Antihypertensive treatment:Vasodilator

Vasodilators can be used as a part of antihypertensive treatment.

About calcium channel blockers:I AM HERE

Oral vasodilators are seldom used today due to their side effects (tachycardia). The example of parenteral vasodilator is sodium nitroprussides. 

This table is based on Dr.Subrat's notes (hypertension 4). I put them into table so it is easy to read. Besides, I highlight the similarities between the medication with same colours to help in memorising. 

Drugs act on RAAS - ACEI,ARB,Renin inhibitor

To understand how the drugs work, we must understand how RAAS work.
ACE= angiontensin-converting enzyme

This diagram summarises how the system work (from google). Note that angiotensin II (Ag II) increases aldosterone secretion which increase the reabsorption of sodium & chloride ions as well as excretion of potassium ions.

The main target of drugs are renin, ACE and angiotensin II receptors (where Ag II bind to and generate responses).

   This diagram gives an overview with main points for each drugs.

Renin inhibitors

• interact with ACEI /ARB especially in diabetic pt

-aliskiren can increase adverse events (non-fatal stroke, renal complications, hyperkalemia, hypotension) with no apparent additional benefits when added to treatment with an ACEI or ARB in diabetic patients.

ACEI:

• Uses:

1. can be used in all grades of heart failure. It is usually combined with a beta blockers.
2. antihypertensive treatment. 
3.It is particularly indicated for hypertension in pt with type 1 diabetes with nephropathy.
4. used in early and long-term management of pts who have had a myocardial infarction.

• Side effects

1. Profound hypotension
2. dry cough and angioedema are related to bradykinin (ACEI blocks ACE, preventing the deactivation of  bradykinin).

3.GIT effects: nausea,vomiting,constipation, abdominal pain etc.

• Captropril has other minor side effects due to sulphydryl group, include:altered taste, skin rash, drug fever, neutropaenia, proteinuria.

• contraindicated in pregnancy
• Drug-drug interaction:

(i) hyperkalaemia with K+-sparing diuretics or with K+ supplements.

Explaination: 

        1. Ag II =>potassium excretion.

        2. ACEI (-) AgII,=> (-) potassium excretion (K+retain in the body)

       3. K+ sparing diuretics and K+ supplement also retain K+ in the body=>hyperkalaemia

(     (ii) NSAIDs 

     -may reduce hypotensive effect by blocking bradykinin-induced vasodilation (partly PG-mediated) 

•       History of Development (covered in Semester 4 Biotechnology)  

       1. ACE is a zinc protease and carboxypeptidase is a zinc protease too.
        2. Benzylsuccinic acid can inhibit carboxypeptidase, thus make it a model for designing ACEI. 3.However, there is a difference between carboxypeptidase and ACE: ACE cleaves a dipeptide wherease Carboxypeptidase cleaves 1 peptide chain.
      4. It is proposed that the linker between carbonyl groups should be longer and a series of dicarboxylic acids were proposed but they are not very stable/potent.
     5. the carboxyl group (COO-) group binding to Zn2+ was exchanged with thiol group (SH).
   

(from Dr.Mai Chun Wai notes on Drug Design Based On Protein Structure)

   From here I just screenshot the notes from Drug Design Based On Protein Structure by Dr.Mai Chun Wai, because I think his explanations are clear with figure of structure.

    

ARB

The side effects do not include dry cough and angiodema as it has no effect on bradykinin.
   1. antihypertensive
    2.alternative to an ACEI in the management of heart failure (HF) / diabetic nephropathy.


Reference: Dr.Subrat notes on hypertension 3, British National Formulary (May), Drug Design Based On Protein Structure by Dr.Mai Chun Wai

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Related: drug acts on sympathetic N.S:http://louisastudy129.blogspot.my/2016/06/antihypertensive-treatment-drugs-act-on.html

Drugs act on sympathetic nervous system: Alpha & Beta blocker, Centrally acting drug

Today post focuses on drugs that alter sympathetic nervous system. They are

(i)  Adrenoceptor blockers- a-blockers, b-blockers

(ii) Centrally acting drugs

To understand the mechanism of adrenoreceptor blockers, let us revise on the functions of different receptors.

1. How do alpha blockers work and how to relate them to their side effects?
 Activation of alpha 1 leads to vasoconstriction-> increase the blood pressure (BP).
Blocking alpha-1 prevent vasoconstriction -> decrease in BP (alpha-1 selective).
therefore, the main side effects include first dose phenomenon and orthostatic hypotension (postural hypotension).

 Activation of alfa-2 :inhibits the release of noradrenaline (NA)->decrease heart rate and contractility.
the non-selective alpha blocker blocks alfa-2->  increase heart rate and contractility.
Side effect: decrease BP (from blocked alpha-1) + increase HR (from blocked alpha-2) = reflex tachycardia.

2.How do beta blockers work?
Non-selective beta blocker block both beta-1&2.
Blocking beta-1 (in heart)->decrease heart contractile force and HR->side effect:bradycardia.
Blocking beta-2 ->inhibit the relaxation bronchus muscles->contraindicated in patient (pt) with COPD/asthma.
                          ->also inhibit vasodilation->peripheral vasoconstriction.

Summary

alpha blockers

• Type

this is a screenshot from Dr.Mai Chung Wai's notes on Drug Design Based On Protein Structure, covered in Sem 4 Biotechnology.

• Use

-can be used with other antihypertensive drugs in the treatment of resistant hypertension.

Beta blocker

• Type

beta 1 selective: Practolol, Atenolol, Metoprolol (P.A.M)

non-selective: propranolol,pindolol,timolol

• Uses 

1. Management of stable angina & acute coronary syndromes

2. Hypertension treatment

3.reduce recurrence rate of myocardial infarction.

4.Management of arrhythmias

5.Heart failure treatment

• Development:

The following diagrams are the screenshoots from Dr.Mai Chung Wai's notes on Drug Design Based On Protein Structure, covered in Sem 4 Biotechnology.

                            

The development of beta blockers.

                                  

Structure of propanolol. It is good to memorise these properties for examination purpose.

for selective beta1 blocker, para-substitution is essential.

The table below summaries the properties of alpha and beta blockers.

                                             Table 1: summary of alpha and beta blockers.

Beta 1 selective blockers are useful in pt with impaired pulmonary functions and diabetics pt.

Centrally acting drugs

Table 2: centrally acting drugs

oopsss hope my handwriting is understandable.

To remember the name of centrally acting drugs, you can try to think of MCM.

a brand endorsed by EXO (based on google, not sure about 2016 tho)

Hypertension at a glance: Introduction & Treatments

Hypertension is covered in Cardiovascular System module, Semester 2, Bachelor of Pharmacy in IMU.

First,we must know what hypertension (HPN) is.
These notes are based on Dr.Subrat lecture slides. When comes to studying I prefer to use mind map and tables.

Introduction:
Before that, let us revise what are the functions of some adrenergic receptors. Familiar with these receptors is definitely going to help us in understanding the mechanism of HPN and its pharmacological treatments.


It is the best if you can memorise this! In higher semester you are going to deal with these too. OK lets us move on to HPN.


 Hypertension (HPT) is defined as persistent elevation of SBP of > 140mm Hg and / or DBP of > 90mm Hg.

This is the simple outline of introduction of hypertension. 

The risk factors and effects are pretty easy to understand. The risk factors for primary hypertension include overweight, smoking, alcohol, sedentary lifestyle etc. Hypertension cause damage to arteries and increase the risk of getting other diseases.

RAAS stands for Renin-Angiotensin Aldosterone system. There are plenty of information on internet about this system. As a student, you must understand and remember this mechanism well, as this will help you in the following semester.

source: google image

I think this summarises the introduction of hypertension. Wow it really take a lot of time to type this up.  

Overview of the pharmacological treatment:

1. Drugs act on RAAS: click me
2. Drugs act on sympathetic nervous system: poke here!!
3.Diuretics:Diuretics
4.Calcium Channel Blockers: Cardiac muscles and CCB
5. Vasodilators: http://louisastudy129.blogspot.my/2016/06/antihypertensive-treatmentvasodilator.html