Biguanides

metformin

Mechanism

↓ gluconeogenesis

appears to inhibit complex 1 of respiratory chain

↑ insulin sensitivity
↑ glycolysis
↓ serum glucose levels
↓ postprandial glucose levels

Clinical use

first-line therapy in type II DM

Toxicity

no hypoglycemia
no weight gain
lactic acidosis is most serious side effect 
contraindicated in renal failure 

Antiarrhythmic Drugs

Cardiac Arrhythmias 
Can originate in any part of the conduction system or from atrial or ventricular muscle.
Result from
– Disturbances in electrical impulse formation (automaticity) 
– Conduction (conductivity) 
– Both

MECHANISMS OF ARRHYTHMIA
ARRHYTHMIA – absence of rhythm
DYSRRHYTHMIA – abnormal rhythm

ARRHYTHMIAS result from:
1. Disturbance in Impulse Formation
2. Disturbance in Impulse Conduction
- Block results from severely depressed conduction
- Re-entry or circus movement / daughter impulse

Types of Arrhythmias

• Sinus arrhythmias 
– Usually significant only 
– if they are severe or  prolonged 

• Atrial arrhythmias 
– Most significant in the presence of underlying heart disease
– Serious: atrial fibrillation can lead to the formation of clots in the heart 

• Nodal arrhythmias 
– May involve tachycardia and increased workload of the heart or bradycardia from heart block 

• Ventricular arrhythmias 
– Include premature ventricular contractions (PVCs), ventricular tachycardia, and ventricular fibrillation 

Indications
• To convert atrial fibrillation (AF) or flutter to normal sinus rhythm (NSR) 
• To maintain NSR after conversion from AF or flutter 
• When the ventricular rate is so fast or irregular that cardiac output is impaired
– Decreased cardiac output leads to symptoms of decreased systemic, cerebral, and coronary circulation 
• When dangerous arrhythmias occur and may be fatal if not quickly terminated 
– For example: ventricular tachycardia may cause cardiac arrest 

Mechanism of Action 
• Reduce automaticity (spontaneous depolarization of myocardial cells, including ectopic pacemakers) 
• Slow conduction of electrical impulses through the heart
• Prolong the refractory period of myocardial cells (so they are less likely to be prematurely activated by adjacent cells 
 

Clavulanic acid is often combined with amoxicillin to treat certain infections caused by bacteria, including infections of the ears, lungs, sinus, skin, and urinary tract. It works by preventing bacterium that release beta-lactamases from destroying amoxicillin.

Prostaglandines:

Every cell in the body is capable of synthesizing one or more types of PGS. The four major group of PGs are E, F, A, and B.

Pharmacological actions:

stimulation of cyclicAMP production and calcium use by various cells

CVS
PGE2 acts as vasodilator; it is more potent hypotensive than Ach and histamine

Uterous
PGE2 and PGF2α Contract human uterus

Bronchial muscle

PGF2α and thromboxan A2 cause bronchial muscle contraction.

PGE2 & PGI2 cause bronchial muscle dilatation

GIT: PGE2 and PGF2α cause colic and watery diarrhoea

Platelets

Thromboxan A2 is potent induce of platelets aggregation

Kidney

PGE2 and PGI2 increase water, Na ion and K ion excretion (act as diuresis) that cause renal vasodilatation and inhibit
tubular reabsorption

USE
PGI2: Epoprostenol (inhibits platelets aggregation)
PGE1: Alprostadil (used to maintain the potency of arterioles in neonates with congenital heart defects).
PGE2: Dinoproste (used as pessaries to induce labor)
Synthetic analogue of PGE1: Misoprostol (inhibit the secretion of HCl).

SYMPATHOMIMETICS 

β2 -agonists are invariably used in the symptomatic treatment of asthma. 

Epinephrine and ephedrine are structurally related to the catecholamine norepinephrine, a neurotransmitter of the adrenergic nervous system 

Some of the important β 2 agonists like salmeterol, terbutaline and salbutamol are invariably used as bronchodilators both oral as well as
aerosol inhalants 

SALBUTAMOL
It is highly selective β2 -adrenergic stimulant h-aving a prominent bronchodilator action.
It has poor cardiac action compared to isoprenaline.

TERBUTALINE
It is highly selective β2  agonist similar to salbutamol, useful by oral as well as inhalational route.

SALMETEROL

Salmeterol is long-acting analogue of salbutamol 

BAMBUTEROL

It is a latest selective adrenergic β2 agonist with long plasma half life and given once daily in a dose of 10-20 mg orally.

METHYLXANTHINES (THEOPHYLLINE AND ITS DERIVATIVES)

THEOPHYLLINE
Theophylline has two distinct action:
smooth muscle relaxation (i.e. bronchodilatation) and suppression of the response of the airways to stimuli (i.e. non-bronchodilator prophylactic effects). 

ANTICHOLINERGICS

Anticholinergics, like atropine and its derivative ipratropium bromide block cholinergic pathways that cause airway constriction.

MAST CELL STABILIZERS

SODIUM CROMOGLYCATE

It inhibits degranulation of mast cells by trigger stimuli. 
It also inhibits the release of various asthma provoking mediators e.g. histamine, leukotrienes, platelet activating factor (PAF) and interleukins (IL’s) from mast cell 

KETOTIFEN
It is a cromolyn analogue. It is an antihistaminic (H1  antagonist) and probably inhibits airway inflammation induced by platelet activating factor (PAF) in primate. 
It is not a bronchodilator. It is used in asthma and symptomatic relief in atopic dermatitis, rhinitis, conjunctivitis and urticaria.

LEUKOTRIENE PATHWAY INHIBITORS

MONTELUKAST

It is a cysteinyl leukotriene receptor antagonist indicated for the management of persistent asthma. 

Meperidine (Demerol)

Meperidine is a phenylpiperidine and has a number of congeners. It is mostly effective in the CNS and bowel

• Produces analgesia, sedation, euphoria and respiratory depression.
• Less potent than morphine, 80-100 mg meperidine equals 10 mg morphine.
• Shorter duration of action than morphine (2-4 hrs).
• Meperidine has greater excitatory activity than does morphine and toxicity may lead to convulsions.
• Meperidine appears to have some atropine-like activity.
• Does not constrict the pupils to the same extent as morphine.
• Does not cause as much constipation as morphine.
• Spasmogenic effect on GI and biliary tract smooth muscle is less pronounced than that produced by morphine.
• Not an effective antitussive agent.
• In contrast to morphine, meperidine increases the force of oxytocin-induced contractions of the uterus.
• Often the drug of choice during delivery due to its lack of inhibitory effect on uterine contractions and its relatively short duration of action.
• It has serotonergic activity when combined with monoamine oxidase inhibitors, which can produce serotonin toxicity (clonus, hyperreflexia, hyperthermia, and agitation)