Pharm Exam 1

Volume of distribution

is the amount of drug (C) in the body in relation to the amount in the blood or plasma

• V = amount of drug in the body / C 

  • V = this

  • Amount of drug in the body = usually the dose given (mg)

  • C = plasma concentration of the drug (mg/L)

High

____ molecular weight drugs (>1000) do not diffuse readily between compartments of the body which means the VOD is reduced

Protein bound

____ drugs tend to stay in the blood because it needs to be unbound to move out into tissues which means the VOD is reduced.

Inversely

Kidney disease causes decreased clearance and clearance and half life are ____ related.

Prodrug

an inactive precursor chemical that is readily absorbed and distributed and then converted to the active drug by biological processes inside the body

• If its metabolism is inhibited then it won’t work and desired effects will not be achieved.

Phase 1

usually convert the parent drug to a more polar metabolite by introducing or unmasking a functional group (–OH, –NH2, –SH). Often these metabolites are inactive, although in some instances, activity is only modified or even enhanced. ____ metabolites that are sufficiently polar may be readily excreted.

• Oxidation

• Reduction

• Hydrolysis

Phase 2

products are not eliminated rapidly and undergo a subsequent reaction in which an endogenous substrate such as glucuronic acid, sulfuric acid, acetic acid, or an amino acid combines with the newly incorporated functional group to form a highly polar conjugate that is easily excreted. (may occur before or after the other phase)

• Glucuronidation

• Sulfation

• Acetylation

• Methylation

• Glutathione conjugation

• Glycine conjugation

Intravenous

route to achieve 100% bioavailability of a drug and it also has the most rapid onset

Bioavailability

fraction of unchanged drug reaching the systemic circulation following administration by any route

pKa

pH in which concentrations of ionized and nonionized forms are equal. Tells us how easily a drug gives up a proton

•  A drug becomes ionized when pH differs greatly from this

Base

When pH is < pKa (ionized)

when pH is > pKa (nonionized & neutral)

Acid

When pH is < pKa (nonionized)

When pH is > pKa (ionized)

nonionized

We want these types of drugs because they cross membranes easily and are lipid soluble

Steady state

this is when the amount of drug going into the body = the amount coming out. The drug concentration in the body remains constant between doses

• it takes 4-5 half lives to reach

 t1/2 X 5

Steady state formula

Benzodiazepines

Positive allosteric modulator of GABA-A receptor; enhances GABA's effect to increase chloride influx, causing hyper polarization and CNS inhibition.

• Increases frequency of GABA-A channel opening, leading to more Cl⁻ entry → hyperpolarization → sedation, anxiolysis, muscle relaxation.

• Safe in overdose because they do not activate GABA-A receptors directly—only enhance GABA’s action. Less effect if no GABA is present.

Potency

The dose required to produce 50% of a drug’s maximal effect (ED50).
More ____ = less drug needed.

• depends in part on the affinity of receptors for binding the drug and in part on the efficiency with which drug receptor interaction is coupled to response

Efficaciousness

the limit of the dose response or maximum effect a drug can produce regardless of dose

• more ___ = stronger total effect

Competitive antagonist

inhibit the agonist response if concentration is increased (high antagonist concentrations prevent the response almost completely). Conversely, high concentrations of agonist can surmount the effect of a given concentration of the antagonist (antagonist increases the agonist concentration required for a given degree of response so the agonist concentration effect curve is shifted to the right)

• reversible, dose dependent, but maximal efficacy remains the same

Noncompetitive antagonist

once a receptor is bound by these, an agonist CANNOT surmount the inhibitory effect regardless of their concentration (In many cases they bind in an irreversible or nearly irreversible fashion, sometimes forming covalent bonds with the receptor). The remaining unoccupied receptors may be too low for the agonist (even at high concentrations) to elicit a response comparable to the previous maximal response.

Therapeutic Index

measures how safe a drug is by comparing the dose that causes toxicity to the dose that gives a therapeutic effect

• TI = TD₅₀/ED₅₀

• The higher the number the better

Highly

small molecular size, lipid soluble, and nonionized drugs are ____ permeable

Relative

Impermeability of the placenta to polar compounds is ____ rather than absolute

• If high maternal fetal concentration gradients are achieved, polar compounds also cross the placenta in measurable amounts. (the uncharged and lipid soluble parts can cross)

• Other than that the same permeability factors apply

Placenta

has ability to push drugs out to protect fetus from certain type of drugs, it also has drug metabolizing abilities so break drug up before it can get across to the fetus

breastfeeding

Avoid these drugs in ______

• Lithium, amiodarone, atenolol

Half life

the time it takes for 50% of a drug in the body to be eliminated.

• most important factor in determining the dosage interval in prescribing a drug

Phase 1 or 2 determinants

• Presence of a functional group (if drug already has functional group it may skip phase I and go to phase II) 

• Enzyme availability & affinity (liver enzymes may favor one pathway over the other) 

• Drug solubility (if already polar, it may be excreted after phase I) 

• Drug dose (at high doses, phase II pathways get saturated leading to reliance on alternate routes) 

Neonate/Infant

Blood brain barrier is a selective barrier made of tight junctions between endothelial cells in brain capillaries. It protects the brain by limiting the entry of toxins, pathogens, and many drugs. Only small, nonpolar, lipid-soluble, or actively transported substances can usually cross.

• In the _____ the BBB is underdeveloped, weaker, and more permeable.

• Inflammation opens up the BBB

Clearance

this is reduced in children & elderly

• In children because they are underdeveloped

• In elderly because kidney function declines and blood flow to liver also declines which decreases function and causes drugs to not be broken down as quickly

Body surface area

most accurate way to calculate dosages for children.

• Weight is less reliable due to obesity endemic which can lead to overdosing

Elderly

in these patients receiving antihypertensive drugs, check regularly for orthostatic hypotension because of the danger of cerebral ischemia and falls.

Thiazide diuretics

side effects of these medications primarily concerning in elderly include

• Hypokalemia (arrhythmias),

• Hyperglycemia (in diabetic may tip them over edge) in non diabetic can cause DM

• Hyperuricemia (aggravates gout) 

B lactamase

mechanism bacteria use to resist antibiotics that uses _____ (enzyme made by bacteria) to inactivate the B lactam ring found in

• Penicillin

• Cephalosporins

• Carbapenems

• Monobactams

Bacteria resistance mechanisms

• inactivation of antibiotic by B lactamase is most common,

• modification of target protein receptors, impaired penetration of drug to target proteins (P glycoprotein)

• antibiotic efflux (related to p glycoprotein) it will throw out antibiotic from cell.

• Mycobacterium, E.coli, and staph aureus

Transduction

bacteriophages (viruses that infect bacteria) carry resistance genes and insert them into bacteria DNA

Transformation

bacteria pick up DNA from environment (this is how penicillin gets resistance)

Conjugation

transfer of dna from one organism to another through mating

Increased

Active inflammation of the meninges can cause _____ penetration into the CNS/CSF. The type of antibiotic is also a factor, its size, lipid solubility, pH, & protein binding ability can all affect ability to penetrate CNS.

No

Are antibiotics given for viral diseases?

Cephalosporins

penicillins share features of chemistry, mechanism of action, pharmacology, and immunologic characteristics with _____, monobactams, carbapenems, and β­lactamase inhibitors. They are all β ­lactam compounds & named so because of their four membered lactam ring.

• With ____They share allergy and resistance characteristics due to this (MOA, chemistry, and allergy profile)

enterococcus spp

Linezolid, Daptomycin, Tigecycline, Vancomycin, & Ampicillin offer good ____ coverage

• Ceftaroline has some activity against faecalis only

Factors that contribute to antibiotic resistance

• Overuse of antibiotics

• inappropriate antibiotic prescription

• non adherence to antibiotic

• broad spectrum antibiotics 

• Viral infections treated with abx,

• bacteria have short reproductive cycles which allows them to adapt and resist

MRSA

these drugs are good for ____

• Vancomycin (most effective)

• Ceftaroline (only b lactam that can kill this)

• Fosfomycin (mainly for UTIs)

Streptococcus pneumoniae

most common cause of community acquired pneumonia

Gram positive

• Cocci

  • Staphylococcus aureus

  • Streptococcus pneumoniae

  • Group A, H hemolytic (pyogenes)

  • Group B, group D

• Bacilli

  • Bacillus spp

  • Diphtheroids

Gram negative

• Enterobacteriaceae

  • E. coli

  • Klebsiella spp

  • Proteus spp

  • Salmonella spp

  • Serratia spp

  • Shigella spp 

• Bacilli

  • Haemophilus influenzae

  • Campylobacter spp

  • Helicobacter pylori

  • Legionella spp

  • Pseudomonas aeruginosa

• these type of bacteria are harder to treat & found in hospitals mainly

Aerobic

These type of bacteria require oxygen to grow

• Pseudomonas aeruginosa

• Mycobacterium tuberculosis

Anaerobic

These type grow in absence of oxygen

• Can be obligate (die with O₂) or facultative (can survive with or without O₂)

• Clostridium spp.

• Bacteroides fragilis

Cell wall antibiotics

inhibit cell wall synthesis by blocking peptidoglycan cross-linking.

• Penicillins

• Cephalosporins

• Cephamycins

• Carbapenems

• Monobactams

• Vancomycin

• Telavancin

• Dalbavancin

• Oritavancin

• Bacitracin

Meningitis

Most antimicrobials do not penetrate uninflamed meninges to an appreciable extent. In the presence of _____ however, the cerebrospinal fluid concentrations of many antimicrobials increase

Oxacillin

Which penicillin causes hepatitis?

<1%

What is the percentage of serious reactions to penicillins?

Probenecid

This drug increases the level of penicillin/cephalosporins by inhibiting renal excretion of them, raising their blood levels.

Penicillin

• Cephalosporins are structurally similar to _____ but have greater resistance to β-lactamases and a broader spectrum of activity. They are more effective against organisms like E. coli and Klebsiella spp.

• However, they are NOT active against Listeria monocytogenes or Enterococcus spp., except for ceftaroline, which has some Enterococcus activity.

• As you move through 1-5 generations of cephalosporins they get more and more broad spectrum

equal

The crossover from penicillin to cephalosporin allergy is ___ to <1%

3rd, 4th, & 5th generation

if a patient has a penicillin allergy, and cephalosporin must be given, these generations are used due to their much lower risk of cross-reaction, because their side chains are different.

• ceftriaxone, cefepime, ceftaroline

Vancomycin

bactericidal against Gram-positive bacteria, including beta-lactamase–producing Staphylococcus and those resistant to nafcillin and methicillin (i.e., MRSA). It works by binding to D-Ala-D-Ala on peptidoglycan precursors, inhibiting cell wall synthesis.

• It is only effective against actively growing and dividing bacteria, and kills staphylococci slowly during their replication phase.

90%

____ % of Vancomycin is excreted unchanged by the kidneys via glomerular filtration (GFR).

• In renal impairment, it can accumulate to toxic levels, so dosing must be adjusted based on creatinine clearance.

C Difficile

These drugs are given to treat

• Oral Vancomycin (1st line): never IV, must be in contact with GI tract

• Fidaxomicin (Dificid) (1st line): often preferred due to less risk of recurrence compared to vancomycin (more expensive)

• Metronidazole (Flagyl): Alternative or backup option for mild cases or when other drugs aren't available, can cause disulfiram-like (Antabuse) reaction if taken with alcohol

Ototoxic & Nephrotoxic Antibiotics

• Aminoglycosides (gentamicin, tobramycin, amikacin, streptomycin, neomycin): strongly ototoxic & nephrotoxic

• Vancomycin: nephrotoxic; but ototoxicity is rare

Erythromycin

Macrolides, especially _____ , inhibit CYP450 enzymes (CYP3A4), leading to increased levels of other drugs like

• Warfarin

• Cyclosporine

• Methylprednisolone

• Antifungals

• DOACs.

  This can cause toxicity or enhanced drug effects.

Red man syndrome

Infusion related reaction caused by histamine release after vancomycin administration. Skin is flushed, the patient gets hypotensive, and rash and itching occurs. 

• Always listen to chest and check blood pressure after you notice rash

Tetracycline

These drugs reduce the half life of _____ by inducing CYP450 enzymes, leading to increased metabolism of tetracyclines. which shortens their half-life and decreases effectiveness.

• Phenytoin – anti-seizure

• Carbamazepine – anti-seizure & mood stabilizer

• Phenobarbital (and other barbiturates) – sedative/anti-seizure

• Chronic alcohol use – induces liver enzymes

• Rifampin – antibiotic (often used for TB)

Hepcidin

a hormone made by the liver that controls amount of iron absorbed & stored through oral or dietary intake.

• When iron is low, ____ is low which allows for increased absorption of iron

• When iron is adequate, ____ is released which prevents excess absorption of it.

Intravenously

Giving iron _____ bypasses the stomach and hepcidin cannot regulate it so you get increased risk of overdose, sensitization, & allergic reaction.

• reduces dose of iron that can be given safely

• used in situations where rapid replacement is needed or patient unable to absorb iron

Orally

Giving iron ____ is safe because hepcidin controls how much is absorbed and overdose is rare

Ferritin

The best lab test to estimate total body iron stores.

• It is a water-soluble complex of ferric hydroxide and apoferritin

• Stores iron in the ferric (Fe³⁺) state to keep it soluble and non-toxic.

• levels reflect iron stored inside cells like intestinal epithelium, macrophages in the liver, spleen, & bone marrow as well as liver parenchymal cells.

1mg

The daily rate of iron turnover in males is about ______ per day.

• most iron is conserved

• iron loss higher in females due to menstruation

Hemolysis

Hemodialysis causes ____ of RBCs due to mechanical damage.

• Also leads to release of iron which leads to anemia

Acute blood loss

causes normocytic, normochromic anemia (red cells are normal in size and color, just fewer in number)

Chronic blood loss

This leads to iron deficiency anemia, where red blood cells become microcytic (small) and hypochromic (pale) because hemoglobin synthesis is impaired.

GI tract

Most common reason for iron deficiency anemia in adult men and postmenopausal women is blood loss from the _____

Impaired

• Gastrectomy

• Severe small bowel disease

• General malabsorption syndromes

• Inflammation of the gut

Can all lead to _____ absorption of iron

Anaphylaxis

Adverse effects of IV iron include headache, lightheadedness, fever, arthralgia, n/v, flushing, urticaria, and rarely ______

Dexferrum

If using high molecular weight iron like _____ , always give a test dose to check for hypersensitivity

Infed

If using a low molecular weight iron like ___, it is safer and less likely to cause hypersensitivity.

Hemochromatosis

Chronic iron toxicity that leads to organ damage is called

• Has 2 causes

  • Genetic mutation (most often HFE gene) causes the body to absorb too much iron from the diet, even when not needed.

  • Secondary (from repeated blood transfusions) especially in patients with thallasemia or sickle cell disease. Can occur in liver disease, excessive iron intake, or ineffective erythropoiesis

Polymerize

Under stress conditions like low oxygen, dehydration, acidosis, or cold, HbS _____ (molecules stick together in long chain) which causes RBCs to sickle

Sickled

cells are less flexible, clump in small vessels, and cause blockages, leading to ischemia, pain crises, and organ damage.

Hemoglobin

B12-deficient RBCs are normochromic because ______ synthesis is unaffected.

Pernicious

type of megaloblastic anemia that results from an autoimmune attack on the parietal cells of the stomach that produce intrinsic factor (IF) or IF itself.

Intrinsic Factor

required to absorb B12 in the distal ileum, without it vitamin B12 is deficient leading to impaired DNA synthesis of RBCs

• you get large, immature red blood cells that are macrocytic & normochromic

Megaloblastic anemia

To diagnose this we use two substances found in blood or urine that increase

• Homocysteine: elevated in both b12 & folate deficiency

• Methylmalonic acid (MMA): elevated only in b12 (used to differentiate)

  • methylmalonyl coA is precursor (not tested in labs)

Protein C

is a vitamin K–dependent anticoagulant protein made by the liver

• When activated, it inhibits clotting by inactivating factors Va and VIIIa, which are essential for making thrombin.

Protein S

Vitamin K–dependent and acts as a cofactor that enhances Protein C’s activity. Helps Activated protein C (APC) more effectively inactivate Va and VIIIa.

DIC

• Massive tissue injury

• Advanced cancers

• Obstetric emergencies such as abruptio placentae or retained products of conception

• Bacterial sepsis

are ALL associated with

Platelets

The substances are released by ____ and initiate the clotting cascade

• adenosine diphosphate (ADP), thromboxane A2 (TXA2), and serotonin (5­HT)

Adenosine diphosphate (ADP)

Activates and recruits additional platelets & promotes platelet aggregation

Thromboxane A2 (TXA2)

Promotes vasoconstriction and platelet aggregation.

• Aspirin blocks this by inhibiting COX

Serotonin (5HT)

causes vasoconstriction to reduce blood loss

Von Willebrand Factor (VWF)

Factor released by the vessel wall to attract platelets to the injury site

• It binds to exposed collagen and acts as a bridge between the vessel wall and platelets

Heparin

main action of this medication is to enhance the activity of Antithrombin III (ATIII)

• increases it’s activity 1000­ fold

• prevents NEW clots, does not affect existing ones

Antithrombin III

natural anticoagulant that inhibits multiple clotting factors, especially:

• Thrombin (Factor IIa)

• Factor Xa

• Factor IXa

Low Molecular Weight Heparin (LMWH)

primarily inhibits Factor Xa with minimal effects on antithrombin

• has shorter chain

• has a longer half life

• can be given at home subQ

• No labs, just monitor bleeding

• protamine does not reverse well, mostly wait it out

• example: Enoxaparin (Lovenox)

Unfractionated Heparin (UFH)

Primarily inhibits Thrombin (IIa) by linking it to antithrombin with long chain. Also affects Factor Xa, also IXa

• has shorter half life

• given in the hospital

• aPTT must be monitored

• protamine reverses well

Protamine

this drug reverses heparin and must be given slowly to prevent (hypotension) and carefully because high doses can cause bleeding

Vitamin K

Without this the body can't activate clotting factors II, VII, IX, and X

Warfarin (Coumadin)

this drug inhibits vitamin K epoxide reductase, the enzyme responsible for recycling vitamin K.

• You measure Protime (PT) in these patients and compare it to International ratio (INR)

Aspirin

drug that irreversibly inhibits the enzyme cyclooxygenase (COX)

• inhibit platelet for the full lifespan of the platelet 7-10 days

• unlike this drug, NSAIDS inhibit COX reversibly

Cyclooxygenase (COX)

converts arachidonic acid into prostaglandins and thromboxane A₂

• prostaglandins: causes pain

• thromboxane A2: causes blood clotting