HIGH YIELD PHARMACOLOGY

ANS PHARMACOLOGY

PARASYMPATHETIC DIVISION = “rest and digest” Decreased heart rate Bronchioles constrict Increased motility and secretion in the digestive tract Increased secretion from the salivary glands, pancreas Sweating Release of urine

AUTONOMIC NERVOUS SYSTEM

SYMPATHETIC DIVISION = “fight or flight” Increased heart rate Blood vessels to the heart and the extremities dilate Liver produces glucose to provide energy for muscle

contraction Bronchioles dilate Pupils dilate Urinary retention

AUTONOMIC NERVOUS SYSTEM

NICOTINIC RECEPTORS Found in autonomic ganglia of the PNS and the SNS Ligand-gated Na+/K+ channels Activated by nicotine and ACh

MUSCARINIC RECEPTORS Found in neuromuscular junctions G protein-coupled receptors that act through 2 nd messengers 5 subtypes: M1, M2, M3, M4, M5 Activated by muscarine and ACh

CHOLINESTERASE INHIBITORS are indirect agonists End in -stignine

BOTULINUM TOXIN prevents release of neurotransmitter at all cholinergic terminals

ACETYLCHOLINE RECEPTORS

ATROPINE (from Atropa belladonna) Increased heart rate Increased conduction velocity through the AV node Bronchodilation Increased body temperature (decreased sweating)

Blockage is reversible i.e. can be overcome by a larger concentration of acetylcholine or muscarinic agonist

MUSCARINIC RECEPTOR BLOCKERS

ALPHA RECEPTORS

ALPHA RECEPTORS

β1 (heart and kidney) Increase intracellular cAMP Increased heart rate and contractility Increased renin release Increased lipolysis

β2 (respiratory and vascular smooth muscle) Increase intracellular cAMP Vasodilation Bronchodilation (hormonal epinephrine) Increased heart rate and contractility Increased lipolysis Increased insulin release

ADRENERGIC RECEPTORS

ADRENERGIC AGONISTS

EFFECTS OF ADRENERGIC AGONISTS

DIRECT SYMPATHOMIMETICS

Increase the release of stored catecholamines Amphetamine

Block reuptake of catecholamines Duloxetine, cocaine

Block the enzymatic breakdown of norepinephrine MAO and COMT inhibitors

INDIRECT SYMPATHOMIMETICS

CARDIAC PHARMACOLOGY

CARDIAC FAILURE Cardiac glycosides Sympathomimetics Phosphodiesterase-3

inhibitors Vasoconstrictors

HYPERTENSION Diuretics Vasoconstrictors Sympatholytics

ARRHYTHMIAS Class I: Fast Na+

channel blockers Class II: Beta

blockers Class III: K+

channel blockers Class IV: L-type

Ca2+ channel blockers

Adenosine

OVERVIEW

At a given left ventricular end-diastolic pressure, cardiac output is lower than in a normal heart

Diuretics reduce LVEDP

Inotropic drugs shift the curve upward, toward normal

HEART FAILURE

Inhibits sodium-potassium ATPase, which increases intracellular Ca2+ and force of contraction

Increases vagal tone Decreases heart rate Decreases conduction

velocity at the AV node Increases refractory period

Toxic effects = sinus bradycardia and SA block

CARDIAC GLYCOSIDES (DIGITALIS)

ELECTRICAL EFFECTS OF DIGITALIS

Delayed afterdepolarizations may develop resulting in triggered tachyarrhythmias

1. DIURETICS: decrease sodium retention and blood volume

2. VASODILATORS: relax vascular smooth muscle in resistance vessels

3. ACE INHIBITORS: reduce peripheral vascular resistance and blood volume

4. SYMPATHOLYTICS: reduce peripheral vascular resistance and cardiac output

ANTIHYPERTENSIVES

DIURETICS

ACE inhibitors inhibit the production of angiotensin II from angiotensin I

Counteract the effects of renin-angiotensin system without reflex sympathetic activation

Lower blood pressure principally by decreasing peripheral vascular resistance

Tx long-term treatment of congestive heart failure, post-myocardial infarction, and hypertension

ACE INHIBITORS (-PRILS)

RENIN-ANGTIOTENSIN SYSTEM

Vasodilator of both arterioles and veins Can cause decreased cardiac

output

Administered intravenously to treat hypertensive emergencies

NO causes vasodilation through activation of guanylate cyclase in vascular smooth muscle

Often administered with a β-blocker

NITROPRUSSIDE

GOAL = SNS

PHOSPHODIESTERASE-3 INHIBITORS

Milrinone

Mechanisms of arrhythmia Increased automaticity of pacemaker or nonpacemaker cells Reentrant pathways Triggered activity

Goal of antiarrhythmia drugs:

ANTIARRHYTHMIA DRUGS

CLASS IA: moderate block ↓↓ phase 0 upstroke rate; prolonged AP duration Quinidine

CLASS IB: mild block ↓phase 0 upstroke rate; shortened AP duration Lidocaine

CLASS IC: marked block ↓↓↓ phase 0 upstroke rate; no change in AP duration Flecainide

CLASS I: BLOCK FAST NA+ CHANNELS

CLASS II: β-BLOCKERS (-OLOLS)

CLASS III: BLOCK K+ CHANNELS (–TILIDES)

CLASS IV: BLOCK L-TYPE CALCIUM CHANNELS

VerapamilDiltiazem

ADENOSINE

Administered intravenously, adenosine is the most effective drug for the rapid termination of reentrant SVT,

such as AV nodal reentrant tachycardia.

RESPIRATORY PHARMACOLOGY

ASTHMA Characterized by acute episodes of bronchoconstriction

caused by underlying air-way inflammation Leukotrienes and histamine induce smooth muscle

contraction, mucus secretion, and recruitment of inflammatory cells

CHRONIC BRONCHITIS Pulmonary obstruction caused by excessive production of

mucus due to hyperactivity of mucus-secreting goblet cells

RHINITIS Decrease in nasal airways due to thickening of the mucosa

and increased mucus secretion

GLUCOCORTICOIDS

LEUKOTRIENE INHIBITORS

MAST CELL STABILIZERS

ANTI-INFLAMMATORY DRUGS