Kinins
Peptide that are mediated in the inflammation.
Action of kinin:
On CVS: vasodilatation in the kidneys, heart, intestine, skin, and liver. It is 10 times active than histamine as vasodilator.

On exocrine and endocrine glands: kinin modulate the tone of pancreas and salivery glands and help regulate GIT motility, also affect the transport of water and electrolytes, glucose and amino acids through epithelial cell transport.

Distal (Potassium Sparing) Diuretics

Agents:

spironolactone
triamterene

Mechanism of action

Inhibition of Na/K exchange at aldosterone dependent distal tubular site

Spironolactone - competes with aldosterone for regulatory site

Triamterene - decreases activity of pump directly
•    Either mechanism decreases potassium wasting
•    Either mechanism produces poor diuresis (when used alone)
o    relatively unimportant Na recovery site

Diurectic activity increased if:

•    sodium load (body) is high 
•    aldosterone concentrations are high 
•    sodium load (tubule) is high - secondary to diuresis

Other electrolytes unaffected

Toxicity

•    spironolactone may produce adrenal and sex hormone effects with LONG-TERM use
•    Both drugs may produce electrolyte imbalance
 

Neurophysiology

Nerve fibers exhibit wide range of sensitivity to nerve blockade-in order of increasing resistance to block are the sensations of pain, cold, warmth, touch, pressure, proprioception and motor function

Nerve Fibers:

Myelinated = faster conducting

Unmyelinated = slower conducting

- Small non-myelinated fibers (C- pain fibers) and smaller myelinated pre-ganglionic B fibers are more readily blocked than are larger myelinated fibers responsible for muscle activity and touch [A-alpha and A-beta].

- Clinically, a person would notice complete lack of sensation to a pinprick, while at the same time still be able to move their fingers.

EPHEDRINE

It act indirectly and directly on α and β receptors. It increases blood pressure both by peripheral vasoconstriction and by increasing the cardiac output. Ephedrine also relaxes the bronchial smooth muscles.

Ephedrine stimulates CNS and produces restlessness, insomnia, anxiety and tremors.
Ephedrine produces mydriasis on local as well as systemic administration.
Ephedrine is useful for the treatment of chronic and moderate type of bronchial asthma, used as nasal decongestant and as a mydriatic without cycloplegia. It is also useful in preventing ventricular asystole in Stokes Adams syndrome.

Sulfonylureas

1st generation
tolbutamide
chlorpropamide

2nd generation

glyburide
glimepiride
glipizide

Mechanism

glucose normally triggers insulin release from pancreatic β cells by increasing intracellular ATP
→ closes K+ channels → depolarization → ↑ Ca2+ influx → insulin release

sulfonylureas mimic action of glucose by closing K+ channels in pancreatic β cells 
→ depolarization → ↑ Ca2+ influx → insulin release

its use results in

↓ glucagon release
↑ insulin sensitivity in muscle and liver

Clinical use

type II DM

stimulates release of endogenous insulin 
cannot be used in type I DM due to complete lack of islet function

Toxicity

first generation

disulfiram-like effects
especially chlorpropamide

second generation

hypoglycemia
weight gain

Beta - Adrenoceptor blocking Agents

These are the agents which block the action of sympathetic nerve stimulation and circulating sympathomimetic amines on the beta adrenergic receptors. 

At the cellular level, they inhibit the activity of the membrane cAMP. The main effect is to reduce cardiac activity by diminishing β1 receptor stimulation in the heart. This decreases the rate and force of myocardial contraction of the heart, and decreases the rate of conduction of impulses through the conduction system.

Beta blockers may further be classified on basis of their site of action into following two main classes namely 

cardioselective beta blockers (selective beta 1 blockers) 

non selective beta 1 + beta 2 blockers 

Classification for beta adrenergic blocking agents.

A. Non-selective (β1+β2)

Propranolol  Sotalol  Nadolol Timolol  Alprenolol Pindolol 

With additional alpha blocking activity

Labetalol  Carvedilol  

B. β1 Selective (cardioselective)

Metoprolol  Atenolol  Bisoprolol  Celiprolol  

C. β2  Selective

Butoxamine 

Mechanisms of Action of beta blocker

Beta adrenoceptor Blockers competitively antagonize the responses to catecholamines that are mediated by beta-receptors and other
adrenomimetics at β-receptors 

Because the β-receptors of the heart are primarily of the β1 type and those in the pulmonary and vascular smooth muscle are β2 receptors, β1-selective antagonists are frequently referred to as cardioselective blockers. 

β-adrenergic receptor blockers (β blockers)
1. Used more often than α blockers.
2. Some are partial agonists (have intrinsic sympathomimetic activity).
3. Propranolol is the prototype of nonselective β blockers.
4. β blocker effects: lower blood pressure, reduce angina, reduce risk after myocardial infarction, reduce heart rate and force, have antiarrhythmic effect, cause hypoglycemia in diabetics, lower intraocular pressure.
5. Carvedilol: a nonselective β blocker that also blocks α receptors; used for heart failure.