Pharmacology Exam I Drugs

Front 1

Anticholinesterases

Back 1

Physostigmine, edrophenium, neostigmine


Block the breakdown of ACH in blood into choline and acetate by inhibiting acetylcholinesterase so indirectly you get more of ACH.
Used in the treatment of Myesthenia Graves (muscle weakening disease where form autoimmunity against nicotinic M receptors on muscle)
Note: physostigmine is stimulatory to the brain because it is not permanently charged.
Can use physostigmine to treat Alzheimer’s disease. It however can increase salivation and muscle contraction.
Non specific Ach increasers- get muscle stimulation (Nic M) and parasympathetic stimulation (Muscarinic)
Anticholinesterases have been developed as nerve gases→ SLUDGE
Neostigmine used also to treat NMJ blockade (from curare).
Physostigmine used to treat antimuscarinic overdose (atropine).

Front 2

Nicotine

Back 2

Direct-acting Nicotinic cholinergic receptor agonist AND Depolarizing Ganglionic Blocking Agent


Acts on nicotinic receptors in brain- why dependence issues- receptors are down regulated.
Acts on nicotinic N receptors in parasympathetic and sympathetic preganglionics.
Autonomic system controlling tissue predominates:
Heart (symp) ---- so increase HR and blood pressure (stimulation of adrenal medulla resulting in increased norepinephrine and epinephrine)
GI (para) ------- so increase motility and secretions (why ulcers in smokers- more acid)
Respiratory----more respiration
Doesn’t stimulate salivary gland b/c no nic receptors here, that’s why it’s direct acting.
As a Blocking Agent:
An alkaloid that in large doses blocks cholinergic receptors by persistent occupation of the site (prevents repolarization). Can be accomplished with large smoke intake or certain insecticides.
Results in reduced blood pressure, increased HR (compensatory), confusion, convulsions, and respiratory failure.

Front 3

Buproprion (Welbutrin)

Back 3

An antidepressant (weak inhibitor of dopa, serotonin, and NE reuptake) that contains no Nicotine

Tobacco-sessation product

Front 4

Atomoxitiene

Back 4

Dual selective NE and serotonin reuptake inhibitor that treats ADHD as well because people self medicate with cigarettes. Reduces nicotine cravings and recidivism.

Tobacco-sessation product

Front 5

Naltroxone

Back 5

FDA approved for preventing recidivism. An opiate receptor antagonist (endorphins and enkephalins released with alcohol and narcotics).
Nicotine replacements

Tobacco-sessation product

Front 6

Nicotine Polacrilex nicorette gum

Back 6

3 steps down starting with 1/ 2hrs. Two strengths available.

Front 7

Transdermal Patches

Back 7

Nicotrol transdermal patch- indic. >10 cig/day, 6 wk therapy
Nicoderm CQ patch- ind >10/day 3 steps down over 10 wks, if < 10/day 2 steps down for 8 wks.

Front 8

Belladona Alkaloid

Back 8

muscarinic blocker (parasymp n.s.)

i.e. Atropine


Competitively block at the muscarinic receptor so Ach can’t stimulate. The sympathetic system predominates:
Cause same response as other anticholinergic drugs.
Readily enter the CNS.
Large doses block cholinergic transmission at autonomics and neuromuscular junction. (specificity limited)
Used: to do eye exam (mydriasis and cycloplegia), reduce side effects of myasthenia gravis treatment, motion sickness, asthma, enureseis, parkinsons (restore DOPA/Ach balance), prevents bradycardia.

Front 9

Phentolamine

Back 9

An alpha blocker

An antihypertensive drug that depletes NE stores or preventing its release from nerve terminals. This drug directly blocks the alpha 1 and 2 receptors.

Front 10

Warfarin

Back 10

An anticoagulant


Treats people with clotting disorders which can plug arteries leading to MI or stroke or pulmonary embolism.
Works by inhibiting the synthesis of vitamin K clotting factors in the liver.
Highly protein bound- protein bumping occurs!!!
A member of the cp450 system (CYP-2C9). If take with ibuprofen (also protein bound)- can increase dose by 4x. Has a low therapeutic index too (~4)

Front 11

Tolbutamide

Back 11

Treats diabetic hypoglycemia


Highly protein bound.
A member of the cp450 system (CYP-2C9) If take with NSAIDS or sedative Chlorohydrate can increase the free Tolbutamide → hypoglycemia → death

Front 12

Pennicilin

Back 12

An antibiotic


Has a very short ½ life because it’s actively pumped into the kidney by an energy dependent system.
Very effective killer so don’t need to dose more than 6 hours.
If used with Probenecid (competitive antagonist at kidney absorption system) longer duration in blood and more effective.

Front 13

Aspirin

Back 13

NSAID

A weak acid that is easily absorbed in acidic stomach.
Overdoses lead to GI pain, tinnitus, hyperventilation (low pH), kidney failure (prostaglandins are good for it)
Can treat overdose by alkalinizing the urine with IV sodium bicarbonate or administering carbonic anhydrase inhibitor Acetazolamide (increase bicarbonate in urine).

Front 14

Weak bases

Back 14

Narcotics like codeine, heroin, or naloxone
Can treat an overdose with ammonium chloride to lower the pH of the urine and ion trap the positively charged base in the tubules.

Front 15

Pilocarpine

Back 15

Muscarinic cholinergic agonist

Increases parasympathetic system activity.
Used to induce salivation.
Direct acting, so doesn’t stimulate Nicotinic M- of skeletal muscle. Indirect drugs can stimulate both nic M and musc.

Indicated for: glaucoma (to open up canals of schlemm) and xerostomia (increase salivation)

Front 16

Carbachol

Back 16

Direct Acting Cholinomimetic
Similar to giving straight acetylcholine.
Can directly activate both muscarinic and nicotinic cholinergic receptors (parasympathetic and somatic stimulation)
Indicated for: glaucoma

Front 17

Anticholinergic Drugs

Back 17

Actions:
GI- reduced motility and secretions
CV- tachycardia
Eye- ciliary muscle relaxes, mydriasis (dialation)
Exocrine- decreased sweating, salivation, and mucous formation. (remember sweat glands release AcH)
Smooth muscle- relaxation (in bronchioles/GI)
CNS- Drowsiness

Front 18

ADRs and Contraindications of Belladona Alkaloids
Eg. Atropine

Back 18

ADR’s:
GI- dry mouth, Cardiovascular- tachycardia, CNS- headache, confusion, drowsiness, Ocular- intraocular tension, Urinary- retention, impotence
Contraindications:
Narrow-angle glaucoma, Myasthenia Gravis, Asthma, Severe Coronary artery disease

Actions increased with antihistamines, antipsychotics, and antidepressants.

Front 19

Tertiary Amines

Back 19

Subtype of muscarinic blockers


Eg. Dicyclomine, Tropicamide, Benzotropine, and Diphenhydramine

Very lipid soluble so easily get to the CNS.
Well absorbed by p.o.
Wide distribution
Used as antispasmodics to treat urinary problems, mydriatics for eye exams, and antiparkinsonian agents.

Triad of effects: anti-histamine, anti-cholinergic, local anesthetic

Front 20

Dicyclomine

Back 20

A Tertiary Amine Muscarinic Blocker
An antispasmodic used for irritable bowel syndrome.
The effects range from slight to no anticholinergic activity.

Front 21

Tropicamide

Back 21

A Tertiary Amine Muscarinic Blocker
Used as a mydriatic to induce mydriasis and cycloplegia for an eye exam.
Possible toxic reactions if systemically absorbed: amnesia, hallucinations, cardiac arrhythmias, and death (in children)
Has a short duration of action (6 hours) (atropine up to 12 days)

Front 22

Benztropine

Back 22

A Tertiary Amine Muscarinic Blocker
Used as an antiparkinsonian agent which decreases ACH for corresponding decrease in Dopamine (restores this balance). Also used to treat extrapyramidal disorders where dopamine sites are blocked creating greater action of ACH.
More selective than belladonna alkaloids
Clinical use limited by ADRs: constipation, urinary retention and tachycardia.
Increase dose depending on patients response.

Front 23

Diphenhydramine (Benadryl)

Back 23

A Tertiary Amine Muscarinic Blocker
Used as an antiparkinsonian agent as well as to treat extrapyramidal disorders.
An antihistamine with central anticholinergic activity.
Has less peripheral side effects than other drugs (constipation, urinary retention, tachycardia).
Sedative effect is useful for patients with insominia.

Also great for treating motion sickness

Front 24

Quaternary Amines

Back 24

Muscarinic blockers (e.g. Glycopyrrolate)
Not very lipid soluble- doesn’t cross BBB, stays in peripheral nervous system.
Duration of action is greater than that of tertiary amines.
Uses: reduce gastric acid secretion in treatment of peptic ulcer.
Effects depend on dosage:
(small) inhibition of sweating, salivation, and bronchial secretions → mydriasis, cycloplegia, tachycardia → decreased motility in GI and urinary → decreased gastric acid secretion→ delirium (large dose)
If desired effect is decreased gastric acid secretion will have many ADR’s before get there (sweat, tachycardia, etc)

Front 25

Glycopyrrolate

Back 25

A Quaternary Amine (type of muscarinic blocker)
Used to treat gastric acid secretion in ulcer.
Not lipid soluble.
Used as an anesthetic med to decrease saliva, reduce secretions in GI and respiratory tracts, and prevent bradycardia.

Front 26

Ganglionic Blocking Agents

Back 26

A type of anticholinergic
Synaptic transmission in the ANS is mediated by Ach.
Anticholinergic drugs that act primarily at the postsynaptic cholinergic site with in the autonomic ganglia are ganglionic blocking agents.
Subdivided into Depolarizing drugs (nicotine) and Non-depolarizing drugs (mecamylamine)

Front 27

Mecamylamine

Back 27

A nondepolarizing ganglionic blocker
Competitively blocks ACH at postsynaptic receptor.
Nonselective- reduces ACH in sympathetic and parasympathetic (blocks out autonomic system)
Net effect dependent upon which division of the ANS predominates:
Sympathetic interferences→ vasodialation leading to orthostatic hypotension, decreased venous return leading to decreased cardiac output.
Parasympathetic interferences → decreased GI motility, dry mouth, urinary retention, constipation, cycloplegia and mydriasis, impotentce.
Powerful blood pressure-lowering drugs but not used because many side effects.

Front 28

Neuromuscular Blocking Agents (description)

Back 28

Interfere between somatic motor neurons and skeletal muscle resulting in paralysis.
With large doses can extend cholinergic antagonism to autonomic ganglia and parasympathetics→ increase HR, arrythmias, hypotension.
Do not penetrate BBB at therapeutic levels.
Release histamine from cells→ bronchospasm, increased secretions, hypotension, tachycardia, urticaria.
All skeletal muscles not equally susceptible to blockers:
(low doses) rapidly contracting small muscles like eyes, fingers and speech→ limbs, neck and trunk → respiration like intercostal muscles and diaphragm (high doses)
Small margin of safety. Small OD→ hypotension, respiratory depression.

Front 29

Neuromuscular Blocking Agents (uses and interactions)

Back 29

Uses: adjuncts to general anesthetics (relax muscle), facilitation of intubation, improvement of respiration in patients on mechanical ventilation.
Additional drugs are required for pain control because these drugs don’t reduce consciousness or provide analgesia.
Interactions:
Causing additive effects:
Antibiotics like aminoglycosides, lincoamides, polymixins
Inhalation anesthetics (enflurane>isoflurane> halothane), ketamine, local anesthetics, lithium, quinidine.
Causing reduced effects: cholinergic drugs, corticosteroids, ranitidine, theophyhlline.

Front 30

Succinylcholine (ADR’s, Contraindications, Interactions)

Back 30

A neuromuscular blocker (somatic n.s.)
ADR’s: muscle twitching, muscle pain, tachycardia, hypertension, arrhythmias, respiratory depression, apnea, increased salivation, increased intraocular pressure. Malignant hyperthermia (genetics leading to muscle ridgidity, tachycardia, hyperthermia, metabolic acidosis- increased likelihood in presence of general anesthesia.
Contraindications: malignant hyperthermia, narrow angle glaucoma (blindness), genetic deficiency of cholinesterases.
Interactions: may cause arrhythmias in patients on digitalis or quinidine (releases K from myocytes). Effect of succs is intensified by cholinesterase inhibitors.

Front 31

Succinylcholine (general)

Back 31

A neuromuscular blocker (somatic n.s.)
A depolarizing indirect (at receptor level) blocker.
Blocks by depolarizing the motor end plate until it becomes unresponsive to Ach by occupying receptor site. Prevents repolarization. Patients will at first fasciculate before flaccid (relaxed )paralysis of 10 to 30 minutes. This is non-competitive and cannot be overcome by administering and anticholinesterase. Some people (0.1%) with defective plasma cholinesterases will be paralyzed for a long time after use.
Cholinesterases are transformed into succinylmonocholine which is a weaker active metabolite that is slowly hydrolyzed.
Normal dosage paralysis lasts 5-10 minutes.

Front 32

Curare

Back 32

A neuromuscular blocker (somatic n.s.)
Reversible competitive antagonist of Ach at nicotinic M receptors that blocks the contraction of striated muscle by attaching to the motor end plate.
Blocks nicotinic M receptors only- won’t affect parasympathetic system.
A non-depolarizing competitive blocker. Can be overcome by administering an anticholinesterase (such as neostigmine or physostigmine).
First anti-depolarizing muscle relaxant (d-tubocurarine active chemical)

Front 33

Tubocurarine (mostly obsolete)

Back 33

A nondepolarizing neuromuscular blocker
Basically curare.
Can be used to diagnose Myasthenia Gravis:
Have MG if muscle weakness results or a very small dose elicits an exaggerated response.
Causes histamine release- (blood vessel dilation results leading to anaphylactic shock)
Use with diazepam may increase possibility of malignant hyperthermia.

Front 34

Atracurium

Back 34

A nondepolarizing neuromuscular blocker
Less likely to release histamine than tubocurarine.
Hypotensive effect is minimal.
May need to reduce dosage if administered under isoflurane or enflurane.
Quick onset and rapidly inactivated in plasma.
Recovery begins within 20 minutes.
Repeated doses have no effect on duration of blockade.
ADR’s: mild hypotension [at high doses→ erythema, itching, urticaria, wheezing, hypotension, tachycardia]

Front 35

Vecuronium

Back 35

A nondepolarizing neuromuscular blocker
Effects similar to atracurium except fewer or no histamines are released.
Fewer side effects result

Front 36

Hexafluorenium

Back 36

Anticholinesterase
A reversible inhibitor of plasma cholinesterases.
Unlike other anticholinesterases, does not affect intracellular cholinesterases.
Uses: exclusively used with succinylcholine to delay enzymatic hydrolysis leading to a reduction in muscle fasciculations and prolong muscle paralysis.
Duration is approximately 30 minutes and is unaffected by general anesthetics.
ADR’s: primarily due to enhanced succinylcholine activity (see ADR’s here)

Front 37

Treatment for non-depolarizing neuromuscular overdose

Back 37

Overdosage treated by:
Artificial respiration with oxygen
Vasopressors
Cholinesterase inhibitors (treatment of OD on non-depolarizing blockers)
Cholinesterase inhibitor treatment of OD is contraindicated for overdosage with depolarizing blockers (succinylcholine)- will further stimulate and intensify paralysis.

Front 38

Direct Acting Skeletal Muscle Relaxants (general)

Back 38

Act on the muscle itself by interfering with Ca2+ not on nerves.
-reduce release of Ca2+ from binding sites in sarcoplasmic reticulum.
-reduced contractility of skeletal muscles.
-affects fast reflex muscles more than slow voluntary muscles (b/c have more input- more sites to block)

Front 39

Dantrolene

Back 39

A direct acting skeletal muscle relaxant
Orally taken to treat muscle spasticity resulting from chronic neurologic disorders (cerebral palsy, multiple sclerosis, stroke). Treat to make patient more comfortable not the underlying cause.
Takes 1-2 weeks for therapeutic effects to be seen.
IV injected for emergency management of malignant hyperthermia: reduced release of Ca2+, impairs catabolism in muscle cells, reduces elevation in body temp due to increased muscle activity.
ADR: hepatotoxicity especially with high doses or long-term treatment (hepato. risk is greater in females and pts > 35yrs.)
Discontinue therapy if no observable benefit in 45 days.

Front 40

Treatment of Spasticity

Back 40

Spastic disorders are abnormalities in skeletal muscle tone due to pathology in descending CNS motor tracts.

Characteristics include:
-tonic stretch reflexes are hyperreactive
-jerky and exaggerated movements
-muscle weakness and pain
-loss of dexterity

Treatments include Baclofen and Diazepam (Valium)

Front 41

Baclofen

Back 41

A centrally acting skeletal muscle relaxant
Treats muscle spasms in the CNS by reducing monosynaptic and polysynaptic signal transmission in the spinal cord.
Molecular structure like GABA- activates GABA-B receptors, increases K+ efflux leading to hyperpolarization (less firing), and reduced Ca2+ action.
Net result→ decreases the release of excitatory NT (aspartate and glutamate)
Typically administered orally, but can be given intrathecal infusion with implantable pump for those not responding well to oral therapy.
Abrupt withdrawl may cause hallucinations

Front 42

Diazepam (Valium)

Back 42

A centrally acting skeletal muscle relaxant- a benzodiazepine
Increases GABA-A action by increasing Cl- influx resulting in hyperpolarization and reduced muscle activity.
Not as effective as Baclofen
Also used as an anti-anxiety drug and can be a drug of abuse.
Causes some CNS sedation.

Front 43

Treatment of Spasms

Back 43

Centrally acting skeletal muscle relaxants are used
Classified as interneuronal or polysynaptic blocking drugs- are less sensitive than diazepam or baclofen.
Used to treat pain and discomfort of muscle spasms associated with anxiety or acute musculoskeletal disorders (inflammatory states or peripheral injuries like strains).
Have weak synaptic blocking activity- primary goal is to decrease muscle tone without loss of voluntary control and loss of consciousness.
Most central muscle relaxants produce sedation.
Directly depress higher centers that regulate motor activity- contributes to relaxant effect.
Example: Methocarbamol (relaxant and sedative)

Front 44

Cyclobenzaprine

Back 44

A centrally acting skeletal muscle relaxant
Used similar to methocarbamol to treat spasms. This agent, however, possesses anticholinergic action.
Structural relationship to tricyclic antidepressants.
Not effective in treatment of muscle spasms cause by CNS pathology- treats symptoms.

Front 45

Epinephrine /adrenaline (description and uses)

Back 45

Direct acting endogenous catecholamine
Directly activates alpha and beta-adrenergic receptor sites.
It is rapidly broken down (why not take orally)
No penetration of BBB→ minimal CNS activity
Good absorption through nasal, ophthalmic, inhalation and parenteral routes.
Uses: relief of nasal, ocular, pulmonary congestion
Pressor agent in acute hypotensive states (epi pen used for anaphylactic shock- beta1 dialates bronchioles, beta2 increases HR)
Relief of symptoms of allergic reactions. Restore normal HR during cardiac arrest.
Produce bronchodilation (asthma)
Prolongate duration of local anesthetic. (cause vasoconstriction)

Front 46

Direct acting endogenous catecholamine
Directly activates alpha and beta-adrenergic receptor sites.
It is rapidly broken down (why not take orally)
No penetration of BBB→ minimal CNS activity
Good absorption through nasal, ophthalmic, inhalation and parenteral routes.
Uses: relief of nasal, ocular, pulmonary congestion
Pressor agent in acute hypotensive states (epi pen used for anaphylactic shock- beta1 dialates bronchioles, beta2 increases HR)
Relief of symptoms of allergic reactions. Restore normal HR during cardiac arrest.
Produce bronchodilation (asthma)
Prolongate duration of local anesthetic. (cause vasoconstriction)


Epinephrine (ADR’s)

Back 46

Direct acting endogenous catecholamine
Increases blood pressure resulting in hypertension and heart rate resulting in tachycardia.
Cerebral hemorrhage and arrythmias.
Risk of ADR’s is increased if administered in the presence of halogenated hydrocarbons (like lidocaine).
Drying of mucosal membranes.
TCA’s and MAO inhibitors may increase potentcy.
Bronchodialation is blocked by propanolol.
BP effects are antagonized by vasodialators (nitrites and alpha-adrenergic blockers like phentolamine)
BP effects are enhanced by beta-blockers (propanolol) and diuretics.

Front 47

Norepinephrine (levarterenol)

Back 47

Direct acting Endogenous Catecholamine
Direct activation of alpha adrenergic sites resulting in strong vasoconstriction.
Some ionotropic action on cardiac beta receptors resulting in increased force of contraction.
Increases blood pressure and coronary artery blood flow, but also increases workload of heart.
Uses: a BP raiser in acute hypotensive states
ADR’s: reflex bradycardia(compensates for increased HR), hypertension, cerebral hemorrhage, arrythmias (similar to epi) and tissue necrosis.
Contraindicated for vascular thrombosis and hypovolemic shock.
BP effects may be enhanced by Tricyclic Antidepressants and MAO inhibitors

Front 48

Dopamine

Back 48

Direct acting endogenous catecholamine
Direct activation of dopaminergic receptors in renal and mesenteric vasculature→ vasodialation and increased renal blood flow.
Activates myocardial beta receptors → increased force of contraction and cardiac output.
High doses activate alpha receptors leading to vasoconstriction.
Causes less myocardial oxygen demand and fewer arrhythmias than E and NE.
Uses: Gets heart back to more stable contraction following shock.
ADR’s: Tachycardia, mild hypotension, arrhythmias. High doses may cause hypertension and decreased urinary outflow. BP effects are enhanced by Tricyclic Antidepressants and MAO inhibitors.

Front 49

Vasopressor Amines

Back 49

Alpha 1 adrenergic synthetic catecholamines
Have both direct and indirect adrenergic activity.
Causes lots of systemic vasoconstriction.
Used primarily in acute hypotensive situations:
-maintenance of BP in shock following hemorrhage
-fluid replacement must be in progress or perfusion of vital organs may decrease (phenylephrine is used)
-maintenance of BP during inhalation anesthesia
-production of vasoconstriction in area of local analgesia.

Front 50

Nasal Decongestants (phenylephrine)

Back 50

Alpha 1 adrenergic synthetic catecholamines
Direct vasoconstriction (alpha 1) of mucosal arterioles: reduces local blood flow, edema and fluid exudation.
Tachyphylaxis to decongestant effect- rapid tolerance developed to drug (need higher doses for same effect)
Chronic use leads to rebound congestion (resulting from physical dependence- should only be used 1x a day).
Readily absorbed through mucous membranes; large doses may produce systemic effects. (cocaine also a decongestant)
ADR’s include: stinging burning, drying of nasal mucosa, tachycardia, hypertension arrythmias, reflex bradycardia.

Front 51

Vasopressor Amines

Back 51

Alpha 1 adrenergic synthetic catecholamines
Have both direct and indirect adrenergic activity.
Causes lots of systemic vasoconstriction.
Used primarily in acute hypotensive situations:
-maintenance of BP in shock following hemorrhage
-fluid replacement must be in progress or perfusion of vital organs may decrease (phenylephrine is used)
-maintenance of BP during inhalation anesthesia
-production of vasoconstriction in area of local analgesia.

Front 52

Nasal Decongestants (phenylephrine)

Back 52

Alpha 1 adrenergic synthetic catecholamines
Direct vasoconstriction (alpha 1) of mucosal arterioles: reduces local blood flow, edema and fluid exudation.
Tachyphylaxis to decongestant effect- rapid tolerance developed to drug (need higher doses for same effect)
Chronic use leads to rebound congestion (resulting from physical dependence- should only be used 1x a day).
Readily absorbed through mucous membranes; large doses may produce systemic effects. (cocaine also a decongestant)
ADR’s include: stinging burning, drying of nasal mucosa, tachycardia, hypertension arrythmias, reflex bradycardia.

Front 53

Ophthalmic Decongestants (phenylephrine)

Back 53

Alpha 1 adrenergic synthetic catecholamines
Produce alpha 1 induced arteriolar constriction and mydriasis (pupil dialation)
Epinephrine (beta adrenergic effect decreases formation of aqueous humor)
Phenylephrine is more selective for alpha1:beta (20:1)
Unlike anticholinergics don’t cause cycloplegia (paralysis of accommodation) or increase in intraocular pressure (IOP).
Contraindicated in narrow-angle glaucoma (production if mydriasis)(more riskier)
Uses: examination of eye, treatment of open angled glaucoma (increased outflow and decreased production of aqueous humor)
Symptomatic relief for minor eye irritations due to colds, hay fever, or dust.
ADR’s: stinging burning, drying of eyes, tachycardia, hypertension arrythmias, reflex bradycardia.

Front 54

Dipivefrin

Back 54

Alpha 1 adrenergic synthetic catecholamines
A lipid soluble prodrug of epinephrine
Penetration into cornea is greater than epinephrine (lipophilic)
Used to reduce IOP for chronic open-angled glaucoma.
Fewer ADR’s than Epinephrine: less drug required (better absorption)
Contraindicated in narrow-angle glaucoma

Front 55

Clonidine

Back 55

Alpha 2 Adrenergic agonist
Activates alpha 2 sites on presynaptic membrane reducing NE transmission→ reduces vasoconstriction.
Pharmacologic effects: include hypotension, sedation and analgesia.
Reduces blood pressure by acting on alpha 2.

Front 56

Dobutamine

Back 56

Beta 1- adrenergic synthetic catecholamines
Direct activation of Beta 1 adrenergic receptors on myocardium (selective)
Minimal action at alpha or beta 2 sites.
Increases contractile force- less tachycardia and peripheral vascular resistance than isoproterenol.
Use: Acute treatment of heart failure due to depressed contractility.
ADR’s: tachycardia, mild hypertension, premature ventricular contractions, halogenated hydrocarbons (lidocaine) may increase arrhythmias.

Front 57

Bronchodilators

Back 57

Beta 2- adrenergic synthetic catecholamines
Used in the treatment of bronchial asthma and other chronic obstructive pulmonary diseases. (treat symptoms)
Relax bronchiolar smooth muscle
Activate adenyl cyclase→ cyclic AMP
Epinephrine and isoproterenol activate all beta-adrenergic sites and their use is associated with many ADR’s (cardiac stimulation)

Front 58

Albuterol

Back 58

Beta 2- adrenergic synthetic catecholamines
Greater selectivity for beta 2 receptors on bronchiolar smooth muscle than epinephrine or isoproterenol.
Lower incidence of cardiac side effects (tachycardia and increased cardiac output).
Complete separation of beta1 and 2 activity isn’t achieved.
Relaxes bronchiolar, vascular, and uterine smooth muscle.
Uses: relief of bronchospasm associated asthma- can’t be used chronically because will increase HR.
ADR’s: tachycardia, arrhythmias, increased BP.

Front 59

Isoxsuprine

Back 59

Beta 2- adrenergic synthetic catecholamines
A smooth muscle relaxant used to treat peripheral vascular insufficiency (?) and cerebrovascular insufficiency (?).
Diminishes vascular resistance and increases resting blood flow in skeletal muscles.
This drug primarily increases blood supply to nondilated, nonischemic areas that are not in critical need of improved perfusion.
Hypotensive effect may actually reduce cerebral blood flow and perfusion to vital organs.
ADR’s: lightheadedness, hypotension, tachycardia

Front 60

Isoproterenol

Back 60

Beta 1 and Beta 2 adrenergic synthetic catecholamine
Nonselective: Activates all beta receptors
Oral and sublingual tablets aren’t reliable because could be chewed and increase the dose by 3x leading to tachycardia.
Causes cardiac stimulation, vasodilation and bronchodilation
Relaxation of smooth muscle of GI tract and uterus.
Uses: Relief of bronchospasm, management of shock, cardiac arrest, AV block.
ADR’s: headache, palpitations tremors, bronchial irritation, tachycardia, disrythmias.
OD may cause cardiac arrest (so much stimulation of heart it freezes)
If combined with epinephrine in local anesthetics may cause cardiac arrythmias.
Reversed by propanolol and other beta blockers.

Front 61

Ephedrine

Back 61

Alpha and Beta adrenergic synthetic catecholamine
Similar action to amphetamines- used to be sold OTC.
Professional athletes die from this→ vasoconstriction if overdose→ build up heat and die
Direct: activation of alpha and beta adrenergic receptors
Indirect: release of NE from presynaptic membrane
Results in tachycardia, increased BP and cardiac output, mydriasis, relaxation of bronchiolar and GI smooth muscle, bronchodilation (less intense than epinephrine), CNS stimulation.
Uses: Broncodilation in chronic pulmonary diseases, decrease nasal congestion, treatment of narcolepsy, has been used for ADD
ADR’s: similar to epinephrine (can develop tolerance quickly)

Front 62

CNS Stimulants and Anorexiants

Back 62

Amphetamine derivatives and ephedrine.
Uses: Control of obesity (decrease appetite; anorexiant)- not effective
Relief of depression (limited)
Treatment of ADD

Widely abused drugs.

Front 63

Phenylpropanolamine

Back 63

A CNS Stimulant and Anorexiant (like amphetamines)
Has been taken off the market as a diet aid (as an adrenergic drug can lead to heart attacks)
Has been used as a sympathomimetic decongestant and an OTC diet aid (Dexatrim).
Anorexiant effect by decreasing appetite in hypothalamus.
Not very effective after a few weeks because you develop tolerance. Thus need higher doses that can lead to increased cardiac stimulation and increased blood pressure.

Front 64

Phenoxybenzamine

Back 64

Nonselective Alpha Adrenergic Blocking Agent
Block alpha 1 sites (post-synaptic) on vascular smooth muscle (antagonizes E and NE vasoconstriction) and alpha 2 sites (on presynaptic membrane- allows increased release of neurotransmitters).
Long acting and noncompetitive (forms stable covalent bond with alpha receptor site). Blockade can last for days.
Blocks primarily at alpha 1 sites.
Increased blood flow to skin, mucosa, and viscera.
Orthostatic hypotension- alpha 1 sites are blocked so when a person stands up blood pools in the legs→ pass out.
Uses: Control hypertension in those with pheochromocytoma (tumor of adrenal medulla→ extra catecholamines)
Treatment of pulmonary hypertension.
Peak effect: occurs in 4 to 6 hours.
ADR’s: Nasal congestion, Miosis, Dizziness, Orthostatic hypotension, tachycardia, shock

Front 65

Phentolamine

Back 65

Nonselective Alpha Adrenergic Blocker
Similar to phenoxybenzamine except it’s reversible (good) and there is competitive antagonism at presynaptic and postsynaptic alpha sites.

Can be used chronically because it’s reversible.

Also causes direct relaxation of vascular smooth muscle.

Front 66

Prazosin (minipres)

Back 66

Selective Alpha 1 Adrenergic Blocker
Primarily block post-synaptic alpha 1 receptors on blood vessels.
Reversible and competitive with E and NE.
Dilates both arterioles and veins
Blood pressure is lowered even when patient is supine
Significant hypotension can occur during initial dose (first dose effect- it’s very powerful)
Used for treatment of hypertension (can be used with other antihypertensive drugs)

Front 67

Yohimbine

Back 67

Selective Alpha 2 Adrenergic Blocker
Blocks Alpha 2 sites resulting in increased release of catecholamines at peripheral sites (primarily NE)
Complex mechanism: also increases peripheral cholinergic activity and central activity leading to increased BP and HR.
Used to treat orthostatic hypotension and impotence.

Front 68

Beta Adrenergic Blocking Agents

Back 68

Produce reversible and competitive blocking at beta receptors.
Antagonize the effects of catecholamines released from adrenergic nerve endings and the adrenal medulla.
Decrease many actions of catecholamines:
Myocardial stimulant, vasodilator, bronchodilator, metabolic

Front 69

Nadolol and Propanolol

Back 69

Nonselective Beta Adrenergic Blocking Agents
Block BOTH beta 1 and beta 2 receptors- not good for people with cardiac AND pulmonary problems.

Front 70

Metoprolol

Back 70

Selective Beta 1 Adrenergic Blocker
Selectivity for cardiac beta-1 sites (doesn’t cause pulmonary constriction)
If a person with respiratory problems give this- not propanolol.

Front 71

Beta Blockers (general)

Back 71

Decrease heart rate and force of contraction
Lower BP
Membrane stabilizing action (like quinidine)- cardiac stabilizing
Opthalmic- reduces formation of aqueous humor, no miosis or hyperemia.
Uses: Antianginal, Antihypertensive, Antiarrhythmic
Oral absorption is good
First pass effect is significant for metoprolol and propanolol. Food increases bioavailability of these drugs.
Most metabolized in liver
Short half life of 3-9 hours.

Front 72

Beta Blockers (ADR’s, Contraindications, Withdrawl, Interactions)

Back 72

ADRs: tachyarrythmieas (heart beast faster), chest pain, cardiac failure, dizziness, bizarre dreams, diarrhea, anorexia, bronchospasms, joint pain.
Contraindications: right ventricular failure, severe congestive heart failure
Withdrawl: must be gradual because upregulation occurs during chronic administration (if go cold turkey, more receptors for catecholamines→ more cardiac activity)
Interactions: prolongs insulin-induced hypoglycemia and masks symptoms of hypoglycemia, decreases clearance of lidocaine, enhances muscle relaxing action of NMB drugs

Front 73

Carvedilol and Labetalol

Back 73

Alpha and Beta Adrengergic Blockers
Used in surgery to shut everything down.
Used as an antihypertensive agent
Decreases BP (alpha 1 block) and no significant reflex tachycardia (beta-1 block)
Contraindicated: patients with asthma (beta2 block)

Front 74

Quinidine, Paroxitene, Fluoxitine, Setraline

Back 74

Block CYP2D6 and block conversion of Codeine into morphine (active metabolite)

Quinidine = old anti arrythmic
All others are serotonin selective reuptake inhibitors

Front 75

Digoxin

Back 75

CHF

Cardiac glycoside
Natural product of Foxglove plant

Front 76

Naloxone

Back 76

Opioid antagonist, reduces potency of opioid

Front 77

Buprenorphine

Back 77

Opioid partial agonist -- reduced the intrinsic activity compared to opioid agonists -- would shift curve to the left

Front 78

Probenecid

Back 78

Competitive competes for same pump in kidney tubules Penicillin
Increases duration of Penicillin in the body

Front 79

Lithium

Back 79

Actively secreted into kidney tubule

NSAIDs inhibit its active secretion into the kidney tubule

Front 80

Neostigmine

Back 80

Anti-cholinesterase used to treat myasthenia gravis (where nicotinic M cholinergic receptors are being destroyed

Front 81

Physostigmine

Back 81

Anticholinesterase used to treat Alzheimer's

Front 82

Ipratropium

Back 82

Used for asthma, muscarinic cholinergic antagonist

Front 83

Haloperidol

Back 83

Dopamine receptor agonist, blocks alpha -1
Used in treatment of schizophrenia, but people develop Parkinson-like symptoms

Front 84

Cocaine

Back 84

First local used, an ester

legal in hospitals for topical purposes in nasal surgery and eye surgery
Only local with profound vasoconstriction

Abuse potential

End result:
accumulation of NE (blocks reuptake), amphetamine effect accelerates release of NE, sensitization of alpha and beta receptors, CNS stimulation, vasoconstriction, B1 stimulating: tachycardia and increased contraction force

Avoid using w/ epinephrine (you'll get epi build up)
Cocaine + vasoconstrictors = hypertension, cardiac arrhythmias, death

End result:
blocks reuptake of dopamine, accelerating dopamine release, stimulating B1 receptors driving the heart -- excess dopamine gives you the high

Front 85

Esters

Back 85

Benzocaine
Procaine (Novacaine)
Tetracaine

Bad because they release PABA, which a lot of people are allergic to

Metabolized in blood stream via cholinesterase's

ring structure makes it lipid soluble, water solubility make it injectable (except Benzocaine)

Benzocaine used topically in orajel - overdose can lead to methemoglobinemia

Front 86

Amides

Back 86

All injectable local anesthetics

Lidocaine
Etiodcaine (conjoner of lidocaine - not marketed anymore)
Mepivacaine - doesn't need a vasoconstrictor because it doesn't dilate as much, so it lasts longer
Bupivacaine (mepivacaine derivative, also more potent)
Prilocaine (doesn't dilate as much, need to use higher concentrations compaired to mepivacaine)
Articaine (both ester and amide), increased reports of parasthesias in mandibular infiltrations

Front 87

Vasoconstrictors

Back 87

Increase duration of local anesthetics, reducing blood levels
Stimulate alpha and beta receptors
Epinephrine and levonefrin
Hemostatic effects by stimulating alpha 1 receptors

Front 88

Concerns w/ vasoconstrictors

Back 88

BP > 200/115
myocardial infarction within 6 months
stroke within 6 months
bypass surgery within 6 months
unstable angina
uncontrolled CHF or arrhythmias
uncontrolled hyperthyroidism
sulfite sensitive asthma or allergy
Taken cocaine, beta blockers or tricyclic anti-depressants

Front 89

Physostigmine

Back 89

Anti-cholinesterase, for nicotonic receptor stimulation

(could be for increased salivation)

Used to combat overdose for atropine or other anti-muscarinic drugs

Front 90

Acetylcholine

Back 90

Direct-acting cholinomimetic (for muscarinic receptor stimulation)

Front 91

Bathanocol

Back 91

Direct-acting cholinomimetic (for muscarinic receptor stimulation)

Front 92

Carbachol

Back 92

Direct-acting cholinomimetic (for muscarinic receptor stimulation)

Aka cholinergic
can directly activate both muscarinic and nicotinic cholinergic receptors

Indicated for glaucoma (you want a pure muscarinic agonist)

Front 93

Cevimeline

Back 93

Direct-acting cholinomimetic used for radiation induced xerostomia or Sjoren's syndrome

Front 94

Ambenonium

Back 94

Anticholinesterase (for nicotinic M cholinergic receptor stimulation

Used in treatment of myasthenia gravis and secrete ACh

Front 95

Edropohnium

Back 95

Anticholinesterase (for nicotinic M cholinergic receptor stimulation

Used in treatment of myasthenia gravis and secrete ACh

Used to reverse effects of curare induced neuromuscular blockade

Front 96

Neostigmine

Back 96

Anticholinesterase (for nicotinic M cholinergic receptor stimulation

Used in treatment of myasthenia gravis and secrete ACh

Used to reverse effects of curare induced neuromuscular blockade

Front 97

Donepezil

Back 97

Anticholinesterase (for nicotinic m chloinergic receptor stimulation)

Used in treatment of Alzheimer's disease

Front 98

Rivastigmine

Back 98

Anticholinesterase (for nicotinic m chloinergic receptor stimulation)

Used in treatment of Alzheimer's disease

Front 99

Tacrine

Back 99

Anticholinesterase (for nicotinic m chloinergic receptor stimulation)

Used in treatment of Alzheimer's disease

Front 100

Bethanocol

Back 100

Direct acting cholinomimetic used to aid in bladder atony -- help with urinary retention

Front 101

Nerve Gas

Back 101

Irreversibly and covalently bind cholinesterases
Lipid soluble on skin
SLUDGE syndrome
Sarin, Soman, Tabun

Front 102

Malathion

Back 102

Insecticide, anticholinesterase

Same effects as nerve gas but not as powerful

Front 103

Mementine

Back 103

Used in treatment of Alzheimer's
N-methyl-D-aspartate recepto antagonist; excitatory amino acid glutamate and aspartate contribute to neuronal destruction associated w/ Alzheimer's, so this blocks neurotoxic excitatory amino acids

Usually combined with anti-cholinesterases

Front 104

Ginko biloba

Back 104

Used in treatment of Alzheimer's

Has some antiplatelet activity

Front 105

Verenicline

Back 105

Chantix

Partial agonist at alpha-4 beta-2 nicotinic acetylcholine receptor (partially activates nicotinic receptors)

Blackbox warning for suicidal ideation

FDA approved w/ Buproprion (only 2 FDA approved for tobacco cessation)

Front 106

MAOIs

Back 106

Monoamine oxidase inhibitors

Block inactivation of tyramine in the stomach leading to an overload on norepinephrine release leading to a hypertensive crisis or cardiac arrhythmia

Phenelzine
Isocarboxid
Tranylcypromine

Front 107

Fentanyl orallete

Back 107

Opiate more powerful than morphine, given submucosally like a lollipop to kids
High first pass effect so 80% of it is inactivated before it gets in the blood stream

Front 108

Glyburide

Back 108

Oral anti-diabetic

Highly protein bound, NSAIDs can protein bump significantly increasing blood levels sending patient into significant hypoglycemia

Front 109

Propofal

Back 109

Short acting general anesthetic drug
4-8 min
Extremely high volume of distribution, extremely lipid soluble

Front 110

Calcium channel blockers

Back 110

Used in treatment of angina, hypertension and cardiac arrhythmias
End in -pine

Vasodilators so they cause postural hypotension

substrate of cyp 3A4

Front 111

Haloperidol

Back 111

Dopamine receptor agonist
Used to treat schizophrenia (too much dopamine) but as a result some people develop Parkinson like symptoms
Also blocks alpha 1 receptors, so orthostatic hypotension is a possibility