Follows the patient’s status most closely

Detect mistakes made by pharmacists and prescribers

Observe and evaluate drug responses and intervene if required

Must know the response that a medication is likely to elicit

Last line of defense for the patient

Ethically and legally unacceptable to administer a drug that is harmful to the patient even though the medication has been prescribed by a licensed prescriber and dispensed by a licensed pharmacist

Determining how much of administered dose gets to its sites of action

Impact of the body on drugs

AD ME

absorption distribution metabolism excretion

Channels and pores - Concentration gradient 

Polar molecules= Uneven distribution of a charge/No net charge.Ions= Molecules that have a net electrical charge

Transport systems P-glycoprotein Direct penetration of the membrane

absorbed  along the GI tract—stomach, small intestine, and large intestine (but not the oral mucosa or distal rectum)

must go through the liver, via the portal vein, on their way toward the heart and the general circulation.

For some drugs, passage is uneventful. Others undergo extensive metabolism.

Still others undergo excretion into the bile, after which they re-enter the small intestine (via the bile duct), and then either (1) undergo reabsorption into the portal blood, thereby creating a cycle known as enterohepatic recirculation, or (2) exit the body in the stool.

Albumin is the most prevalent protein in plasma and the most important of the proteins to which drugs bind.

Only unbound (free) drug molecules can leave the vascular system. Bound molecules are too large to fit through the pores in the capillary wall.

this means medications can stay in the system and reach toxic levels if bound to albumin???

Effectiveness

Safety

Selectivity

Reversible action

Predictability

Ease of administration

Freedom from drug interactions

Low cost

Chemical stability

Simple generic name

(Easy to say,take,buy,store,no interactions,consitantly effective)

biotransformation

Defined as the enzymatic alteration of drug structure Most often takes place in the liver through a process of enzymatic transformation CYP450. This can transform the drug into an active, inactive, or less potent compound.

Preclinical testing Clinical testing Phase I Phase II and III Phase IV: postmarketing surveillance

Most important: Be neither the first to adopt the new nor the last to abandon the old. Balance potential benefits against inherent risks. New drugs generally present greater risks than old ones.

If you took a preparation of hydrocodone (T1/2 is 4 hours) containing 10 mg, list the amounts left in the blood at 1T1/2, 2T1/2, 3T1/2, 4T1/2:

5 mg left at the end of 4 hours

1.5 mg left after 8 hours,

0.75 mg left after 12 hours,

0.375 mg left after 16 hours, and roughly 0.16mg left after 20 hours.

1 T1/2 = 50% left 2 T1/2 = 25% left 3 T1/2 = 12.5% left 4 T1/2 = 6.25% left 5 T1/2 = 3.125% left

The range bewteen a drug being effective for theraputic application and when the drug is unable to ellicite more of an effective response but instead becomes toxic. 

maximal efficacy: maximal response a drug can produce. The efficacy of a drug is indicated by the height of its dose-response curve.

Potency is how much drug needed to get desired response.

Potency is usually not an important quality in a drug unless you have to take ten pills instead of 1.

1. Preadministration assessment 
2. Dosage and administration 
3. Evaluating and promoting therapeutic effects
4. Minimizing adverse effects 
5. Minimizing adverse interactions 
6. Making PRN decisions 
7. Managing toxicity

why,admin,effect,adverse, interact,prn, toxic

Drug name

therapeutic category

Dosage size

Dosing schedule

Route and technique of administration

Expected therapeutic response and when it should develop

Nondrug measures to enhance therapeutic responses

Duration of treatment

Method of drug storage

Symptoms of major adverse effects and measures to minimize discomfort and harm

Major adverse drug-drug and drug-food interactions

Whom to contact in the event of therapeutic failure, severe adverse reactions, or severe adverse interactions

type,dose,route,schedule,treats,outcome,adverse, contraindications,when to call

Judge the appropriateness of the prescribed regimen.

Identify potential health problems that the drug might cause.

Determine patient’s capacity for self-care.

(right drug, adverse, patient adherence)

Tight junctions between cells that compose the walls of capillaries in the CNS.

Drug must pass direct lipid soluble or must be able to use an existing transport system.

a molecule metabolized by the isoenzyme

Drugs and other substances can be Inhibitors or Inducers of the isoenzyme action

Ex. Caffeine is a CYP1A2 substrate and Ciprofloxacin (antibiotic) is a CYP1A2 inhibitor – so if your patient drinks 4 cups of coffee and starts on Cipro, may experience insomnia,

other caffeine effects Nicotine is a CYP1A2 inducer and Theophylline (respiratory med) is a CYP1A2 substrate – so if your patient cuts back on nicotine the isoenzyme will decrease in action and there may be increased therapeutic effect and adverse effects of the theophylline

Define an agonist, name the medication and it's receptor:

Molecules that activate receptors.Endogenous regulators - make process go faster or slower based on receptors potential.

Muscarinic agonist: Bethanechol

Adrenergic Agonists:

Epinephrine (a1,2 Beta1,2) not dopamine

Norepinephrine (a1,2 beta1) no beta 2 and no dop

Dopamine - (a1,Beta1, dop)

Albuterol - (beta 2)

prevents receptor activation by endogenous regulatory molecules

Anticholenergenic/muscarinic blockers/antimuscarinic:

Atropine (Muscarinic)

Tolterodine (nonselective muscarinc)

Ipratropium Bromide (muscarninc)

Antiadrenergenic:

Phenoxybenzamine (nonselective alpha blocker)

Alfuzosin (apha1 blocker)

Propranolol ( nonselective beta blocker

Labetalol (nonselective Beta and Alpha1)

Atenolol (beta 1 blocker)

Metoprolol (beta 1 blocker)

Bind irreversibly Reduce maximal response(fewer available receptors) not permanent (cells breaking down “old” receptors synthesizing new)

 chantix ??

Compete with agonists for receptor binding Bind reversibly to receptors

Equal affinity: receptor occupied by whichever agent is present in the highest concentration

These are agonists that have only moderate intrinsic activity.

The maximal effect that a partial agonist can produce is less than that of a full agonist.

Can act as antagonists as well as agonists 

Continuous exposure to agonist

Desensitized or refractory=Down-regulation

Continuous exposure to an antagonist= Hypersensitive and upregulation

Treats:rheumatoid arthritis osteoarthritis, bursitis, fever,dysmenorrhea

1st gen NSAID - Anti-inflamatory COX 1&2 inhibitor

Adverse: Ulcers, bleeding, renal impairment. Increase risk of Stroke and MI

Treats:pain, fever, inflamation

CAT: 1st gen NSAID

Action: Nonselective inhibitor of COX1,2 irreversible inhibitor TXA2 

Adverse:Bleeding platelet agg lasts(8days). GI,Ulcers,Renal impairment-prostaglandin deprived.

Contraindication: Glucocorticoids,Warfarin, Heprin, alcohol. Reye’s syndrome- kids chicken pox, influenza. Pregnancy Anemia, postpartum hemorrhage, may prolong labor, close fetus ductusateriosus. Acute poisonings

Treats:fever, headache but not inflammation in body

Category: NSAID,

Action:Inhibits Cox in CNS only.

Adverse: hepatotoxin via P450

Contraindications:alcohol,warfarin,

Other:May blunt immune response to vaccine

Treats:Anti-Inflammatory allergy, Motion sickness, insomnia, cold.

Action: Blocks h1 receptors (vasodilatation, increased capillary permeability, bronchoconstriction, CNS sleep/wake cycle-memory)  

Adverse: anticholenergenic -(dry mouth, dry mucous membranes, urinary hesitancy, constipation, palpitations) Depresses CNS – lipid soluble, crosses BBB,Respiratory depression,Cardiac dysrythmia: prolongs QT interval Contraindicated: alcohol,3rd trimester, nursing mothers, newborns asthmatics- thickens mucous, anaphylaxis

Other: Severe tissue injury-avoid IV gangrene and amputation. IM is ok and oral is preferred

Treats: Rheum arthritis, lupus, IBS, Allergic conditions, Asthma, Dermatologic disorders, Neoplasms, Suppression of allograft rejection. Prevention of RDS in premature infants

Action:Immunosuppressant, Anti-inflammatory, Increase RBC, decrease WBC,increase blood glucose, decrease protein metabolism, promote glycogen storage, fat breakdown.

Adverse:Increase blood glucose, decrease protein metabolism,pot belly, moonface, neck hump/cushings

Contraindications:Adrenal hypoplasia- times of stress fatal Osteoporosis, lowered immune, and glycosuria. Myopathy,electrolyte disturbances,Growth retardation,insomnia, irritability, delirium, hallucinations Cataracts, glaucoma: Peptic ulcer disease,pregnancy and lactation Drug interactions NSAIDs- ulcers Insulin-may need to increase. Vaccines /live 

Treats: RA

Action: Suppress B and T lymphocytes, Slow progression of joint deformity

Adverse: GI disturbances,Dermatologic,Hepatic fibrosis, bone marrow suppression, GI ulceration, pneumonitis. 

Contraindications: teratogenic, Sulfa allergy

Treats: Stimulates immunity for Measles, Mumps, Rubella.

Action:3 live virus stimulate adaptive active immunity Adverse:Sore, red, glandular swelling in cheek, neck, jaw. Transient rash

Contraindications:allergy to egg or gelatin, pregnancy, children with thrombocytopenia, neomycin allergy, moderate febrile illness,immunocompromised, Glucocorticoids, anticancer drugs, HIV

Action:Weakened virus introduced for active adaptive immune sytem

Adverse:May get flu, Runny nose, cough, fever, vomit, muscle aches, headache, sore throat. Contraindications:Anaphylaxix, Rare-Guillian Barre Syndrome  Bells palsey, Under 2 over 49, pregnant, immunocompromised

Action:Attenuated virus (weakened)

Adverse: Malaise, fever, myalgia, Rare-Guillian Barre Syndrome.

Contraindications: febril Fever illness, egg allergy, under 6 months, immunocompromised

Treats:Antimicrobials Menningitis Pneumonia Streptococcus infections throat and pericarditis syphilis

Action:Beta-Lactam antibiotic weaken cell wall, bact. takes up water and bursts. Not effective against gram neg cell walls. -+bacteria have beta-lactamase producing bacteria. MRSA resistant mutated low PBP’s produced. - nonteratogenic

Adverse:Sore red at site

Contraindications:Neurotoxic if injected into nerve(seizures), or intra atrial –(necrosis) Allergy (Immediate, Accelerated, late), Probenecid/ procaine = hyperkalemia,death Other:Never mix penicillin with Aminoglycoside in IV, inactivates Aminoglycoside

Cephalosporins

Cefazolin

Cefaclor

Cefoperazone *

Cefepime

Treats: Cefazolin-  g+Staphlococci, Streptococcus, Cefaclor G-, Cefoperazone G- MRSA, Cefepime menningitis

Action:Beta-Lactam binds to penicillin binding proteins (PBP), autolysin bacterioside, low toxicicity, . 1st 2nd generation not used often. 3rd and 4th penetrate cerebral spinal fluid used meningitis, nonteratogenic

Adverse:Low toxicity, well tolerated. Oral take with food, IM very sore, IV slow, 2nd gen Use may contribute to C-Diff.

Contraindications:allergy, bleeding, thrombophlebitis Probenecid Alcohol Drugs that promote bleeding Calcium and ceftriaxone

Treats:MRSA, c-diff

Action:Inhibits cell wall synthesis. Binds to cell wall not PBP. Used for severe infections only. Works on MRSA. Oral dose for c-diff after metronidazole

Adverse:Nephrotcicity,red, burn, itch- slowly infuse. thrombophlebitis at site of iv. Thrombocytopenia, allergy

Nonteratogenic 

Treats: Rickettsial disease, Chlamydia, Brucellosis, Cholera, acne, mycoplasma pnemoniare, lyme disease

Action: Suppress bact. Growth, inhibit protein synthesis

Adverse: GI upset avoid hs dose

Contraindications:Absorption inhibited by chilation(calcium), milk, iron, antacids, GI irritation Diarrhea, super infection(another bact not affected by Tet), high doseIV=hepatotoxic, renal toxic, photosensitivity, Pregnancy (affects fetus adult teeth)children under 8, kidney disease, c-diff

Treats:Whooping cough, ditheria, clamydia, Group A strep

Action:Broad spectrum – inhibits protein synthesis, used for penicillin allergic, bacteriostat

Adverse:GI pain, nausea, vomit, GI, Super infection, QT interval prolongation and sudden cardiac death

Contraindications: Increases with Warfarin, carbamazepine, opylline, Promotes C.diff

Treats:G+or-, Group Astrep, gas gangrene, abdominal infections, B.Fragilis

Action:Binds to 50s subunit to inhibit protein synthesis. Does not cross BBB Adverse:Diarrhea

Contraindications:fatal c-diff

Treats:aerobic gram-negative bacilli. Pseudomonas aeruginosa, e.coli, serratia.

Action:Narrow-spectrum antibiotics Bactericidal. Don’t readily cross membranes “polycations” positively charged.

Adverse:serious injury to inner ear and kidney Not absorbed from the GI tract Microbial resistance, Nephrotoxicity Ototoxicity Other:Must be given IM or IV. Binds to kidney and ear

Contrainidcation: teratogenic 

Treats:UTI, MRSA

Action:Broad-spectrum antibiotics Suppress bacterial growth by inhibiting bacteria from folic acid synthesis

Contraindications:Stevens-Johnson syndrome Hematologic effects Kernicterus- newborn Renal damage from crystalluria Inhibits hepatic metabolisim of other drugs,infants under 2m, preg. breastfeed

Trimethoprim - Trimethoprim-sulfamethoxazole (TMP-SMZ) combo

Treats:Escherichia coli, Proteus mirabilis, Klebsiella pneumoniae, Enterobacter, coagulase-negative Staphylococcus Urinary tract

 Action:Inhibits dihydrofolate reductase Broad-spectrum antibiotics Suppress bacterial growth by inhibiting bacteria from folic acid synthesis.

Contraindications:Hematologic effects, hyperkalemia, Folate deficient Gastrointestinal Nausea and vomiting Rash Hypersensitivity reactions (Stevens-Johnson syndrome) Blood dyscrasias Kernicterus - preg. breastfeed Renal damage: crystalluria

Treats:MRSA Anthrax respiratory,(UTI), GI, bones, joints, skin, soft tissue

Action:Disrupt DNA replication and cell division Contraindications:Tendon rupture, teratogenic,Promotes cdiff, > 60 years, glucocorticoids, kidney, heart, or lung transplantation. Absorption reduced by: Aluminum Mag antacids Iron Zinc salts, Sucralfate, dairy products.

Treats:UTI, e.coli, staph, strep, neserria, bacteriodes Action:Broad spectrum, enzymatically activated then damages DNA

Adverse:2-4 days Dyenpnea, pain,fever, chills, hypersensitivity months, hematologic;agrannulocytosis, leucopenia, thrombocytopenia, megaloblastic anemia,

Contraindications: Pregnant, infants, hepatotoxic – test liver funct, tertatogenic,

Treats: Alzheimer

Action:Increase cognition, behavior, and function and may slow disease progression slightly. Prevent ACh break down and increases its availability. Adverse:Dizzy, GI symptoms  and bronchoconstriction

Contraindications:first-generation antihistamines, tricyclic antidepressants, conventional antipsychotics) reduce responses to cholinesterase inhibitors.

Treats:Moderate - Severe Alzheimer

Action:Receptor antagonist blocks calcium influx when extra cellular glutamate is low.

Adverse:Dizziness, headache, constipation Contraindications:Combined with Amantadine and ketamine undesireable addictive effect.

Treats: Epilepsy

Action:selective inhibition of sodium channels Varied oral absorption, Nystagmus Sedation Ataxia Diplopia Cognitive impairment Gingival hyperplasia Skin rash 

Contraindications:pregnancy Cardiovascular effects Other:Half-life: 8 to 60 hours large variable monitor

Treats:Epilepsy Bipolar disorder Trigeminal and glossopharyngeal neuralgias

Action:Suppression of sodium influx Suppression of calcium influx Antagonism of glutamate Potentiation of GABA

Adverse:nystagmus, ataxia leukopenia, anemia, thrombocytopenia, Hypo-osmolarity,rash, photosensitivity

Contraindications: teratogenic, increases rate that drugs are inactivated, Suicide risk, avoid grapefruit juice: increases drug plasma levels by 40%

Treats: Bipolar, epilepsy

Action:binds to GABA receptors causing them to respond more to GABA.

Adverse:Lethargy, depression, learning impairment

Contraindications: teratogenic, dependency

Treats:Epilepsy

Action:may enhance GABA release

Adverse: somnolence, dizzy, ataxia, nystagmus Contraindications: unknown pregnancy

SSRIs Selective Serotonin Reuptake Inhibitors - Fluxotine Sertraline (Zoloft)

Paroxetine (Paxil, Paxil CR, Pexeva)

Treats: Depression, bipolar, OCD,panic, bulimia, PTSD

Action:blocks serotonin uptake increases amount of transmitters to eventually increase amount of serotonin uptake into neurons->decreasing depression.

Adverse:70%sexual dysfunction,weight gain, serotonin syndrome(agitation,hallucinations, altered mental status, tremor, fever) W/D dizzy, headache, termor. Can cause neonatal abstinence syndrome (baby w/d) infant Pulmonary hypertension, possible heart defects

Other:Suicide risk, bruxism (teeth grinding)GI bleeding.

Contraindications: MAOIS, TCI, Anticoagulants

SNRIs- Serotonin/Nor-epinephrine Reuptake Inhibitors

Venlafaxine (Effexor)

Treats: Depresion,anxiety

Action:blocks serotonin, NE and weakly blocks dopamine Adverse: hypertensio, sexual dysfunction, pupil dilation, hyponatremia,suicide

Contraindications: MAOI's 

Treats:depression,diabetic neuropathy

Action:Inhibits serotonin and NE reuptake Weakly inhibits dopamine reuptake

Adverse:Nausea, Somnolence Dry mouth Sweating Insomnia Blurred vision Effects in pregnancy and lactation Drug interactions

Contraindications:Alcohol MAOIs Drugs that inhibit CYP1A2 or CYP2D6 Other:

Treats:Depression, bipolar, fibromyalgia

Action:blocks uptake of NE and 5-HT, increases transmitters and sensitivity

Adverse:Orthostatic hypotension,anticholenergenic effects (blocks muscarinic dry mouth, urinary hesitancy, tachycardia),Diaphoresis, sedation, cardiac toxicity, seizures, hypomania, suicide, yawngasm :-) Contraindications:MAOI's, direct acting sympathomimetic drugs (prolonged in system-increased sensitivity)Blocks indirect acting sympathomimetic, intensify anticholinergenic -antihistamines and sleep aids. Overdose

Treats:depression, panic, OCD

Action:Blocks liver enzyme MAO A and B from converting NE,dopamine, and serotonin.

Adverse:orthostatic hypotension,

Contraindications:hypertensive crisis:dietary tyramine (cheese, sausage, aged fish) All drugs

Treats:Anxiety, insomnia, seizure

Actions: intesnify GABA effects(not agonist) Adverse:Acute toxicicty, CNS depress, amnesia, paradoxical effects(opposite), respiratory depress,

Contraindications:teratogenic, dependance,

Other:IV induces severe hypotension and cardiac arrest

Treats:Depression, seasonal affective disorder, smoking cessation.

Action:blocks NE and dopamine not SSRI or MAOI

Adverse:headache, nausia, dry mouth, seizure Contraindications:SSRI's or MAOI's Other:

Treats:mild depression

Action:may equal TCA's Adverse: induces p-450 liver enzyme drug metabolizing, induces P-Glycoprotien (transport drugs through intestinal lumen and urine)

Contraindications: serotonin syndrome if combined with other SSRI's 

Treats:acute manic depression, depression, Action:unknown exactly, ion critical to neuronal function may block SSR, NE, Dop Adverse:small therapurtic index-monitor plasma, weakness, tremor, GI, polyuria, goiter, leukocytosis

Contraindications:teratogenic nephrotoxic,diuretics, don't change to low sodium diet-restricts excretion of lith -> toxicity, NSAIDS,Anticholenergenic (antihistamines, TCA's)

Treats:insomnia Category:hypnotic

Action:binds where benodiazepines do on GABA receptors

Adverse: CNS depressants, alcohol, unknown safe in pregnancy

Treats:Seizure disorders Induction of anesthesia Insomnia

Action:Binds to the GABA receptor–chloride channel complex

Adverse:CNS depression,Respiratory depression, Suicide, Abuse, Use in pregnancy, Exacerbation of intermittent porphyria Hangover, Paradoxical excitement, Hyperalgesia Cardiovascular effects

Contraindications:CNS depressants drug-metabolizing enzymes Chloral hydrate Meprobamate

Treats:insomnia from antidepresents, depression

Category:hypnotic Action:Blocks 5HT uptake

Adverse:prolongs QT, prolonged painful erection

Contraindications:drugs that inhibit metabolisim Other:

Muscarinic agonists (Parasympathetic/ cholenergenic)

Bethanechol 

Treats:urge incontinence

Action:Sweat glands, decrease heart rate, smooth muscle,Contraction in lung (constriction) GI tract (increased tone/motility) Bladder (contraction of detrusor) Vascular (relaxation, vasodilation, hypotension) Eye (pupillary constriction and ciliary contraction)

Adverse:Cardiovascular system Alimentary system Urinary tract Exacerbation of asthma Dysrhythmias in hyperthyroid patients

Muscarinic Antagonists (Anticholenergenic)

Atropine, Tolterodine

Treats:Preanesthetic medication, Disorders of the eye Bradycardia, Intestinal hypertonicity, and hypermotility, Muscarinic agonist poisoning, Peptic ulcer disease Asthma Biliary colic

Action: block acetylcholine at muscarinic receptors.

Adverse:Xerostomia (dry mouth) Blurred vision and photophobia Elevation of intraocular pressure, Urinary retention, Constipation, Anhidrosis, Tachycardia, Asthma Contraindications:Other muscarinc blockers.

Parasympatholytic drugs

Antimuscarinic Antinicotinic drugs

muscarinic/nicotinic blockers

Muscarinic: agonist                           antagonist

salvia          salivation                      Dry mouth

CNS    enhanced cognition            confusion, hall

Heart    brady cardia                       tachycardia  

detrusor     contract                         relax

GI               increase                        relax

eye iris        contract                        relax

Treats:Asthma,COPD

Action:causes broncodialtion

Adverse:increase intraocular pressure w/glaucoma Contraindications: not many anticholenergenic dry mouth,constipation, urinary hesitancy)

Treats:Muscle relaxation during surgery Facilitation of mechanical ventilation Adjunct to electroconvulsive therapy Endotracheal intubation Diagnosis of myasthenia gravis

Action:Paralysis Adverse:Respiratory arrest Cardiovascular effects,Prolonged apnea in patients with low pseudocholinesterase activity Malignant hyperthermia, Postoperative muscle pain, Hyperkalemia Contraindications:other Cholinesterase inhibitors, Antibiotics Other:Cannot cross Blood-brain barrier No impact on CNS (paralysis, not sedation) Placenta Minimal effects on fetus Drugs: Antibiotics, Aminoglycosides,

Adrenergic Agonists  and receptor actions:

Epinephrine

Norepinephrine

Dopamine

Albuterol

Phenoxybenzamine

Alfuzosin 

(Sympathomimetic)

                 Agonist         

Alpha 1   dilate pupil                       

 constrict arterioles,veins

bladder,ejeculate

Alpha 2 (inhibits transmitter release) *extra

Beta 1 increase heart

rate, force, renin,

Beta 2- bronich dilation

utuerus relax,contr.skelatal muscle

Dopamine: Kidney dilation

Adrenergenic agonist: Epinephrine

Action Treatment and Receptors?

Treats:Delays absorption of local anesthetic Controls superficial bleeding Elevates blood pressure Mydriasis during ophthalmologic procedures Overcomes AV block Restores cardiac function in arrest Bronchial dilation in asthma Treatment of choice for anaphylactic shock receptors: A1,A2,B1,B2

Adrenergenic Agonist: Norepinephrine

receptors and actions

A1,A2,B1 receptors

Increased heart rate and force

dilation lung

uterus relax

Skelatal muscle contraction

Treats: Asthma, treat preterm labor,

Action: Activates beta 2 receptor, dilates bronchiols, relaxes uterine smooth muscle

Adverse: tremor

Contrainidications: hyperglycimia in diabetic patients,