Targets of Antihypertensive Drugs Flashcards
Significance of the penultimate position proline in angiotensin III
Puts a stop to aminopeptidase activity
Full words for AT1 receptor
Angiotensin II type I receptor
Three ways that renin release is regulated?
- NaCl reabs. in macula densa
- Blood pressre in preglomerular vessels
- Activation of beta-adrenergic receptors on JGCs
What type of receptors are AT1s
G protein couples, Gi and Gq (also coupled to phospholipase A2
Where are AT1s located?
BV, Brain, Adrenal, Kidney, Heart
Net job of AT1 receptors
Increase BP
Three types of reactions of angiotensin II that lower BP?
Altered Peripheral Resistance
Altered Renal Function
Altered Cardiovascular Structure.
How does angiotensin II modify peripheral resistance?
RAPID PRESSOR RESPONSE
Directed vasoconstriction
Enhancement of NE transmission –> inc sympathetics
Catecholamines from the adrenals
How does angiotensin II modify renal function?
SLOW PRESSOR RESPONSE
Increased Na reabsorption
Aldosterone release
Altered hemodynamics (constriction, increased renal symp tone)
How does angiotensin II modify cardiovascular structure?
Vascular and Cardiac hypertrophy and remodeling
Increased protooncogenes, growth factors
Increased afterload, increased wall tension
Three types of inhibitors of RAA system
Renin Inhibitors
ACE Inhibitors
Ang Receptor Blockers
Three types of ACE inhibitors
- Sulfhydryl-containing
- Dicarboxyl-containing
- Phosphorous-containing
Which type of ACE inhibitor is Catopril? What does it do?
Sulfhydryl-containing
It binds in the active site of ACE, blocking Ang I
ACE inhibitors will cause an increase in the levels of…
BRADYKININ
Captopril. Half life? Side effects?
Short – Under 3 hours
SE – Altered metallic taste from thiol, rash
Name two dicarboxyl-containing ACE inhibitors
Enalopril, Lisinopril
Enalopril important features…
Prodrug, long half life
What is unique about Moexipril
This is the one ACE inhibitor that is cleared hepatically. THe others are kidney cleared.
Important details about Lisinopril?
Active molecule, not a prodrug
Lysine derivative of enalaprilat
Half life of 12 hours
Important example of a phosphinate containing ACE inhibitor?
Fosinopril (Monopril)
Important details abotu fosinopril?
Requires clevage by hepatic esterases
Extensive hepatic metabolism, excreted in urine/bile
Half life 11.5 hrs
Clinical uses of ACE inhibitors
HTN
LV Systolic Dysfunction
MI
Diabetic Nephropathy
Adverse effects of ACE inhibitors?
Hypotension, Dry Cough, Hyperkalemia, Acute Renal Failure, Angioedema
ACE inhibitor drug-drug interactions?
Antacids drop bioavailability
NSAIDS reduce efficacy
K+ supplements can cause hyperkalemia
Can increase plasma levels of digoxin and lithium
Contraindications for ACE inhibitors
Pregnancy
High doses in paitents with renal insufficiency
Whats in the same of all of the Ang Type II receptor antagonists
Sartan
Actions of AT1 receptor antagonists
No effects on bradykinin levels
blocks all ang II activity (pressor effects, etc.)
Uricosuric effect
Clinical uses for AT1 receptor antagonists
HTN
CHF
Diabetic Nephropathy
Stroke Prophylaxis
Adverse effects of AT1 receptor antagonists?
Hypotension
Hyperkalemia
Teratogenic Potential
Name the renin inhibitor we discussed
Aliskiren (Tekturna)
Aliskiren SE and Contraindications.
SE – Diarrhea
Contra – Pregnancy and Nursing Mothers
