Pharmacology of Hypertension

Question 1

Aliskiren 
class-
type- 
primary target-
action- 
physiology- 6 steps, go down both routes and tell me what they do 
clinical-

Answer 1

class- Renin Inhibitor
type- small mol
primary target- Renin
action- Competitive Inhibitor
physiology:
dec. Renin
dec. RAAS
- dec. Ang II -> dec vasoconstriction, Na+ reab + ADH
- Aldosterone production -> dec. ENaCs and Na+/K+ ATPase expression
- both decrease water reab and therefore dec blood vol

clinical- essential hypertension

Question 2

Enalapril 
class-
type- 
primary target-
action- 
physiology-
one main step and what will this do?
ALSO...
clinical- 2

Answer 2

class- Ace Inhibitor 
type- small mol
primary target- ACE
action- competitive inhibitor 
physiology:
dec. Ang II-> dec vasoconstriction + Na+ reab + ADH
ALSO
dec. bradykinin breakdown, bradykinin accumilates causing a cough 
clincal- EH and HF

Question 3

Vasartan 
class-
type- 
primary target-
action- 
physiology- go down both routes
clinical- 2 
also...

Answer 3

class- Angiotenisin Receptor Blocker
type- Small mol.
primary target- AT1 (this is the receptor for ATII remember!)
action- competitive inhibitor
physiology:
- dec. Ang II -> dec vasoconstriction, Na+ reab + ADH
- Aldosterone production -> dec. ENaCs and Na+/K+ ATPase expression
- both decrease water reab and therefore dec blood vol

clinical: EH and HF
No cough as bradykinin will not breakdown

Question 4

Atenalol 
class- 
type- 
primary target-  what do they normally do +ALSO?
action- 
physiology- 
- 
also...
-
also...

clinical-3

Answer 4

class- Beta Blocker 
type- small mol.
primary target- B1 receptors (on SA node, inc. HR via +ve chronotropic effect and inc SV via +ve inotropic effect ALSO SECRETE RENIN)
action- Competitive Antagonist
physiology- 
dec.HR and dec. SV -> dec CO
also...
dec. renin secretion via juxtamedularry feedback, dec. RAAS
also...
dec. sympathetic outflow 
clinical- EH, Angina and arrhythmias

Question 5

Amlodipine
class-  
type- 
primary target-
action- 
physiology- 3 steps, think how it works! its class! 
clinical-2

Answer 5

class- Ca2+ ion channel blocker
type- small mol
primary target- L-type voltage-gated Ca2+ ion channel
action- Gating Inhibitor
physiology-
1) smooth muslce is targetted more than cardiac muslce
2) dec. Ca2+ mobilisation in smooth muscle (less influx)
3) vasodilation
clinical- angina and EH

Question 6

2 types of hypertension
1) 90% and the cause?

2) 10% and some eg’s of causes 5

examples of endogenous risk factors/ contributors (3/5)
examples of exogenous risk factors/ contributors (2/3)

Answer 6

1) Essential Hypertension
idiopathic, cause unknown, not one major cuase

2) Secondary hypertension
- renal disorder
- pregnancy -> pre-eclampsia
- drugs such as cocaine
- endocrine such as primary hyperaldosteronism or cushings syndrome

examples of endogenous risk factors/ contributors

• RAAS
• CNS
• Arterial
• Obesity
• ethnicity

examples of exogenous risk factors/ contributors

• Diet
• Smoking
• Stress

Question 7

How does the body affect BP?

 Endothelium: 3 vasoactive agents 
1) NO -> how does this work 4 steps (horrible) 
what does an atheroma do?
2) ..... vasodilator or constrictor?
3) ..... vasodilator or constrictor? 

Autonomic NS
3 adrenoreceptors where are they found and what do they do?

Vasoactive peptides 
1) 
2) 3 examples here -> what do they do and how 4 steps (horrible)
3) 
4) classic peptide, the system? 
this peptide is a good target for drugs

Answer 7

Endothelium:
1) NO
inc. guanylyl cyclase-> inc cGMP-> inc. pKG -> smooth muscle relxation
atheroma causes decrease in NO production -> vasoconstriction
2) prostaglandins (PGI2) -> vasodilator
3) Endothelin -> vasoconstrictor

Autonomic NS: when activated all increase BP (sympathetic)
a1 + NA -> on vessels -> vasoconstrict
B1 + NA -> on SA node + cardicas tissue -> inc. force and rate of heart contractions
B2 + NA -> found on bronchioles -> vasodilator

Vasoactive peptides
1) Bradykinin -> vasodilator and ACE inhibs block
2) Natreuretic peptides: ANP, BNP, CNP
they increase Na+ and water excretion
NPR1 is guanylyl cyclase -> inc. cGMP -> smooth muscle relax -> vasodilation
3) Vasopressin -> ADH it is a vasocontrictor via inc. H2O reab.
4) Renin , RAAS
systemic vascular resistance

Question 8

RAAS 
function of Renin?
function of ACE? 

functions of AngII and what receptor does it bind to? (6)

what and how does Aldosterone do? (4 steps) and where is it produced + its repceptor?

Answer 8

Renin cleaves AAs from Angiotenisongen -> AngI
ACE celaves AAs from AngI -> AngII

Ang II + AT1

1) Inc. Aldosterone production
2) smooth muslce contraction -> vasoconstriction
3) Inc. Na+ reab IN PCT
4) Inc. ADH production -> vasocontriction
5) Inc. Endothelin production -> vasoconstrictor
6) central and peripheral sympathetic stimulation

Aldosterone + MR
Produced in Zona glomerulosa in adrenal gland
1) nuclear hormone receptors activated
2) changes transcrption
3) inc. ENaCs expression
4) inc. Na+/K+ATPase
both increase Na+ and water reab which inc. blood vol.

Question 9

ENaCs 
where are they found? and on which membrane? 
they're NOT...
function:
via 

Na+/K+ ATPase
found where and on what membrane?
what comes in and out?
function?

Answer 9

ENaCs
late DCT and CD on apical membrane 
they're not voltage-gated!
function:
inc. Na+ reab. via inc. Na+ permeability

Na+/K+ ATPase
DCT and on basolateral membrane 
3Na+ OUT and 2K+ IN 
function:
preserves Na+/K+ gradient across membrane