ANTICHOLINERGIC DRUGS
Blocks the action of Ach on autonomic effectors.

Classification
Natural Alkaloids - Atropine. Hyoscine

Semi-synthetic deriuvatives:- Homatropine, Homatropine methylbromide, Atropine methonitrate.

Synthetic compounds 

(a) Mydriatics - Cyclopentolate. Tropicamide.
(b) Antisecretory - Antispasmodics - Propantha1ine. Oxy-phenonium, Pirenzipine.
c) Antiparkinsonism- Benzotopine, Ethopropazine, Trihexyphenidyl, Procyclidine, Biperiden 
Other drugs with anticholinergic properties • Tricyclic Antidepressants • Phenothiazines • Antihistaminics • Disopyramide

MUSCARINIC RECEPTORS SUBTYPES & ANTAGONISTS 
• M 1 Antagonists – Pirenzepine, Telenzepine, dicyclomine, trihexyphenidyl 
• M 2 Antagonists – Gallamine, methoctramine 
• M 3 Antagonists – Darifenacin, solifenacin, oxybutynin, tolterodine

Pharmacological Actions
CNS - stimulation of medullary centres like vagal. respiratory. vasomotor and inhibition of vestibular excitation and has anti-motion sickness properties.
CVS - tachycardia.
Eye - mydriasis
Smooth muscles - relaxation of the muscles receiving parnsympathetic motor innervation.
Glands - decreased secretion of sweat and salivary glands
Body Temperature - is increased as there is stimulation of  temperature regulating centre.
Respiratory System- Bronchodilatation & decrease in secretions. For COPD or Asthma - antimuscarinic drugs are effective
GIT - Pirenzepine & Telenzepine - decrease gastric secretion with lesser side effects.

Sympatholytics And Alpha Adrenergic Blockers 

Types 
1.    Alpha 1-receptor blockers: prazocin,doxazocin. 
2.    Centrally acting alpha 2- agonists: methyldopa, clonidine. 
3.    Peripherally acting adrenergic antagonists: reserpine. 
4.    Imidazoline receptor agonists: rilmenidine, moxonidine. 
 
Advantages 

- Alpha1- receptor blockers and imidazoline receptor agonists improve lipid profile and insulin sensitivity. 
- Methyldopa: increases renal blood flow. Drug of choice during pregnancy. 
- Reserpine: neutral metabolic effects and cheap. 

Indications: 

- Diabetes mellitus: alpha1- receptor blockers, imidazoline receptor agonists. 
- Dyslipidemia: alpha 1- receptor blockers, imidazoline receptor agonists. 
- Prostatic hypertrophy: alpha 1- receptor blockers. 
- When there is a need for rapid reduction in blood pressure: clonidine. 

Side Effects 

- Prazocin: postural hypotension, diarrhea, occasional tachycardia, and tolerance (due to fluid retention). 
- Methyldopa: sedation, hepatotoxicity, hemolytic anemia, and tolerance. 
- Reserpine: depression, lethargy, weight loss, peptic ulcer, diarrhea, and impotence
- Clonidine: dry mouth, sedation, bradycardia, impotence, and rebound hypertension if stopped suddenly. 

Considerations 
- Prazocin, methyldopa, and reserpine should be combined with a diuretic because of fluid retention. 

Direct Arterial Vasodilators 

Types: hydralazine, diazoxide, nitroprusside, and minoxidil

TRIMETHOPRIM

It is a diaminopyrimidine. It inhibits bacterial dihydrofolate reductase( DHFRase).

In combination with sulphamethoxzole it is called Co-trimoxazole.

Spectrum of action

 S. Typhi. Serratia. Klebsiela and many sulphonamide resistant strains of Staph.aureus. Strep pyogens

Adverse effects

Megaloblastic anemia. i.e.. due to folate defeciency.

Contraindicated in pregnancy.

Diuretics if given with co-trimoxazole cause thrombocytopenia.

Uses

I. UTI. 2. RTI. 3. Typhoid. 5. Septicemias. 5. Whooping cough

DOBUTAMINE

It is a derivative of dopamine and has relatively β1 -selective action and it also activates α1 receptors and do not have D1  receptor agonistic property. It increases the force of myocardial contraction and cardiac output without significant change in heart rate, blood pressure and peripheral resistance. It is used as inotropic agent and for short term management of CHF and also in patients who are unresponsive to digitalis.

Heparin:

• Inhibits blood coagulation by forming complexes with an α2-globulin (Antithrombin III) and each of the activated proteases of the coagulation cascade (Kallikrein, XIIa, XIa, IXa, Xa, and Thrombin). After formation of the heparin-ATIII-coagulation factor, heparin is released and becomes available again to bind to free ATIII.
• Blocks conversion of Prothrombin to Thrombin and thus inhibits the synthesis of Fibrin from Fibrinogen.
• Inhibits platelet function and increases vascular permeability. May induce moderate to severe thrombocytopenia.
• Is prescribed on a “unit” basis.
• Heparin is not effective after oral administration and is generally administered by intravenous or subcutaneous injection. Intramuscular injections should be avoided.
• Heparin does not cross the placenta and does not pass into the maternal milk.
• is contraindicated in any situation where active bleeding must be avoided.

Ulcerative lesions, intracranial hemorrhage, etc.

Overdosage:

• Simple withdrawal.

• Protamine sulfate: Highly basic peptide that binds heparin and thus neutralizes its effects.

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.