Midterm pharma

• Autonomic Nervous System


  Parasympathetic - acetylcholine - rest and digest

  Sympathetic - norepinephrine and epinephrine - fight and flight
• Cholinergic drugs


  Cholinergic agonists or stimulants

  Promote the action of the neurotransmitter acetylcholine

  Also called parasympathomimetic drugs because they produce effects that imitate parasympathetic nervous system
• Two major classes of cholinergic drugs

  • Cholinergic agonists: mimic the action of the neurotransmitter acetylcholine

  Anticholinesterase: inhibits the destruction of acetylcholine at the cholinergic receptor sites
• Cholinergic agonists


  • Acetylcholine

  Bethanecol

  Carbachol

  Pilocarpine
• Cholinergic agonists


  • Mimic the action of the neurotransmitter acetylcholine by directly stimulating cholinergic receptors

  Poorly penetrate the CNS and have primarily peripheral effects

  Rapidly destroyed in the body

  Rarely administered by IM or IV (cholinergic crisis)

  Usually administered topically, orally, or by SQ injection

  Metabolized by cholinesterases and excreted by the kidneys
• Pharmacodynamics of cholinergic agonists

  • Work by mimicking the action of acetylcholine on the neurons in certain organs of the body (target organs)

  Stimulate the muscle and produce: salivation, bradycardia, vasodilation, bronchoconstriction, increased GI activity, increased bladder tone and contraction, pupil constriction
• Anticholinesterase drugs


  Block the action of the enzyme acetylcholinesterase, which breaks down acetylcholine, at the cholinergic receptor sites

  As acetylcholine builds up, it continues to stimulate the cholinergic receptors
• Reversible anticholinesterase drugs


  • Ambenonium, donepezil, edrophonium, neostigmine, physostigmine salicylate, pyridostigmine, tacrine
• Irreversible anticholinesterase drugs


  Have long lasting effects and are used primarily as toxic insecticides, pesticides or nerve gas; echothiophate has therapeutic usefulness
• Pharmacokinetics of anticholinesterase drugs


  • Most are readily absorbed from the GIT, SQ and mucous membranes

  Neostigmine should be taken at a higher dose

  Only physostigmine can cross the blood-brain barrier

  Donepezil is highly bound to plasma proteins, tacrine is about 55% bound

  Most are metabolized in the body and excreted in the urine; donepezil and tacrine are metabolized in the liver
• Pharmacodynamics of anticholinesterase drugs

  • Promote the action of acetylcholine at the receptor sites

  Reversible drugs block acetylcholine breakdown for minutes to hours, irreversible drugs last for days or weeks
• Cholinergic blocking drugs


  Also known as anticholinergic drugs

  Major drugs: atropine, belladonna, homatropine, hyoscyamine sulfate, scopolamine hydrobromide

  Synthetic derivatives/quaternary ammonium drugs: cliidinium, glycopyrrolate, propantheline

  Tertiary amines: benztropine, dicyclomine, ethopropazine, oxybutynin, trihexyphenidyl
• Pharmacokinetics of cholinergic blocking drugs

  • Belladonna alkaloids are absorbed from the eyes, GIT, mucous membranes and skin; quaternary and tertiary amines are primarily absorbed through the GIT

  Belladonna alkaloids are distributed more widely than the quaternary drugs

  Belladonna alkaloids have low to moderate binding with serum proteins; metabolized in the liver and excreted by the kidneys
• Pharmacodynamics of cholinergic blocking drugs

  • Can have paradoxical effects on the body depending on the dosage and condition being treated

  Produce a stimulating or depressing effect depending on the target organ
• Adrenergic drugs


  Also known as sympathomimetic drugs

  Classifications based on chemical structure: catecholamines, non-catecholamines

  Classifications based on mechanism of action: direct-acting, indirect-acting, dual-acting
• Catecholamine adrenergic drugs


  • Stimulate the nervous system, constrict peripheral blood vessels, increase heart rate, dilate bronchi

  Examples: dobutamine, dopamine, epinephrine, norepinephrine, isoproterenol
• Pharmacokinetics of catecholamine adrenergic drugs

  • Can't be taken orally; SQ absorption is slowed by vasoconstriction, IM is more rapid

  Widely distributed, metabolized predominantly in the liver but also in other tissues

  Excreted primarily in the urine
• Pharmacodynamics of catecholamine adrenergic drugs

  • Primarily direct-acting; activation of alpha receptors causes excitation, activation of beta receptors mostly causes inhibition

  Potent inotropes
• Non-catecholamine adrenergic drugs


  • Effects: local/systemic vasoconstriction, nasal/eye decongestion, bronchodilation, smooth muscle relaxation

  Examples: mephentermine, metaraminol, methoxamine, phenylephrine, albuterol, ephedrine, ritodrine, terbutaline
• Pharmacokinetics of non-catecholamine adrenergic drugs

  • Absorption depends on route of administration

  Inhaled drugs absorbed from bronchi, oral drugs well absorbed from GIT

  Some (ephedrine) cross blood-brain barrier

  Metabolism and inactivation occur primarily in the liver but also in other tissues

  Excreted primarily in the urine
• Pharmacodynamics of non-catecholamine adrenergic drugs

  • Direct-acting: stimulate alpha or beta 2 activity

  Indirect-acting: stimulate release of norepinephrine

  Dual-acting: have both direct and indirect effects
• Adrenergic blocking drugs


  Also known as sympatholytic drugs

  Work by blocking impulse transmission at the adrenergic neurons or adrenergic receptor sites
• Alpha-adrenergic blockers


  • Action not well understood, absorption varies

  Work by interfering with synthesis, storage, release and reuptake of norepinephrine or antagonizing catecholamines at alpha receptor sites

  Increase local blood flow and reduce blood pressure

  Indicated for hypertension, peripheral vascular disorders, pheochromocytoma
• Beta-adrenergic blockers


  • Most widely used adrenergic blockers

  Prevent stimulation of the sympathetic nervous system by inhibiting the action of catecholamines at beta-adrenergic receptor sites
• Muscle relaxants


  Relieve musculoskeletal pain or spasm and severe musculoskeletal spasticity

  Used to treat acute, painful musculoskeletal conditions and muscle spasticity associated with conditions like MS, cerebral palsy, stroke, spinal cord injuries
• Pharmacokinetics of centrally-acting muscle relaxants

  • Absorbed in the GIT, widely distributed, metabolized in the liver and excreted through the kidneys

  Onset: 30 min to 1 hour orally, duration varies from 4 to 6 hours (cyclobenzaprine 12-25 hours)
• Pharmacodynamics of centrally-acting muscle relaxants

  • Do not relax skeletal muscles directly, depress the central nervous system
• Skeletal muscle relaxants


  Duration varies from 30 min to 1 hour for oral, 4 to 6 hours for cyclobenzaprine
• Skeletal muscle relaxants


  • Do not relax skeletal muscles directly or depress neuronal conduction, neuromuscular transmission, or muscle excitability
  • Depress the CNS
• Dantrolene sodium


  • Major effect is on the muscles
  • High therapeutic doses are toxic to the liver
• Sedatives


  Reduce activity or excitement
• Hypnotics


  Sedatives given in large doses
• Main classes of synthetic drugs used as sedatives and hypnotics

  • Benzodiazepines
  • Barbiturates
  • Nonbenzodiazepine-nonbarbiturate drugs
• Benzodiazepines


  • Minor tranquilizer; anxiolytic
  • Therapeutic effects include daytime sedation, sedation before anesthesia, sleep inducement, relief on anxiety and tension, skeletal muscle relaxation and anticonvulsant activity
• Examples of benzodiazepines


  • estazolam
  • flurazepam
  • lorazepam
  • quazepam
  • temazepam
  • triazolam
• Barbiturates


  • Major pharmacologic action is to reduce the overall CNS alertness
  • Low dose: depress sensory and motor cortex of the brain causing drowsiness
  • High dose: cause respiratory depression and death because of their ability to depress all levels of the CNS
• Nonbenzodiazepines-nonbarbiturates


  • Act as hypnotics for short-treatment of simple insomnia
  • No special advantages over other sedatives
  • Lose their effectiveness by the end of the 2nd week except zolpidem (35 days)
• Examples of nonbenzodiazepines-nonbarbiturates


  • chloral hydrate
  • ethchlorvynol
  • zolpidem
• Antianxiety drugs


  Also known as anxiolytics, used primarily to treat anxiety disorders
• Main types of antianxiety drugs

  • Benzodiazepines
  • Barbiturates
  • Buspirone