Pharmacology Flashcards
Pharmacokinetics
Study of how drugs move throughout the body; includes absorption, distribution, metabolism and elimination.
Pharmacodynamics
Study of what a drug does to the body; generally determined by the drug’s affinity and activity at its site of action, which often times is a receptor
Bioavailability
Ability of a drug to be absorbed and used by the body
Half-life
The time it takes for the amount of a drug’s active substance in the body to reduce by half
Drug metabolism - First pass effect
Pharmacological phenomenon in which a drug undergoes metabolism at a specific location in the body thereby reducing the availability of the drug to travel to distant sites.
Drug metabolism - Cytochrome P450 system
Group of enzymes that metabolizes drugs; largely concentrated in the liver.
Strong inhibitor drugs
Clarithromycin
Darunavir
Ketoconazole
Lopinavir
Nirmatrelvir-ritonavir
Saquinavir
Voriconazole
Moderate Inhibitor drugs
Amiodarone
Cimetidine
Cyclosporine
Diltiazem
Erythromycin
Fluconazole
Grape fruit juice
Letermovir
Verapamil
Strong Inducer drugs
Apalutamide
Carbamazepine
Encorafenib
Fosphenytoin
Lumacaftor-ivacaftor
Mitotane
Phenobarbital
Primidone
Rifampin
Moderate Inducer drugs
Bexarotene
Cenobomate
Dexamethasone
Eslicarbazepine
Mitapivat
Modafinil
Pexidartinib
Rifabutin
St. John’s Wort
Drug Elimination - Glomerular Filtration
Works to filter waste and excess fluid from the blood into the urine
Drug elimination - Glomerular Barrier
Restricts passage of plasma proteins, such as albumin, red blood cells, and o their large blood constituents.
Drugs that bind to albumins, barbiturates, benzodiazepines penicillin, valproate, phenytoin, warfarin and NSAIDs
Drug Elimination - Renal excretion and aging
Glomerular filtration rate decreases by approximately 1% per year.
Non-steroidal Anti-Inflammatory Drugs (NSAIDs)
Primary effect of NSAIDs is to inhibit cyclooxygenase (an enzyme that produces prostaglandins)
Prostaglandins: hormone-like substances that affect several bodily functions (Inflammation, pain)
Two Variants of Cyclooxygenase
COX 1: Helps to regulate normal cellular functions (Vascular homestasis, platelet aggregation, kidney function)
- Aspirin inhibits platelet aggregation associated with COX-1 in an irreversible manner.
COX 2: Expressed in the brain, kidney, bone and likely the female reproductive system
- COX-2’s expression is increased during states of inflammation and is inhibited by glucocorticoids
Medications to avoid with NSAIDs
Phenytoin
Warfarin
Methotrexate
ACE Inhibitors
Glucocorticoids
Population that should avoid NSAIDs
Peptic ulcer disease
Gastrointestinal disease
Cardiovascular disease
Kidney disease
Gram stain
Categorizes bacteria into either gram-negative or gram-positive bacteria
- Gram-positive bacteria: Retain the violet and appear purple with gram staining
- Gram-negative bacteria: take up the safranin counterstain and appear pink
- Gram variable: Meaning they may stain either negative or positive (Example: Gardnerella Vaginalis)
CAN NOT BE VISUALIZED BY GRAM STAIN
- Mycoplasma species: lacks a cell wall
- Chlamydia and Mycobacterium: Cell wall structure does not retain gram stain reagents.
Gram-Positive Bacteria
Streptococcus
Staphylococcus
Enterococcus
Clostridium Difficle
Listeriosis
Diptheria
Botulism
Tetanus
Anthrax
Gram-Negative Bacteria
Neisseria Meningitidis or Neisseria Gonorrhoeae
Moraxella Catarrhalis
Escherichia
Klebsiella
Enterobacter
Pseudomonas
Haemophilus
Acinetobacter
Moraxella
Prevotella
Porphyromonas
Beta Lactam antibiotics
Includes Penicillins and cephalosporins (Both contain beta lactam ring in their chemical make up)
- Resistance due to beta lactamase
- Clavulanic acid protects against beta lactamase
Penicillin G
Active against: Gram positive cocci, gram positive rods (listeria), gram negative cocci (neisseria), most anaerobes, spirochetes
Anti-Staphylococcal Penicillins
Nafcillin, Oxacillin, Dicloxacillin
Active against: Penicillinase-producing staphylococci, staphylococcus aureus
Broad spectrum penicillins
Second generation: Ampicillin, Amoxicillin
Active against: Gram-negative bacilli, the majority of strains of Escherichia coli, Proteus mirabilis, Salmonella, Shigella, and Haemophilus Influenzae
- Generally PO Amoxicillin is preferred over ampicillin
- Ampicillin is preferred for the treatment of shigella
Third generation: Ticarcillin
Fourth Generation: Piperacillin
- Broad spectrum agents are active against gram-negative bacilli
Cephalosporins - First Generation
Cephalexin
Active against: Most gram-positive cocci, most strains of Escherichia coli, proteus mirabilis, and klebsiella pneumoniae
Cephalosporins - Second Generation
Cefuroxime, Cefaclor, Cefprozil
Active against: Haemophilus Influenzae, Moraxella Catarrhalis
Cephalosporins - Third Generation
Ceftibuten, Cefixime
Active against: Enterobacterales, Neisseria, H. Influenzae
Cephalosporins - Fourth Generation
Cefepime
Active against: Enterobacterales, Neisseria, H. Influenzae, P. Aeruginosa
Cephalosporins - Fifth Generation
Ceftaroline
Active against: Methicillin-resistant staphylococci, Penicillin-resistant pneumococci, enteric gram-negative rods.
Tetracyclines
Doxycycline, Minocycline
Active against: Many aerobic gram-positive and gram-negative bacteria and atypical pathogens such as mycoplasma and chlamydia
- Associated with permanent tooth discoloration in children < 8 years of age and with accumulating in fetal bones and teeth if it’s administered to pregnant women. - First line treatment for chlamydia and the prophylaxis/treatment of Lyme disease - Avoid concurrent use with penicillins
Sulfonamides
Trimethoprim/Sulfamethoxazole (Bactrim)
Active against: Variety of aerobic gram-positive and gram-negative bacteria, methicillin-resistant staphylococcus aureus
Fluroquinolones
Ciprofloxacin, Levofloxacin
Active against: Aerobic enteric gram-negative bacilli, many common respiratory pathogens, Pseudomonas selected gram-positive organisms, anaerobes, mycobacteria, tuberculosis, anthrax
- Ciprofloxacin: Activity against aerobic enteric gram-negative bacilli (Example: E. Coli), Pseudomonasaeruginosa - Levofloxacin: Activity against gram-positive organism (Example: Streptococcus pneumoniae and staphylococcus aureus)
Potential adverse effects with fluroquinolones: C. Diff infection, tendinopathy, tendon rupture, neuropathy, QT Interval prolongation, small alleged risk of aortic dissection and rupture.
Beta Blockers
They block beta adrenergic receptors
- Beta-1: Found mainly in the heart and kidneys - Beta-2: Found mainly in smooth muscle tissue, within the respiratory system, blood vessels and nervous system - Beta-3: Found mainly in fat cells and within the bladder
Cardioselective Beta Blockers (B1 receptor)
Acebutolol
Atenolol
Betaxolol
Bisoprolol
Esmolol
Metoprolol
Nebivolol
Non-selective beta blockers
Carvediolol
Labetolol
Nadolol
Penbutolol
Propranolol
Sotalol
Timolol
Angiotensin Converting Enzyme Inhibitors (ACEI)
- Prevents the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor
- First line treatment for hypertension
- Preferred option in patients with chronic kidney disease, and heart failure
Examples: Lisinopril, Benazepril, Captopril, Enalapril
Side effects: Related to either decreased angiotensin II or increased kinins
- Decreased angiotensin II:
- Hypotension, acute kidney injury, hyperkalemia and pregnancy complications
- If hyperkalemia occurs and is unable to be managed or if creatinine increases > 30% baseline within the first 6 - 8 weeks, ACE termination should be considered.
- Increased Kinins:
- Dry hacking cough, angioedema (rare but life threatening)
IMPORTANT POINTS
- Contraindicated in pregnancy
- ACE Inhibitors and ARBs CAN NOT be taken together.
Calcium Channel Blockers
- First line treatment for hypertension
- Can be used as monotherapy or adjunct treatment
- Significant amount of data supporting CCBs reduction in subsequent cardiac events
- Metabolized through the cytochrome P450 system
Calcium Channel Blockers - Non-Dihydropyridines
- Weaker vasodilator, works more to decrease the contractility of the heart
- Used for hypertension (not often), chronic stable angina, cardiac arrhythmias
EXAMPLES: Verapamil & Diltiazem
Side effects: Constipation, bradycardia, decreased cardiac output, gingival hyperplasia
Calcium Channel Blockers - Dihydropyridines
- Potent vasodilators with minimal cardiac effects
- Used for hypertension or chronic stable angina
EXAMPLES: Amlodipine, Nifedipine, Nicardipine
Side effects: Headache, lightheadedness, flushing, dependent peripheral edema, gingival hyperplasia
- Treat peripheral edema by reducing CCB dose, switch to a non-dihydropyridine and/or add a RAS-blocking agent (ACE or ARB)
Statins
Statin therapy is first line treatment for dyslipidemia
3-types: Low intensity, moderate intensity, and high intensity.
Low intensity Statin
Lovastatin (20mg)
Pravastatin (10-20mg)
Simvastatin (10mg)
Fluvastatin (20-40mg)
Moderate intensity Statin
Lovastatin (40-80mg)
Pravastatin (40-80mg)
Simvastatin (20-40mg)
Atorvastatin (10-20mg)
Rosuvastatin (5-10mg)
High intensity Statin
Atorvastatin (40-80mg)
Rosuvastatin (20-40mg)
BEFORE initiating Statin therapy
Get baseline aminotransferase levels
- In the presence of liver disease
- Pravastatin and Rosuvastatin are preferred
- Alcohol abstinence is imperative
- Start at a very low statin dose and titrate based on aminotransferase levels
- Re-evaluate in 4-12 weeks and re-check aminotransferase levels
- Checkk thyroid function (TSH)
- Hypothyroidism is a potential cause for dyslipidemia and can make patients more susceptible to muscle injury
Muscle injury associated with Statin use
Risk is highest with statins extensively metabolized by the Cytochrome P450 3A4
- Examples: Lovastatin, Simvastatin, Atorvastatin
IF muscle injury occurs:
- STOP statin
- Evaluate potential contributing factors
- Hypothyroidism
- Vitamin D deficient
- Medicate interactions
- Treatment options
- Restart at lower dose
- Switch statin agent
- Attempt alternate day dosing
- Switch to non-statin cholesterol lowering agent.
Digoxin
- Cardiac glycoside that is used for heart failure and supraventricular arrhythmias
- Inhibits the sodium potassium pump, which causes a temporary increase in intracellular sodium, causing calcium to influx through the sodium calcium exchange pump, leading to increased contractility.
- Narrow therapeutic index
- Heart failure: The therapeutic serum concentration is 0.5-0.9 ng/mL
- Atrial Fibrillation: The therapeutic serum concentration is 0.8-2 ng/mL
Digoxin Toxicity: Arrhythmias, gastrointestinal symptoms, confusion and vision changes (Halos or xanthopsia)
Levothyroxine
- Synthetic T4
- First line treatment for hypothyroidism
- Levothyroxine’s onset of action when taken orally is 3-5 days but does not reach its peak therapeutic effect until 4-6 weeks later
DOSING
Being at full dose UNLESS
- Patients with cardiac history and > 60 years on low dose (25-50 mcg/day)
- Re-check TSH in 4-6 weeks and titrate dose if needed slowly
- Take on empty stomach
Metformin
- First line treatment for Type 2 Diabetes
Decreases hepatic glucose by inhibiting gluconeogensis, decreases intestinal absorption of glucose and improves insulin sensitivity.
Benefits:
- Decreases A1C by 1-2%, not known to cause hypoglycemia, has shown to decrease food intake and body weight and may help reduce likelihood of cardiac events
Side effects:
- Diarrhea!
- Stop and wait for diarrhea to resolve before attempting metformin again at a lower dose and slowly titrate to desired dose.
Contraindications:
- Hypersensivitiy to metformin or any component of the formulation: severe renal dysfunction (eGFR <30), acute or chronic metabolic acidosis with or without coma.
Risk factors for lactic acidosis:
- Impaired kidney function (eGFR <30)
- Active liver disease
- Metabolic acidosis
- Dehydration
- Sepsis
- History of lactic acidosis
Selective Serotonin Reuptake Inhibitors (SSRI)
First line treatment for unipolar depression
- Also used for anxiety disorders eating disorders, obsessive-compulsive disorders and PTSD.
SSRIs work by blocking the reabsorption of serotonin, allowing more serotonin to be available.
EXAMPLES: Fluoxetine (Prozac), Paroxetine (Paxil), Sertraline (Zoloft), Citalopram (Celexa), and Escitalopram (Lexapro)
Side effects: GI Discomfort (Diarrhea), sexual dysfunction and weight gain
IMPORTANT POINTS
- Start at sub therapeutic dose and titrate up
- Screen the patient for bipolar disorder before beginning SSRI
- IF SSRI is stopped, taper is slowly.
