Quiz 1 Exam 2 Flashcards
Define drug resistance.
Drug resistance is the development of a reduced drug response.
What are the 5 causes for drug resistance?
- Increased efflux (PK)
- Decreased uptake (PK)
- Drug inactivation (PK)
- Mutations in the drug target (PD)
- Reversal of drug action (PD)
__________ is an example of intrinsic drug resistance.
MRSA (Methicillin-resistant Staphylococcus aureus)
Intrinsic in terms of drug resistance means it will have no initial response to the drug.
What is intrinsic drug resistance?
This is the innate ability of a species to resist the action of a drug as a consequence of the structural or functional characteristics of that species
What is acquired drug resistance?
Occurs when the species acquires the ability to resist the actions of a particular drug
What is an example of a ligand-gated ion channel?
The nicotinic receptor. This receptor is bound by acetylcholine and allows for the passage of Na+ into the cell.
How many subunits are on the nicotinic receptor?
5 subunits; 2 alpha, 1 beta, 1 gamma, and 1 delta unit.
Where does acetylcholine bind on the nicotinic receptor?
Acetylcholine molecules bind to the 2 alpha subunits on the nicotinic receptor.
In the human genome, ______- _______ genes code for transport proteins.
500-1200
What is a basolateral membrane?
The basolateral membrane has contact with the blood vessel and the epithelial cell.
What is an apical membrane?
The apical membrane is the surface of the cell that faces the lumen.
Are transporter/carrier proteins faster or slower than ion channels?
Transporter/carrier proteins are much slower than ion channels as they are more complex.
What are the two types of transporter-carrier proteins?
Active (require energy and go against conc. gradient) and passive (no energy and go with conc. gradient)
What is the main efflux transporter?
ABCs (ATP-Binding Cassette Proteins)
What are the main uptake/influx transporters?
SLCs (Solute Carrier Family)
Efflux transporters like the ABCs contribute to __________________.
Multi-drug resistance
Efflux transporters like ABCs typically contain __ nucleotide bindings domains and at least 2 _______________ domains.
2
Transmembrane
What do the transmembrane domains on efflux transporters like the ABCs define?
The transmembrane domains on ABCs define substrate specificity, which is typically very broad.
What is the evolutionary reason for the development of efflux transporters?
They prevent toxins from entering vital organs at BBB, BTB, placenta, and ovaries.
What are the 3 genes families of efflux transporters?
- MDR1 (ABCB1, p-glycoproteins)
- MRPs (Multi-drug Resistance Proteins)
- MXR (BCRP-breast cancer resistance protein)
Increased activity of multi-drug resistance pumps like ABCB1, ABCC1, and ABCG2 _________ resistance to anti-cancer drugs.
Increases
(B1, C1, and G2)
How do ABC efflux transporters transport things out of the cell?
They bind ATP and become a barrel shape to form a pore with a 5 nanometer diameter.
What are the general characteristics of substances effluxed by MDR1/ ABCB1/ p-glycoprotein?
Hydrophobic neutral and cationic compounds. Very broad in general though.
What are the 4 compounds discussed that inhibit MDR1?
Tamoxifen
Progesterone
Cyclosporin A
Quinidine
What are the 3 discussed SLC uptake transporters?
- Organic cation transporters (OCTs)
- Organic anion transporters (OATs)
- Nucleoside transporters
What is the function and type of organic cation transporter located at the basolateral membrane of renal epithelial cells?
OCT1:
Uptake organic cations from the blood which is the 1st step of renal excretion. Found also in tubular epithelium.
What is the function and type of organic cation transporter located in hepatocytes?
OCT1:
Uptake cations into liver cell which is the 1st step before drug metabolism.
What is the function and type of organic cation transporter located in the brain?
OCT2:
Transport of monoamine NTs like dopamine. They reuptake NTs into the presynaptic site.
OCT3:
Transport serotonin
What is the function of the organic anion transporters in the liver?
They mediate the uptake of bile acids.
What is the function of the organic anion transporters in the renal epithelial cells?
They uptake organic anions which is the first step in renal secretion.
What is the function of the nucleoside transporters in the SLC family?
They uptake purine and pyrimidine nucleosides. There are some that are equilibrative (no energy) and concentrative (need energy).
Which family member of the SLCs is responsible for the uptake of nucleoside analog drugs?
Nucleoside transporters
This nucleoside transporter, _______, is important in determining the response to nucleoside analongs with ____________ properties.
ENT2
Anti-retroviral
Low expression/ low activity polymorphisms in ___________ (reduced folate carrier) _______ patients to methotrexate.
SLC19A1
Densensitize
MDR-1/ P-glycoproteins in the brain is associated with __________ and ___________ to nortriptyline.
Drug-resistant epilepsy
Postural hypotension
The goal of asymmetrical distribution of transporters on the BBB is to ____________________.
Shuttle things out rather than shuttle them in.
What are 3 molecules that use transport proteins to pass the BBB?
Glucose, AA, and nucleosides
What are 2 molecules that use receptor-mediated endocytosis to pass the BBB?
Insulin and transferrin
What are 2 things that use adsorptive endocytosis to pass the BBB?
Albumin and other plasma proteins
In terms of drug inactivation, what does a beta-lactamase do?
Beta-lactamase (penicillinase) inactivates antibiotics via hydrolysis.
In terms of drug inactivation, what does N-acetyltransferase do?
NATs transfer chemical groups. An example of this is isoniazid.
What are the 3 enzymatic ways in which drug inactivation in drug resistance is mediated?
Hydrolysis, group transfer, and redox mechanisms
In terms of drug inactivation, what does Thioredoxin do?
Thioredoxin inactivates peroxides by serving as an electron donor to peroxidases.
What are redox-cycling antibiotics?
Antibiotics that kill the pathogen through redox cycling by generating free radicals to kill the bacteria.
How do some pathogens combat redox-cycling antibiotics
Pathogens have increased levels of glutathione transferase which detoxifies peroxidases and underlie antibiotic resistance.
CYP3A4 oxidizes common chemotherapeutic drugs to inactivate them like _________ and ___________.
Ifosfamide and cyclophosphamide
CYP3A4 oxidizes common chemotherapeutic drugs to activate them like _________ and ___________.
Etoposide and doxorubicin (prodrugs)
In human DNA, genetic information is stable. There are DNA repair mechanisms that reverse mutations. In cancer cells, DNA is less stable due to defects in DNA repair called _______________.
Mutator phenotype
Drug target __________ affect drug action.
Mutations
Gleevec (imatinib) is a small molecule kinase inhibitor that target BCR-ABL in chronic myeloid leukemia. However a common mutation in ___________ makes BCR-ABL resistant to this drug and others.
T315I
Some oncogenes suppress _____________
Apoptosis (programmed cell death)
The abundance of ________ family proteins resist apoptosis.
BCL-2 (pro-surivival)
The _______ domains of the pro-apoptotic BCL-2 family members can ____________ anti-apoptotic BCL-2 family proteins.
BH3
neutralize
An example of a DNA repair mechanism is _____________.
Nucleotide excision repair
What is nucleotide excision repair?
A mutation is sensed in DNA and a repair molecule is sent to fix it. Eventually several molecules, cut the DNA from both side and resynthesize the correct DNA.
Nucleotide excision repair contribute highly to ________ life expectancy.
increased
In cancer cells with intact DNA repair, what drugs should be avoided?
Avoid drugs that cause injury to the DNA like conventional anti-cancer drugs include alkylating agents as the cell can still repair the DNA damage.
_____________ protects cells from alkylating agents via DNA repair.
MGMT
Drug resistance could be overcome by depletion of ___________.
MGMT
Define transduction in terms of genetic pathogen drug resistance.
Transduction is when a bacteriophage can transfer a resistant gene from one bacterium to another, even across different species.
Define transformation in terms of genetic pathogen drug resistance.
Transformation is when fragments of free DNA like plasmids, in the environments can be taken up.
Define conjugation in terms of genetic pathogen drug resistance.
Conjugation is the transfer of genetic material between 2 bacteria.
What is HAART in HIV therapy?
2-3 Nucleoside analogs
1-2 Protease inhibitors or 1 RT inhibitor
What are the 2 main functions of SSRIs?
- Desensitize presynaptic receptors
- Block feedback-inhibition of serotonin release
Define desensitization.
Desensitization is the induction of a temporary state of tolerance. The initial response to the agonist is good but it gradually diminishes with time. Desensitization reversies with removal of the agonist.
What are the 2 mechanism of desensitization?
- Change in receptor (agonist-induced changes diminishes ability of receptor to interact with G proteins)
- Loss of receptors (internalization of receptors into endocytic vesicles)
Desensitization is a ____________ response.
Rapid
Define tolerance.
Tolerance is the repeated administration that progressively reduces the effect of a drug.
T or F: Tolerance cannot be overcome and is not reversible.
False.
Tolerance can be overcome with a dose increase and is reversible after discontinuation of a drug.
What are the 2 mechanism of tolerance?
- Accelerated metabolism and disposition (PK tolerance)
- Loss of efficacy through changes in the drug target (PD tolerance)
Tolerance is __________ while desensitization is __________.
Chronic
Acute
Pharmacokinetic examples of tolerance include…
Reduced absorption
Altered distribution
Increased metabolism
Increased excretion
Pharmacodynamic examples of tolerance include…
Reduction in receptor number
Reduced affinity
Altered signal transduction
What are the differences between tolerance and resistance?
Tolerance and resistance both represent a lack of responsiveness but resistance cannot be overcome by a dose increase and is not reversible through discontinuation of a drug.
Define cross-tolerance.
Cross-tolerance occurs when someone is tolerant to the effects of a certain drug and also develops a tolerance for another drug (typically seem with drugs that have similar functions and effects).
Define dependence.
Dependence means that a continued presence of a drug is required for normal functioning.
What 2 things occurs with dependence?
Tolerance and withdrawal
What is physical dependence?
This is an abstinence syndrome due to an altered physiological state.
What is psychological dependence?
This means there is an emotional drive or craving for the drug which may lead to compulsive drug use.
Define withdrawal.
Withdrawal is a physiological response to the termination of drug therapy (abstinence syndrome)
What is the difference between withdrawal and tolerance?
Withdrawal includes cravings while tolerance does not include cravings.
Neonates and newborns consist of up to ______% body water which is mostly extracellular fluid.
70
Neonates and newborns are more likely to become ___________ due to the large amount of extracellular body water.
Dehydrated
The adult extracellular fluid is around _______%.
20
Water-soluble drugs like acetaminophen are more __________ in a child than in an adult.
Dilute
As growth occurs in different life stages, total body water ___________ but blood volume ___________.
Increases
Decreases
Surface area to volume ratio ___________ with increased weight.
Decreases
Does glomerular filtration rate decrease or increase with age?
It increases when referring to neonates to adults
The mL/kg blood volume is determined by weight and _________ as a child grows.
decreases
What is the typically blood volume in a neonate?
85-90mL/kg
What do both children and elderly struggle with when taking medications?
Swallowing solids is difficult
T or F: Most requirements are very similar in the pediatric and geriatric population.
True
What are 3 functions that are reduced in the geriatric population?
- Reduced albumin synthesis (reduced plasma-protein drug binding)
- Reduced kidney and liver function (slower drug elimination)
- Reduced cardiovascular function
What can result in the geriatric population due to their decreased cardiovascular function?
They will have an increased response to beta-blockers and anti-hypertensives.
T or F: Hepatic enzymes are mature in the pediatric population.
False. Hepatic enzymes are not mature in this population.
What is the kidney filtration rate in the pediatric population?
2mL/kg/hr compared to adults which is 0.5-1mL/kg/hr
Do children need more oxygen?
Yes. Children need 6mL/100g/min as their CNS is still developing.
T or F: The BBB is less permeable in the pediatric population?
False. The BBB is more permeable
Adult hearts can compensate with increasing heart rate and volume which children can only compensate with _________.
Increased heart rate leading to tachycardia.
What is the typical pulse and respirations in premature and newborn infants? Is this slower or faster than adults?
Premature: 140+, 30-40 respirations
Newborn: 120-160, 30-50 respirations
Both are these are much faster than adults
What is the rule of 6’s?
This is a rule for mixing drug infusions. 6 steps and one multiplication by 6.
During drug elimination involving both metabolism in the liver and excretion within the kidneys and intestines, can the drug act on the tissues?
No
What are the 4 main functions of the liver?
- Synthesis- bile, clotting factors, albumin
- Storage- glucose, vitamins, minerals
- Phagocytosis- blood cells
- Intracellular enzyme proteins
What two drug can inhibit CPY450s responsible for the metabolism of metoprolol and warfarin?
Paroxetine and fluoxetine
What is meant by a class of drugs?
Drugs in the same class have the same MOA but different PKs and safety.
________________, like ritonavir and indinavir inhibit what enzyme and can lead to increased levels of drugs like nifedipine.
HIV-1 Protease inhibitors
CYP3A
How does the administration of a lipophilic drug in an obese patient differ than the administration of a lipophilic drug in a patient with a normal BMI?
It is difficult to reach steady state in obese patients- Adipose tissue takes up lipophilic drugs, making it difficult to reach steady state. Once adipose tissue is saturated, you must be careful to not overdose the patient. Giving mg/kg dose is more
accurate than a ‘one size fits all’ dose.
How does the body water composition differ in neonates/newborns in comparison to
adults?
Most of the body water in in neonates/newborns is extracellular
What is drug disposition?
This is how we get rid of the drugs via metabolism and excretion.
Does hepatic and/or renal impairment affect drug disposition?
Renal and/or hepatic impairment can impact drug disposition and require an adjustment in dosing.
What are the two ways in which hepatic dysfunction manifests?
Hepatocellular disease and Cholestatic disease
What is hepatocellular disease?
This includes liver disease, inflammation, and necrosis. Overall liver dysfunction.
What is cholestatic disease?
This is bile flow inhibition due to gallstones, malignant obstruction, primary biliary cirrhosis, and certain drugs.
T or F: Liver disease does not cause drug accumulation.
False. Liver/ hepatic disease causes drug accumulation as well as drug activation.
What are the 5 measures of the Child-Pugh liver dysfunction classifications?
- Total bilirubin
- Serum albumin
- PT INR (Prothrombin International Normalized Ratio)
- Ascites
- Hepatic Encephalopathy
Do N-acetyltransfereases (NAT1 and NAT2) have small or large substrate specificity?
Large substrate specificity
N-Acetyltransferases have an impact on the predisposition to drug ___________ and ___________.
Efficacy and toxicity
What is the main hazard surrounding renal impairment?
Compromised drug elimination
What is the advanced stage hazard of renal impairment?
- Kidney has altered metabolic capacity
- Production of nephrotoxic compounds
What is the main measurement of renal impairment?
Estimated creatinine clearance (mL/min)
What is the creatinine clearance for normal renal function?
> 80mL/min
Why is creatinine clearance used as the measurement for renal impairment?
Creatinine is ONLY cleared by the kidneys.
What is the equation for creatinine clearance?
Androgens ______________ drug metabolism while estrogens ______________ drug metabolism.
Increase
Decrease
Cardiac output in women is _______________% less than in men.
10-20%
The ______________ cycle affect drug responses including fluctuations in p-glycoproteins.
Menstural
___________ is absorbed more slowly in women than in men.
Aspirin
The ___________ of drug _________ and ____________ for heart function are slower in women.
Renal clearance
Quinine and Quinidine
__________ relieves symptoms of IBS in women but NOT in men.
Alosetron
____________ is more effective in men.
Ibuprofen
The painkiller/opioid ___________ is more effective in women.
Pentazocine
What is chronopharmacology?
This is the how the metabolism fluctuates with circadian rhythm.
Steroid hormones fluctuate __________.
Diurnally
During what time period does cholesterol levels peak?
PM
Gastric acid peaks during the _________ time period. Therefore, _____________ blockers should be given at night.
PM
Histamine (H2)
______________ are more frequent in the AM. Therefore, products like ____________ and ___________ are given at night and designed to be absorbed in the early AM.
Angina and Heart Attacks
Covera-HS and Verelan PM (Verapamil products)
What drug was designed to dampen the morning insulin spike, should be taken within 2 hours of waking, and has been unsuccessful?
Bromocriptine
What are the two factors that affects the antibiotic drug response?
- Genetic predisposition in the host
- Pathogen genomics including virulence and anti-infective resistance
What is virluence?
Virulence is the capability of the pathogen to cause disease in the host overtime.
Typically as pathogen develop, their infectivity and ability to procreate ___________ while virulence __________. This is how COVID has developed.
Increases
Decreases
T or F: Polymorphisms are disease causing.
False. Polymorphisms themselves are not disease causing.
Polymorphisms in what gene for pathogen detection effect the response to meningococcal bacteremia?
Mannose binding lectin on codons 52, 54, and 57.
Polymorphisms in what gene for pathogen detection effect the response to gram-negative septic shock?
Toll-like receptor 4 on D299G
Polymorphisms in the TNF-a gene effects how what diseases are dealt with?
Meningococcal bacteremia
Cerebral malaria
Septic shock
Virulence for pathogens in encoded on genes for what 4 things?
- Chromosome
- Plasmid
- Bacteriophage
- Transposons
What is an example of anti-infective resistance regarding mtuberculosis?
M. Tuberculosis treated with isoniazid differentially expresses 14 genes.
How C. Albicans developed anti-infective resistance?
C. Albicans develops resistance to azole antifungal agents via overexpression of efflux pumps (p-glycoprotein) and overexpression of ERG11 that encodes lanosterol demethylase.
Host-pathogen interactions is a complex situation with many variables. What are some of those variables?
- Host immune response
- Pathogen response to host contact
- Drug targets
- Drug metabolism and transport
What is the gastric cancer cascade?
Normal mucosa to gastritis to adenocarcinoma due to Helicobacter Pylori bacteria.
What does Helicobacter Pylori Bacteria do?
This bacteria induces gastritis and increases the risk of stomach neoplasia.
Hosts with polymorphisms in the promoter region of type 1 cytokines that are associated with higher expression have an increased risk of developing gastric cancer. These underlying polymorphisms include changes to…
IL-1Beta
IL-1Beta Receptor
TNF-alpha
IL-10
How do high expression polymorphisms in IL-1Beta and IL-1Beta receptor increase the risk for gastric cancer?
Increased activity of these immune cells do not damage H.pylori but instead damage to stomach mucosa.
What is the treatment for stomach ulcers due to H. Pylori?
Clarithromycin, Metronidazole, and Amoxicillin. However, H. Pylori can become resistance to these with a A2144G mutation in the 23s rRNA gene.
Which statement about toxicity is correct?
A. Whether a compound is toxic depends on its structure
B. Whether a compound is toxic depends on it concentration
C. How a compound is toxic depends on its structure
D. How a compound is toxic depends on it concentration
E. A and D
F. B and C
F. Whether a compound is toxic depends on its concentration and how a compound is toxic depends on its structure.
What is the relationship between side effects and adverse effects?
A. All side effects are adverse effects
B. Side effects are characterized by having an untoward (unexpected) impact
C. All adverse effects are off-target effects
D. All adverse effects are side effects
E. None is correct
?
Which of the following medications is more effective in men?
A. Pentazocine
B. Ibuprofen
C. Acetaminophen
D. Aspirin
B. Ibuprofen
Pentazocine is more effective in women and aspirin is absorbed more slowly in women.
What is the main mantra of drug treatment?
MAXIMIZE EFFICACY AND MINIMIZE TOXICITY
Previously discussed in the last exam, it is know that translocation of genes 22 and 9 causes the BCR-ABL mutation in the tyrosine kinase receptor (philadelphia chromosome) which induces chronic myeloid leukemia (CML). What are the 3 pathways that this mutation activates?
- P13K/AKT pathway (major anti-apoptotic pathway)
- Jak/STAT (immune cell proliferation over activation)
- RAS (proliferation via cross-talk)
Based on the following image, what are the consequences of inhibiting RAS to target chronic myeloid leukemia?
If you inhibit RAS, you inhibit all other downstream pathways. The efficacy of the molecule would be very good but there would be lots of toxicity as every cell need the RAS pathway in order to proliferation.
Based on the following image, what are the consequences of inhibiting the BCR-ABL tyrosine kinase with Gleevec therefore inhibiting the Jak/STAT pathway?
When you inhibit Jak/STAT activation with Gleevec, the toxicity of the drug is low while the efficacy is high. Inhibiting Jak/STAT also inhibit P13K/AKT activation inhibiting both immune cell proliferation and the anti-apoptotic pathway.
Based on the following image, what are the consequences of inhibiting the P13K/AKT as a target in chronic myeloid leukemia?
A drug that inhibits the P13K/ AKT pathway will have a low toxicity and low efficacy because the two other pathways are still active.
Drug toxicity, poisoning, is only a matter of ______.
Dose
Can water be toxic?
Yes. If water is over-consumed than it can cause isohyotonic hypertension which is the disruption of salt homeostasis resulting in confusion, coma, seizures, and death.
Acute ___________ toxicity can cause confusion and seizures.
Oxygen
In certain disease, _______ oxygen is needed to main adequate blood oxygen and a hyperbaric oxygen chamber can be used to increase _________ to force more oxygen into the lungs.
100%
Pressure
Chronic oxygen toxicity can cause lung __________ and ____________. This is because oxygen can break into biradicals to create reactive oxygen species.
Damage and cancer
What are side effects?
Side effects are distinct for the intended drug action but have the same or different molecule mechanism.
Are side effects that have the same molecular mechanism easy or difficult to treat?
Difficult to treat
Are side effects that have a different molecular mechanisms easy or difficult to treat?
Easier to treat
T or F: Side effects are only negative.
False. Side effects can be beneficial, neutral, or harmful
T or F: Every side effect is an adverse effect.
False. Not every side effect is an adverse effect.
T or F: Side effects include all effects produced by the drug, even the intended effect.
False. Side effects are all effects except the intended effect of the drug.
What is finasteride?
Finasteride is a type II 5a-reductase inhibitor (5a-reductase is the enzyme that converts non-potent testosterone to potent dihydrotestosterone)
In terms of finasteride treatment of propecia, what is the intended effect?
Reduce male-type baldness
Finasteride (proscar) is also used with the intended effect of treating ____________________________.
Benign Prostate Hyperplasia (BPH)
What are 2 discussed side effects that target the actual drug target in the use of finasteride to treat male-type baldness?
- Protection of prostate from dihydrotestosterone even in low doses
- Diminished libido
What are the 2 discussed side effects that target the actual drug target in the use of finasteride to treat benign prostate hyperplasia (BPH)?
- Reduce male-pattern baldness which is too late for a lot of patients
- Diminished libido
What is the side effect discussed that has an unknown mechanism of action in the use of finasteride for both the treatment of male-type baldness and benign prostate hyperplasia?
Anxiety and Depression
What is the adverse reaction discussed that is unrelated to any drug target in the use of finasteride for both the treatment of male-type baldness and benign prostate hyperplasia?
Anaphylactic reaction
What is the WHO definition of an adverse effect?
Any noxious, unintended and undesired effect of a drug, which occurs at doses used in humans for prophylaxis, diagnosis, and therapy.
What is the definition of idiosyncrasy?
Quantitatively or qualitatively different from the expected response.
What is the difference between an idiosyncrasy and an allergic response?
Idiosyncrasy does not involve an antibody-antigen immune response while an allergic response does. Allergies are treated with immunosuppressants while idiosyncrasy are treated with antagonists.
What is the difference between an idiosyncrasy and an overdose?
Idiosyncrasy occurs at the therapeutic dose while an overdose is above the therapeutic dose.
T or F: Idiosyncrasy can not be reproduced and are not genetically determiend.
False. Idiosyncrasy are specific and reproducible. In part they can also be genetically determined.
In some patient who were given succinylcholine for anesthesia for electroshock therapy, their paralysis lasted much longer than normal. It was found these patients had low substrate affinity polymorphism at the __________________ enzyme leading to the reduced ability to metabolize the drug.
Plasma Cholinesterase
What is the definition of an allergy?
A qualitatively altered drug reaction.
T or F: Non-anaphylactic allergic reactions occur after one dose of a drug.
False. Non-anaphylactic reactions occurs after repeated dosing of a drug while anaphylaxis occurs on the first exposure to the drug.
Do allergic reactions target the drug target or is it an off-target effect?
Allergic reactions are off target effects separate from the method of action of the drug.
What are the 4 major types of hypersensitivity associated with drug reactions?
Type 1: IgE-mediated acute allergic reaction
Type 2: Antibody responses to drug-modified host protein
Type 3: Serum sickness
Type 4: Cell-mediated allergy
Explain type 1 hypersensitivity to drugs.
Type 1: IgE-mediated acute allergic reactions (stings, pollens, and drugs given by infusion) leading to anaphylaxis, urticaria (hives), and angioedema. Type 1 is an emergency situation.
Explain type 2 hypersensitivity to drug.
Type 2: Antibody responses to drug-modified host protein. It involves IgG or IgM, complement-dependent lysis or antibody-dependent cellular cytotoxicity.
Explain type 3 hypersensitivity to drugs.
Type 3: Serum sickness immune complexes containing IgG resulting in multi-system complement-dependent vasculitis.
What is vasculitis?
Inflammation of blood vessels and can be life-threatening
Explain type 4 hypersensitivity to drugs.
Type 4: Cell-mediated allergy involving T-cells including allergic contact dermatitis from topically applied drugs (penicillin cream) or site of intradermally injected antigen.
What are the 6 different treatment for a drug allergy?
Isoproterenol or Theophylline
Epinephrine
Antihistamines
Prednisone
Glucocorticoids
Leukotrine inhibitors
What is the MOA for Isoproterenol and Theophylline used in drug allergy treatment?
Reduces the mediator release from mast cells and basophils and produces bronchodilation. However, these two medications are not the best choices.
What is the MOA for epinephrine used in drug allergy treatment?
Opposes histamine
Relaxes bronchial smooth muscle
Contracts vascular muscle to relieve bronchospasm and hypotension
What is the MOA of antihistamines used in drug allergy treatment?
They relieve bronchoconstriction and increase capillary permeability.
What is the MOA of prednisone used in drug allergy treatment?
Immunosuppressive
Blocks proliferation of IgE-producing cells
Inhibits IL-4 production by T helpers cells in the IgE response
What is the MOA of glucocorticoids used in drug allergy treatment?
Toxic to lymphocytes
Reduced tissue injury and edema
Facilitate catecholamine actions in cells resistant to EPI or isoproternol
How are leukotriene inhibitors used in the drug allergy treatment?
They are useful in acute allergic and inflammatory disorders as it targets the leukotrienes in the lungs.
What is the main priority if a drug allergy occurs?
Discontinue the offending drug. If no drugs exist for a switch, desensitization may be possible.
What is teratogenesis?
Induction of developmental defect that are generally non-inheritable in the fetus of the exposed mother.
Thalidomide was used as a tranquilizer, painkiller, and treatment for insomnia. It also was an antiemetic and was used for morning sickness in pregnant women. However, this resulted in birth defects called ____________.
Phocomelia (lack of limbs)
How did thalidomide induce phocomelia?
This drug was found to be a prodrug where its metabolite produced anti-angiogenesis effects therefore it prevented new blood vessel growth in the fetus which resulted in the loss of limbs.
T or F: Thalidomide is absolutely banned everywhere and is used for no diseases.
False. Thalidomide is used to treat cancers by inducing anti-angiogenesis in tumors.
What are the three new pregnancy categories for all drugs?
Pregnancy section- includes pregnancy exposure registry, risk summary, clinical considerations and data.
Lactation section
Females and males of reproductive potential
What is the connectivity rule that often applies to teratogenesis?
Teratogenesis leads to mutagenesis which leads to carcinogenesis.
What are the susceptible populations to drug-drug interactions
Those using polypharmacy:
- elderly
- chronically ill
Explain the drug-drug interaction between digoxin and quinidine.
Digoxin and Quinidine are competitors for P-glycoproteins. Digoxin (atrial fibrillation and CHF) levels therefore increase if quinidine is occupying the efflux transporter resulting in higher concentrations of digoxin and leading to toxicity.
T or F: Drug-drug interactions at the drug target are common while drug-drug interactions affecting transport and metabolism are rare.
False. Drug-drug interactions the drug target are rare. Drug transport and metabolism are the main interactions for drug-drug interactions. This is because there are a limited amount of genes encoding for transport and metabolism of drugs that have to deal with millions fo substrates.
Explain the drug-drug interaction between digoxin and rifampin.
Rifampin induces the expression of ABCB1 therefore decreasing the blood concentrations of digoxin.
Explain the clinical trial that found evidence that grapefuit juice causes drug-drug interactions.
Questions asked if felodipine (HBP) interacts with alcohol and alcohol was masked with grapefruit juice. Those who drank grapefruit juice had increased blood levels of felodipine causing higher drug effects and adverse effects with felodipine.
____________ glass of grapefruit juice within 24 hours can suffice to elicit the maximum food-drug interaction.
One
_________________ is the compound within grapefruit pulp that interferes with ______________.
Furanocoumarins
CYP3A4
What are medication errors?
Any mistake at any stage of the medication use process that is preventable.
What is the difference between adverse reactions and medication errors?
Medication errors are preventable while adverse reactions can be preventable, non-preventable, or potential.
Why is drug research and knowledge is women limited?
In the 1970s, the FDA excluded women of childbearing age into phase 1 and 2 trials therefore excluding them from all research. By 2016, they realized the PK and PD were different in men and women and needed to include women in trials and they needed to know drug therapy effects in pregnancy.
What are the 10 normal changes that are anticipated during pregnancy?
- Cardiac output (stroke volume x HR) increases through week 30 and then fluctuates with postural changes
- Renal function increases proportional to cardiac output
- Systemic vascular resistance decreases (decreased BP)
- Hormonal changes- increases in progesterone, estrogen, steroids, and HCG
- Body fat increases- weight increases due to fluid and body fat
- Total blood volume increases proportional to cardiac output
- Constipation-due to progesterone increases, growing fetus, and decreased GIT motility
- Nausea and vomiting- due to increased HCG or other factors
- Increased insulin resistance
- GIT issues- heartburn as progesterone relaxes the LES
How is gestational age calculated?
From 1st day of last menstrual period
________ in ___________ women have a baby with a birth defect which is around ________%.
1 in 33
3-5%
What is the largest cause of teratogens?
Unknown (65-73%)
What is the smallest cause of teratogens?
Environmental (10%) like maternal medications (1-3%). Maternal medications that are known to act as teratogens include Angiotensin converting enzyme inhibitors, carbamazepine, isotretinoin, lithium, methotrexate, phenytoin, valproic acid, and warfarin.
When do the major congenital abnormalities occur during fetal development?
Most occur during the embryonic period (3-8 weeks)/ 1st trimester.
What is the one common birth defect that can occur beyond the typical embryonic developmental period (into the fetus period)?
CNS defects
Why was the old pregnancy categories regulated by the FDA difficult to use?
They used categories A, B, C, D, and X to determine risk. A and X were easy to understand while B, C, and D are open to interpretation.
What did the old pregnancy category A state?
A stated that there are controlled studies on pregnant women and it shows no risk in the first trimester.
What did the old pregnancy category X state?
X stated that there are poven fetal risks that outweigh any possible benefit.
________ of medications do not sufficient evidence available for healthcare professionals to determine if the risk of teratogenicity outweighed the benefit of therapy.
91.2%
When recommending drugs for pregnant and lactating women, always check ________ sources and look at the ________.
2
Date
What is a great resource of pregnancy and lactation drug facts?
Briggs
What is included in the new FDA labeling for pregnancy?
- Background risk
- Risk summary
- Clinical considerations
- Data
Pregnancy drug exposure registry also included.
What is included in the new FDA labeling for lactation?
- Risk summary- extent of meds into breast milk, effect of drug on milk production, and possible effects on infant
- Clinical considerations- ways to minimize exposure to infants and monitor infant and dosing adjustments.
- Data
What are the 3 things included in the new FDA labeling section for males and females of reproductive health?
- Pregnancy testing
- Contraception
- Infertility
What are the 5 functions of the placenta?
- Acts as a barrier- increased maternal circulation increases crossing of drugs
- Facilitate maternal to fetal gas transfer
- Produces hormones- HCG
- Provide structure for nutrient exchange
- Remove waste products from fetal circulation
Does a drug have to cross the placenta to harm the fetus?
No. For example the drug could cause hypoxia by inhibiting oxygen binding to hemoglobin therefore decreasing oxygen to the fetus.
What are the 6 factors that alter placental crossing?
- Fetal to maternal concentration gradient
- Molecular weight- decreased weight leads to increased transport
- Protein binding-decreased binding leads to increased transport
- lipid solubility- increased lipophilicity increases transfer
- Half-life- long half-life drugs are more likely to cross
- Maternal blood flow- increase BF leads to increased transfer
What is a concern if a mother is taking a drug which results in subtherapeutic levels of the drug?
Inadequate levels are not controlling the disease state therefore there is risk to mother and fetus
Overall ________ activity increases during pregnancy.
CYP
What might occur to a narrow therapeutic index drug metabolized by CYP enzymes during pregnancy?
They body is clearing the drug faster since CYP is increased therefore it could yield a subtherapeutic dose.
What are the key things that need to be evaluated when counseling pregnant women on drugs?
- Is that drug necessary?
- What is the route of administration?
- Stage of pregnancy
- Review available information
- What is risk to mother and fetus if you do not treat the condition?
- Consult and obstetrician
Is the amount of drug exposure during breastfeeding typically more/less/the same as during pregnancy?
Typically, we think of drug exposure during lactation to be less than in pregnancy as infants have more developed metabolism. However, it does depend on the drug and the pKa of the drug.
What is the American Academy of Pediatrics recommendation for breastfeeding?
They recommend exclusive breastfeeding for the first 6 months of life. It benefits both mom and infant.
What are 6 factors that influence medication crossing into breastmilk?
- Maternal plasma concentration of drug (high concentrations of drug will cross more readily)
- Lipid solubility of drug (lipid soluble to cross)
- Molecular weight (low to cross)
- Extent of protein binding (low binding to cross)
- Half-life (long to cross)
What are the 3 ways that drug transfer to breast milk is calculated?
- Milk to plasma ratio (conc. of drug in milk vs in plasma of mother. Limited use as calculating plasma in mother is difficult)
- Relative infant dose calculation (% of infant dose in mg/kg/day by milk divided by maternal dose in mg/kg/day, most commonly used)
- Fetal to maternal concentration gradient (avoid topical around nipple area)
When are most adverse effects in infants seen from medication transfer into breast milk?
First 2 months of life
What is a reference that can be used to look at drug data relating to drug transfer into breast milk?
Hale’s Medications and Mother’s Milk
T or F: Medication deemed acceptable for a breastfeeding patient might not be acceptable for a pregnant patient.
True
The pediatric population makes up around _________ of the population in the US.
22%
What is postmenstrual age?
This is gestational age and postnatal age. It is a good tool for determining organ function in premature neonates.
What does it mean by saying that neonates are big bags of water with a slow leak?
It means neonates have a very large volume of distribution with a decreased ability to clear drugs.
Jeff is a 5kg, 23-day old, full-term male who is prescribed gentamicin for a serious bacterial infection. Which of the following is an appropriate dose?
20mg every 24 hours
Neonates have _________ HCl production in the stomach. This leads to a _________ pH of the stomach.
Decreased
Higher
How does the idea that neonates have increased pH of the stomach due to decreased HCl production impact drug absorption?
Weak acids are typically absorbed in the stomach in adults due to the uncharged form of the weak acid (HA) being dominant when pH is less than pKa. However, in neonates the weak acid protonated form dominates (A-) therefor weak acids are poorly absorbed.
Neonates do not absorb ___________ as it is a weak acid.
Amoxicillin
If neonates are given amoxicillin, do they need to be given more or less than a child?
Neonates do not absorb amoxicillin therefore they need a substantially higher amount of it compared to a child.
___________ thickness increases with age. Neonates are born with very __________ skin.
Skin
Thin
Neonates have more skin (larger surface area) to absorb drugs but less volume (body mass) to distribute it to. Therefore, with drugs like _____________, neonates have apnea and seizures as there is too much surface area but not enough weight.
Hexachlorophene
Neonates often need higher doses of ___________ drugs as they have large amounts of excess free water.
Hydrophilic
What is the general consensus regarding metabolism is neonates?
Metabolism is widely variable.
Glomerular filtration rate _________ asymptotically with age as the kidneys get smarter and learn their function
Increases
What are the two most common reasons for adverse episodes?
Drug interactions and polypharmacy
Patient JM has been taking sustained-release nifedipine for the last 3 years. She recently started taking a new HIV drug containing ritonavir. What should be done to the drug regimen to prevent adverse events?
A. Increase nifedipine dose
B. Decrease nifedipine dose
C. Increase ritonavir dose
D. Decrease ritonavir dose
B. Decrease nifedipine dose
Many HIV protease inhibitors (ritonavir) inhibit CYP3A.
Nifedipine is metabolized by CYP3A. Inhibiting nifedipine’s metabolizing enzyme, causes the drug to build up, and puts the patient as risk for hypotension and flushing.
For a patient that was a slow acetylator, what could occur?
Acetylation is the transfer of acetyl groups from acetyl-CoA to certain drug compounds. There are only two genes: NAT1 and NAT2. Genetic variations in NAT can lead to a patient being a slow/fast acetylator. Acetylation inactivates a drug
(metabolism), so if a patient was a slow acetylator, the dose of the drug may need to be decreased as they are at risk for toxicity.
What is the leading cause of acute liver failure in the US?
Drug-induced liver injury
Which of the following is true regarding overall health and drug response?
A. GIT disturbances impact administration of IV drugs
B. Dehydration changes the distribution of lipophilic drugs
C. Chronic disease have little impact on body mass index when dosing drugs
D. Fever may alter PK and PD
D. Fever may alter PK and PD
Dehydration (or edema) changes body water composition. This changes the distribution of hydrophilic drugs. Wasting skews lean body mass, often seen in late stage chronic diseases.
Why are some verapamil products designed to be given at night?
Angina and heart attacks are more frequent in the AM. Some products are given at night, so they are absorbed in the early AM.
If a medication is dosed in only mg/kg, you tend to __________ small individuals and __________ larger individuals.
Underdose
Overdose
Children (not neonates here) have more torso than limbs so they can clear drugs faster due to their ______________ ratio compared to adults.
Organ/kilo
___________ is the most dosing error-prone antibiotic.
Augmentin
In the pediatric population, dosing is based on __________.
Weight
What are the 5 essential functions of the kidneys?
- Acid/base balance- Control pH levels with the lungs
- Blood pressure- RAAS
- Bones- makes active form of vitamin D
- Red blood cells- makes erythropoietin to stimulate bone marrow to make more RBC
- Waste removal
What is creatinine?
Creatinine is a waste product made by the muscle that is only excreted by the kidneys.
What is the purpose of finding a person’s creatinine clearance?
To give an estimation to their kidney function
What is a person’s creatinine clearance a measure of?
Creatinine clearance is an estimate of glomerular filtration rates of the kidneys. CrCl is larger than GFR.
What is acute kidney injury (AKI)?
AKIs are sudden loss of kidney function caused by decreased blood flow, kidney damage, or UTI.
What is chronic kidney disease (CKD)?
CKD is present when the GFR is less than 60mL/min or kidney damage has been present for more than 3 months. There is decreased kidney function and increased kidney damage seen with protein in urine.
What is end-stage renal disease (ESRD)?
ESRD is permanent kidney failure that leads to transplant or dialysis.
What are the two biggest risk factors for chronic kidney disease (CKD)?
Diabetes and high blood pressure
T or F: There is an age-related decline in renal function as seen with the average GFR for different age groups.
True
What is the creatinine clearance equation, also known as the Cockcroft-Gault Equation?
What is a normal GFR for the kidneys?
Greater than or equal to 90mL/min
What is the ideal body weight equation for men?
50+2.3(inches over 5 feet)
What is the ideal body weight equation for women?
45.5+2.3(inches over 5 feet)
Why is the Cockcroft-Gault Equation multiplied by 0.85 when done for females?
It is multiplied by 0.85 because female kidneys are smaller and slower filtration rates.
What is the equation called the Modification of Diet in Renal Disease (MDRD)?
This equation is used to determine the STAGE of kidney disease
What are the 9 functions of the liver?
- Converts ammonia to urea
- Converts glucose to glycogen
- Gluconeogenesis
- Metabolizes medications
- Produces proteins- like albumin
- Produces cholesterol
- Produces clotting factors
- Waste removal
What are 6 different liver function tests (LFTs)?
- Alanine transaminase (ALT)
- aspartate Transaminase (AST)
- Alkaline phosphatase (ALP)
- Albumin
- Bilirubin- waste product of RBC
- prothrombin time (part of INR)
What are the two most common liver function tests?
Alanine transaminase and aspartate transaminase
T or F: There is a single lab test that can tell us how a patient’s liver is doing or how impaired liver function is.
False. There is no single test that tells us that.
Why would we even need to check serum creatinine or liver function tests for a patient?
It is important to check because several medications need a baseline to start or start at all based on those values.
What are the 6 major factors for drug-induced nephropathy?
- Age greater than 60
- Underlying renal impairment (GFR less than 60mL/min)
- Taking multiple potential nephrotoxins
- Diabetes
- Heart failure
- Volume depletion
What are the 4 ways in which pharmacists can minimize risk for drug-induced nephropathy?
- Calculate estimated creatinine clearance using the Cockcroft-Gault equation
- Assess renal function based on the Modification of Diet in Renal Disease (MDRD) equation (only used for staging the disease)
- Avoid 2 or more nephrotoxic drugs at the same time
- Maintain patient hydration status
What are the main 5 reasons to check for hepatic and/or renal function?
- Screen for possible disease
- Monitor any disease progression
- Measure severity of disease
- Determine if dose adjustment is needed or to avoid medication
- Monitor possible side effects of medications
What is the child pugh score?
This is used for staging in liver disease and is only used in those with diagnosed liver disease.
Increased bilirubin levels in the child pugh score for the liver means _________ impairment.
More
___________ albumin levels in the child pugh score for the liver means ____________ impairment.
Decreased
More
Increased PT INR levels in the child pugh score means _________ impairment.
More
________ increases with liver disease.
Volume of distribution
Sex is __________ while gender is __________.
Biological
Societal
What are some diseases that have higher prevalence in women than in men?
- Alzheimer’s disease
- Breast Cancer
- Cataracts
- Chronic pain
- Depression
- Fibromyalgia
- IBS
- Lupus
- Migraines/Headaches
- MS
- Osteoporosis
12 Rheumatoid arthritis (women 2-3x more likely to develop autoimmune disease - Thyroid dysfunction
What are some disease that have a higher prevalence in men than in women?
- Gout (men get it younger than women)
- Hearing loss
- Myocardial infarction
- Bladder, kidney, lung, pancreatic, and prostate cancer
What was the first example of dosing differences seen in men and women?
Zolpidem (Ambien). Women clear this drug at a slower rate than men therefore for dosing, women start at 5mg while men start at 5-10mg.
In terms of absorption, what are the 3 characteristics discussed that are different between men and women?
Women have:
- less alcohol dehydrogenase- alcohol is broken down slower
- Less gastric acid secretion- lower bioavailability for drugs that need acidic environments for absorption like ketoconazole
- Slower GI transit time-delayed and increased absorption
In terms of distribution, what are the 3 characteristics discussed that are different between men and women?
Women have:
- more fat than men- lipophilic medications last longer like BZs
- less plasma volume- hydrophilic drugs distribute into a smaller plasma volume like alcohol
- weigh less- affects drugs that require a loading dose
In terms of metabolism, what are some characteristics discussed that are different in men and women?
Men have:
-faster metabolism- affects drug dosing
-enzyme effectiveness is different in general for men and women
In terms of excretion, what are some characteristics discussed that are different in men and women?
Women have:
-lower glomerular filtration rate- therefore slower clearance of renally eliminated drugs
Men have:
-better kidney function
Are men or women more likely to have adverse events from medications?
Women are more likely to have adverse effects from medications due to greater prevalence of polypharmacy and other multifactorial reasons.
In terms of cardiovascular sex differences, women are at a higher risk for drug-induced __________ prolongation.
QTc
In terms of cardiovascular sex differences, men and women can present with similar symptoms for a myocardial infarction but females have a higher chance of presenting with what other symptoms?
Unexplained fatigue, GI upset, and shortness of breathe
What is the equation for adjusted body weight (ABW)?
IBW + 0.4 x (Total body weight - IBW)
What are the different BMI classifications?
Normal: 18.5-24.9
Overweight: 25-29.9
Obese: greater than or equal to 30
What are the limitations of BMI?
BMI does not look at body composition, there are no differences for sex, age, and race, and it lacks extrapalatability
What are the main differences between individuals with obesity and those without?
Those with obesity:
1. Increased adipose tissue
2. Increased body fat%
3. increased lean body mass (organs and skeletal)
4. Increased cardiac output
5. Increased blood volume
6. Increased renal function
T or F: There are massive changes in drug absorption between non-obese and obese patients.
False. There is little to no change in drug absorption between obese and non-obese patients.
What are the differences in drug distribution between obese and non-obese patients?
Those with obesity:
- lipids soluble drugs have increased volume of distribution
- water soluble drugs have similar volume of distribution
What are the differences in drug metabolism between obese and non-obese patients?
Metabolism may or not be increased by fatty liver disease presence could lead to cirrhosis which would affect metabolism.
T or F: It is easy to quantify the overall effect that obesity have on kidney function in terms of drug elimination.
False. it is difficult to quantify the overall effect
How do you know what weight you should use for obese patients for drug dosing?
Unfortunately there is no correct answer. Typical guidelines are to use the protocol given by the institution you are working at.
What are the 4 general considerations when giving medications to those with obesity?
- Very limited data in the obese population
- Typically start with lower doses and titrate up. Make sure to monitor this
- Consider organ dysfunction
- Consider body weight on a case-by-case basis
- Pay extra attention to Narrow TI drugs, anti-infectives, anticoagulants, cardiovascular drugs, and CNS drugs
In obese individuals, lipid soluble drug have an __________ volume of distribution, while water soluble drug have __________ volume of distribution.
Increased
Similar
______________ patients are __________ CYP2D6 metabolizers which includes drugs like codeine and beta-blockers.
European Whites
Poor
____________ patients are __________ CYP2C19/17 metabolizers which includes drugs like omeprazole.
Ethiopians, Swedes, Chinese, and Japanese
Ultra-extensive
African American patients have an increased risk for what 3 issues?
- Type 2 diabetes
- Sickle cell anemia
- Glucose-6-phosphate dehydrogenase deficiency leading to hemolysis
__________ patients have the risk factor allele called __________ which increases risk of severe cutaneous adverse reactions to _________.
Korean, Thai, and Han Chinese
HLA-B5801
Allopurinol
How does calcium interact with doxycycline?
Divalent and trivalent cations from calcium decrease the oral absorption of doxycycline. Therefore, the efficacy of doxycycline is decreased.
How does food interact with bisphosphonates like Alendronate (Fosamax)?
Food decreases the absorption of Fosamax.
How does vitamin K (green leafy vegetables) interact with wafarin?
Vitamin K antagonizes the effects of warfarin.
What is drug disposition?
A general term for absorption, distribution, metabolism, and excretion of a drug. Hepatic and renal impairment may effect drug disposition.
In regards to transport proteins, there is ___________ distribution. Why is this?
Asymmetrical
This is so our cells can transport things in and out in a specific direction because of where the transporters are located.
T or F: Any mutation or fault in an uptake transporter can cause a significant deficiency of drug into its target site therefore causing a reduction in the amount delivered to the drug site.
True
What are the 5 main drug transporters in the brain and what do they transport?
- MRP5- efflux transporter of organic anions
- OCT2- transport of dopamine
- OCT3- transport serotonin
- OAT1- Organic anion uptake transporter
- OATP1- Organic anion uptake transporter in capillaries of BBB
Cigarette smoking has interactions that both _______ therapeutic effects and ________ risk for adverse events.
Lower
Increase
What compound in cigarettes is responsible for the drug iteractions?
Polycyclic Aromatic Hydrocarbons (PAHs)
Polycyclic Aromatic Hydrocarbons (PAHs) in cigarettes ___________ these types of CYP450s, __________.
Induce
CYP1A1 and CYP1A2
What are the 4 drugs discussed that are effected by Polycyclic Aromatic Hydrocarbons (PAHs) due to its effect on CYP1A2?
Caffeine, Clozapine, Olanzapine, and Theophylline
Does caffeine have more or less of an effect with smokers?
It has less of an effect as Polycyclic Aromatic Hydrocarbons (PAHs) induces CYP1A2 therefore increasing its metabolism and degradation within the body.
T or F: Tobacco use with oral contraceptives does induce the oral contraceptive and causes decreased efficacy.
False. Tobacco use does not induce oral contraceptives and does not decrease efficacy
35 year old women and older who smoke should refrain from estrogen based oral contraceptives as it increases the risk for _________________ and __________________.
Ischemic stroke and myocardial infarction
What is fraility?
Frailty is defined as having 3 or more of the following:
-Fatigue or poor endurance
-Low physical activity
-Muscle weakness
-Slowed performance
-Loss of weight
What does frailty lead to and cause?
Increases disease burden, hospitalization and disability rate, and increased chance of adverse events
What are some prevention strategies to prevent fraility?
Exercise and physical activity
Nutrition
Social engagement
Medical screenings
T or F: Medications do not play a role in the fall risk of the geriatric population.
False.
What are the 5 main assessments that should be given to a geriatric individual?
- Standard assessment (Quest-SCHOLAR-MAC)
- Mini-cognitive assessment
- Nutritional health checklist
- Vision and hearing assessment
- Balance and fall prevention
- Activities of daily living (eating, bathing, bathroom, transfer, etc)
What are the I’s of geriatrics?
Immobility, Isolation, Incontinence, Infection, Inanition, Impaction, Impaired senses, Instability, Intellectual impairment, Impotence, Immunodeficiency, Insomnia, and Iatrogenesis
What is Beers Criteria?
Beers criteria was created by the American Geriatric Society and is used for those over 65 not in hospice or end-of-life care. It is a resource that recommends drugs to avoid, adjust, and use with caution (potentially inappropriate medications PIMs). It give potential drug-drug interactions as well. Also use with clinical judgement.
What are the main drugs that should be watched and monitored according to the Beers Criteria in the geriatric population?
Anticoagulants, antiplatelets, opioids, SGLT2 inhibitors, dose adjustments in kidney disease, and drug interactions
What is the STOPP/START criteria?
It is a tool use to alert doctors to START the right treatment and STOP potentially inappropriate prescriptions in the geriatric population.
What is deprescribing?
A process of identifying and discontinuing drugs in instances in which existing or potential harm outweighs existing or potential benefits within the patient’s goals, life expectancy, functioning, and preferences.
What are the 3 goals of deprescribing?
- Reduce medication burden
- Reduce adverse event risk
- Improve or preserve cognitive function
Which ADME parameter is most impacted in geriatric patients?
Excretion
How is absorption impacted in the geriatric population?
Decreased gastric acid production leading to increased pH.
Delayed gastric emptying- in body longer but not getting absorbed
Skin atrophy- increased transdermal absorption
Decreased tissue blood perfusion and saliva production
How is distribution impacted in the geriatric population?
Increases in lean body mass and adipose tissue while there are decreases muscle mass, plasma albumin, and total body water. However, it is hard to predict drug distribution in the geriatric population.
How is metabolism impacted in the geriatric population?
Decreased liver mass and blood flow with variable effects in CYP450 metabolism.
How is elimination impacted in the geriatric population?
Elimination is most impacted in the geriatric population. There is decreased kidney mass, kidney blood flow, and number of functional glomeruli. Serum creatinine and creatinine clearance calculations here may be misleading because in general they have less muscle mass therefore would have less creatinine.
In general, when dosing drugs for the geriatric population, you should start ________ and go ________.
Low
Slow
