Israel Pharmacist Licensing Exam cheat sheet

Receptor agonist vs antagonist: a full agonist produces maximal intrinsic activity (α=1); a partial agonist has α between 0 and 1 and can reduce the effect of a full agonist; a competitive antagonist shifts the dose-response curve right without lowering Emax, while a non-competitive antagonist lowers Emax.

Therapeutic index = TD50/ED50; drugs with a narrow index (warfarin, digoxin, lithium, phenytoin, aminoglycosides, vancomycin) require therapeutic drug monitoring.

Autonomic rule: sympathetic postganglionic fibers release norepinephrine onto alpha-1 (vasoconstriction), beta-1 (heart rate and contractility), beta-2 (bronchodilation, uterine relaxation); parasympathetic fibers release acetylcholine onto muscarinic receptors.

Anticholinergic toxidrome: dry skin, mydriasis, tachycardia, urinary retention, delirium; cholinergic toxidrome (organophosphate): SLUDGE plus bradycardia and miosis, treated with atropine and pralidoxime.

Anticoagulant reversal: warfarin with vitamin K (phytomenadione) and PCC/FFP; unfractionated heparin with protamine sulfate; dabigatran with idarucizumab; rivaroxaban/apixaban with andexanet alfa or PCC.

Antibiotic mechanism classes: beta-lactams inhibit cell-wall transpeptidation; aminoglycosides bind the 30S subunit; macrolides and clindamycin bind the 50S subunit; fluoroquinolones inhibit DNA gyrase/topoisomerase IV; vancomycin binds D-Ala-D-Ala.

CYP interactions: CYP3A4 inhibitors include azole antifungals, macrolides, grapefruit juice, and ritonavir; inducers include rifampicin, carbamazepine, phenytoin, and St John's wort; inhibition raises substrate levels rapidly, induction takes 1-2 weeks.

Adverse-effect mnemonics tied to mechanisms: ACE inhibitors cause dry cough via bradykinin accumulation; NSAIDs cause gastric injury via COX-1 inhibition and renal afferent vasoconstriction; statins cause myopathy via HMG-CoA reductase inhibition in muscle.

Lipinski's rule of five for oral bioavailability: molecular weight ≤500, logP ≤5, hydrogen-bond donors ≤5, hydrogen-bond acceptors ≤10; violation of two or more predicts poor absorption.

Ionization and pH: a weak acid (e.g., aspirin, pKa ~3.5) is largely unionized and more lipid-permeable in the acidic stomach; a weak base (e.g., codeine) is more unionized and absorbed in the more alkaline intestine.

Ester prodrugs (e.g., enalapril, oseltamivir, sulfasalazine's azo bond) are hydrolyzed in vivo to release the active drug; the prodrug is designed to improve absorption or mask a polar group.

Bioisosteric replacement: -OH/-NH2, -CH3/-Cl/-CF3, -O-/-S-/-NH-, and carboxylate/tetrazole substitutions preserve steric and electronic properties while altering potency or metabolism.

Stereochemistry matters clinically: S-warfarin is 3-5 times more potent than R-warfarin and is metabolized by CYP2C9; S-omeprazole and esomeprazole are the active enantiomers; thalidomide enantiomers differ in teratogenicity.

SAR of beta-lactams: the beta-lactam ring is essential for acylation of penicillin-binding proteins; the thiazolidine (penicillin) or dihydrothiazine (cephalosporin) ring and side-chain substituents govern spectrum, beta-lactamase stability, and oral absorption.

Metabolic soft spots: para-hydroxylation of phenyl rings, N-dealkylation, and glucuronidation at hydroxyl or carboxyl groups; blocking a labile position with fluorine or a methyl group prolongs half-life.

Salt and polymorph selection: salt formation (hydrochloride, sodium, mesylate) alters solubility, dissolution rate, and stability; different polymorphs have different lattice energies and therefore different dissolution and bioavailability.

Biopharmaceutics Classification System: Class I high solubility/high permeability, Class II low solubility/high permeability (dissolution-rate limited), Class III high solubility/low permeability (permeability limited), Class IV low/low; in-vitro–in-vivo correlation is most reliable for Class II immediate-release products.

Dissolution testing: USP Apparatus I is the rotating basket (100 rpm typical), Apparatus II the paddle (50-75 rpm); the Noyes-Whitney equation describes dissolution rate as proportional to surface area and solubility and inversely to particle size.

Tablet excipients by function: diluents (lactose, microcrystalline cellulose), binders (PVP, starch paste), disintegrants (croscarmellose sodium, sodium starch glycolate), lubricants (magnesium stearate), glidants (colloidal silica), and coating polymers (HPMC).

Powder flow is described by the Hausner ratio (tapped/bulk density) and Carr's compressibility index; a Hausner ratio below 1.25 indicates good flow, above 1.5 poor flow.

Modified-release mechanisms: matrix (HPMC hydrophilic or insoluble wax), reservoir/membrane diffusion, osmotic pump (OROS), and ion-exchange resin; dose dumping is the main safety risk of alcohol-affected or split modified-release dosage forms.

Sterility and preservation: multi-dose aqueous preparations require an antimicrobial preservative (e.g., benzalkonium chloride, parabens) unless the product itself is self-preserving; preservative efficacy is tested by the pharmacopoeial challenge test.

Ophthalmic and parenteral quality attributes: ophthalmic solutions are isotonic (~300 mOsm/kg) and buffered near pH 7.4 when compatible; parenterals must be pyrogen-free, and large-volume products must be isotonic.

Stability and shelf life: Arrhenius kinetics relate degradation rate to temperature; Q10 approximation predicts roughly a 2-3 fold rate increase per 10 °C; ICH long-term conditions are 25 °C/60% RH and accelerated 40 °C/75% RH for 6 months.

First-order elimination: half-life t1/2 = 0.693 × Vd/CL; after 4-5 half-lives about 94-97% of steady state is reached, and the same interval is needed for washout.

Volume of distribution Vd = Dose/C0 (extrapolated); a large Vd (>1 L/kg) indicates extensive tissue distribution (e.g., digoxin, chloroquine) and limits removal by hemodialysis.

Clearance CL = Dose/AUC for a single dose; for oral dosing, bioavailability F = (AUCoral × DoseIV)/(AUCIV × Doseoral); hepatic clearance depends on intrinsic clearance and on liver blood flow for high-extraction drugs.

Loading dose = (Vd × target concentration)/F; maintenance dose rate = (CL × target concentration)/F; adjust for renal function using Cockcroft-Gault creatinine clearance.

Aminoglycoside monitoring: peak (typically 30 minutes after a 30-minute infusion) relates to efficacy, trough to toxicity; vancomycin AUC24/MIC 400-600 is the preferred target for serious MRSA infection, with trough 10-15 mg/L or 15-20 mg/L for severe cases.

Digoxin: therapeutic range roughly 0.5-2 ng/mL (0.5-0.9 ng/mL in heart failure); toxicity is worsened by hypokalemia, hypomagnesemia, hypercalcemia, and renal impairment.

Phenytoin shows saturable (Michaelis-Menten) metabolism: a small dose increase can produce a disproportionate rise in serum level; the free fraction rises in hypoalbuminemia, so measure free phenytoin when albumin is low.

Nonlinear kinetics: at steady state on repeated dosing, accumulation ratio = 1/(1 - e^(-0.693·τ/t1/2)); for a drug given every half-life, accumulation is about 2-fold.

The Pharmacists' Ordinance (Pekudat HaRokechim) is the core Israeli statute governing pharmacist licensure, pharmacy permits, and dispensing; the Ministry of Health's Pharmaceutical Division (Agaf HaRokechut) administers it.

Pharmacist registration requires recognition of the degree, passing the Ministry of Health licensing examination (in Hebrew), and registration in the pharmacists' register; practice is regulated through the district health offices.

Prescription-only versus over-the-counter status is set by Ministry of Health registration of the product; narcotics and psychotropics are additionally controlled under the Dangerous Drugs Ordinance and require special prescription forms and record-keeping.

Prescription validity and substitution: a prescription is dispensed as written unless generic substitution is permitted; the pharmacist must verify dose, directions, and prescriber authority and must not dispense expired or improperly stored stock.

Record retention and narcotics registers: controlled-drug receipts and dispensations must be recorded and retained for inspection periods defined in regulation; discrepancies must be reported to the Ministry of Health.

Patient confidentiality is a statutory duty under the Patient's Rights Law (1996); disclosure without consent is permitted only for defined exceptions such as court order, statutory reporting, or immediate danger to others.

Ethical duties include informed consent for counseling and substitution, avoiding conflicts of interest, reporting adverse drug reactions to the national pharmacovigilance center, and refusing to dispense when a prescription is forged or unsafe.

Advertising and promotion of medicines to the public is restricted; prescription-only medicines may not be advertised to the lay public, and promotional claims must match the approved product label (summary of product characteristics).

Prescription screening sequence: patient identity and age, drug name and strength, dose and frequency, route and duration, prescriber signature and license, allergies, interactions, and appropriateness for renal/hepatic function and pregnancy.

The 'five rights' of dispensing: right patient, right drug, right dose, right route, right time; add right documentation and right counseling as the extended standard.

Look-alike/sound-alike pairs to verify by spelling back: Losec/Lasix, hydrALAZINE/hydrOXYzine, glipiZIDE/glyBURIDE, and insulin products differing only by suffix; read back telephone orders.

Prescription abbreviations to clarify, never assume: 'U' for units (write 'units' to avoid 10-fold errors), 'QD'/'QOD', trailing zeros (write 1 mg, never 1.0 mg), and leading zeros (0.5 mg, never .5 mg).

Counseling structure: open-ended question about what the patient already knows, key benefits and common adverse effects, administration with or without food, what to do about a missed dose, and when to seek help.

Medication reconciliation at transitions of care reduces discrepancies; the pharmacist compares the pre-admission list with discharge orders and resolves duplications, omissions, and dose changes.

Adherence support: pill organizers, simplified regimens, once-daily formulations where equivalent, refill synchronization, and motivational interviewing; ask about cost barriers before assuming non-adherence.

Documentation of pharmaceutical care: record the identified drug-related problem, the recommendation made, the prescriber's response, and the outcome in the patient record for continuity and legal defensibility.

Drug-related problems are classified as indication, effectiveness, safety, and adherence; each identified problem should be linked to a specific intervention and monitoring parameter.

High-alert medications per ISMP include concentrated electrolytes, insulin, heparin, opioids, neuromuscular blockers, and chemotherapy; independent double-checks and standardized concentrations reduce harm.

Beers criteria and the anticholinergic burden scale flag potentially inappropriate medicines in older adults: benzodiazepines, long-acting sulfonylureas, first-generation antihistamines, and anticholinergics increase falls and confusion.

Adverse drug reaction causality: the Naranjo score and WHO-UMC categories (certain, probable, possible, unlikely) guide reporting; serious reactions must be reported to the national pharmacovigilance center.

Renal dose adjustment: use Cockcroft-Gault creatinine clearance, not eGFR alone, for drug dosing; avoid or reduce gabapentin, metformin (eGFR <30), nitrofurantoin (eGFR <30), and NSAIDs in advanced CKD.

Antimicrobial stewardship: de-escalate from empirical broad-spectrum therapy once culture results are available; verify allergy labels because reported penicillin allergy often is not true allergy and leads to inferior outcomes.

Pediatric dosing is weight-based (mg/kg) with maximum adult dose caps; verify concentrations of oral liquids and never assume a teaspoon equals 5 mL without a measuring device.

Error analysis: a root-cause analysis distinguishes active errors from latent system failures (look-alike packaging, unclear labeling, staffing); just-culture reporting increases voluntary disclosure.

Plant-derived drugs and sources: morphine and codeine from Papaver somniferum, digoxin from Digitalis lanata, quinine from Cinchona bark, atropine from Atropa belladonna, paclitaxel from Taxus brevifolia, and artemisinin from Artemisia annua.

Biosynthetic classes: alkaloids (nitrogen-containing, often basic), glycosides (cardiac glycosides, saponins), terpenes and essential oils, and polyphenols (flavonoids, tannins); each class has characteristic extraction and assay methods.

Biologic manufacturing: recombinant proteins are produced in CHO or E. coli expression systems, purified by chromatography, and characterized by potency, identity, purity, and glycan profile; process changes can alter immunogenicity.

Biosimilars are approved on the basis of comparability to a reference biologic, with analytical, functional, nonclinical, and clinical similarity data; they are not generic small molecules and require immunogenicity monitoring.

Monoclonal antibody nomenclature: -mab suffix; -o- indicates mouse, -u- human, -zu- humanized, -xi- chimeric, and -zu- with -mab humanized; -ximab chimeric, -zumab humanized, -mumab fully human.

Vaccine and biologic cold chain: most vaccines require 2-8 °C storage with no freezing; mRNA vaccines have stricter frozen requirements; temperature excursions require assessment against manufacturer stability data before use.

Immunogenicity risk factors: non-human sequences, aggregation, glycosylation differences, anti-drug antibodies that neutralize efficacy (e.g., anti-IFN antibodies causing loss of response) or cause hypersensitivity.

Pharmacognosy quality control: identity by macroscopic/microscopic and chromatographic fingerprinting, assay of marker compounds, limits for heavy metals, pesticides, aflatoxins, and microbial contamination per pharmacopoeial monographs.

USP <797>-aligned risk levels: low-risk (fewer than three sterile products, no preservatives, closed transfer), medium-risk (multiple additives or pooling), and high-risk (non-sterile starting materials or open systems); beyond-use dates lengthen as risk decreases.

ISO cleanroom classes: an ISO Class 5 laminar-airflow hood provides the critical zone; the buffer room is ISO 7 and the ante-room ISO 8; first air must pass over critical sites, and airflow must not be obstructed.

Aseptic technique essentials: hand hygiene and garbing sequence (shoe covers, head cover, mask, gown, gloves), 70% isopropyl alcohol disinfection with friction and drying time, no talking over critical sites, and needle-free transfer devices where possible.

High-risk compounding requires terminal sterilization or filtration (0.22 micron) when feasible; preservative-free preparations are mandatory for intrathecal, epidural, and neonatal use.

Hazardous drug handling (USP <800>): closed-system transfer devices, biological safety cabinets or containment ventilated enclosures, double gloving with chemotherapy-rated gloves, and surface deactivation and decontamination.

Hospital pharmacy logistics: formulary management, unit-dose distribution, automated dispensing cabinets with override auditing, and crash-cart standardization reduce errors and waste.

Total parenteral nutrition: verify osmolarity limits for peripheral versus central administration, calcium-phosphate compatibility (solubility falls with pH and temperature), and the sequence of adding phosphate and calcium to prevent precipitation.

Beyond-use dating and stability: assign BUDs from the compounding date based on risk level and preservative status; verify compatibility of the drug with the container (adsorption to PVC, leaching of plasticizers) before extending storage.

Israel's National Health Insurance Law (1994) mandates coverage through one of four health funds (Clalit, Maccabi, Meuhedet, Leumit); a defined basket of services (sal ha-briut) is updated annually by a public committee.

Vaccination schedule anchors: routine childhood immunization includes DTaP-IPV-Hib, MMR, hepatitis B, and pneumococcal conjugate vaccines; annual influenza vaccination is recommended for adults over 65, pregnant women, and chronic-illness patients.

Herd immunity threshold = 1 - 1/R0; measles R0 of 12-18 requires roughly 92-95% two-dose coverage, which is why outbreaks follow drops in coverage.

Vaccine adverse events: anaphylaxis is rare (~1 per million doses) and managed with intramuscular adrenaline 0.5 mg (1:1000) in adults; syncope is prevented by 15-minute observation after vaccination.

Screening principles (Wilson-Jungner): the condition must be important, have a detectable early stage, an accepted treatment, a suitable test, and be cost-effective; examples include mammography and colorectal cancer screening.

Epidemiology measures: incidence counts new cases per population-time; prevalence counts existing cases; relative risk and odds ratio quantify association; sensitivity and specificity describe test performance independent of prevalence.

Antimicrobial resistance is a One Health problem: steward human prescribing, limit agricultural use, enforce infection control, and use surveillance networks to track resistance patterns.

Health-system literacy for pharmacists: know the referral pathways between community pharmacy, health-fund clinics, hospital emergency departments, and public health services, and know which body handles adverse-event reporting and drug shortages.

Receptor theory: Kd is the dissociation constant (inverse of affinity); EC50 is the concentration producing half-maximal effect; a competitive antagonist raises apparent Kd but leaves Emax unchanged, and a non-competitive antagonist reduces Emax.

Narrow therapeutic index drugs requiring TDM: digoxin, lithium, phenytoin, warfarin, theophylline, aminoglycosides, vancomycin, and ciclosporin.

Beta-blocker selectivity: beta-1 blockade lowers heart rate and blood pressure; non-selective agents also block beta-2 and can precipitate bronchospasm in asthma.

Anticholinergic burden in older adults causes confusion, constipation, urinary retention, and falls; common culprits include oxybutynin, amitriptyline, and diphenhydramine.

Opioid triad of toxicity: miosis, respiratory depression, and coma; naloxone reverses it but has a shorter half-life than many opioids, so re-dosing and observation are required.

Statin mechanism: HMG-CoA reductase inhibition reduces hepatic cholesterol synthesis and upregulates LDL receptors; myopathy risk rises with high dose, interacting drugs, and hypothyroidism.

Antiplatelet distinctions: aspirin irreversibly acetylates platelet COX-1 for the platelet lifespan (~7-10 days); clopidogrel is a prodrug requiring CYP2C19 activation, so poor metabolizers have reduced response.

Diuretic sites: acetazolamide acts on proximal tubule carbonic anhydrase, furosemide on the Na-K-2Cl cotransporter in the loop of Henle, thiazides on the distal convoluted tubule, and spironolactone on the aldosterone receptor in the collecting duct.

pKa and percent ionization: for a weak acid, % ionized = 100/(1 + 10^(pKa - pH)); for a weak base, % ionized = 100/(1 + 10^(pH - pKa)).

Lipinski's rule of five: molecular weight ≤500, logP ≤5, hydrogen-bond donors ≤5, hydrogen-bond acceptors ≤10; two or more violations predict poor oral absorption.

Prodrug examples: enalapril to enalaprilat, oseltamivir to oseltamivir carboxylate, clopidogrel to its active thiol metabolite, and sulfasalazine cleaved by colonic bacteria.

Bioisosteres: -OH/-NH2, -CH3/-Cl/-CF3, -O-/-S-/-NH-, and carboxylate/tetrazole replacements preserve steric and electronic properties while changing potency or metabolism.

Stereoselectivity: S-warfarin is 3-5 times more potent than R-warfarin and is metabolized by CYP2C9; esomeprazole is the active S-enantiomer of omeprazole.

Beta-lactam SAR: the beta-lactam ring acylates penicillin-binding proteins; the fused ring and side chains determine spectrum, beta-lactamase stability, and oral bioavailability.

Salt and polymorph selection changes solubility, dissolution rate, and stability; different crystal forms have different lattice energies and therefore different bioavailability.

Metabolic soft spots: aromatic para-hydroxylation, N-dealkylation, and glucuronidation; fluorine or methyl substitution at a labile position slows metabolism and prolongs half-life.

BCS classes: I high solubility/high permeability, II low solubility/high permeability (dissolution-rate limited), III high solubility/low permeability (permeability limited), IV low/low; IVIVC is most reliable for Class II immediate-release products.

Dissolution apparatus: USP I rotating basket (100 rpm), USP II paddle (50-75 rpm); the Noyes-Whitney equation states dissolution rate is proportional to surface area and solubility and inversely related to particle size.

Tablet excipients: diluents (lactose, MCC), binders (PVP, starch paste), disintegrants (croscarmellose sodium, sodium starch glycolate), lubricants (magnesium stearate), glidants (colloidal silica), coatings (HPMC).

Powder flow: Hausner ratio = tapped density/bulk density; below 1.25 indicates good flow, above 1.5 poor flow; Carr's compressibility index is a related measure.

Modified-release mechanisms: hydrophilic or wax matrix, reservoir membrane diffusion, osmotic pump (OROS), and ion-exchange resin; dose dumping is the main safety risk if the form is crushed or split.

Preservatives in multi-dose aqueous products: benzalkonium chloride, parabens, and chlorbutol; efficacy is verified by the pharmacopoeial preservative challenge test.

Ophthalmic products are buffered near pH 7.4 when compatible and isotonic (~300 mOsm/kg); parenterals must be pyrogen-free, and large-volume products must be isotonic.

Stability: Arrhenius kinetics relate degradation rate to temperature; the Q10 approximation predicts a 2-3 fold rate increase per 10 °C; ICH accelerated conditions are 40 °C/75% RH for 6 months.

First-order elimination: t1/2 = 0.693 × Vd/CL; about 94-97% of steady state is reached after 4-5 half-lives, and the same interval is needed for washout.

Vd = Dose/C0; a large Vd (>1 L/kg) indicates extensive tissue distribution (digoxin, chloroquine) and limits removal by hemodialysis.

CL = Dose/AUC for a single dose; oral bioavailability F = (AUCoral × DoseIV)/(AUCIV × Doseoral).

Loading dose = (Vd × target concentration)/F; maintenance rate = (CL × target concentration)/F; adjust with Cockcroft-Gault creatinine clearance.

Aminoglycosides: peak (about 30 minutes after a 30-minute infusion) relates to efficacy, trough to toxicity; vancomycin target is AUC24/MIC 400-600 for serious MRSA infection.

Digoxin therapeutic range is roughly 0.5-2 ng/mL (0.5-0.9 ng/mL in heart failure); toxicity is worsened by hypokalemia, hypomagnesemia, hypercalcemia, and renal impairment.

Phenytoin has saturable Michaelis-Menten metabolism, so small dose increases cause disproportionate level rises; measure free phenytoin when albumin is low.

Accumulation ratio at steady state = 1/(1 - e^(-0.693·τ/t1/2)); dosing every half-life gives about 2-fold accumulation.

The Pharmacists' Ordinance (Pekudat HaRokechim) governs licensure, pharmacy permits, and dispensing; the Ministry of Health Pharmaceutical Division (Agaf HaRokechut) administers it.

Licensure requires degree recognition, passing the Ministry of Health licensing examination in Hebrew, and entry in the pharmacists' register; district health offices oversee practice.

Prescription-only versus OTC status is set at product registration; narcotics and psychotropics fall under the Dangerous Drugs Ordinance with special forms and record-keeping.

Controlled-drug receipts and dispensations must be recorded and retained for regulatory inspection; discrepancies must be reported to the Ministry of Health.

Patient confidentiality is a statutory duty under the Patient's Rights Law (1996); disclosure without consent is limited to defined exceptions such as court order or statutory reporting.

Prescription-only medicines may not be advertised to the lay public, and promotional claims must match the approved product label.

Ethical duties include informed consent for counseling and substitution, avoiding conflicts of interest, and reporting adverse drug reactions to the national pharmacovigilance center.

A pharmacist must refuse to dispense a forged, unsafe, or unauthorized prescription and must document the refusal and the reason.

Prescription screening order: patient identity and age, drug name and strength, dose and frequency, route and duration, prescriber signature and license, allergies, interactions, and organ-function appropriateness.

The five rights are right patient, drug, dose, route, and time; documentation and counseling are the extended standard.

Look-alike/sound-alike pairs to verify by spelling back: Losec/Lasix, hydrALAZINE/hydrOXYzine, glipiZIDE/glyBURIDE, and insulin products differing only by suffix.

Abbreviations to clarify: 'U' for units, QD/QOD, trailing zeros (write 1 mg, not 1.0 mg), and leading zeros (0.5 mg, not .5 mg).

Counseling structure: open-ended question about existing knowledge, key benefits and common adverse effects, food instructions, missed-dose advice, and when to seek help.

Medication reconciliation at care transitions compares pre-admission and discharge lists and resolves duplications, omissions, and dose changes.

Adherence support: pill organizers, simplified regimens, once-daily equivalents, refill synchronization, and motivational interviewing; check cost barriers before labeling non-adherence.

Document the drug-related problem, recommendation, prescriber response, and outcome in the patient record for continuity and legal defensibility.

Drug-related problems fall into indication, effectiveness, safety, and adherence categories; each needs a specific intervention and monitoring parameter.

ISMP high-alert medications include concentrated electrolytes, insulin, heparin, opioids, neuromuscular blockers, and chemotherapy; independent double-checks and standardized concentrations reduce harm.

Beers criteria flag benzodiazepines, long-acting sulfonylureas, first-generation antihistamines, and anticholinergics as potentially inappropriate in older adults because of falls and confusion.

ADR causality uses the Naranjo score and WHO-UMC categories (certain, probable, possible, unlikely); serious reactions are reported to the national pharmacovigilance center.

Use Cockcroft-Gault creatinine clearance for renal dosing; avoid metformin and nitrofurantoin below eGFR 30 and NSAIDs in advanced CKD.

Antimicrobial stewardship: de-escalate broad-spectrum empirical therapy when cultures return; verify penicillin allergy labels, which are often not true allergy.

Pediatric doses are weight-based (mg/kg) with adult maximum caps; verify liquid concentrations and dispense a measuring device rather than assuming a teaspoon is 5 mL.

Root-cause analysis separates active errors from latent system failures such as look-alike packaging and unclear labeling; just-culture reporting increases voluntary disclosure.

Plant sources: morphine and codeine from Papaver somniferum, digoxin from Digitalis lanata, quinine from Cinchona bark, atropine from Atropa belladonna, paclitaxel from Taxus brevifolia, artemisinin from Artemisia annua.

Natural-product classes: alkaloids (nitrogen-containing, often basic), glycosides (cardiac glycosides, saponins), terpenes and essential oils, and polyphenols (flavonoids, tannins).

Biologic manufacturing uses CHO or E. coli expression, chromatographic purification, and characterization by potency, identity, purity, and glycan profile; process changes can alter immunogenicity.

Biosimilars are approved by comparability to a reference biologic with analytical, functional, nonclinical, and clinical similarity data; they are not generic small molecules.

Monoclonal antibody suffixes: -ximab chimeric, -zumab humanized, -mumab fully human, -omab mouse; the -mab stem denotes a monoclonal antibody.

Cold chain: most vaccines require 2-8 °C with no freezing; mRNA vaccines have stricter frozen requirements; temperature excursions are assessed against manufacturer stability data.

Immunogenicity risk factors include non-human sequences, aggregation, and glycosylation differences; anti-drug antibodies can neutralize efficacy or cause hypersensitivity.

Pharmacopoeial quality control of botanicals: identity by macroscopic, microscopic, and chromatographic fingerprinting, marker-compound assay, and limits for heavy metals, pesticides, aflatoxins, and microbes.

USP <797> risk levels: low-risk (fewer than three sterile products, closed transfer), medium-risk (multiple additives or pooling), high-risk (non-sterile starting materials or open systems); beyond-use dates lengthen as risk decreases.

Cleanroom classes: ISO Class 5 critical zone in the laminar-airflow hood, ISO 7 buffer room, ISO 8 ante-room; first air must pass over critical sites without obstruction.

Garbing sequence: shoe covers, head cover, mask, gown, then gloves; disinfect with 70% isopropyl alcohol using friction and allow full drying before entry.

High-risk compounding requires terminal sterilization or 0.22-micron filtration when feasible; preservative-free preparations are mandatory for intrathecal, epidural, and neonatal use.

Hazardous drugs (USP <800>): closed-system transfer devices, biological safety cabinets or containment ventilated enclosures, chemotherapy-rated double gloves, and surface decontamination.

TPN: check osmolarity limits for peripheral versus central administration and calcium-phosphate compatibility, which falls with rising pH and temperature.

Assign beyond-use dates from the compounding date based on risk level and preservative status; verify container compatibility (PVC adsorption, plasticizer leaching) before extending storage.

Unit-dose distribution, automated dispensing cabinets with override auditing, and standardized crash carts reduce hospital medication errors and waste.

Israel's National Health Insurance Law (1994) mandates coverage through four health funds (Clalit, Maccabi, Meuhedet, Leumit); the basket of services (sal ha-briut) is updated annually by a public committee.

Routine childhood immunization includes DTaP-IPV-Hib, MMR, hepatitis B, and pneumococcal conjugate vaccines; annual influenza vaccination is recommended for adults over 65, pregnant women, and chronic-illness patients.

Herd immunity threshold = 1 - 1/R0; measles R0 of 12-18 requires roughly 92-95% two-dose coverage, which is why outbreaks follow coverage drops.

Anaphylaxis after vaccination is rare (~1 per million doses) and is treated with intramuscular adrenaline 0.5 mg (1:1000) in adults; 15-minute observation prevents syncope injury.

Wilson-Jungner screening criteria require an important condition, detectable early stage, accepted treatment, suitable test, and cost-effectiveness; examples are mammography and colorectal screening.

Incidence counts new cases per population-time; prevalence counts existing cases; sensitivity and specificity describe test performance independent of prevalence.

Antimicrobial resistance is a One Health problem requiring human prescribing stewardship, limits on agricultural use, infection control, and surveillance networks.

Know referral pathways among community pharmacy, health-fund clinics, emergency departments, and public health services, and which body handles adverse-event reports and drug shortages.

Kd measures affinity (lower Kd, higher affinity); EC50 is the concentration giving half-maximal effect; competitive antagonism raises apparent Kd with unchanged Emax, non-competitive antagonism lowers Emax.

Narrow therapeutic index drugs needing TDM: digoxin, lithium, phenytoin, warfarin, theophylline, aminoglycosides, vancomycin, and ciclosporin.

Beta-1 blockade lowers heart rate and blood pressure; non-selective beta-blockers also block beta-2 and can precipitate bronchospasm in asthma.

Anticholinergic burden causes confusion, constipation, urinary retention, and falls; culprits include oxybutynin, amitriptyline, and diphenhydramine.

Opioid toxicity triad: miosis, respiratory depression, and coma; naloxone reverses it but is shorter-acting than many opioids, so re-dosing and observation are required.

Statins inhibit HMG-CoA reductase, reduce hepatic cholesterol synthesis, and upregulate LDL receptors; myopathy risk rises with high dose, interacting drugs, and hypothyroidism.

Aspirin irreversibly acetylates platelet COX-1 for the platelet lifespan (~7-10 days); clopidogrel is a CYP2C19-activated prodrug, so poor metabolizers respond less.

Diuretic sites: acetazolamide on proximal carbonic anhydrase, furosemide on the loop Na-K-2Cl cotransporter, thiazides on the distal convoluted tubule, spironolactone on the aldosterone receptor.

Percent ionization: for a weak acid, 100/(1 + 10^(pKa - pH)); for a weak base, 100/(1 + 10^(pH - pKa)).

Lipinski's rule of five: molecular weight ≤500, logP ≤5, hydrogen-bond donors ≤5, hydrogen-bond acceptors ≤10; two or more violations predict poor oral absorption.

Prodrugs: enalapril to enalaprilat, oseltamivir to oseltamivir carboxylate, clopidogrel to its active thiol metabolite, and sulfasalazine cleaved by colonic bacteria.

Bioisosteres: -OH/-NH2, -CH3/-Cl/-CF3, -O-/-S-/-NH-, and carboxylate/tetrazole replacements preserve steric and electronic properties while changing potency or metabolism.

Stereoselectivity: S-warfarin is 3-5 times more potent than R-warfarin and is metabolized by CYP2C9; esomeprazole is the active S-enantiomer of omeprazole.

Beta-lactam SAR: the beta-lactam ring acylates penicillin-binding proteins; the fused ring and side chains determine spectrum, beta-lactamase stability, and oral bioavailability.

Salt and polymorph selection changes solubility, dissolution rate, and stability; different crystal forms have different lattice energies and therefore different bioavailability.

Metabolic soft spots: aromatic para-hydroxylation, N-dealkylation, and glucuronidation; fluorine or methyl substitution at a labile position slows metabolism and prolongs half-life.

BCS classes: I high solubility/high permeability, II low solubility/high permeability (dissolution-rate limited), III high solubility/low permeability (permeability limited), IV low/low; IVIVC is most reliable for Class II immediate-release products.

Dissolution apparatus: USP I rotating basket (100 rpm), USP II paddle (50-75 rpm); the Noyes-Whitney equation states dissolution rate is proportional to surface area and solubility and inversely related to particle size.

Tablet excipients: diluents (lactose, MCC), binders (PVP, starch paste), disintegrants (croscarmellose sodium, sodium starch glycolate), lubricants (magnesium stearate), glidants (colloidal silica), coatings (HPMC).

Powder flow: Hausner ratio = tapped density/bulk density; below 1.25 indicates good flow, above 1.5 poor flow; Carr's compressibility index is a related measure.

Modified-release mechanisms: hydrophilic or wax matrix, reservoir membrane diffusion, osmotic pump (OROS), and ion-exchange resin; dose dumping is the main safety risk if the form is crushed or split.

Preservatives in multi-dose aqueous products: benzalkonium chloride, parabens, and chlorbutol; efficacy is verified by the pharmacopoeial preservative challenge test.

Ophthalmic products are buffered near pH 7.4 when compatible and isotonic (~300 mOsm/kg); parenterals must be pyrogen-free, and large-volume products must be isotonic.

Stability: Arrhenius kinetics relate degradation rate to temperature; the Q10 approximation predicts a 2-3 fold rate increase per 10 °C; ICH accelerated conditions are 40 °C/75% RH for 6 months.

First-order elimination: t1/2 = 0.693 × Vd/CL; about 94-97% of steady state is reached after 4-5 half-lives, and the same interval is needed for washout.

Vd = Dose/C0; a large Vd (>1 L/kg) indicates extensive tissue distribution (digoxin, chloroquine) and limits removal by hemodialysis.

CL = Dose/AUC for a single dose; oral bioavailability F = (AUCoral × DoseIV)/(AUCIV × Doseoral).

Loading dose = (Vd × target concentration)/F; maintenance rate = (CL × target concentration)/F; adjust with Cockcroft-Gault creatinine clearance.

Aminoglycosides: peak (about 30 minutes after a 30-minute infusion) relates to efficacy, trough to toxicity; vancomycin target is AUC24/MIC 400-600 for serious MRSA infection.

Digoxin therapeutic range is roughly 0.5-2 ng/mL (0.5-0.9 ng/mL in heart failure); toxicity is worsened by hypokalemia, hypomagnesemia, hypercalcemia, and renal impairment.

Phenytoin has saturable Michaelis-Menten metabolism, so small dose increases cause disproportionate level rises; measure free phenytoin when albumin is low.

Accumulation ratio at steady state = 1/(1 - e^(-0.693·τ/t1/2)); dosing every half-life gives about 2-fold accumulation.

The Pharmacists' Ordinance (Pekudat HaRokechim) governs licensure, pharmacy permits, and dispensing; the Ministry of Health Pharmaceutical Division (Agaf HaRokechut) administers it.

Licensure requires degree recognition, passing the Ministry of Health licensing examination in Hebrew, and entry in the pharmacists' register; district health offices oversee practice.

Prescription-only versus OTC status is set at product registration; narcotics and psychotropics fall under the Dangerous Drugs Ordinance with special forms and record-keeping.

Controlled-drug receipts and dispensations must be recorded and retained for regulatory inspection; discrepancies must be reported to the Ministry of Health.

Patient confidentiality is a statutory duty under the Patient's Rights Law (1996); disclosure without consent is limited to defined exceptions such as court order or statutory reporting.

Prescription-only medicines may not be advertised to the lay public, and promotional claims must match the approved product label.

Ethical duties include informed consent for counseling and substitution, avoiding conflicts of interest, and reporting adverse drug reactions to the national pharmacovigilance center.

A pharmacist must refuse to dispense a forged, unsafe, or unauthorized prescription and must document the refusal and the reason.

Prescription screening order: patient identity and age, drug name and strength, dose and frequency, route and duration, prescriber signature and license, allergies, interactions, and organ-function appropriateness.

The five rights are right patient, drug, dose, route, and time; documentation and counseling are the extended standard.

Look-alike/sound-alike pairs to verify by spelling back: Losec/Lasix, hydrALAZINE/hydrOXYzine, glipiZIDE/glyBURIDE, and insulin products differing only by suffix.

Abbreviations to clarify: 'U' for units, QD/QOD, trailing zeros (write 1 mg, not 1.0 mg), and leading zeros (0.5 mg, not .5 mg).

Counseling structure: open-ended question about existing knowledge, key benefits and common adverse effects, food instructions, missed-dose advice, and when to seek help.

Medication reconciliation at care transitions compares pre-admission and discharge lists and resolves duplications, omissions, and dose changes.

Adherence support: pill organizers, simplified regimens, once-daily equivalents, refill synchronization, and motivational interviewing; check cost barriers before labeling non-adherence.

Document the drug-related problem, recommendation, prescriber response, and outcome in the patient record for continuity and legal defensibility.

Drug-related problems fall into indication, effectiveness, safety, and adherence categories; each needs a specific intervention and monitoring parameter.

ISMP high-alert medications include concentrated electrolytes, insulin, heparin, opioids, neuromuscular blockers, and chemotherapy; independent double-checks and standardized concentrations reduce harm.

Beers criteria flag benzodiazepines, long-acting sulfonylureas, first-generation antihistamines, and anticholinergics as potentially inappropriate in older adults because of falls and confusion.

ADR causality uses the Naranjo score and WHO-UMC categories (certain, probable, possible, unlikely); serious reactions are reported to the national pharmacovigilance center.

Use Cockcroft-Gault creatinine clearance for renal dosing; avoid metformin and nitrofurantoin below eGFR 30 and NSAIDs in advanced CKD.

Antimicrobial stewardship: de-escalate broad-spectrum empirical therapy when cultures return; verify penicillin allergy labels, which are often not true allergy.

Pediatric doses are weight-based (mg/kg) with adult maximum caps; verify liquid concentrations and dispense a measuring device rather than assuming a teaspoon is 5 mL.

Root-cause analysis separates active errors from latent system failures such as look-alike packaging and unclear labeling; just-culture reporting increases voluntary disclosure.

Plant sources: morphine and codeine from Papaver somniferum, digoxin from Digitalis lanata, quinine from Cinchona bark, atropine from Atropa belladonna, paclitaxel from Taxus brevifolia, artemisinin from Artemisia annua.

Natural-product classes: alkaloids (nitrogen-containing, often basic), glycosides (cardiac glycosides, saponins), terpenes and essential oils, and polyphenols (flavonoids, tannins).

Biologic manufacturing uses CHO or E. coli expression, chromatographic purification, and characterization by potency, identity, purity, and glycan profile; process changes can alter immunogenicity.

Biosimilars are approved by comparability to a reference biologic with analytical, functional, nonclinical, and clinical similarity data; they are not generic small molecules.

Monoclonal antibody suffixes: -ximab chimeric, -zumab humanized, -mumab fully human, -omab mouse; the -mab stem denotes a monoclonal antibody.

Cold chain: most vaccines require 2-8 °C with no freezing; mRNA vaccines have stricter frozen requirements; temperature excursions are assessed against manufacturer stability data.

Immunogenicity risk factors include non-human sequences, aggregation, and glycosylation differences; anti-drug antibodies can neutralize efficacy or cause hypersensitivity.

Pharmacopoeial quality control of botanicals: identity by macroscopic, microscopic, and chromatographic fingerprinting, marker-compound assay, and limits for heavy metals, pesticides, aflatoxins, and microbes.

USP <797> risk levels: low-risk (fewer than three sterile products, closed transfer), medium-risk (multiple additives or pooling), high-risk (non-sterile starting materials or open systems); beyond-use dates lengthen as risk decreases.

Cleanroom classes: ISO Class 5 critical zone in the laminar-airflow hood, ISO 7 buffer room, ISO 8 ante-room; first air must pass over critical sites without obstruction.

Garbing sequence: shoe covers, head cover, mask, gown, then gloves; disinfect with 70% isopropyl alcohol using friction and allow full drying before entry.

High-risk compounding requires terminal sterilization or 0.22-micron filtration when feasible; preservative-free preparations are mandatory for intrathecal, epidural, and neonatal use.

Hazardous drugs (USP <800>): closed-system transfer devices, biological safety cabinets or containment ventilated enclosures, chemotherapy-rated double gloves, and surface decontamination.

TPN: check osmolarity limits for peripheral versus central administration and calcium-phosphate compatibility, which falls with rising pH and temperature.

Assign beyond-use dates from the compounding date based on risk level and preservative status; verify container compatibility (PVC adsorption, plasticizer leaching) before extending storage.

Unit-dose distribution, automated dispensing cabinets with override auditing, and standardized crash carts reduce hospital medication errors and waste.

Israel's National Health Insurance Law (1994) mandates coverage through four health funds (Clalit, Maccabi, Meuhedet, Leumit); the basket of services (sal ha-briut) is updated annually by a public committee.

Routine childhood immunization includes DTaP-IPV-Hib, MMR, hepatitis B, and pneumococcal conjugate vaccines; annual influenza vaccination is recommended for adults over 65, pregnant women, and chronic-illness patients.

Herd immunity threshold = 1 - 1/R0; measles R0 of 12-18 requires roughly 92-95% two-dose coverage, which is why outbreaks follow coverage drops.

Anaphylaxis after vaccination is rare (~1 per million doses) and is treated with intramuscular adrenaline 0.5 mg (1:1000) in adults; 15-minute observation prevents syncope injury.

Wilson-Jungner screening criteria require an important condition, detectable early stage, accepted treatment, suitable test, and cost-effectiveness; examples are mammography and colorectal screening.

Incidence counts new cases per population-time; prevalence counts existing cases; sensitivity and specificity describe test performance independent of prevalence.

Antimicrobial resistance is a One Health problem requiring human prescribing stewardship, limits on agricultural use, infection control, and surveillance networks.

Know referral pathways among community pharmacy, health-fund clinics, emergency departments, and public health services, and which body handles adverse-event reports and drug shortages.