A 43 year old male is brought to the ER by a friend. He is salivatingexcessively and he has had diarrhea and urinary incontinence.He is a migrant worker and had been picking vegetables in a fieldwhen the symptoms started. On physical exam he is wheezing.Which of the following drugs would have the best potential toimprove his symptoms? A. Acetylcholine (make it worse)B. Nicotine (paralysis)C. Edrophonium (bad effect)D. Atropine

D. Atropine

Absorption applies to all _________of administration except ________

and _______?

routes of entry, except topical(drugs applied directly on thetarget tissue) and IV (drug isalready in circulation, directly putin)

Absorption Of Indirect Cholinesterase Inhibitors:Organophosphates: Topical absorption is ________ (they can beabsorbed from whatever body surface they are placed on (skin,mucous membrane, eye, gut or lungs) & once absorbed they getinto the ________ nervous system.Because of their absorption they are good for killing _______; theycan be absorbed through the bugs exoskeleton & then affect it'snerves (more seen in pesticides than anything human). healthcare providers have a risk of exposure through their skin iftreating a patient with a nerve gas or insecticide toxicity

excellent, central, bugs

Absorption Of Indirect CholinesteraseInhibitors: Quaternary compounds:Topical absorption is ______ & they don'tget into the _______ nervous system verywell.

poor, central

AcebutololAtenololEsmolol

Metoprolol

Selective β1 - blockers

Acetylcholine has an extremely_____ duration of action-works ____

& is gone ____

short, fast, fast

Acetylcholine has limitedabsorption from the _______, somust give _________ (__, __, or __)

stomach, Parenterally (route otherthan the gastro-intestinal tract) M

and N receptors equally, SQ, IM, orIV)

ACh binds _______ well to both N &M receptors, but drugs do ____.Most drugs bind better to one

subtype or other

equally, not

ACh receptors are receptors thatbind to ACh: Divided into 2 types

muscarinic and nicotinic

Actions of the body on the drug. Thisdetermines how and to who you give adrug. E.g. Does the body absorb it wellfrom the stomach so it can be givenorally, or does it need to be givendirectly into a vein?

Pharmacokinetics

Actions of the drug on the bodythat determine how the drug isused therapeutically. E.g. Doesdrug decrease blood pressure? Ordoes it block histamine?

Pharmacodynamics

Activation of muscarinic receptors onpresynaptic nerves inhibit furtherneurotransmitter releaseSo, the release of ACh fromparasympathetic nerve inhibits releaseof _________ from sympathetic nerves

NE

Activation of these receptorsmediate platelet aggregation and

inhibit insulin secretion frompancreas

Alpha 2

Additional Effects On Glands Of ACh:Increase _____, ______ and ____________gland secretion.Get sweaty, tearing eyes, & runny nosy.Clinically: give to help special cases of____ eyes

sweat, lacrimal andnasopharyngeal, dry

Adrenergic agonist are also given to_______ blood flow to certain areas as inwound stitching. Alpha receptors aregiven to cause vasoconstriction around awound to decrease blood flow from thewound while stitching the woundclosed.

reduce

Adrenergic agonists are used to increase blood______ & ______? A patient with a very low BP doesnot get enough blood to the organs like the brain& heart. Stimulating alpha receptors causes________ of the blood vessels in the periphery(periphery being anything that is not an organ),increasing BP & perfusion to critical organs

flow & BP, constriction

Adrenergic fibers have a morenarrow focus than cholinergic

fivers and are only found in the________?

SNS

Adrenergic Neurons? release Norepinephrine,Epinephrine, Dopamine

Adrenergic Receptors: Bind ______,______, or __________ to target

organs of the __________ nervoussystem

bind NE, Epi, or Dopamine to targetorgans of the Sympathetic Nervous

System

Adverse reactions of Alpha antagonists: 1. _______ ______.When you stand up, gravity sends blood to the legs. The bodyreflexively constricts veins to push blood back into body towardsbrain. Alpha blockers block this reflex, so blood stays in legs & BP goesvery low when standing. These drugs can cause light-headedness& passing out2. Reflex ___________3. Miosis (pupil ___________)4. Nasal stuffiness

Postural hypotension, tachycardia,constriction

After _____ half-lives get to steadystate level.

five (five doses)

AlbuterolClonidineMidodrine

OxymetazolinePhenylephrine

Terbutaline

Noncatecholamines

All ACh receptors are the ________subtype (the nicotinic subtype arepreganglionic & skeletal muscleNOT at PNS target organs)

muscarinic

All drugs have some inherent_______. The ____ weighs whetherthe potential benefits of the drug

outweigh the risk.

Risks, FDA (most chemotherapy isNOT safe, but is relatively safe

when compared to the risk of thecancer

All preganglionic nerve fibers ofthe ANS release ______ to transmit

their signal

ACh

Almost all drugs __________ bind toplasma proteins, primarily _______?

reversibly, albumin (drugmolecules dissociate from plasmaproteins to maintain balancebetween free drug and bounddrug)

Alpha 1,2 and beta 2 adrenergicreceptors are found on arterial_______ muscle cells. Agonists(sympathomimetics) effect:

smooth

Alpha 1 blockade ______ vascularand other smooth muscles.

Beta 1 blockade _______stimulation of the heart.

relaxes, reduces

Alpha 1 Mediate _________ ofvascular smooth muscle, the irisdilator muscle, and smooth musclein the lower urinary tract (bladder,urethra, and prostate)

contraction, dilator

Alpha 2 receptors are in the CNS and whenstimulated they elevate _____ & make more_____, decrease/suppress _______Clinical use; narcolepsy, ADD, +/- weightcontrol. Only adrenergic agonists that get intothe CNS have an effect here, more nextsemester

mood, alert, appetite

Alpha antagonists prevent arteriesfrom _________ by blocking alpha 1& 2. This _________ BP. Clinical use:

_____

constricting, lowers, HTN

Alpha constriction of blood flow usedwith local anesthesia so ________ don'tbleed when you _____. Epi also is part ofthe ACLS protocols for its ___ effect &__________ for stimulation of all receptors

wounds, stitch, BP, anaphylaxis

alpha, no beta, constricts bloodvessels, no heart effects (until lose

selectivity)

Phenylephrine

______, ______, ________, and _______are affected the most by a drug

because they are highly perfused.

Brain, Heart, Liver, Kidneys

_____, _______, and _______ tissue are thelowest perfused and may require ahigher does of a drug if you need toreach those lower perfused tissues andmay need to take drug longer.

Skin, Bone, and Adipose tissue

Another clinical use of anticholinergicsis cholinomimetic poisoning, such asorganophosphates, insecticides or nervegases. Toxicity occurs from ACh excessso give ________ to try and block effect.Works best with ________ inhibitors andnot well with ________ inhibitors.

atropine (muscarinic/cholinergicblocker), reversible, irreversible

Anticholinergic Organ System Effects:CVS: ________ heart rate with _____ effecton BP _________ AV conduction. Atropineis part of the ACLS (acute cardiac lifesupport) for significant _________.

Increase (Tachycardia), little,Increase, bradycardias (slow heart

rate)

Anticholinergic Organ System Effects: Eye:Pupillary constrictor muscles are _______ andget _____ pupils (mydriasis) & cycloplegia(_______ of the _________ muscles for nearvision causing ______ vision). ____ eyes (from_________ tearing) Clinical use: for eye examwhen want _______ pupil & ________ lens

inhibited (relax), dilated, paralysis,accommodation, blurred, Dry,decreased, dilated, paralyzed

Anticholinergic Organ System Effects: GITract: _________ secretions and _______ ofthe GI tract. (increased gastric emptyingtime and intestinal transit time =__________). Clinical use: treat symptomsof ________, ______ spasms

decreased, motility, Constipation,diarrhea, intestinal

Anticholinergic Organ System Effects:GU Tract: ______ smooth muscle of thebladder wall and ______ voiding. (Don'ttend to urinate as much).Clinical use: relieve bladder _______ andhelps those who ________ frequently(overactive bladder)

relaxes, slows, spasm, urinate

Anticholinergic Organ System Effects:Respiratory: Think ____________ & ________secretions. This effects is seen more in an airway or lungthat is _________ than it is in a healthy lung. Clinical use: ________ and occasionally in________.

Bronchodilation, decreased,diseased, chronic obstructive

pulmonary disease (COPD), asthma

Anticholinergic Organ System Effects: SweatGlands: _________ sweat, ________ temperature Leading to cutaneous _________ and skin becomes____, ____ & ______.Clinical use: ______, A major source of morbidity &mortality. When an anticholinergic drug causesdeath most often does so by __________.

decreased, increased, vasodilation,hot, dry & flushed, none,

hyperthermia

Anticholinergic Toxicity: Adults: getannoying but generally not _____ effects. _____ mouth, eye _____, _____cardia, ___,____, ______ skin, agitation and delirium.Think: "___ as a bone, _____ as a bat, ____as a beet, _____ as a hatter"

severe, Dry mouth, mydriasis,tachycardia, hot dry flushed skin,agitation and delirium. "dry as abone, blind as a bat, red as a beet,mad as a hatter"

any substance that uses chemistryto bring about a biologic change

Drug

At ____ doses see selectivity morethan at _____ doses, and if give

enough of the drug can activate____ SNS receptors.

low, high, other

Atropine is a muscarinic antagonist

Atropine is a well known drug that in overdose situations cancause an extremely high temperatures by interfering with thepatient's ability to sweat. Which of the following is a mechanism ofaction for atropine that is compatible with this?

A. It is an adrenergic receptor agonistB. It is an adrenergic receptor antagonistC. It is a muscarinic receptor antagonistD. It is an muscarinic receptor agonist

It is a muscarinic receptorantagonist

At this level the amount of thedrug accumulated or taken in

equals the amount of drugeliminated by the body.

Steady state

Basic Neurotransmission in ANS: 1.______ ________ is propagated along the nerve to the presynaptic terminal2. The _____________ is synthesized in nerve terminals and stored in membrane boundvesicles3. Nerve cells release ___________/chemicals into the synaptic cleft in response tonerve stimulation4. The chemicals bind to _______ on adjacent nerves to activate the next cellThe next cell can be another nerve cell (ganglion), muscle cell, gland cell or effectororgan5. Finally, neurotransmitter action is terminated either by _______ or neuronal________?

1. Action Potential2. Neurotransmitter

3. Neurotransmitters4. Receptors

5. Metabolism or neuronal reuptake

Beta 1 selective (block beta 1 morethan beta 2)

Metoprolol, atenolol

Beta 2 blockade increases airway________. No clinical use; avoid in

________

resistance, asthma

Beta 2 receptor stimulation _______ theuterus. Alpha receptors on the bladder,urethral sphincter & prostate helpcontrol ______. Clinical use: premature______ and certain types of urinary__________.

voiding, labor, incontinence

Beta blockade ________ aqueoushumor production & intraocular

pressure. Use in _________.

decreases, glaucoma

Beta blockade ______ recoveryfrom hypoglycemia (your SNS kicksin when hypoglycemic). No clinicaluse but care on meds that causehypoglycemia (Diabetics)

inhibits

Binds & activates receptor to getless than a maximal pharmacologic

effect

Partial agonist

Binds & activates the receptor toget maximal pharmacologic effect

Full agonist

Bind to and activateadrenoceptors. Divided into direct

acting agonist

Direct Acting Agonist,catecholamines andnoncatecholamines

Biotransformation of drugs is doneby the __________ to help eliminatedrugs. Which will change a drug soit can be eliminated more easily bythe kidney or GI tract.

Liver

Black widow spider venom: causesexcess release of _____ andreceptor activation causing severecontraction and pain in ______

ACh, contraction, muscles

Blockade of alpha 1, block smoothmuscle ________ at base of bladderand prostate so urine flows more______. Clinical use: Benignprostatic hypertrophy (BPH)

contraction, easily

Blocking nicotinic receptors is clinically useful atthe ___________ junction. Can cause paralysis byblocking nicotinic receptor _______ OR byconstantly ________ the receptor as with AChindirect acting agents. (This is an example of howdrugs can do what appears to be opposing thingsand you end up getting a similar physical result)

neuromuscular (blocker binds toach receptor preventing ach frombinding and stimulating) directly,

activating

blocks beta 1 and 2 equally and isthe prototype

Propranolol

Blood pressure drug A is more potent than B ifyou need 5mg of A to get its maximal effect and50mg of drug B to get its maximal effect. Drug Bis more efficacious (effective) if it lowers theblood pressure more than drug A at its maximaldose. So B is more efficacious drug even if it isless potent. What drug would be better to use?

So ultimately B would be the betterdrug even though you would needmore of it to get the desired effect.

Botulinum Toxin A: blocks release of AChinhibiting _________ transmission causingmuscle __________. Current uses of BotulinumA: treat localized spasms of eye, face, hands;symptoms of Parkinson's disease (tremor,dystonia, excessive saliva), excessive sweatingof palms & soles

ACh, neuromuscular, relaxation

Brand names are ______ to ______________but have no relationship to _______ or___________ activity. When the drug goesoff patent the company still retains therights to the trademark name, but anycompany can create a new trademarkfor that drug and start manufacturing it?

easy to remember, chemical orpharmacologic activity

Bronchodilation (β2) Clinically usedin asthma for effects onrespiratory system, or inpregnancy to relax uterus andprevent labor (2 of them?)

Terbutaline, albuterol

Capacity-Limited Elimination or zero order is Important clinicallyfor only 3 drugs _______, __________, and ________? At lowconcentrations there is no problem, as the drugs behave like firstorder elimination drugs (%out). At high doses get problemsbecause1. Clearance mechanisms are _________& clearance ________ asconcentration increases, ______ state not achieved & blood levelkeeps risingIn overdose (or high dose) situations the drug levels rise fasterthan predicted at low doses, quickly become toxic and lethal

aspirin, ethanol, and phenytoin,saturated, decreases, steady

Capacity-Limited Elimination or zero order: Is not______ but when it occurs is very important.Clearance rate _______ depending on drug __________. Generally at low concentration drugs act like aregular drug. At higher concentrations, however, aset ______ of the drug is eliminated NOT a ____? Ifgraphed it is straight ______ _____, loosing certain mgat a set rate

common, varies, concentration, setamount, not a % (So at higher

concentration 50mg eliminated not50%)

Cardiac stimulation ((β1) andbronchodilation ((β2): Clinical Use:Asthma, atrioventricular block, and

bradycardia

Isoproterenol

Cardiac stimulation (β1) andvasodilation (β2) Clinical use:Cardiogenic shock, acute heartfailure, and cardiac stimulationduring heart surgery

Dobutamine

Cardiovascular Effect ACh: Low dose ______ blood vessels, ________ bloodpressure (BP) and ________ heart rate (HR)Clinically don't use drugs with these effects inheart disease. Need to know about theseeffects b/c of cardiac side effects that occurwhen give muscarinic drugs for other reasons

dilates, decreases, decreases

CarvedilolLabetalol

α and β blockers

Characteristics fo Phase III clinicaltrials: involves _________ of patientswith _______ ______? Study design:______-_____ trial: This means?

1000's of patients with the disease,Double-blind: subject and providerdon't know who is getting the drugand who is not

Characteristics of Phase 1 clinicaltrials: Involves 20-50 _______human volunteers. Study design is_____ trial: the subject and theprovider both know?

healthy, open trial (both the subjectand the provider know what drug

the subject is getting)

Characteristics of Phase II ClinicalTrials: Involves 100-200 patientswith the ________. ______-______trial: which means?

disease, single-blind trial: Providerknows what drug the subject isgetting but the subject doesn't

A child with asthma is being treated with anadrenoceoptor agonist to prevent bronchospasm. Whichside effect is typically associated with this drug?

A. SedationB. Rapid heart rateC. Muscle weaknessD. High blood pressureE. Blurred vision

B. Rapid heart rate (Beta agonist)not alpha agonist which would have

more of an affect on high BP

Cholinergic Effects(SLUDGE)antilcholinergic: opposite

SLUDGE!

S: salivationL: lacrimationU: urinationD: defication

G: gastricE: emptying

Cholinergic fibers primarily affectthe ______________ Nervous

System, but have found effectselsewhere

Parasympathetic

Cholinergic Neurons? release acetylcholine

Cholinergic Neurotransmission:1.___________ nerve is stimulated causing an action potential2. The action potential induces ______ influx into the neuron. 3. _______ mediates the release of neurotransmitters (ACh) into thesynapse4. ACh binds to ACh receptors to elicit response5. ACh breaks down into ______ and is taken up in the _________neuron

Parasympathetic, calcium, calcium,choline, presynaptic neuron

Clonidine: activates both ____receptors and _______ receptors in

CNS-_________ blood pressure

α2, imidazline, decreases

CNS (Central Nervous System) & IndirectCholinesterase Inhibitors: Low dosehave an ______ effect, high dose cause_______, respiratory ___________, & ______Clinically indirect cholinomimetics areused in low doses to help __________.

alerting, seizures, respiratorydepression, & coma, Alzheimer's,We use special ones that only getinto the CNS and go no where else

CNS Effects Of ACh: _____,_____thermia and anti-________(anti-_____) Not used clinically forthis, but a potential source of sideeffects.

Tremor, hypothermia and anti-nociception (anti-pain)

CNS Effects Of Nicotine: Low doses there is increased _______,higher doses _____, ______ , increased_________ & eventual _____. Also addictionresults from receptor stimulation incertain brain areas

alertness, tremor, emesis(vomiting), increased respiration &

eventual coma

Competitive/reversible alphablocker. Causes vasodilation,decreases blood pressure.

Phentolamine

Competitivie antagonists are ________. Drugbinds and then dissociates from the receptor.This is a continuous process of binding andunbinding until the antagonist diffuses awayfrom the receptor and then the effect ends.This is the most _______ type of antagonistused.

reversible, common

Concentration of a drug needed toreach maximal effect. Relating to

_________.

Potency, dosage

Cons of a drug with a long half-life?1. onset is ________

2. Reach _______ ______ _____3. Get ______ of _______

Onset is slower, reach steady stateslower, get rid of slower

Cons of a drug with a short half-life?

1. Need to take ______ _____, soless _________?

Need to take more often, so lessconvenient

The Cytochrome P450 system is abunch of very important ____ _liver enzymes responsible forcatalyzing most of the drug__________ in liver?

Phase I, biotransformation(cytochrome P450 is really

important)

D1 receptors, no alpha or betaeffect. Clinically: treats severe HTN

b/c dilates blood vessels

Fenoldopam

Decreased sympathetic outflowfrom central nervous system (α2and imidazoline) Clinical use:Hypertension, opioid dependence

Clonidine

Direct-Acting ACh Receptor Agonistdrugs bind and activate ______receptors. They differ in regards totheir affinity for _________ and________ receptors

ACh, muscarinic, nicotinic

DobutamineDopamine

EpinephrineIsoproterenol

Norepinephrine

Catecholamines:

Dopamine is released bypostganglionic _________ fibers and

effect _____ vascular smoothmuscle?

SNS, renal

Dopamine receptors are activated by_________ but _____ by other adrenoceptoragonistsHave D1-receptors mediating vascularsmooth muscle __________ and D2-receptors modulating ____________ release

dopamine, not, relaxation,neurotransmitter

Drug A has a half-life of 4 hours, drug B a half-life of 8 hours. A patient presents with anacute knee strain, swollen and tender. You tellthe patient to rest, ice and elevate the leg. Thepatient wants something additionally that willwork fast to help relieve the pain. Which drugwould have the fastest onset?

Drug A because it is quicker, willwork faster, good for acute pain

Drug Facts and Comparisons is an_________ source of drug

information but is very _________.

Unbiased, expensive

Drug plasma concentration will rise and fallaccording to the rates of 3 processes:1. _________: refers to the movement of drug into thebloodstream2._________: refers to the process of a drug leavingthe blood stream and going into the organs andtissues3._________: removing drug from the blood bymetabolism and/or excretion

1. Absorption, 2. Distribution: 3.Elimination

These drugs bind and activate AChreceptors and facilitate ACh signal

transduction

Direct-acting agonist

These drugs increase the synapticconcentration of ACh by inhibitingcholinesterase (agent responsiblefor breaking down ACh)

Indirect-acting agonist

These drugs prevent the breakdown ofACh at all cholinergic synapses. Anotherway to look at it is these drugs increaseACh effect by increasing the amount ofACh at the receptor site. These drugsDO NOT interact with ACh receptors

Indirect-Acting AcetylcholineReceptor agonists (called

cholinesterase inhibitors as well)

Drugs that mimic or blockneurotransmitters effect thefunctions of the _____ (ex.Respiration, heart rate, bloodpressure)

ANS

Drugs that selectively antagonizeα1 receptors end in _______

(zosin)

Drugs that selectively block eithermuscarinic or nicotinic receptors.These drugs affect almost everyorgan system and have manyclinical applications.

Acetylcholine Receptor Antagonist

A drug that blocked muscarinicreceptors would block the ______

response and _____________

PNS, sweating

a drug that blocked primarilynicotinic receptors would affect

__________

everything

A drug that is a mixed alpha & betaagonist _______ the heart rate & _______the BP b/c alpha effect on the bloodvessel beats the ______ beta 2 effect onthe blood vessels, elevating the BP

increases, elevates, weaker

A drug with a 2 hour life-life:For the first half-life: Time expired will be ___________ % of drugeliminated __________ % of drug left in the body? Second half-life:Time expired will be ___________ % of drug eliminated __________ %of drug left in the body? Third half-life: Time expired will be___________ % of drug eliminated __________ % of drug left in thebody? 4th half-life: Time expired will be ___________ % of drugeliminated __________ % of drug left in the body? 5th half-life: Timeexpired will be ___________ % of drug eliminated __________ % ofdrug left in the body?

1. 2 hours, 50%, 50%2. 4 hours, 75%, 25%3. 6 hours, 87.5%, 12.5%4. 8 hours, 93.75 or 94%, 6.25%5. 10 hours, 96.875% or 97%, 3.125%

Each drug has 3 or more names:1. ________ name2. ________ name3. _______ name

1. Chemical name2. Generic name3. Brand names

Edrophonium is a ______competitive inhibitor (agonist) with

effects lasting ___ ______

weak, 10 minutes

Effect drug has (how effective drugis, how well it works) More _______

relevant

Efficacy, clinically

The effect of a drug depends on which__________ it binds to.If there is no receptor for a drug there is___ _______ of a drug. If receptors for the drug are only in thebrain, it will only have effects on thebrain.

Receptor, no effect

Effect of Cytochrome P450 Enzymes1. Drugs can _________ the cytochrome P450effect2. Cytochromes P450 can ________ drug effects3. Drugs can ___________ the cytochrome P450effect4. Cytochrome P450 can ________ drug effects

1. Increase2. Increase3. Decrease4. Decrease

The effect of different drugs mixedtogether that use P450 is difficultto ________, one drug may have_____ effect, another ____ effect.

predict, more, less

Effect of hormones takes much _______ tosee than other water soluble drugs. Alsoit takes _______ to get rid of their effectb/c it takes time to start making proteins& time to stop

longer, longer

The effect of the competitive antagonist drug is ____________dependent. If you give enough of the drug, you can get a highconcentration of the drug at the receptor site and get more effectof the antagonistThis idea is used clinically in heroin overdoses. Heroin is a strongnarcotic receptor agonist. Naloxone (Narcan) a narcotic receptorantagonists is given in increasing doses to reverse the effects ofthe heroin. Can be overcome by giving a large dose of an _______to reverse any adverse effects

concentration dependent, agonist

Effects are confusing. If a drugmetabolism is dependent on the

Cytochrome P450 enzymes thereis a potential for many

drug interactions

______ effects are the mostimportant/life threatening toxicity

with adrenergic agonists

CVS

Effects OF Beta Blockers: ______ BP &_______ HR, also ________ contraction andwork of heart. Clinical Use: HTN, Angina, myocardialinfarction, chronic heart failure, cardiacarrhythmias

Decrease, decrease, decrease

Epinephrine activates ____receptors and therefore

epinephrine is most like activatingthe entire ______

all, SNS

Epinephrine is released by the_______ ________ with NE

adrenal medulla

Epi stimulates ____ adrenergicreceptors ______Beta 1 & alpha effects overwhelmbeta 2 effects and overall you getan increased ____ & ______ ________

all, equally, BP & cardiac output

Estrogen in the body can make breastcancers grow. Estrogen ________ aredrugs given to prevent growth of breasttumors. They work because they bind tothe receptor and block the growth effectof naturally-occurring estrogen(endogenous estrogen)

antagonists

Example: The first half life of a100mg drug is?

50mg

Excessive doses of catecholamines ______ blood flow tovital organs, such as the kidneys, or cause _________cardiac stimulationThis can lead to _____, cardiac ___________ & cardiac ________leading to myocardial infarction (MI) & heart failure fromstressing the heart too much. These ADRs primarilyoccur if the heart is already sick. How do you know theheart is ______? Usually there is either a history of somesort of heart disease or the patient is ______

reduce, excessive, HTN,arrhythmias, ischemia, sick, elderly

Eye Effect Of ACh: _________ of irissphincter causing _________ of pupil(miosis)? __________ of ciliary body whichcontrols _________ (allows the eye to seeup close) Combinations of these effectsdrains anterior chamber of eye helps_______ (more in optho)

contraction, constriction,contraction, accommodation,

glaucoma

Factors affect distribution:1. _______ ______ flow

2. Plasma ______ ______3. _________ size

4. ______ solubility

1. Organ blood flow2. Plasma Protein Binding

3. Molecular Size4. Lipid Solubility

Factors that affect liver Metabolism1. _______2. _______, charbroiled food induce liver enzymes,grapefruit juice inhibits enzymes in liver3. _______, at extremes don't metabolize at same rateas those in the middle4. ______: ______ metabolize alcohol more slowly 5. _______, especially failure of kidney, liver, or heart

1. Genetics2. Diet3. Age

4. Sex, women5. Diseases

First Order Elimination: Rate ofelimination is ______ proportional to the__________ of the drug. Same amount ofdrug eliminated per fraction of time,and it is a _____ of drug present, NOT aset ______. (Greater concentration =greater concentration eliminated

directly, concentration %, setamount, (50% of drug is eliminated,

not 50mg)

The fraction of unchanged drugreaching systemic circulation

following administration by anyroute.

Bioavailability

Ganglion Effects Of Nicotine: the effect thatoccurs depends on which one (SNS or PNS) winsout (split effect)Cardiac effects: ____ response usually wins so get_______ HR and BPGastrointestinal (GI) & genitourinary (GU) ______usually wins so get _____, _______, _______ & _________

SNS, increasedPNS, nausea, vomiting, diarrhea &

urination

Gastrointestinal Effects Of ACh: Increase _________ of GI tractSalivary glands & gastric glands are stimulated. Peristalsis(motility) of intestine are ________ & sphincters are __________Clinically used when want to increase _______ movement &________ salivation In certain rare types of _________ would use but, doesn't happenoften so limited useHigh doses of these agonist can produce excessive _______, _______,and _________ cramping

secretions, increased, released,intestinal, increase, constipation,

salivation, diarrhea, intestinal

The generic names given use stems(prefixes, suffixes or infixes) to helpplace drugs in ______ ______ groups? Soyou can get significant _____________information from the name? Examplebeta blockers have _______ in name?Generic name is an __________ standard?

Similar drug, pharmacologic, olol,international

Genitourinary Effects Of ACh:ACh _______ the bladder muscle and ________the sphincter of the bladder. These effectspromote _________ of the bladder. Give anAch-like drug to promote ________. High doses of these agonist can produceurinary _________?

contracts, relaxes, emptying,urination, incontinence

Half-life is important clinicallybecause it gives information about

the ________ interval?

dosing

Hormones are ______ soluble and bind todrug-receptor complexes a littledifferently: Hormones diffuse throughthe _______ ___________, bind to receptorsin the _________, bind to genes & activatethem. Genes then produce proteinswhich have a pharmacologic effect.

Lipid, cell membrane, nucleus

How effective a drug is at blocking thereceptor depends on which _____ thereceptor is in & the source of the _______trying to block. Blockers work better atblocking other drugs (cholinomimetics)than at blocking?

tissue, agonist, natural occurringACh

Ibuprofen (taken every 4-6 hours)has a ______ half-life and works______ if you are in pain _______ andwant relief right now this will givemore rapid relief

Short, faster, acutely

If a drug has a long half-life (e.g. 24hours_ then does _____ ______,

usually _____ day?

less frequently, 1xday

If a drug has a short half-life (e.g. 4-6 hours) then it needs to be dosed______ ________, usually _____ a day?

more frequently, 4xday

If a PNS response is activated thepreganglionic PNS fibers get activated,postganglionic PNS fibers then _________is released to act on the _____ receptorson the PNS target organs.

acetylcholine, Ach

If a receptor tightly binds to a drug youdon't need as _______ of the drug (i.e. youneed a lower dose) to get thepharmacologic effect. If a drug is loosely bound to a receptoryou need ______ drug to get itspharmacologic effect

much, more

If bad asthma and need a highdose of Terbutaline ____ specificityfor _____, stimulate ______ also andget a heart effect (Heart will ____)

lose, beta 2, beta 1, race

If giving a drug for neurogenic bladderto promote voiding can have side effectsof __________ GI motility and get _________.(Often one organ system is the desiredeffect and other organs are undesiredand therefore toxicities)

increased, diarrhea

If Phase I-III clinical trials look good then the drugcompany submits a ______ _______ Application tothe _______? The average amount of time the FDAhas to review the application is ______ ____? But itcan take less than this time if the new drug fulfillsa ______ ______ or is unique, this was brought aboutby the need for drugs to combat _____ this wouldbe an accelerated drug approval.

New Drug, FDA, one year, GreatNeed, HIV

If phase I is unable to make the drug polarenough to be excreted from the kidney thanphase II reactions occur. Phase II adds a ________to a drug such as glucuronic acid, sufuric acid,acetic acid or amino acid. This is called ________and it makes the drug even more ______ sohopefully the ________ can excrete it in the urine.

compound, conjugation, polar,kidney

If the brain activates the SNS a message issent out through the preganglionic SNS nervefibers, through the ganglion to thepostganglionic fiber, releasing _____________that activate __________ receptors causing aSNS response in a target organ (alpha 1,beta1, beta2, D receptors)

catecholamines, adrenergic

If the _______ changes the drug thiscan be used many ways

therapeutically

liver

If you give 100mg and 50mg getsinto the system then _______ is

bioavailable?

50%

If you want to test how much drugis in the blood for a certain drugdose given at a certain interval youneed to wait for ________ ______ tobe reached before testing

steady state

If you want to use drugs to effectthe way the ANS functions youneed to manipulate/affect its

______

nerves

Imidazoline Receptor is activatedby adrenoceptor agonist andsubstances containing ______

structuresFound in _____

Imidazoline, CNS

In 1951, the Durham-HumphreyAmendment divided drugs into

two classes:

Prescription (Rx): Drugs that can only begiven under the supervision of a healthcare professional, they are not safe foruse directly by the patientOver-the-counter (OTC): Drugs that arelabeled so patients can use them safelywithout a health professional

IN 1962 all new drugs had to meetcriteria but many older drugs weregrandfathered in. These grandfathereddrugs were allowed to stay on themarket b/c they were safe, but might notbe ______?

not be effective

In 1962 the Kefauver-Harris DrugAmendment was passed ensuring drug_______ and greater drug ______ So now drugs had to be proven ________AND __________ before being introduce tothe market

efficacy and greater drug safety,SAFE AND EFFECTIVE

In anaphylaxis, a severe allergicreaction, get bronchospasm (lung)& low BP (CVS). Treatment is a drugthat stimulates all receptors suchas __________

Epinephrine

In clinical use Alpha agonists are usedto ______ the eye for an exam & are usedfor treatment of _______ (Remember alsouse PNS drugs in eye, same diseasedifferent MOA

dilate, glaucoma

Indirect-Acting Acetylcholine Receptoragonists are divided into two groups: 1. _________ cholinesterase inhibitors(Quaternary Compounds)2. _________ cholinesterase inhibitors

Reversible and Irreversible

INdirect Cholinesterase inhibitorsare called cholinomimetics b/c they

_______ ACh effect

increase

Infants, children & elderly getannoying effects but are also moresusceptible to ________ and ______.

hyperthermia and death

Inhalation: Bioavailabiltiy ________,Characteristics: __________?

often very rapid onset

The initial response to a drugdecreases while the patientcontinues to receive the drugbecause the receptor numbersdecrease

Desensitization/Tachyphlaxis

In level two (preclinical) tests for_______, sub-______, and ______toxicity are done as are tests of________ potential, _______potential, and effect on ________?

Tests for acute, sub-acute, andchronic toxicity are dones as aretests of carcinogenic, mutagenic,and effect on reproduction.

In other words most drugs interact withthe body by associating with specificmolecule in the body. This molecule iscalled _______. The association of thedrug with the molecule changes themolecule chemically or physically givingthe drug _______?

receptor, effect

in the presence of a full agonist, apartial agonist will act like an __________because it will prevent the full agonistfrom binding the receptor and exertingthe maximal effect

antagonist

Intramuscular: Bioavailabiltiy ________,Characteristics: __________?

75 to 100, large volumes oftenfeasible, may be painful

Intravaneous: Bioavailabiltiy________, Characteristics of onset:

__________?

100%, most rapid onset

The iris has alpha receptors, stimulationcauses ________ (eye ________) and anincreased drainage of _________ _________with a decreased production of _________?

alpha, mydriasis, dilation, aqueoushumor, fluid

Irreversible antagonist drugs bind and_______ let go of the receptor. Antagonisteffect is only overcome when a new________ is made. Duration of effect ofantagonist depends not on drugconcentration but on how quickly thebody makes a _____ _______.

never, receptor, new receptor

____________ is a measure ofabsorption

Bioavailability

is an alpha 1 and beta antagonists.Blocks alpha and beta receptors.

Mostly beta

Labetalol

is a scientific name based onchemical structure? it is _______,difficult to ________ and not usedonce ________ name is generated?

Chemical name, long, difficult toremember, generic

Is a strong beta receptor agonist with little alphaeffect? The rate & force of contraction of the heartincreases from the beta 1 receptor activation. Noalpha effect means no blood vessel constriction sono increased BP and BP may actually decrease fromthe beta 2 receptor activation which dilatesperipheral blood vessels. Clinical Use: Asthma,atrioventricular block, and bradycardia

Isoproterenol

Isoniazid is a drug to treattuberculosis, it needs acetylation &______ acetylators have a higherrisk of toxicity and should receiveless of this drug

Slow

______________ is the Primarysympathetic NeurotransmitterReleased by postganglionic SNS

fibers and adrenal medulla

Norepinephrine (NE):

Is the ratio of desired effect toundesired effect of a drug

Therapeutic Index, You don't needto give it a number, justunderstand the description of adrug as narrow or wide therapeuticindex.

Is the study of drugs in the bodyand focuses on the changes in drug

plasma concentration

Pharmacokinetics

Is the time it takes to decrease theconcentration of the drug in the

body by ½ (50%).

Half-life

It takes _____ half-lives to eliminatethe drug from the body

5

Large amounts of NE & Epi causesevere _____________-thus this drug

help decrease _____

hypertension, BP

Large molecules tend to beconfined to the?

Plasma compartment

A large volume of distributionmeans the drug goes

Everywhere, all tissues probablyexposed

Level 1. First, it is tested _ ______ tosee if it has ________ against amodel of the _______. This is verexpensive. Very ______ drugs getpast this level?

1. In vitro ("test tubeexperiments"), activity, disease,

few

Level 2 (preclinical) takes _____ to_____ years, and is also ________?This level can often catch commonbut not _______ toxicities?

3 to 6 years, expensive, rare

Level 2 (preclinical testing). Tests in________ are done to try anddetermine _______ toxicity and toweigh potential _________ of thedrugs vs. the _______ of ________.

2. Animals, human toxicity,benefits vs. risks of toxicity

Level 3 (clinical trials) or ______ testingtakes ______ to _______ years. To do thistesting the company developing thedrugs must file an application for an__________ ______ _______.

Human, 4 to 6 years.Investigational new drug (IND)

Level three (clinical trials): Threetypes of trials involving humansare done _______, ______, ______,_______ and _______ involves postmarketing ______?

phase I, phase II, phase III, phase IV(post-marketing surveilance)

Lipid soluble drugs can act ________ onthe cell because they can _______ throughthe lipid membrane. There are not asmany lipid soluble drugs as watersoluble drugs, but an important groupof lipid soluble drugs are __________.

directly, diffuses, hormones

lipid soluble drugs tend to stay in__________ with lots of ________?

Tissues with lots of fat

The liver uses 2 primary types ofreactions to change the drugs:

phase I and phase II

A lot of room between therapeuticand toxic doses, low potential for

toxicityamoxicilian is an example

Wide therapeutic index

Major clinical use forIsoproterenol?

When want to increase HR and notBP. This would occur when heart isbeating too slow but BP is normal.(many use this drug until can getpacemaker in)

The major site of pharmacologicintervention is where the nerves

_________ with one another

Communicate

A man complains of urinary urgency, frequency,and nocturia and is found to have benignenlargement of the prostate gland. Which of thefollowing is the best choice? 1. Carvedilol2. Phentolamine3. Metoprolol 4. Alfuzosin

4. Alfuzosin

Many of a drugs effects can beexplained through the _______

_______

receptor concept

A measure of the bodies ability toeliminate a drug. Usually renal(kidney) clearance. Occasionallyhepatic (liver) cleared.

Clearance

Mechanism Of Action: Indirect CholinesteraseInhibitors: These drugs inhibitacetylcholinesterase, an enzyme that breaksdown ______. Inhibiting this enzyme makes its so no _________ ofAch occurs, increasing the time Ach is in thesynapse (space between nerve & effector cell),________ the ACh effect.

ACh, breakdown, increasing

Metyrosine: used in patients with anadrenal medullary tumor(pheochromocytoma) by inhibiting _____and _____ release. Large amounts of NE& Epi cause severe hypertension-thusthis drug help decrease BP

NE & Epi

Moderately perfused tissues are? Skeletal muscle

Muscarinic activation leads to___________, glandular ___________,

__________ of heart rate &conduction

vasodilation, glandular secretions,slowing of heart rate & conduction

Muscarinic (M): found on _____target organs (nerves activated

when ____ is activated) & ________________

PNS, PNS, sweat glands

Muscarinic receptor antagonistcompete with ____ for muscarinicreceptors and parasympatheticjunctions and ______ nervestimulation. These are reversibleantagonists.

ACh, inhibit, reversible

Muscarinic receptor blockers areused to ______ smooth muscle,

______ gland secretions and ______the heart

relax, decrease, stimulate

Muscarinic receptors are found in______ muscle, ________ tissue, and

glands at __________ junctions

smooth, cardiac, parasympathetic

NadololPindolol

PropranololTimolol

Nonselective β - blockers

The _______ name gives pharmacologic orchemical information about a drug. The___________ names is the name used ontests and boards. But many in clinicalyear or practice will use _________ names.

Generic, Generic, Brand

NE has the same _____ _ and _______effects as epi and less _____ __effects. NEincreases BP and increases heart rate &the force of contraction of the heart.Clinically it can be used in many of samesituations as epi, but epi is prototype

beta 1 and alpha, beta 2

NE is release into synapse by_______

calcium

Neostigmine & physostigmine bind_______, agonize better & last up to

__ _______

tighter, 6 hours

The nerves are the mostsusceptible to manipulation at thesite of ______________ transmission

neurochemical

Neuromuscular Junction & Indirect CholinesteraseInhibitors: Clinically used for 2 infrequent cases: 1. Myasthenia gravis (a disease where the immunesystem destroys ______ receptors in CNS), these drugshelp to increases ____ at the receptors that are left. 2. To reverse muscle ________ induced by other drugs,usually after __________.

ACh, ACh, paralysis, anesthesia (A shortacting cholinesterase inhibitor increasesthe concentration of ACh at the receptorpushing off the paralyzing drug bindingto the receptor, reversing muscleparalysis )

New Drug Development Today:1. _________ modifying a known molecule2. Screening previously found compound for_________ activity3. Using biotechnology and cloning to makecompounds found in the _______?4. Combining known drugs to get _________ effect?

1. Chemically2. Unrecognized

3. Found in the Body4. Synergistic (drugs that work

together, for greater effect)

Nicotine is the prototype for drugsthat just stimulate the ________

receptor.

nicotinic

Nicotinic (N): found in the ______,on _______ muscle, and in the _____

ganglion, skeletal, brain (Activationin ganglion excitesneurotransmission, Activation inskeletal muscle causes contraction)

Nicotinic receptor blockers areprimarily used to _____ ________

muscle

relax skeletal

Nicotinic receptors are Found at_________, _______ __________

junctions & CNS

ganglion, somatic neuromuscularjunctions & CNS

No one drug only binds to one receptor. Mostdrugs bind to many different sites in the body, somany ______ and side ________. Any one receptor islikely found on _____ cell types, so activating onereceptor has many effects. The same receptoron one type of tissue will give a therapeutic effectand on another tissue give a toxic effect

effects, effects, many

Norepinephrine is released bypostganglionic ______ fibers and

______ _______

SNS fibers and adrenal medulla

Not a lot of room betweentherapeutic and toxic effect- highpotential for toxicity (need tomonitor very closely) vancomysinis an example.

Narrow therapeutic index

Once a drug is started in ______________ trials companies apply tothe United States Adopted NamesCouncil for a unique, __________name: a ______ name?

Human clinical trials,nonproprietary (no brand name): a

generic name

Once A Potential Drug Is Identified:It goes through several _____ of

_______ before it hits the market.

levels of testing

Once in the synapse NE activates____ and ____ receptors

alpha and beta

Only certain postganglionic nervesrelease ACh:1. Those that activate the ____2. Those that go to the _____ nervoussystem (voluntarily controlled)3. Those that activate the _______ _______This is a SNS response- it is unusual

1. PNS2. Somatic (Skeletal muscle)

3. Sweat glands (This is the onlySNS response activated by ACH

only drugs with _______ -________________ can penetrate the blood-

brain barrier?

High lipid solubility

Only noncompetitive/irreversible alphablocker. Duration of action is 3-4 days (thetime it takes to make a new alpha receptor).Forms a stable bond with the alpha receptorCauses vasodilation and decreases bloodpressure. Clinically used for HTN inpheochromocytoma (adrenal medulla tumor)

Phenoxybenzamine

Oral: Bioavailabiltiy ________,Characteristics: __________?

5 to 100, most convenient, firstpass effect may be significant

Organophosphates are _________inhibitors & their effects last

________ of hours (time it takes tomake new _______)

irreversible, hundreds, enzymes

Organ System Effects Of Anticholinergics: CNS:_______ is distributed to the CNS and can produceeither ________ or excitement. Standard dosesinitially cause mild stimulation, followed bylonger-lasting _______ effectException: very sensitive person (elderly) or highdose, then it causes a ________state/delirium/hallucinations

Atropine, sedation or excitement,sedative, confusional

Organ System Effects OfAnticholinergics: CNS: _________vgets intoCNS causing __________ @ low doses, @high doses causes ________,hallucinations & coma. Major clinicaluse: ________ sickness (scopolaminepatch) and _____ patients

Scopolamine, drowsiness,excitation, Motion, hospice

Organ System Effects Of IndirectCholinesterase Inhibitors: These drugs amplify___________ effect and the organs effects arevery similar to direct acting agents These drugs are not often used in same wayas _______ cholinomimetics b/c of their sideeffects.

acetylcholine, direct

The original company that creates adrug has exclusive rights to that druguntil the ______ _______? So the companygenerates a ___________ name (owns it)called the ______ _____. This is atrademark, so only company can use it.

patent expires, proprietary, brandname

Other Clinical Uses Of Beta Blockers:1. Prevention of ________2. Local _________3. Muscle _______ (probably by decreasing SNS input)4. _______ withdrawal (treats symptoms in some)5. ______ especially performance associated, gets ridof symptoms of anxiety but not the anxiety itself

1. Migraines2. Anesthetic

3. tremors4. ETOH

5. Anxiety

Part of Prescribing information Con'd: 6. __________ who touse care with (e.g. elderly) when giving (overlaps withrelative contraindications) 7. ____________ reactions: mostcommon ones, or common and serious, usually gives % ofpatients who get. Also includes rares of rare. 8. Drug_______ and __________ potential. 9. ________ (what happens iftake too much) 10. Dosage and administration 11. How_________ (does it come as capsule tablet or liquid)

6. Precautions, 7. Adverse, 8.Abuse and Dependence potential.

9. Overdose, 11. Supplied

Parts of the prescribing Information:1. Description of drug includes ___________characteristics and ___________ group? 2. Clinical__________? 3. _________ and __________ (what the FDAsays it can be used for)? 4. ______________: Absolute(never give) vs. relative (if benefits outweigh risksgive the drug even though it may have a negativeeffect)? 5. _____________: Anything to be careful of islisted here

1. Chemical characteristics andpharmacologic group, 2. ClinicalPharmacology, 3. Indications andusage, 4. Contraindications, 5.Warnings

The passage of drug moleculesfrom the site of administration into

circulation

Absorption

A patent on a new drug lasts _____ years from thetime it is approved. With all the phases of trials anew drug often only gets to the market with ____years left to make money. Once the patentexpires anyone can manufacture the drug aslong as they can show it is ______________ to theoriginal drug. This is faster and easier and why_______ are cheaper?

17 years, 14 years, bioequivalent,generics

People who acetylate faster canget the drug out

Faster

People who acetylate slower getthe drug out much _______ and

creates _______ _______ of _______

slower and creates greater risks oftoxicity

Pharmacogenetics is clinically_______, but not ________ yet (DUETO COSTS) so not commonly used

relevant, practical

Pharmacogenetics looks for: ___________ is a phase II reaction, done bythe liver. Fast ________ are the dominantgene. Some have an autosomalrecessive trait that causes ________ tooccur more slowly.

Acetylation, acetylators, acetylation

Phase 1 Clinical trials: Answers thequestion, is the new drug ________? Do__________ and ________ have similarreactions? Can the data from _________testing be used? ___________ questionsare also answered?

Safe, humans and animals,preclinical (level 2),

pharmacokinetic questions

Phase II Clinical Trials: Answers thequestion is it ________? Give the

drug to those with _______ and seeif it ______?

Effective, disease and see if itworks

Phase III Clinical Trials: Answersthe question does it _____ _____?Refined and more specific study of_________ and __________?

Really work, effectiveness andtoxicities

Phase I liver reactions: Make the drug more____________ which makes the drugs lessinteractive with the receptors in the body andmore __________? Usually adding -OH, -NH2, -SH. By adding one of these chemical groupsto the drugs and making them more chargedthey can then be excreted by the ________?

Polar, Charged, Kidney

Phase IV Clinical Trials occur? if there isan area of ______ with the new drug theFDA may have the company continue tocollect data and continue to do studieseven with the new drug on the market?This is called ______-_______ _______ anddoes not happen with?

After the FDA gives approval forthe release of a drug, concern,

Post-maketing Surveillance, with allnew drugs

Phenoxybenzamine is clinicallyused for _____ in

pheochromocytoma which is an?

HTN which is an adrenal medullatumor

Phentolamine is Clinically used in _____ inpheochormocytoma and to treat _______ & ________after injection of alpha agonist(If using epi, might panic and stick your fingerinstead and it will cause necrosis and ischemia,so use agnoist to save finger)

HTN, necrosis & ischemia

Physician's Desk Reference is a bunch ofpackage inserts put together and sold. Ithas increased _____ because it is acommercial reference. Many ________aren't there?

bias, generics

Piroxicam (taken once daily) has a much______ half-life than ibuprofen. If you are in daily pain because of a _____term condition such as osteoarthritisPiroxicam is much more convenient totake, take it once and it lasts all day

Longer, long-term

PNS: _______ heart and ________ digestion.It is energy _________.SNS: ________ heart, ________ heart rate,__________ blood sugar. Useful to use upenergy if would have to fight or fly

slows, stimulates, conserving, Stimulates, increases, increases

Prescribing information (packageinsert/PI) is a document generated bythe __________ and approved by the_______? It is the source of a large amountof information concerning any drug.

Manufacturer, FDA

Prevent the action of agonist byoccupying binding sites on the receptor.Binds to receptors but doesn't activatereceptor (blocks real action ofreceptor/agonist)

Antagonist

The primary action of water soluble drugs is:Drug binds to __________. ___________ is modified sending amessage/causing a change in the cell. Mostdrugs are ______ soluble and cannot diffusethrough the lipid membrane so the drug sends amessage through the membrane as opposed toacting directly on the cell.

Receptor, Receptor, water

Primary neurotransmitter of theANS

acetylcholine

Pros of a drug with a long half-life?1. ________ to take because more

_______

1. Easier to take because moreconvenient

Prototype of the ACh receptor agonist. Itis an exact replica of the endogenousneurotransmitter. The pharmacologiceffect is not the exact same as what thenerves make & release, but ACh comesvery close. Stimulates __ & ___ receptors________

Acetylcholine, M and N receptorsequally

Pure alpha agonist drugs _______BP through blood vessel _________

increases, constriction

Pure beta agonist drugs _______ cardiacoutput & heart rate. BP may go up ordown depending on which wins (beta 1or beta 2): If there is a beta 2 effect onlyBP _________ b/c beta 2 ______ peripheralblood vesselsIf there is a beta 1 effectBP

increases, decreases, dilates.increases

The rate at which a drug isdistributed to various organs aftera drug does is administereddepends largely on the proportionof?

Cardiac Output received by theorgans

receptors are located in smoothmuscles, exocrine glands, and

central nervous system

α1

_________ receptors are present inthe CNS, every ganglion in PNS,SNS and neuromuscular junctionso a lot happens when they getactivated

Nicotinic

These receptors mediate smoothmuscle contraction

Alpha 1

These receptors mediate smoothmuscle relaxation

Beta 2

These receptors produce cardiacstimulation

Beta 1

Rectal: Bioavailabiltiy ________,Characteristics: __________?

less first pass-effect than oral

Refers to the amount of a drug inthe blood when it is at a stable

level.

Steady State

Renal vasodilation (D1), cardiacstimulation ((β1), and increased bloodpressure ((β1 and α1) Clinical use:Cardiogenic shock, septic shock, heartfailure, and adjunct to fluidadministration in hypovolemic shock

Dopamine

Respiratory Effect Of ACh: Think _________________________ smooth muscle of bronchial tree, making airways ______,harder to breath_________ secretion of mucus in tracheobronchial tree, fillingairways up with ______, harder to breathClinically: Not used for this effect, need to know b/c of respiratoryside effects when give muscarinic drugs for other reasons.Avoid use/use caution in patients with ______ or obstructive ______disease

BRONCHOCONSTRICTION,Contracts, smaller, Stimulates,

mucus, asthma, obstructive lung

Response of the body to a dosediminishes over multiple doses.

Stopping drug & restarting restoresthe initial response.

Tolerance

The science of substances used toprevent, diagnose and treat disease

Pharmacology

Selective alpha one blockers _______ vascularand other smooth muscles (including those inthe urinary bladder, urethra, and prostate)They also cause ___________ and _________blood pressureThe don't cause as much reflex _________compared to nonselective blockers.

relax, vasodilation, decrease,tachycardia

Skeletal Neuromuscular Junction Effects OfNicotine: Neuromuscular junction where nerveand muscle meet. Initially, voluntary muscles________, but the nicotine keeps stimulating thereceptor so the muscle never ________ b/cconstantly stimulated, so eventually leads to_______. Clinically used to cause muscle _______during _________?

contract, recovers, paralysis,paralysis, anesthesia

A small of volume of distributionmeans only

a few tissues are exposed to thedrug.

Some drugs are destroyed bystomach acid. So we give a________. The _________ resists theacid and then the liver changes the_______ to the active drug,

prodrug, prodrug, prodrug

___________ started in 1862 is ascientific, regulatory, and publichealth agency that regulates foodproducts, drugs, medical devices,and cosmetics.

The Food and Drug Administration(FDA)

Steady state is determined by the______ (how many milligrams) and

how ________ the drug is given(dosing interval)

dose and how frequently

Stimulation of alpha 1 & 2receptors cause _________ ofarteries, increasing arterial

_________ & _________ BP

constriction, resistance, increasing,(alpha 1 effect is stronger)

Stimulation of β2 receptors ______the arteries, __________ BPThis is the __________ of an alphaeffect & much _______ effect, sousually alpha wins out

relaxes, decreasing, opposite,weaker

The study of a drug's effects on thebody. This involves what a drug

does to the body to give its effect

Pharmacodynamics

The study of genetic variations thatcause differences in drug response

among individuals or populations

Pharmacogenetics(Pharmacogenomics):

Study of how genetics affectsmetabolism of drugs

Pharmacogenetics

Subcutaneous: Bioavailabiltiy________, Characteristics:

__________?

75 to 100, smaller volumes than IMmay be painful

The subset of pharmacology thatdeals with undesirable effects of

substances on living systems

Toxicology

Summary Of Direct-Acting MuscarinicReceptor Toxicity (ACh-type Drug): GI-n______, v_______, d______GU-urinary _______, i________Gland effect- ________Respiratory effect- shortness of ________& wheezing

nausea, vomiting, diarrheaurinary urgency, incontinence

sweatingshortness of breath & wheezing

Summary Of Direct-Acting Nicotinic ReceptorToxicity: Essentially a nicotine overdose.Acute-Very ______, 40mg can be _____,stimulates ____ (seizures, coma) & respiratory______ (from muscle paralysis), ___________ &cardiac ___________. Rapidly _________ so if stillalive in 4 hours will probably live

toxic, fatal, CNS, arrest,hypertension, arrhythmias,

metabolized

Sweat glands are activated by theSNS but the postganglionic nervefiber releases ______, which is notusual, usually it is an adrenergicneurotransmitter.

Ach

Sweating:So if the brain activates the SNS you______A patient also sweats & gets anotherwise PNS response when given adrug that stimulates the _____receptors

sweat, ACh

Terbutaline activates the _____receptor more than the _____receptor, so this drug causes moreof a ______ effect than a hearteffect. Terbutaline is used in ______

beta 2, alpha, lung, asthma

There are many clinical applications of_________ blockers. Many drugs that weuse in clinical medicine have a sideeffect of blocking these receptors. Theyhave multiple names?

muscarinic, Antimuscarinic drugsAKA parasympatholytic AKAcholinoceptor blockers AKAanticholinergic drugs: she will useanticholinergic

This brought about theammendment act of 1962?

Thalidomide, a new sleeping pill, is found tohave caused birth defects in thousands ofbabies born in western Europe. News reportson the role of Dr. Frances Kelsey, FDA medicalofficer, in keeping the drug off the U.S. market,arouse public support for stronger drugregulation.

This is the presumed relationshipwith most drugs and is the mostimportant in determining steady

state and half-lives

First Order Elimination

Three organs most often involved ineliminating a drug from the body?

1.GI tract2. Kidneys (DO MOST

ELIMINATING, eliminates small andcharged molecules

3. Liver (do the rest)

The tissues most sensitive tomuscarinic blockade are the

_________, _______ & ______ glands

salivary, bronchial & sweat glands

Toxicity of Indirect Cholinesterase Inhibitors: Generally short acting drugsare gone before too many problems occur. The drugs that bind _______ to the enzyme are around ______ & cause theproblems of excess ACh. Symptoms are:Eye: _________ visionGI: ________, _________ & _________GU: _________Excretions: S_______ symptoms (_______ & __________)Muscle ________ and ________, eventually becoming muscle __________Clinically see this in accidental exposure to pesticides

tighter, longer

Eye: Blurred visionGI: Nausea, vomiting & diarrheaGU: urination Sweating symptoms (tearing & drooling)Muscle twitching and tremors, eventually becomingmuscle paralysisClinically see this in accidental exposure to pesticides

Toxicity/Side Effects/ADRs of adrenergic antagonistsCNS: depression, sedation, sleep disturbances, rarely psychotic reactionsRespiratory: makes __________ worse b/c blocks bronchodilationCVS:Peripheral vascular disease: Beta 2 stimulation vasodilates blood vessels inleg, beta blockers can block this and make peripheral vascular diseaseworseCongestive heart failure: need beta 1 stimulation of heart to make pumpharder (notice that beta blockers treat heart failure also makes it worse)Endocrine: care if diabetic b/c won't know hypoglycemic (the response tohypoglycemia is activation of SNS)

asthma

transdermal: Bioavailabiltiy________, Characteristics:

__________?

usually very slow absorption; usedfor lack of first pass effect;

prolonged duration of action

Treatment Of AnticholinergicToxicity: Is usually treatment of the

_________.

symptoms

The two main organ systems thatwe see differences between direct& indirect cholinomimetics are the______ and the ____________junction.

CNS (central nervous system=brainand spinal cord), neuromuscular

Two types of Adrenergic Receptors 2 Types: α (alpha) & β (beta)

Two types of antagonists: CompetitiveIrreversible

Two very important conceptsrelated inversely to each other?

Half-life and Steady State

Upon nicotinic activation these _______-gated ______ channels are activatedproducing excitation andneurotransmitter releaseStimulate muscle _________ in skeletalmuscle & neuronal _________ in ganglionand brain

ACh, Na, contraction, excitation

Vasoconstriction and increasedblood pressure (α1)

Hypotension and shock

Vasoconstriction and increased bloodpressure (α1), cardiac stimulation ((β1), andbronchodilation ((β2) Clinical Use:Anaphylactic shock, cardiac arrest, ventricularfibrillation, reduction in bleeding duringsurgery, and prolongation of the action oflocal anesthetics

Epinephrine

Vasoconstriction, increased bloodpressure, and mydriasis (α1). Clinicaluse: Nasal and ocular decongestion,mydriasis, maintenance of bloodpressure and treatment of shock

Phenylephrine

Vasoconstriction (α1) Clinical Use:Nasal and ocular decongestion

Oxymetazoline

Vasoconstriction (α1) Clinical use:Orthostatic hypotension

Midodrine

_______ ______ warning is a specialtype of warning. It is the most

serious and highest level ofwarning.

Black Box (warning with a black boxaround it)

Was enacted in 1938 for the FDAto enforce, a piece of legislationthat said drugs have to be provensafe before being sold and haveadequate directions for safe use.

The Federal Food, Drug, &Cosmetic (FDC) Act of 1938

Water soluble drugs tend todistribute through any bodycompartment with ________

(__________ especially)

Water, blood

We can measure the levels of some drugs inthe blood and draw some conclusions butremember.....Seeing amount of drug in bloodis not the same as seeing the amount actuallyinteracting with the receptor For blood draw need to wait until drugreaches _________ state

Steady

What are the pro's of a drug with ashort half-life?1. _______ ______2. Reaches _________ _______ ______3. Get _______ of it ________

Works faster, reaches steady statefaster, get rid of it quicker

What are the three most reliableforms of drug delivery:

Subcutaneous, Intramuscular,Intravenous

What is the major factor affectingthe extent of drug distribution?

Lipid Solubility

What is the single most importantfactor to influence serum druglevels (amount of drug in the

blood)

Clearance

When is staeady state reached? Its the inverse of half-life. A certain% of the drug persists after each

interval

When meds are given orally they areabsorbed in the _______ & ________.Everything absorbed here goes straightto the _________ (portal circulation). Soeverything taken orally sees the ________before it sees any other part of thebody. This whole process is called the?

stomach and intestines, liver, liver,First pass Effect

When stimulated by the medulla thePNS responds with a generally a _______(leading to growth) response whichmeans anything leading to growth. Thistends to involve only ______

tropic, Ach

When stimulated by the medulla theSNS responds with a generally __________(energy expenditure) response leadingto energy expenditure. Involving ___, ____& _________ & _________ receptors (_____ &______)

ergotropic, NE, Epi & dopamine &adrenergic receptors (alpha & beta)

When you go from oral to IV drugsyou need to _______ the does?

Reduce

With a disease of the intestine givedrugs that are _________ by the liver. Sothe drug acts in the intestines where thedisease is (where it is needed) and thentravels to the liver where it is ___________so rest of body never sees the drug.

inactivated by the liver, inactivated

With the majority of drugs theamount of drug eliminated is a ____

of what is there not an actual______ (mg)

% not an actual amount (mg)

Zero-order elimination isimportant clinically for what three

drugs

aspirin, ethanol, and phenytoin

α2 receptor activation leads tofeedback ________ of ______ fromnerve terminals; found in bloodplatelets, intestinal, hepatic, renal,& endocrine tissue

inhibition, NE,

β1 receptors: produce cardiac stimulationleading to_______ chronotropic effect (_______ heart rate)_________ inotropic effect (increased _________)_________ dromotropic effect (increasedcardiac impulse _________. Also increases______ secretion?

Positive, increased, Positive,contractility, Positive, conduction,

renin

β2 activation causes __________ ofbronchial smooth muscle & opens

the airwaysClinical use: _________

relaxation, asthma

β2 receptors: mediate _________ ofbronchial, uterine, and vascularsmooth muscle. In skeletal muscle,they mediate ___________ (increaseglucose in blood)

relaxation, glycogenolysis

β - blockers end in? (olol)