalamine block

A

muscarinic cholinergic receptors

133
Q

Curare and succinylcholine block

A

nicotinic cholinergic receptors

134
Q

Prazosin and phentolamine block

A

Alpha-1 adrenergic receptors

135
Q

Propanolol and metoprolol block

A

Beta-1 adrenergic receptors

136
Q

NSAIDS

A
  • weak acids
  • variable selectivity for isoforms of COX
    • older NSAIDS inhibit both forms of COX
    • newer NSAIDS selectively block COX2
137
Q

New NSAIDS (-coxibs) block

A

COX2

138
Q

Prostanoid biosynthesis pathway

A

PLA2 -> Arachidonic Acid –> COX1 or COX2 –> prostanoids, prostacyclin, TxA2, prostaglandins D,E,F

139
Q

Aspirin MOA

A

acetylate Ser530 in COX –> irreversible inhibition

140
Q

All NSAIDs except aspirin MOA

A

reversible competitive inhibition of COX

141
Q

Clinical utility of NSAIDs

A
  1. anti-pyretic
  2. analgesic
  3. anti-inflammatory
  4. antiplatelet

4As

142
Q

NSAID toxicities

A
  1. gastropathy -blocking cytoprotection
  2. bleeding time increase
  3. hypertension -decreased PGE production –> renoconstriction
  4. gestation prolongation -decrease PGE,F
143
Q

NSAID induced gastropathy

A

COX 1 hypothesis:
COX1 inhibition –> reduced PGE –> less mucous, low pH, reduced TxA2 –> erosion, ulceration, bleeding

*COX 2 also produces PGE but doesn’t have anything to do with TxA2 compounding effect

144
Q

Why were coxibs developed?

A

To bypass the gastropathy and other side effects associated with COX1 inhibition by older NSAIDs

145
Q

What are the deleterious consequences of coxibs?

A

MI risk

  • COX2 blocks PGI2 –> no more vasodilation
  • COX1 remains unblocked –> TxA2 –> thrombosis

Possible renal

  • NSAIDs increase blood pressure due to PGE induced renin –>renal reabsorption –> both COX1 and 2
146
Q

Aspirin dose scale

A
  1. low = COX1
  2. medium - analgesis
  3. high - anti-inflmmatory (can be toxic–> not used)
147
Q

Aspirin toxicities

A
  • Reyes syndrome-hepatic toxicty in kids
  • Salicylism-headache, tinnitus, dizziness, nausea
148
Q

What are eicosonaids and what are their families?

A
  • naturally occuring autocoids derived from arachidonic acid in the cell membrane
    1. prostanoids - from cyclooxygenase
    2. leukotriene - from lipoxygenase
    3. HETE and ETE - from monoxygenase
149
Q

What do we call eicosanoids produced without enzymes?

A

Isoeicosanoids - formed from free radicals

150
Q

What are the 6 prostanoids?

A
  1. Prostaglandins
    • PGD2
    • PGE1&2
    • PGF2/alpha
  2. prostacyclin PGI2
  3. TxA2
151
Q

chemical mediators that are formed in cells and released to act as local mediators are

A

autocoids

152
Q

Which cells have arachidonic acid, phospholipase A2, and COX?

A

All cells

153
Q

What is the role of PLA2?

A

catalyzes the release of AA from the cell membrane

154
Q

Which two factors affect the kind of prostanoids produced?

A
  1. tissue
  2. enzyme isomers

e.g.

  1. platelets = thromboxane synthase = TxA2
  2. GI endothelia = PGE2 isomerase = PGE1 & 2
  3. Vascular endothelia = PGI2 isomerase = PGI2 prostacyclin
155
Q

Which isoform of PLA2 is responsible for the housekeeping functions of healthy cell life?

A

constitutive form: cytosolic PLA2

156
Q

Which PLA2 is expressed during inflammation and in response to chemical and physical stimuli?

A

inducible form: sPLA2

157
Q

Which COX is constitutively expressed?

A

COX1 (PGE1&2 protection in GI, platelet aggregation)

* still contributes to prostanoid formation in inflammation

158
Q

Which COX is found in platelets?

A

COX1

159
Q

Which COX is found in endothelial cells?

A

COX2 (prostacyclin)

160
Q

How is COX2 downregulated endogenously?

A

Glucocorticoids

161
Q

Where is COX2 found?

A

kidney

brain

synovial

macrophages/monocytes

162
Q

Function of TxA2

A
  • produced by platelets, kidney, macrophages
  • COX1
  • induces platelet aggregation, vasoconstriction, and smooth muscle cell proliferation
163
Q

Function of Prostacyclin PGI2

A
  • vascular endothelial cells
  • COX2
  • inhibits platelet aggregation and smooth muscle cell proliferation
  • vasodilator and proinflammatory
164
Q

Function of PGE1 and 2

A
  • cytoprotection in GI tract/stomach (COX1)
    • inhibition of gastric acid secretion, increased mucous production
  • Proinflammatory (COX2)
  • Cox 1 and 2
    • regulate renal blood flow through vasodilation
    • regulate salt homeostasis via renin
    • uterine and GI smooth muscle contraction
165
Q

Function of PGF2alpha

A
  • COX 1 and 2
  • induces vascular smooth muscle, luteal regression, and uterine contraction
  • vasoconstrictor
166
Q

Function of PGD2

A
  • COX1 and 2
  • produced by mast cells
  • cutaneous vasodilation, inhibition of platelet aggregation
  • sleep, chemotaxis of Th2 lymphocytes, hair follicle activity
167
Q

Carboprost MOA

A

PGF2alpha analogue used as an abortifacient and post partum bleeding

168
Q

Misoprotol MOA

A

PGE1 analogue used with RU486 for abortion and on own for gastric cytoprotection

169
Q

Dinoprostone MOA

A

PGE2 analogue used to induce labor

170
Q

Alprostadil MOA (dont need for exam)

A

PGE1 analogue used for eriectile dysfunction and maintain PDA

171
Q

Latanoprost MOA (dont need for exam)

A

PGF2alpha analogue used to reduce intraocular pressure in glaucoma

172
Q

Epoprostenol MOA

A

PGI2 analogue used to treat primary pulmonary hypertension by inducing pulmonary vasodilation

MDTI (10 decks)

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