Things to have memorized for exam 1

1. Absorption of drugs
a. pH effect on drugs
i. ph<pKA: nonionized acids, ionized bases acids retained and bases
excreted
ii. ph>pKA: ionized acids, nonionized bases acids excreted and bases
retained
b. Neutral acid/base = able to pass through membrane and lipid soluble
c. Ion trapping = a change in pH in different body compartments can trap drugs by
changing them from nonionized ionized and now they cannot get back
i. Ionized form of drugs does not contribute to concentration gradient since it
has no pull or desire to move to opposite side
ii. Ex: IV bases (eg. Morphine) can be trapped in stomach if they are secreted
into it because the very low pH will ionize them
d. Drug equivalences (should be based on bioavailabilities or therapeutic effect)
i. Chemical = same [active ingredient]
ii. Pharmaceutical = same [active and inactive ingredients]
iii. Biological = same bioavailability of active ingredient
iv. Therapeutic = same effectiveness in treating disorder
v. Generic = same or similar dissolution rate of generic drug in comparison to
patented
e. First pass effect = biotransformation of drug pre-hepatically and/or hepatically
i. Oral is fully affected but rectal is only 50% affected
ii. All other ROAs, including sublingual, are not affected
f. Hepatic clearance depends on multiple factors
i. Degree of plasma protein binding
ii. Rate of biliary secretion
iii. Rate of hepatic biotransformation
iv. Rate of transport into liver cells
1. This is most easily affected by a decrease of blood flow to liver (eg.
CHF) that decreases drug clearance and necessitates a lower dosage of
drug for pt
g. ROAs
i. Oral
1. Most convenient, economical, safest, and does not need to be sterile
2. Gastric
a. Very low pH of stomach makes organic acids absorbed well due
to them being mostly non-ionized
b. Alcohol is absorbed well
3. GI (intestinal mucosa)
a. Weak bases absorbed well
b. Food and motility affects absorption
4. Contraindications: emetic drug or pt vomiting, pt unwilling/incapable of
oral route; GI system destroys drug, or drug cannot be absorbed by GI
mucosa
ii. Rectal
1. Limited first pass effect but unpredictable absorption
2. Irritating and not convenient
iii. Parenteral
1. IV
a. Advantages
i. Fastest and allows for titration of dose
ii. Able to maintain constant concentration
iii. Able to admin large volumes of flood over long period of
time with continuous infusion

iv. Reduced irritation due to buffering of drug by blood

b. Disadvantages
i. Need to be sterile, proper technique needed
ii. Cannot withdraw drug from vein once it has been
admined
iii. Too rapid of injections serious issues or OD
2. Intra-arterial
a. Used for local perfusion of organ for chemo and for diagnostic
substance injection
3. Intramuscular
a. Quick absorption
i. Delt > vastus lateral > gluteus maximum
ii. Depot forms allow for gradual absorption over long time
iii. Small molecules capillaries
iv. Large molecules lymphatic channels circulation
4. Subcutaneous
a. Water soluble, non-irritant drugs
b. Generally slower absorption due to less blood flow but can be
very fast
c. More safe because you can reduce absorption of drug by
lowering blood flow to area by: immobilizing limb, cool local
area, or apply tourniquet
d. Can admin moderate amounts of fluid due to loose CT
e. Use hyaluronidase to break up CT to increase spread of
substance and absorption rate
5. Bone marrow
a. Almost equivalent to IV, used when extensively burned
6. Intrathecal (spinal)
a. Subarachnoid space to get drugs to spinal nerves or brain
7. Epidural
a. Outside of dura mater so more local effect
8. Intradermal
a. Allergic skin testing
9. Intracardiac
a. Emergency admin of epi to heart to restart it
10.Intraperitoneal
a. Used in lab animals
11.General advantages
a. Placebo/psychological effect where pts believe more is being
down for them and always available ROA
iv. Inhalation
1. Alveoli have large SA for absorption
a. Gases anesthetics with large lipid solubilities and very small
size
b. Aerosols made to deposit on bronchiol surface for local action
(eg. Dilation)
i. Systemic absorption does happen so you have to be
careful with dose
v. Mucous membrane
1. Local effect via conjunctiva, vagina, nasal, rectum, oropharyngeal
a. Some systemic absorption
vi. Skin
1. Local effect; transdermal
2. Highly lipid soluble substances pass readily (insecticides)
3. Skin penetrance rate controlled by size of pores in patch and by L/W
coefficient

a. Use lipid soluble (eg DMSO) vehicle to increase absorption or

use keratolytic or inunction (rubbing)
2. Distribution of drugs
a. Drugs not uniformly distributed in body
b. Plasma protein (mostly albumin) bind drugs and remove them from interaction with
targets and from excretion increases elimination half life of drug by preventing
excretion via kidney
c. Binding fraction is determined by number of binding sites available, concentration
of free drug, and dissociation constant of the drug
i. Decreasing free drug concentration or dissociation constant (ie increasing
binding affinity) increases binding fraction
d. Bound drug acts as a reservoir for the free drug by keeping it from being eliminated
and releasing it from binding according to concentration gradient
e. Albumin
i. Primarily binds acidic drugs and can be altered in concentration
1. Decreased by
a. Decreased synthesis via liver disease, malnutrition/absorption
b. Massive burns, glomerular injury, inflammation
c. Pregnancy, aging, cardiac failure
2. Increased by
a. Acute hydration
f. Alpha-1-acid glycoprotein binds basic drugs
g. Drug interactions are more dangerous when you have greater than 80% bound
fraction of a drug because that means that the therapeutic effect of a drug is
accomplished with just 20% or less of the dose given
i. So, any alteration to a drugs binding (ie competition from another drug) can
cause a toxic effect
h. Cell constituents (mercuric drugs and renal tubules) and skeletal system
(tetracycline in bones) can sequester drugs too
i. Tissues that have highest [drug] are not necessarily the target for that drug
j. Greater lipid solubility of drugs = more rapid effect and more abuse potential (eg.
Morphine vs heroin)
i. Example of latentiation where you add lipophilic groups to drug that are
removed once they reach target and so expose drug to target
k. BBB
i. Drugs enter BBB more readily if they are
1. Lowly ionized at plasma pH
2. Have low binding to plasma proteins
3. Have high L/W coefficient
4. Are very small
l. Placental barrier
i. Most drugs get through, especially during later terms
ii. Highly charged, large ions and drugs do not get through
1. Ie very water soluble drugs do not get in (eg glycopyrrolate and
heparin and NM blockers)
iii. Albumin gets in slower than Igs so there must be selective absorption
because albumin is smaller than Ig so it should get in easier
3. Drug biotransformation
a. Converting a drug to a more water soluble form for excretion
i. Can form more toxic metabolite
ii. Can form inactive metabolite too or can form drug from prodrug
b. Elimination half life is time required for [drug] in plasma to decrease by 50%
i. Not always related to duration of drug action
c. Reactions can be first order (concentration of drug is proportional to elimination
rate) or zero order (constant elimination rate)
d. Phase 1 reaction

e.

f.
g.

h.
i.

j.

k.

4. Drug
a.

i. Usually not enough for complete elimination and are dependent on hepatic
function
ii. Include: oxidation, hydrolysis, reduction
Phase 2 reaction = conjugation reaction producing readily excretable, inactive
metabolite
i. Still mostly done in liver (can also occur in GI, kidneys, or lungs too) but is not
as dependent on liver function for efficacy
ii. Conjugate drug with another molecule
1. Acetylation, methylation, glucuronidation
iii. Usually, but not always, occur after phase 1
Microsomes are vesicles that contain an abundance of smooth ER, containing large
amoutns of mixed function oxidases
Oxidation-reduction enzymes
i. NADPH-Cytochrome c reductase
ii. CYP 450
1. Many different subtypes (CYP3A4 and CYP2D6 are major types)
Burn victims have higher drug clearance due to hyperactive CV status
Enzymes can be induced, resulting in shorter elimination half life and reduced drug
activity
i. Barbiturates
ii. Carbamazepine anticonv
iii. Phenytoin - anticonv
iv. Rifampin - antibiotic
v. St johns wort - antidep
Enzymes can also be repressed/inhibited
i. Cimetidine
ii. Ciprofloxacin - antibiotic
iii. Erythromycin - antibiotic
iv. Ketoconazole - antifungal
v. Oral contraceptives
vi. Protease HIV inhibitors
vii. Hepatic disease
viii. Grapefruit juice
Difficult to measure changes in hepatic biotransformational capacity but can
measure liver enzyme levels or serum bilirubin to estimate liver function by
measuring oxidative metabolism capacity
i. Use antipyrine test
1. Chemical that undergoes extensive oxidative biotransformation, lacks
significant plasma protein binding, and is easily analyzed
2. Compare oral concentration vs urinary level of metabolite
a. Lower level of metabolite = lowered liver function
elimination
Kidney dependent but not completely sufficient (ie need biotransformation too)
i. Glomerular filtration dependent on molecular size, [drug] in blood, plasma
protein binding, and polarity of drug (more polar/water soluble excreted)
ii. pH of urine favors excretion of bases
1. acidifying urine = more excretion of bases and retention of acids in
blood
2. alkalizing urine = more acid excretion and retention of bases in blood
iii. Tubular secretion is energy dependent, can blocked my metabolic inhibitors,
can be saturated, and is available for both anions and cations
1. Compounds can compete with each other for secretion so you can use
this to increase retention of compounds (eg. Penicillin) by
administering competing compound (eg. Probenecid)
2. Secreted compounds are put into urine and so are lost from circulation

3. Plasma binding has no effect on tubular secretion because bound

drugs will leave binding proteins as their unbound partners are
secreted into urine and excreted
b. Liver can excrete drugs into bile intestines
i. If reabsorbed, then drug goes back to Liver and repeats cycle (enterohepatic
circulation)
ii. Elimination of many antibiotics (penicillin, streptomycin, tetracyclines);
organic anions and cations due to lack of reabsorption due to intestinal pH
iii. Steroids are partially excreted in bile and largely reabsorbed by GI
c. Intestines excrete drugs in feces
i. Drug that was not absorbed and/or drug that ended up in intestines due to
bile, saliva, or digestive secretions of stomach or small intestine
d. Lungs eliminate volatile substances
e. Sweat glands are minor but can produce a rash when they excrete drugs
f. Mammary glands excrete drugs @ 1% of maternal dose which can create effect for
baby
5. Therapeutic Drug Levels
a. Indications
i. Efficacy evaluation, narrow therapeutic index with drug, compliance
monitoring, multiple drugs being used and risk of drug interactions, poor
absorption of drugs, or onset of pathology
b. Measure using steady state values achieved by measuring saliva and blood or right
before administering dose (trough level)
c. For some drugs, a clinical value or range has been established for drug efficacy so
you trying to measure blood levels to attain that
d. Urine samples are not sufficient to prove impairment only usage
i. False positives occur
ii. Some tests are too general and will pick up the presence of a drug that is
not there but a related analogue is
iii. False accusation due to environmental exposure (eg. Marijuana) or
biotransformation of legitimate drug into illegal one (ex codeine to morphine)
iv. Prolonged elimination by some drugs can extend presence of drug and its
metabolites in body for long time (eg. 4 weeks for heavy marijuana user)
e. Site of drug action
i. Not always well established
ii. Membrane phenomena = cell membrane permeability altered which can
affect ion transport
iii. Enzyme inhibition which can affect hormones, GI activity, neurotransmission,
muscle contraction
1. Inhibiting anabolic enzymes (ie. Enzymes that produce substances) will
decrease synthesis and effect of endogenous substances (ie. NTs)
2. Inhibiting catabolic enzymes will increase the activity of endogenous
substances by slowing down their breakdown
iv. Enzyme stimulation (eg. Adenylate cyclase) is also possible and common
v. Interactions with NTs also occurs
1. Mimicks of NTs for direction receptor activation
2. NT blocker for competition
vi. Leukotrience receptor antagonist
vii. Monoclonal antibodies
6. Factors Modifying Drug Activity
a. Age
i. Pediatrics are more sensitive with less developed biotransformation and
excretion systems to lower the dose for them
ii. Geriatrics have same pharmacokinetics as average adult but are usually
given lower doses due to aged excretion systems and multiple
pharmacotherapy

b. Body weight
i. 70 kg adult = standard so adjust drug dose accordingly
c. Gender
i. Hormones can play a role
ii. Generally, an equal weight male and female will have the same response to a
drug
d. Pathology
i. Hepatic dysfunction decrease dose
ii. Renal impairment decrease dose
1. Guidelines based on creatinine clearance
a. Mild = 80-50
b. Moderate = 49-30
c. Severe =<30 or on dialysis
e. Pharmacogenetics = abnormal reaction and/or biotransformation due to genetic
difference
i. Reactivity can be quantitatively or qualitatively different from normal
ii. Examples:
1. Abnormally prolonged effect of drug (eg. Succinylcholine)
2. Novel effect (unrelated effect occurs)
f. Pharmacogenomics = more encompassing form of pharmacogenetics
i. Population based; search for genetic differences within a population that
cause abnormal or just above/below average responses to drugs
1. Also involved with susceptibility to health issues
g. Time of admin
i. Nocturnal animals have more active enzymes in darkness/at night, while
humans have less active enzymes at night
h. Concomitant drug therapy
i. Drug interactions can increase or enhance therapeutics and/or toxicity
1. Examples
a. Cholestyramine decreases absorption of many drugs in GI
b. Competition for binding to plasma proteins by phenylbutazone
increases activity of warfarin by displacing it from plasma
proteins
c. Biotransformation of drugs can be changed via enzyme
inhibition/induction
i. Frequency of drug response
i. Uniform response via acute administration where the response from the
previous admin is completely removed prior to the next admin
ii. Chronic admin also gets uniform response by creating steady state condition
after 4 or so half lives of drug
1. Goal is to keep blood concentration inside of therapeutic range
2. Steady state does not equal therapeutic range because you can have a
steady state in subtherapeutic and/or toxic ranges
iii. Cumulation happens usually with longer acting drugs but can occur for any
drug if it is repeatedly admin earlier than elimination half life
j. Tolerance
i. Decreased pharmacological response to usual dose due to enzyme induction
or receptor up/down regulation
ii. Types of tolerance
1. Pseudo tolerance/false tolerance
a. Due to decreases absorption or increased excretion (ie. Not
enzymatic change)
2. Tachyphylaxis
a. Rapid development of tolerance after over a few doses
3. Cross tolerance

a. Tolerance to a class of drugs (either due to structural or action

similarities)
i. Can be tolerant to a drug before ever taking it due to prior
admin of other similar drugs
4. Resistance
a. Reserved for chemotherapy and indirectly for antibiotics (the
microorganisms have the tolerance, not you)
k. Physical dependence
i. Body adjusting to effect of drug by changing receptor number (most
common), affinity, or both
1. Can be upregulated when exposed to receptor blockers and down
regulated when exposed to stims
l. Withdrawal
i. Pt has opposite effect of drug upon cessation of admin (ie. Hyperactive state
when you stop taking depressants)
ii. Takes time to get enough dependence that you can have such a strong
withdrawal reaction
iii. Hyperactive withdrawal is more dangerous (ie. Tremors, seizures,
tachycardia) than hypoactive
1. Alcohol withdrawal is very dangerous, same with opioids
m. Compliance
i. Reasons for non compliance
1. Self conscious of their disease making them different from others so
avoid taking medication so as to not draw attention to their disease
2. Patient does not feel sick when supposed to take dose (due to
therapeutic effect of drug) so avoids taking drug but then becomes ill
a. Many conditions do not hurt or cause distress during early
stages (eg. Hypertension) so pts will not take drugs to save
money because they feel like they do not need them
b. Pts also will cease taking drugs earlier than supposed to
(antibiotics) because they feel better
3. Adverse drug reactions
a. Either actual (side effects) or potential (increased chance of
other issue when you take a drug or fear of addiction)
i. Fear of addiction is unfounded but potential for other
issues is real because you do increase your risk for stroke,
for example, when you take aspirin to reduce chance of
second MI
ii. Increase compliance by
1. Increasing understanding of drugs by pts
a. Including the MOA, potential sides, why they should take drug,
and what can occur if they do not
2. Need to be available to answer pts questions and provide reassurance
7. Drug Toxicity
a. No drug is without adverse effects at some dose
b. Acute toxicity
i. Looking at LD50 vs ED50 to get therapeutic index
ii. Use animal studies
iii. Larger ratio of ED50:LD50 = safer drug but not necessarily better drug
iv. Therapeutic index has no value in predicting hypersensitive pts and is not
useful in evaluation of therapeutic effectiveness
c. Chronic toxicity
i. Study by using drugs in mice which have short life spans so you can see what
6 months of a drug will do to them 10-15 years for us
d. Use animals to see if drug causes irritation, cancer, birth defects, etc
e. Adverse drug reactions

i. Mild = non threatening and annoying

1. Some, like drowsiness, can be an issue if behind a car
ii. Toxic = threatening or severe
f. Toxicity can be predictable or unpredictable
i. Predictable = related to effect of drug
ii. Unpredictable = seemingly unrelated to actions of drug
g. Relative risk
i. All drugs are potentially dangerous but should not cause an issue if drug is for
minor issue
ii. Higher degree of risk is allowed for drugs used to treat serious conditions
1. Benefit to risk ratio is judgement made by patient, not physician
h. Drug allergy/hypersensitivity
i. Had to have taken drug before (knowingly or unknowingly) and that drug
acted as antigen to body
1. Appears to be genetically determined predisposition to having
hypersensitivity reaction
ii. Allergic reactions are different than side affects because they are unrelated to
dose, occur only in susceptible people, and are the same (regardless of action
of drug; ie, not related to action of drug)
i. Iatrogenic disorders
i. Very important to understand the rxs you give pts because bad things can
happen to them otherwise (eg. Extended corticosteroids or extended
metoclopramide therarpies)
j. FDA made Risk Evaluation and Mitigation Safety (REMS) that both pt and physician
have to sign
8. Teratogenicity
a. Selectivity of drugs can cause teratogenic effects without causing any changes to
placenta or mother
b. There are certain periods of sensitivity for teratogenicity
i. During first 2 weeks after conception, it is rare for malformations to occur but
embryo can be killed
1. Not as much differentiation occurring so development is not greatly
affected
ii. Third week to third month is most sensitive
1. Nervous system = 15-25 days
2. Eye = 25-40 days
3. Heart = 20-40 days
4. Legs = 24-36 days
rd
c. After 3 month, drugs can still injure fetus but specific malformations do not occur
d. Malformations
i. Single teratogen can cause multiple malformations (eg. Rubella virus) and
many different teratogens can cause the same malformation
e. Experimental
i. Many things are teratogens in mice but few are in humans
1. Teratogens in mice can be dependent on strain of mice
f. Genetic environmental interaction
i. Genotype affects susceptibility of fetus to teratogen and many environment
induced malformations are phenocopies or phenotypic changes like those
produced by genetic changes
g. FDA pregnancy categories of teratogens
i. A = no fetal risk shown in studies of mice or humans
ii. B = no risk in animals but no controlled studies in pregnant women or
adverse effect (other than decrease in fertility) shown in animals but not
confirmed in controlled studies in women in first trimester and no evidence of
risk in later trimesters
iii. C = animal risk but no controlled studies in humans

1. Benefit of drug must clearly justify potential fetal risk

iv. D = fetal risk shown in humans
1. Drug use may still be acceptable if no other choice (ie. No safer drugs
to use or life threatening illness present)
v. X = contraindicated because known risk clearly outweighs any benefit
vi. N = not classified
9. Substance Abuse
a. Experimentation/Acute use is influenced by peer pressure
b. Dependence/Chronic use is mostly influenced by low self esteem
i. Insignificant factors
1. Family or personal income, area of residence, intelligence
ii. Significant factors
1. Self esteem, immaturity, inability to solve personal problems, easily
frustrated, difficulty with opposite sex, over dependence on family or
friends
c. Family support is very important and adults should serve as positive role models
d. School and education is important in strengthening values and increasing
awareness of how bad drugs are and the side effects
i. Referral to counseling should be provided by school with limited in house
counseling too
e. Drug screening decreases drug use in the military and for employment
i. Primary screen is qualitative not quantitative and has greater change of false
positive
ii. Confirmation test is more scientific and is accurate (determines exact
structure of chemical)
iii. Collection area should be private, coloring agent should be in toilet to not
allow dilution of urine, and shut off valve for sink must be outside of room
iv. Temperature must be within certain range (not more than 1.8 degrees F
between urine and oral temp) and should have normal specific gravity to
ensure urine has not been tampered with
v. Give subject water if they cannot urinate (max 1L; recommended 240 mL of
water)
1. Water intoxication is possible and must be treated slowly to decrease
risk of fatality
f. Big difference between physical dependence (body has adapted to presence of
drug) and addiction (mental disorder or psychological dependence)
i. Can be addicted to anything that fills a need
1. Criteria
a. Impulsive disorder
b. Takes a substantial amount of persons time
c. High rate of recidivism (relapse)
ii. Physical dependence begins with tolerance to a drug or substance
1. Oftentimes, dependence occurs independent of addiction
a. Physical dependence is not a criteria for addiction and a person
does not have to exhibit physical dependence to be an addict
10.
Drug Laws
a. US history
i. First now reg, then only reg on strength and purity (not efficacy), then reg on
safety, and finally reg on efficacy
ii. Drug Abuse Prevention and Control Act made controlled substances a thing
1. Schedule 1 = no accepted medical use and no refills
2. Schedule 2 = accepted medical use but no refills (except in some
exceptions)
3. Schedule 3 5 = 5 refills or Rx for 6 months, whichever happens first
b. Supplements

i. DSHEA dietary sup not represented for use as conventional food or as part
of diet
ii. Safety and efficacy proof rests with feds
iii. Its all about nutritional support (must make claim that supplement helps with
deficiency)
iv. Must have safety label
11.Drug Development
a. Pre clinical = binding studies, animal research, and mostly in vitro stuff
b. Careful planning is needed for clinical trials because you cannot change your
protocol once your study starts unless a very dangerous condition develops
c. Need control groups with placebo
d. Orphan drug act gives tax incentives to companies to develop drugs for conditions
that affect less than 200000 people
e. Phases of clinical trials
i. 1: limited number of human subjects; healthy volunteers with no blinding of
drug because you want pharmacokinetic information
1. Can be extensive phase if drug is new class
2. Actual patients can be used if drug being tested is highly toxic
ii. 2: usually first time drug is given to patients with actual disease and can
have variable number of patients
1. Examining safety and efficacy and trying to figure out final dosage
form
iii. 3: multicenter stage where many more patients are enrolled
1. Extensiveness of this phase is highly variable, depending on results
from phase II
2. Animal testing with emphasis on toxicity and/or teratogenicity still
going on
iv. 4: new drug application put in and drug is either approved or requires more
data
1. If approved, drug is on market and under post marketing surveillance
where patients and physicians submit reports of adverse reactions to
FDA
a. Important because phase 4 population (ie. General population) is
much larger, more variable, and is being managed by less
specialized doctors
i. Pick up very uncommon side effects or hypersensitive pts
12.
Cholinergic Drugs
a. Direct acting
i. Synthetic (structures designed to be more resistant to enzymatic hydrolysis,
have longer duration of action, and be more specific)
1. Miochol
a. Intraocular Ach contract smooth muscle to constrict pupil and
accommodate eye for near vision
2. Bethanechol
a. Muscarinic receptor activator increase GI peristalsis and
detrusor muscle tone
b. Tx fo non obstructive urinary bladder retention and other
bladder retention issues
c. Not as quick or long acting as carbachol
d. ADR
i. GI, urinary issues, asthma-like attacks
3. Carbachol
a. More specific drug for intraocular admission to get pupillary
miosis
b. Long acting and quick onset

c. Topical version (isopto carbachol) exists for chronic tx of

glaucoma
d. ADR
i. Vision issues, GI and peripheral problems (due to systemic
absorption) flushing, sweating, cramping, urinary
urgency
ii. Natural (admin of Ach is not very useful due to short duration and nonspecific
actions)
1. Alkaloids
a. Pilocarpine
i. Causes pinpoint miosis to increase drainage of fluid in eye
and decrease intraocular pressure (ie. Tx for glaucoma)
ii. Used to reverse cycloplegics and mydriatics (antiAch)
after eye exam or surgery
iii. ADR
1. Can have systemic effects again
2. Difficulty in focusing, local irritation, headache
iv. Therapeutic system exists for constant release of
pilocarpine to tx glaucoma
1. Poorly tolerated system
b. Nicotine
i. Activates all cholinergic receptors
1. Stims LC to increase alertness
2. Causes increased BP, HR, and vasoconstriction
ii. ADR
1. Hypertension, GI distress, CNS issues, derm
problems
iii. Tx system for healing to stop smoking with steady state
after about 2 days
b. Indirect
i. Reversible (too much cholinergic crisis, including muscle weakness)
1. Donepezil
2. Edrophonium
a. Used for dx of Myasthenia Gravis (should relieve symptoms)
b. TX for poisoning with Nondepol muscle relaxants
c. Injectable use only and has very short duration of action
d. Used to check and see if proper dose of cholinergic agents are
being used
i. If muscle strength improves then pt was underdosed
ii. If muscle strength worsens than pt has proper dosage or
maybe decrease their dosage
3. Neostigmine
a. Ionized to less BBB penetration and has mostly peripheral action
b. Tx for MG and Nondepol muscle relaxants
4. Pyridostigmine
a. Same usage as neostigmine but used as injectable when a
threat of nerve gas is imminent
5. Pysostigmine (more lipid soluble and better BBB penetration)
a. Tx of glaucoma and reversal of cycloplegia and mydriasis
b. Transdermal = 1-2 hour onset and 12-24 hour duration
c. Systemic = Also used as antidote for anticholinergics
i. Fast acting, shorter duration
ii. Larger amounts of ADRs
ii. Irreversible organophosphorus compounds that complex with enzyme
1. Isoflurophate
a. Ophthalmic use multiweek miosis

c.

d.

13.
a.

b.

i. Maintenance therapy = applied once every 8-72 hours

b. Unstable in water
c. Can absorb through skin
iii. Antidote for irreversible
1. Pralidoxime
a. Complexes with irreversible inhibitor allowing it to precipitate
but must be used within a few hours or else irreversible inhibitor
and enzyme binding will not be able to be released
b. Quick onset and short duration
Enhanced release of Ach
i. Guanidine
1. Tx for MG that enhances release of Ach from NMJ
2. Fairly toxic so only used for Eaton Lambert syndrome (more severe MG)
a. Frequent dosages
3. Large amount of ADRs and toxicity
Alzheimers Disease
i. Changes in cholinergic activity = component of AD
1. Reduced CAT act reduced Ach synthesis
2. Reduced responsiveness of M1 receptor in frontal cortex and
hippocampus
3. Loss of cortical neurons
ii. Genetic factors and may be precipitated by head injuries
iii. Tx
1. Enhancement of central cholinergic activity (lecithin)
a. Needs to be coadmin with cholinesterase blocker
2. 4 AP causes increased Ach release due to blocking K channels longer
repolarization time for neurons more Ca influx increased Ach
release
3. Cholinesterase inhibitors
a. Physostimine slight benefit but short half life
b. Tacrine sig impact but toxic to liver
4. Donezepil
a. Not hepatotoxic
b. Approved for all degrees of dementia
5. Memantine
a. Block NMDA receptors lower excitotoxicity slow progression
of AD
b. Only used for moderate to severse AD
Anticholinergic Drugs
Muscarinic blockers large dosages can become less specific for all classes of
anticholinergic drugs wide range of ADRs (eye, CV, GI, pulm, exocrine glands,
smooth muscle)
i. Decreased GI motility and secretions
ii. Tachycardia (decreased vagus activity)
iii. Urinary retention via relaxation of detrusor and sphincter contraction
iv. Causes cycloplegia (accommodation paralysis) an mydriasis (sphincter
muscle relaxation)
v. Decreases sweating, dry mouth
vi. Drowsiness, disorientation, decreased muscle tone
Belladonna alkaloids rapidly enter CNS but have a lot of sides; MOA = competitive
antagonism of ACH @ postsynaptic muscarinic receptors but large doses start
acting @ NMJ and autonomic ganglia
i. Uses = mydriasis and cycloplegia for eye exam and preop to reduce excess
salivation and prevent bradycardia; motion sickness, reliefe of tremor and
rigidity in parkinsons
1. Safer and less sides if used alongside cholinesterase blocker

c.

d.

e.
f.

g.

ii. ADRs
1. Dry mouth, constipation
2. Confusion, drowsiness
3. Vision issues
4. Urinary retention, anhydrosis
iii. Contraindicated with glaucoma
iv. Have strong interactions with any drug that has anti-ach effect (eg.
Antihistamines, antipsychotics, etc.)
v. Most dangerous thing is systemic absorption
1. Resulting in disorientation, amnesia, hallucinations, CV issues, and
death in children
vi. Atropine
vii. Scopolamine
Tertiary amines non ionized and more lipid soluble
i. Tolterodine
1. Used for urinary leakage by relaxing detrusor muscle
ii. Tropicamine
1. Short duration of action for mydriasis
iii. Benztropin used for reducing extrapyramidal disorders of parkinsons
iv. Diphenhydramine has less peripheral sides than other drugs and can be
helpful at night due to sedation
Quaternary amines low lipid solubility with much longer duration
i. Used to be used for decreasing acid secretion to treat ulcers but have to
increase dosage to large amounts and suffer many ADRs in order to get to
therapeutic level for that
ii. Glycopyrrolate
1. Given with NMJ blocker to reduce cholingeric effects
2. Decreases saliva, secretion of GI and resp, and prevents bradycardia
iii. Tiotropium Spiriva
1. Not fo acute use and not a rescue med
2. Used for long term treatment of COPD
Ganglionic blockers block postsynaptic ACH
Depolarizing initially stim receptors but then block receptors via persistent
occupation of site
i. Nicotine
1. Need to have large doses to block receptors systemic effects
a. Reduced BP, increased HR, confusion, convlusions, resp failure
i. Opposite effects of stimulatory actions of smoking
Parkinson tx anticholinergics
i. Due to DA defic larger Ach influence so have to decrease Ach levels to
normalize
1. Also decreases excessive salivation