Pharmacology Overview Part I

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Pharmacology OverviewPart I

• Becca Maddox
• NURS 2205
• March 25, 2002

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Review of the Nervous System

• Central Nervous System (Brain and spinal cord)
  regulates body functions by either increasing or
  blocking nerve cell activity
• Peripheral Nervous System sends info to the CNS
  and relays instructions from the CNS
• Autonomic Nervous System (Visceral System)
  Controls and regulates the functioning of the
  heart, respiratory system, GI tract, bladder,
  eyes and glands
• Sympathetic (Adrenergic System)
  neurotransmitter is norepinephrine - excites
• Parasympathetic (Cholinergic System)
  neurotransmitter is acetylcholine - inhibits
• Somatic Nervous System Produces locomotion and
  respiration

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Autonomic Nervous System

• The sympathetic and parasympathetic systems act
  on the same body tissues and organs
• Review Figure 20-2 (page 365) for the list of
  responses
• Drugs act on the sympathetic and parasympathetic
  nervous systems by either stimulating or
  depressing responses
• Drugs that mimic the sympathetic nervous system
  and drugs that block the parasympathetic nervous
  system can cause similar responses in the organ
• Review Table 20-1

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Sympathetic Nervous System

• Four types of adrenergic receptor organ cells
  alpha1, alpha2, beta1, beta2
• Drugs that mimic the effect of norepinephrine
  also known as adrenergic agonists because they
  initiate a response at the adrenergic receptor
  sites
• Adrenergic drugs
• Sympathomimetics
• Adrenomimetics

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Sympathetic Nervous System

• Drugs that block the effect of norepinephrine
  also known as adrenergic antagonists because they
  prevent a response at the adrenergic receptor
  sites
• Adrenergic blockers
• Sympatholytics
• Adrenolytics

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Adrenergics

• Responses to receptor site stimulation
• Alpha1 arterioles and venules constrict which
  increases peripheral vascular resistance and
  blood return to the heart
• Alpha2 inhibits release of norepinephrine which
  leads to a decrease in vasoconstriction
• Beta1 increases contractility and heart rate
• Beta2 relaxes smooth muscle of the lungs
  causing bronchodilatation, increases blood flow
  to skeletal muscle, relaxes the uterine muscle
  thus decreasing uterine contraction
• Another adrenergic receptor (in renal,
  mesenteric, coronary and cerebral arteries) is
  dopaminergic and is only activated by dopamine

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Classifications of Adrenergic Agonists

• Direct acting sympathomimetics directly
  stimulate the receptor site
• Epinephrine
• Norepinephrine
• Indirect-acting sympathomimetics stimulate
  release of norepinephrine from the terminal nerve
  endings
• Amphetamine
• Mixed-acting sympathomimetics do both
• Ephedrine

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Catecholamines and noncatecholamines

• Catecholamines are the chemical structures of a
  substance that can produce a sympathomimetic
  response
• Endogenous epinephrine, norepinephrine and
  dopamine
• Synthetic isoproterenol, dobutamine
• Some noncatecholamines can stimulate the
  adrenergic receptors and have a longer duration
  of action phenylephrine, metaproterenol,
  albuterol

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Selectivity vs. Nonselectivity

• Many adrenergic drugs stimulate more than one of
  the adrenergic receptor sites and are therefore
  nonselective
• Side effects can results when drugs are
  nonselective

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Uses for Alpha Agonist Drugs

• Alpha1 causes vasoconstriction
• Nasal decongestants phenylephrine
  (Neo-synephrine)
• Opthalmic decongestants tetrahydrozoline
  (Murine, Visine)
• Hypotensive Crisis - neosynephrine
• Alpha2 reduces sympathetic stimulation and
  vasodilates
• BP Control Clonidine

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Uses for Beta Agonist Drugs

• Beta1 increases contractility and heart rate
• Improve cardiac output Dobutamine
• Beta2
• Bronchodilation Albuterol (Proventil,
  Ventolin), Isoetharine HCl (Bronkosol)
• Stop uterine contractions Terbutaline sulfate
  (Brethine)
• Beta1 and Beta2
• To treat cardiac decompensation Isoproterenol
  (Isuprel)
• Bronchospasm Metaproterenol sulfate (Alupent)

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Uses for Nonselective Alpha and Beta Drugs

• Alpha1 and Beta1
• Hypotensive Crisis Norepinephrine (Levophed),
  Dopamine
• Nasal Congestion Pseudoephedrine (Sudafed,
  Actifed, PediaCare, Co-Tylenol),
  Phenylpropanolamine (Dimetapp, Dristan,
  Triaminic, Contac 12 hour)
• Anorexiant Dexatrim, Dietac
• Alpha1, Beta1 and Beta2
• Epinephrine Used in nonhypovolemic shock,
  cardiac arrest, acute anaphylaxis, acute
  asthmatic attack. Use with caution because heart
  rate and BP will greatly increase. Bronchial
  tubes will dilate.

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Adrenergic Antagonists

• Most adrenergic blockers block either the alpha-
  or beta-receptor
• Alpha blockers
• Selective or Nonselective
• Constricts the pupil (miosis), suppresses
  ejaculation, reduces contraction of the smooth
  muscles in the bladder neck and prostate
• Side effects include dysrhythmias, flushing,
  hypotension, reflex tachycardia

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Adrenergic Antagonists

• Beta blockers decrease heart rate and thus
  blood pressure
• Useful in treating dysrhythmias, mild
  hypertension, mild tachycardia and angina
  pectoris
• Selective vs. Nonselective use nonselective
  beta blockers with caution in COPD patients
• Inderal (propanolol hydrochloride) oldest beta
  blocker, nonselective so many side effects, many
  drugs interact with inderal, AV block can develop
  with digoxin and calcium channel blockers
• Side effects are usually dose-related and include
  bradycardia, dizziness, hypotension, headaches,
  hyperglycemia, intensified hypoglycemia
  agranulocytosis, impotence, and bronchospasms
• Some beta blockers have intrinsic sympathomimetic
  activity. Because of this they can be used in
  patients who experience severe bradycardia with
  other betablockers

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Uses of Adrenergic Antagonists

• Alpha antagonists
• Hypertension Cardura, Minipress, Hytrin
• Treatment of migraines ergot alkaloids that
  constrict the dilated arteries in the brain
  (Ergostat, DHE 45)
• Antidote for dopamine infiltration Regitine
• BPH Hytrin, Cardura
• Alpha1, Beta1 and Beta2
• Hypertension Coreg, Normodyne, Trandate

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Uses of Adrenergic Antagonists

• Beta1 and Beta2
• Hypertension Inderal, Corgard, Visken, Betapace
• Glaucoma - Cartrol
• Beta1
• Hypertension Lopressor, Tenormin
• SVT, Atrial-fib/flutter, hypertension Brevibloc

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Parasympathetic Nervous System

• Cholinergic receptors at organ cells are either
  nicotinic (affects skeletal muscles) or
  muscarinic (stimulates smooth muscle and slows
  the heart rate)
• Many cholinergic drugs are nonselective
• Acetylcholinesterase may inactivate acetylcholine
  before it reaches the receptor cell
• Drugs that mimic the effect of acetylcholine
  also known as cholinergic agonists - initiate a
  cholinergic response
• Cholinergic drugs
• Parasympathomimetics
• Cholinergic agonists

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Parasympathetic Nervous System

• Drugs that inhibit the effect of acetylcholine
  also known as cholinergic antagonists because
  they inhibit the effect of acetylcholine on the
  organ
• Anticholinergic drugs
• Parasympatholytics

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Classifications of Cholinergics

• Direct-acting Act on the receptors to activate
  a tissue response
• Indirect-acting Inhibit the action of the
  enzyme cholinesterase by forming a chemical
  complex, thus allowing acetylcholine to persist
  and attach to the receptor (cholinesterase
  inhibitor or an anticholinesterase drug)
• Reversible bind the cholinesterase for minutes
  to hours
• Irreversible

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Actions of Cholinergics

• Stimulate bladder and GI tone
• Constrict pupils of the eyes (miosis)
• Increase neuromuscular transmission
• Decreased heart rate and blood pressure
• Increased salivary, GI, and bronchial glandular
  secretions

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Toxic Effects

• S Salivation
• L Lacrimation
• U Urinary incontinence
• D Diarrhea
• G GI cramps
• E - Emesis

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Uses for Direct-Acting Cholinergics

• Treatment of glaucoma contricts the pupil thus
  opening the canal of Schlemm allowing drainage of
  aqueous humor and decreasing intraocular pressure
  (Pilocarpine)
• To increase urination Brethanechol chloride
  (Urecholine) increases tone of the detrusor
  urinae muscle.
• To deter smoking Nicoderm, Nicorette gum

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Indirect-acting Cholinergics

• Cholinesterase breaks down acetylcholine
• A small amount of cholinesterase breaks down a
  large amount of acetylcholine
• A cholinesterase inhibitor binds the
  cholinesterase allowing acetylcholine to activate
  the muscarinic and nicotinic cholinergic
  receptors permitting skeletal muscle stimulation
  and increasing the force of muscular contraction
• Additional effects include increased GI motility,
  bradycardia, miosis, bronchial constriction, and
  increased micturition
• Use with caution in patients with bradycardia,
  asthma, peptic ulcers or hyperthyroidism
• Contraindicated in patients with intestinal or
  urinary obstruction

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Uses for Indirect-acting Cholinergics

• Reversible inhibitors
• Diagnosing myasthenia gravis Tensilon
  (short-acting)
• Increasing muscle tone and strength in clients
  with myasthenia gravis (Neostigmine,
  pyridostigmine bromide, ambenonium chloride)
• To produce pupillary constriction in glaucoma
  patients
• Alzheimers disease Cognex
• Muscarinic antagonist poisoning

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Uses for Indirect-acting Cholinergics

• Irreversible inhibitors cholinesterase has to
  regenerate before drug effect diminishes (days to
  weeks)
• Pupillary constriction
• Manufacture organophosphate insecticides
• Pralidoxime (Protopam) is the antidote

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Anticholinergics

• Inhibit acetylcholine by occupying the receptor
  sites
• Major body tissues and organs affected are the
  heart, respiratory tract, GI tract, urinary
  bladder, eye, and exocrine glands
• By blocking the parasympathetic nerves, the
  sympathetic nervous system is allowed to dominate
  i.e. anticholinergic and adrenergic drugs
  produce many of the same responses
• Major responses are a decrease in GI motility, a
  decrease in salivation, dilation of the pupils of
  the eyes (mydriasis) and an increase in heart
  rate
• Other responses are decreased bladder
  contraction, decreased rigidity and tremors

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Uses of Anticholinergics

• Eye examinations
• Decrease GI motility and secretions
• IBS, PUD Bentyl, Pro-Banthine
• Decrease salivation and bronchial secretions
• Pre-op Robinul, Atropine
• Decrease muscle rigidity and tremors
• Parkinsons Cogentin, Artane
• Relaxation of bronchial smooth muscle (asthma,
  COPD, bronchitis, exercise bronchospasms)
  Atrovent
• Treat motion sickness - scopolamine

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Side Effects and Adverse Reactions to
Anticholinergics

• Think opposite of SLUDGE
• Dry mouth
• Decreased perspiration
• Blurred vision
• Tachycardia
• Constipation
• Urinary retention

• Nausea
• Headache
• Dry skin
• Abdominal distention
• Impotence
• Photophobia
• Hyper or Hypotension
• Coma