L14 - drug effects on smooth muscle

Question 1

what organs contain smooth muscle

Answer 1

hollow ones

Question 2

what regulates SM contraction

Answer 2

ANS
hormones
pacemaker cells (GI tract)

Question 3

what type of drugs are used to affect smooth muscle of the cardiovascular system

Answer 3

vasodilators / constrictors

Question 4

what type of drugs are used to affect smooth muscle of the genitourinary system

Answer 4

anti muscarinics (M) 
B3 agonists

Question 5

what type of drugs are used to affect smooth muscle respiratory system

Answer 5

B2 agonists (bronchodilation)

Question 6

what are the two ways drugs can act on smooth muscle to produce effect

Answer 6

1. act on receptors (as agonists/antagonists)

2. act on cell signal transduction (eg channel blockers)

Question 7

effect of NA on blood vessels?

Answer 7

acts on a1 to cause constriction

Question 8

effects of angiotensin 2 on blood vessels

Answer 8

(in blood) causes constriction

Question 9

effects of adrenaline on blood vessels?

Answer 9

acts on a to constrict

acts on B2 to dilate

Question 10

effects of increasing NO on blood vessels

Answer 10

vasodilation

Question 11

describe the composition of actin and myosin in smooth muscle

Answer 11

actin is found within dense bodies
intermediate filaments link dense bodies
myosin found between dense bodies

Question 12

describe process of SM contraction

Answer 12

1. Ca2+ enters cytoplasm from SR and ECF
2. Ca2+ binds to calmodulin and this complex activates MLCK
3. MLCK phosphorylates myosin heads
4. myosin forms cross bridges
5. power stroke

Question 13

what enzyme dephosphorylates myosin

Answer 13

myosin phosphatase

Question 14

what is the effect of myosin phosphatase on SM contraction

Answer 14

causes myosin dephosphorylation - leads to relaxation of SM

Question 15

what is Ca2+ sensitisation

Answer 15

the inhibition of myosin phosphatase (via rho kinase) causing smooth muscle contraction (independent of Ca2+ levels)

Question 16

what is Ca2+ desensitisation

Answer 16

the activation of myosin phosphatase causing SM relaxation (independent of Ca2+ levels)

Question 17

describe the mechanism of smooth muscle contraction via binding of noradrenaline / angiotensin 2

Answer 17

1. bind to receptors (Gq coupled) which activates phospholipase C and rho kinase
2. Phospholipase C breaks down PIP2 to DAG + IP3
   Rho kinase causes Ca2+ sensitisation)
3. IP3 causes Ca2+ release from SR
   DAG opens Na+ and Ca2+ channels
4. this causes depolarisation , which causes opening of voltage gated Ca2+ chnannels
5. contraction

Question 18

what does rho kinase do

Answer 18

inhibits myosin phosphatase leading to Ca2+ sensitisation (SM contraction)

Question 19

what activates rho kinase?

Answer 19

the binding of agonist (NA/angiotensin 2) to G11 coupled receptor on smooth muscle

Question 20

what is EDRF?

Answer 20

endothelium derived relaxing factor - released by endothelium causing vasodilation

Question 21

describe process of vasodilation caused by NO (Ca2+ desensitisation)

Answer 21

1. NO released from endothelium diffuses into SM
2. stimulates guanylate cyclase which converts GTP to cGMP
3. cGMP :
   
   • opens K+ channels (K+ out)
   • activates Ca2+ pumps (Ca2+ out)
4. leads to Ca2+ desensitisation
5. relaxation

Question 22

what are the effects of cGMP

Answer 22

1. opens K+ channels (K+ out )
2. activates Ca2+ pumps (Ca2+ out)

responsible for vasodilation

Question 23

what enzymes break down cGMP

Answer 23

phosphodiesterase’s

Question 24

main uses of vasodilators?

Answer 24

decrease b.p

treat angina

Question 25

what is the effect of Ca2+ channel blockers on contraction/dilation of SM

Answer 25

cause vasodilation

Question 26

what type of drugs cause vasodilation and can treat high b.p (and angina)

Answer 26

Ca2+ channel blockers
ACE inhibitors
AT1 receptor antagonists 
a1 antagonists
minoxidil 
nicorandil 
organic nitrates

Question 27

what factors stimulate the renin-angiotensin-aldosterone system

Answer 27

decrease in

• blood vol
• blood Na+
• blood pressure

Question 28

describe the R-A-A system

Answer 28

1. renin released from JG cells of kidney cleaves angiotensinogen forming angiotensin 1
2. Angiotensin converting enzyme (ACE) converts angiotensin 1 to angioensin 2

Question 29

what is ACE and what does it do

Answer 29

angiotensin converting enzyme

converts angiotensin 1 to angiotensin 2

Question 30

what receptor does angiotensin 2 act on

Answer 30

AT1 receptor

Question 31

what does activation of AT1 receptor by angiotensin 2 cause

Answer 31

1. aldosterone release (increase blood vol,Na,pressure)
2. ADH release (increase water reabsorption)
3. vasoconstriction

Question 32

what does minoxidil do?

Answer 32

causes vasodilation by opening K+ channels leading to hyperpolarisation

Question 33

what does nicranodil do?

Answer 33

K+ channel agonist

stimulates guanylate cyclase

Question 34

give an example of a PDE5 inhibitor

Answer 34

sildenafil

Question 35

what does PDE5 do?

Answer 35

converts cGMP to GMP in blood vessels of penis (lower cGMP means vasoconstriction)

Question 36

what do a1 antagonists do to smooth muscle?

Answer 36

prevent binding of NA so the cellular mechanisms of contraction dont take place - vasodilation

Question 37

what does sildenafil do?

Answer 37

it is a PDE5 inhibitor which increases [cGMP] leading to vasodilation in blood vessels of penis treating erectile dysfunction

also dilates pulmonary arteries

Question 38

what do organic nitrates do?

Answer 38

breakdown to form NO
NO increases [cGMP]
vasodilation

Question 39

what drugs are used to treat an overactive bladder (contraction when it shouldnt)

Answer 39

1. M2 and M3 antagonists
2. B3 agonists
3. botox

Question 40

what tupe of drugs can treat pulmonary hypertension

Answer 40

1. stable PGI2 analogs (ileprost)
2. PDE5 inhibitors (sildenafil)
3. endothelin receptor antagonists (ambrisetan)