Pharmocology Drugs Specifics for Exam 1

Sulfamethoxazole

- Folate Pathway Inhibitor

- Bacteriostatic

- Broad Spectrum

- Often Paired with Trimethoprim to make Bactrim

- Resistance Common

- Common allergen

Trimethoprim

- Inhibits bacterial dihydrofolate reductase.

- Bacteriostatic.

- Inhibits bacterial DHFR 50,000x more selectively compared to human

Ciproflaxacin

- Topoisomerase II Inhibitor

- Bactericidal

- UTI and Pneumonia

- Narrower Spectrum T II inhibitor

- Black Box Warning for tendon rupture and avoid in kids due to cartilage toxicity

Levoflaxacin

- Topoisomerase II Inhibitor

- Bactericidal

- UTI and Pneumonia

- Broader Spectrum T II inhibitor

- Black Box Warning for tendon rupture and avoid in kids due to cartilage toxicity

Fidaxomicin

- Exclusively for C. Diff

- RNA Polymerase Inhibitor

- Bactericidal to C. Diff, low activity against gut flora

- At least as effective as oral Vancomycin

Gentamicin/Tobramycin

- Gram-negative infections

- Aminoglycoside

- Bactericidal

- Lack oral bioavailability due to charge

- Synergistic with beta-lactams

- Ototoxicity, Nephrotoxicity,

Doxycycline

- Tetracycline

- Block tRNA

- Broad spectrum

- Bacteriostatic

- Toxicity to teeth and bones

- Don't take with antacids or iron

Erythromycin/Clarithromycin

- Macrolide

- STI and Respiratory Infection

- Inhibit CYP3A4

- Potential for QT Prolongation

- Bacteriostatic

Azithromycin

- Macrolide

- STI and Respiratory Infection

- High tissue penetration followed by slow release

- Elimination half-life ~ 3 days

- Potential for QT Prolongation

- Bacteriostatic

Linezolid/Tedizolid

- Oxazolidinones

- Bacteriostatic

- Prevent peptide bond formation

- Effective against drug-resistant Gram-positives (MRSA)

- Toxicities: Myelosuppression, neuropathy

Clindamycin

- Lincosamides

- Prevents peptide bond formation

- Strep and Staph infection

- Bacteriostatic

- Toxicity causes C. Diff

Penicillin G

- Beta-Lactam

- Bactericidal

- The first of its kind

- IV only

- Primarily Gram +, Some Gram -,

- Susceptible to Beta-lactamase

- Common Allergen

Benzathine penicillin G

- Beta-Lactam

- Bactericidal

- IM only

- Primarily Gram +, Some Gram -,

- Susceptible to Beta-lactamase

- Common Allergen

Penicillin V

- Beta-Lactam

- Bactericidal

- PO only

- Primarily Gram +, Some Gram -,

- Susceptible to Beta-lactamase

- Common Allergen

Nafcillin

- Beta-lactam

- Bactericidal

- Effective against non-MRSA staphlococci

- Common Allergen

Amoxicillin

- Beta-Lactam

- Bactericidal

- Combined with Clavulanic Acid

- Improved against Gram +/-

- Susceptible to Beta-lactamase without inhibitor

- Common uses: sinusitis, otitis media

Ampicillin

- Beta-Lactam

- Bactericidal

- Combined with Sulbactam

- Improved against Gram +/-

- Susceptible to Beta-lactamase without inhibitor

- Common uses: sinusitis, otitis media

Piperacillin

- Beta-Lactam

- Bactericidal

- Combined with Tazobactam

- Used against Gram -

- Susceptible to Beta-lactamase without inhibitor

First Gen Cephalosporins

- Cefazolin (P), Cephalexin (O), Cefdroxil (O)

- Bactericidal

- Gram +

- Skin Infections, surgical prophylaxis

2nd Gen Cephalosporins

- Cefuroxime

- Bactericidal

- IV or PO

- Increased Gram -, Less Gram +

- Respiratory Infections

3rd generation cephalosporins

- Ceftriaxone (P), Cefpodoxime (O)

- Bactericidal

- Gram +

- Pneumonia, Meningitis

4th Gen Cephalosporins

- Cefepime (P)

- Bactericidal

- Good Gram +/- coverage, reserved for severe infections

- Effective against pseudomonas

5th Gen Cephalosporins

- Ceftaroline (P)

- Bactericidal

- Broadest Spectrum, for severe infections

- Active against certain drug-resistant infections (MRSA)

Carbapenems

- Broad Spectrum

- Bactericidal

- IV only

- Typically for severe life-threatening infections

- Cilastatin inhibits metabolism of Imipenem by renal dihydropeptidase-1, not needed for others

Aztreonam

- Monobactam

- Bactericidal

- Narrow Spectrum

- Aerobic Gram -

- Used in pts with Type I hypersensitivity rxns to other beta-lactams

Vancomycin

- Glycopeptide

- Bactericidal

- Gram +

- Used against C. Diff

- Infusion Rxn: flushed skin, erythematous rash, pruritis due to histamine release

- Time Dependent

Dalbavancin

- Lipoglycopeptide

- Bactericidal

- Gram +

- Used against C. Diff

- Lipid chains that inhance half-life for more convenient dosing

- Time Dependent

Rifampin

- RNA Polymerase Inhibitor and Antimycobacterial

- Binds to RNA Polymerase, inhibits transcription

- Lowers effectiveness of oral contraceptives

- Used against TB and leprosy

- Resistance develops rapidly

- Bactericidal

Isoniazid

- Antimycobacterial

- Inhibits synthesis of mycolic acid

- Hepatotoxicity

- Used against TB and leprosy

- Resistance develops rapidly

- Bactericidal

Metronidazole/Tinidazole

- Nitroimidazoles that damage DNA

- Create Cytotoxic Free-radicals when reduced leading to DNA breakage

- Anaerobic Bacteria (Selective Toxicity)

- Bactericidal

- Concentration Dependent

- Bacterial Vaginosis, parasites and other anaerobic bacteria

- Increases anticoagulant effect of warfarin (CYP2C9) inhibition, a potential carcinogen, avoid alcohol

Daptomycin

- Cell Membrane Active Agent

- Forms pores in cell membrane

- Bactericidal

- Drug-resistant, life-threatening infections

Fosfomycin

- Works through a unique mechanism to inhibit cell wall synthesis (upstream of beta-lactams)

- Used against UTI

Nitrofurantoin

- Used against UTI

- Oral use

- Metabolized by bacteria into toxic compounds

- Absorbed and excreted quickly leading to minimal systemic effect but great UTI clearance

- Bactericidal

Amphotericin B

- Binds to Ergosterol and forms pores in membrane

- Broadest Spectrum antifungal

- Highly toxic but can be mitigated with liposome formulations

Amphotericin B Toxicity

- Fever/chills ("shake and bake")

- hypotension

- nephrotoxicity

- arrhythmias

- anemia

- IV phlebitis

- vomiting

- headache

- constricts afferent arterioles, decreasing clearance of wastes and affecting electrolyte levels

Fluconazole

- Ergosterol synthesis inhibitor

- Widely used antifungal

- Well-tolerated

- Inhibits CYP3A4

Terbinafine

- Ergosterol Synthesis Inhibitor

- Accumulation in skin and nails

- Primarily for superficial infections

Micafungin

- Inhibits synthesis of Glucans (Fungal cell wall)

- Newer Drug

- Well-tolerated

- IV Only

Acyclovir

- ANTI-HSV DRUG

- HSV-1, HSV-2, Varicella Zoster

- Shortens symptom duration, faster healing, reduced viral shedding (less contagious)

- Produces nucleoside triphosphate which prevents elongation of Viral DNA

Oseltamivir

- Anti-Influenza Drug

- FLU A/B

- Neuraminidase inhibitor which prevents viral budding

- Only effective if given within first 48 hours of symptoms

Baloxivir Marboxil

- Anti-Influenza Drug

- Cap-dependent endonuclease inhibitor

- Inibits mRNA transcription

- Only 1 dose

- Shortens symptoms by about 24 hours

Nirmatrelvir/Ritonavir

- Paxlovid, Anti-COVID Drug

- Mpro inhibitor

- Ritonavir inhibits CYP3A4

- Potential for drug interactions due to CYP3A4 inhibition

Remdesivir

- COVID Drug

- Inhibits viral RNA-dependent RNA Polymerase, so virus can't copy RNA

- Originally for Hep C, works against Ebola and other viruses

- Only FDA Approved COVID Drug

- IV only

Molnupiravir

- Anti-COVID Drug

- One taut. looks like Cytidine one looks line uridine

- Leads to error catastrophe

- Possible concern for mutagenicity of the virus

- Does Fetal Harm

Bethanechol

- Direct-acting Muscarinic Agonist

- Resistant to hydrolysis by AChE and very low nicotinic activity

- Treatment of non-obstructive GI hypomobility (post-operative ileus)

- Post-operative or postpartum urinary retention

Pilocarpine

- Direct-acting Muscarinic Agonist

- Used against glaucoma

- Toxicity: dry mouth (xerostomia)

Organophosphates

- Indirect-acting cholinomimetics

- Irreversible Covalent Inhibitors

- Form a stable bond with AChE that does not hydrolyze spontaneously

- Highly potent nerve agent

- Engineered to disperse easily in the air and lipid soluble to allow skin absorption

- Used against Glaucoma

Neostigmine

- Anticholinesterases

- Glaucoma and Myasthenia gravis

- Treats muscle weakness by increasing ACh at the neuromuscular junction

- SOMATIC MOTOR NOT AUTONOMIC

Atropine

- Anticholinergic (Muscarinic Antagonist)

- Used to reverse bradycardia caused by excessive vagal discharge

- Antidote for cholinergic poisoning

- Can cause mydriasis

Scopolamine

- Prevents motion sickness

- Blocks signaling by vestibular apparatus

Oxybutynin/Solifenacin

- M3 antagonist

- Overactive Bladder treatment

- Long-term use associated with increased risk of dementia

- Quaternary amine antagonist may have lower risk due to less CNS penetration

Mirabegron

- Beta-3 Agonist

- Overactive bladder treatment

- Expensive

- Can cause hypertension

Ipratropium

- Short-acting COPD Treatment

- Nonselective M Antagonist but systemic absorption reduces by inhalation and quaternary amine action

- Reduces or prevents Bronchospasm

Tiotropium

- Long-acting COPD Treatment

- Nonselective M Antagonist but systemic absorption reduces by inhalation and quaternary amine action

- Reduces or prevents Bronchospasm

Anti-cholinergic Side Effects

- Dry mouth

- Blurred Vision

- Upset Stomach

- Headache

- Constipation

- Dry eyes

- Dizziness

- Impaired Memory

- Decreased Cognition

- Behavioral Changes

- Anxiety

- Insomnia

Causes of Anticholinergic Toxidrome

- Antidepressants

- Antihistamines

- Antipsychotics

- Nightshade plants

Botulinum Toxin A

- Inhibitor of ACh release

- causes botulism in food

- cleavage of SNARE proteins, prevents NT vesicle fusion

- Most lethal toxin known

- Affects NT release especially ACh and glutamate

Botulinum Toxin

- Botox

- Muscle spasms

- Hyperhidrosis

Alpha-1 Receptors

Causes calcium release inside cells, common use is to stimulate smooth muscle contraction

Alpha-2 Receptors

Location is usually presynaptic, inhibits NT release

Beta-1 Receptors

Increases heart rate

Beta-2 Receptors

Triggers relaxation of smooth muscles along respiratory tract and certain blood vessels

Beta-3 Receptors

Leads to lipolysis, the breakdown of triglycerides in adipocytes (release of energy reserves) and relaxation of the bladder detrusor muscles

Catecholamines

- Dopamine, norepinephrine, and epinephrine are all derived from tyrosine

- Differ in functional groups

Norepinephrine

- Released from sympathetic neurons

- Low potency at Beta-2 receptor

Epinephrine

- Released from the adrenal gland when SNS is activated

- Used as a vasoconstrictor in combo with local anesthetics

Phenylephrine

- Alpha-adrenergic Agonists

- Alpha-1 selective

- Used as decongestant

Oxymetazoline

- Alpha-adrenergic agonists

- Somewhat alpha-1 selective, primarily acts on alpha-1 because it is applied directly to tissue

- Decongestant nasal spray

Clonidine

- Alpha-adrenergic agonist

- Alpha-2 selective

- Decreases sympathetic outflow, reduces blood pressure,

- Still in use but not first line

Prazosin/Doxazosin

- Alpha-adrenergic antagonist

- Alpha-1 antagonist

- antihypertensive

- Used for BPH

- Doxazosin has a longer half-life and once daily dosing

Tamsulosin

- Alpha-adrenergic Antagonist

- Selective for alpha-1a and alpha-1d subtypes in prostate

- Less effective on vasculature

Alpha-blockers side effects

- orthostatic hypotension

- reflex tachycardia

- Nasal congestion

Dobutamine

- Beta-adrenergic Agonist

- Beta-1 Agonist

- Increases CO in Acute HF

- Risk of arrhythmias

Albuterol

- Beta-adrenergic Agonist

- Beta-2 selective

- Used for acute asthma exacerbation

Salmeterol

- Beta-adrenergic Agonists

- Long-acting

- Beta-2 selective

- Asthma

Propranolol

- Non-selective Beta Blocker

- Decreases CO by blocking Beta-1 at heart

- May produce bronchoconstriction by blocking Beta-2 in lungs

- May impair glucose mobilization by blocking Beta-2 in liver

- Inexpensive

Metoprolol

- Beta-selective blocker

- Decreases CO by blocking Beta-1 at heart

- Only interacts at heart

-Metoprolol Tartrate (immediate release)

- Metoprolol succinate (extended release)

Acebutolol

- Has intrinsic sympathomimetic activity

- Functions as partial agonist

- Avoids bradycardia

Labetalol

- Blocks beta-1, beta-2, and alpha-1

- Useful in HTN

Cocaine

- Indirect or mixed acting sympathomimetics

- Inhibits NET and NE re-uptake

Amphetamine

- Indirect or mixed acting sympathomimetics

- Enhances NE release and blocks reuptake

Ephedrine/Pseudoephedrine

- Indirect or mixed acting sympathomimetics

- Probably enhances release and also direct agonist activity

Timolol

- Beta Blocker

- Used in Glaucoma

- Reduces production of aqueous humor

Pilocarpine

- Muscarinic agonist

- Facilitates drainage through trabecular meshwork by contracting iris and ciliary muscles

Physostigmine

- Anticholinesterase

- Facilitates drainage through trabecular meshwork by contracting iris and ciliary muscles