Drugs Flashcards
Examples of Different Types of Receptor Protein Binding
Propranolol*: Binds to regulatory proteins (Non-selective beta blocker)
SSRI’s: Binds to and inhibits 5-HTT serotonin reuptake transporters; serotonin stays in the synapse for longer (antidepressants); resembles brain substrate to pass BBB
Statins: Binds to and inhibits HMG-CoA reductase enzyme which synthesizes (cholesterol)
Vincristine: Binds to and inhibits structural protein microtubules to inhibit mitosis (cancer)
pH/pKa and Absorption of Drugs
Acetylsalicylic Acid (ASA/Aspirin): Nonsteroidal Anti-inflammatory Drug (NSAID)
- Is weakly acidic, not an ion in strong acid fasted stomach environment (absorbed)
- Is an example of zero order elimination (ex., n mL/hour vs m %/hour)
- Also useable for angina
Examples of Phase 1 Metabolism
Action: Hydrophilic functional group site exposure by CYP enzymes.
Codeine: Morphine prodrug; phase 1 metabolized by CYP2D6, demethylated to turn into morphine
- Polymorphism results in ultrarapid metabolism; 13* faster; kills babies
- NO CODEINE FOR BREASTFEEDING MOTHERS; significant amount is in breast milk
Warfarin, Fluconazole*: (Tutorial) Anticoagulant and Antifungal; competes for CYP2C8/9 metabolism and therefore warfarin lasts longer in the body
Examples of Phase 2 Metabolism
Action: Hydrophilic conjugation
Acetaminophen (Paracetamol/Tylenol): Analgesic (pain reliever);
- Toxic in overdose with no GSH (glutathione; utilized by GST [glutathione-S-transferase])
- Ingested in active form and can be biotransformed into NAPQI; must be phase 2 metabolized/deactivated by GST otherwise it’ll react and do bad things
Morphine: Ingested in the active form; must be phase 2 metabolized by glucuronidation (UGT)
- Can form inactive M3G; but 10% of the time forms active Morphine-6-Glucuronide (M6G)
Examples of Excretion (Active, Kidney-Only, Passive-Tubular Reabsorption, Biliary)
Penicillin: An antibiotic. Works via B-lactam ring.
- Has a very short half life (~30 minutes) due to active excretion transport; SLC/OAT transporters
- Probenecid is an anti-uric acid drug that competes for OAT w/ penicillin; increase t1/2 penicillin
Digoxin (Digitalis): Medication used to treat CHF, Arrhythmias; Only elimination is via the kidneys
- Makes heart contractions stronger which in turn increases GFR (glomerular filtration rate)
- Low GFR -> don’t give much; it raises GFR -> need to titrate, give more for the same effect
Methamphetamine: A weak base; pKa = 9.9; bad bad drug -> you want to get rid of it in the kidneys
- Passive Tubular Reabsorption happens if it is not an ion; present as both in natural urine
- Need to acidify urine; go below pKa so it acts as a base; becomes NH3+, no reabsorption
Oral Contraceptives: Given in shockingly small doses; Usually glucuronidated and excreted in the bile
- In the large intestine, beta-glucuronidase enzymes in GI flora cleave off glucuronide
- Drug can reabsorb and its effects can take place again
In the case of broad-spectrum antibiotics; this kills the flora
- Drug is not reabsorbed and can’t take effects -> spontaneous pregnancy
Zero Order and First Order Elimination:
Saturable enzymes vs. unsaturable kidneys
Ethanol: Acted on by alcohol dehydrogenase which is saturable at a rate of 10mL/hour/70kg
- Other zero orders include Phenytoin, ASA, CIsplatin, Fluoxetine, Omeprazole
95% of other drugs: First order elimination
Relevant Drug Class Suffixes:
- osin: A1 antagonists/blockers
- olol: Beta blockers
- pril: Angiotensin-Converting Enzyme Inhibitors (ACEI)
- sartan: Angiotensin-Receptor Blockers (ARBs)
- dipine: Dihydropyridine Calcium Channel Blockers
Cholinergics/ Parasympathomimetics
Can be direct agonist, indirect acting (AChE inhibitor)
Pilocarpine (Direct)/Physostigmine (Indirect)
- MoA: Muscarinic receptor activation in ciliary body contracts, activates trabecular meshwork to drain aqueous humour (indicated in glaucoma) to relieve intraocular pressure
Methacholine
- MoA: Inhaled; directly stimulating cholinergic that constricts bronchioles, increases secretions
Used to diagnose asthma if lung function drops >20%
(No specific drug); Indicated in dry mouth after radiotherapy; head/neck cancer
- Cholinergic stimulation increases secretions in mouth
Anticholinergics/ Anti-Parasympathomimetics
Inhibited PSNS = SympNS domination
Atropine: Prototypical muscarinic blocking drug
- MoA: Competitive muscarinic inhibitor
- Indications:
• Topical: Pupillary DIlation, Asthma/COPD, Gastric hypermotility, Incontinence
• Cholinergic poisoning (anti-Sarin nerve gas)
- Side Effects:
Could give you tachycardia
Adrenergics/ Sympathomimetics
Direct or indirect (increase NE release; amphetamines), or both
General Adverse Effects: Very powerful, can have systemic problems (many are topical)
- CNS: Headaches, restlessness, tremors, nervous, dizzy, excited, insomnia, euphoria
- CV: Tachycardia, HTN, heart palpitations
- Other: Loss of appetite, dry mouth, nausea, vomiting, muscle cramps
Drugs:
- Synthetic Epinephrine
- Phenylephrine
- Dobutamine
- Terbutaline
- Salbutamol
Synthetic Epinephrine
Synthetic Epinephrine: Intramuscular Autoinjector (Epipen)
- MoA: Binds a/B receptors systemically; higher BP to counter shock, bronchodilation, ino/chronotropic
- Indications:
• Anaphylaxis
Phenylephrine
Phenylephrine: a1 agonist
- MoA: Binds selectively to a1 receptors to contract smooth muscle
- Indications:
• Topical Eyedrops for pupillary dilation (like atropine)
• Surgery to prevent hypotension, diffusion of local anesthetic
• Reduces nasal congestion as a spray
Dobutamine
B1 agonist
MoA: Binds to B1 receptors in the heart for positive inotropic, chronotropic effect
Indications:
- Emergency situations; heart block, bradycardia, cardiac arrest
- Stress test to cause arrhythmias in heart clinics
Terbutaline
B2 agonist
MoA: Binds to B2 receptors in uterus to reduce/stop contractions by relaxing smooth muscle
Indications:
- Premature labour
Salbutamol
B2 agonist
MoA: Binds to B2 agonists in the lungs to relax smooth muscle for bronchodilation
Indications:
- Topical inhaler for asthma
Antiadrenergics/ Sympatholytics
Can be a or B antagonists, or both
Drugs:
- Prazosin
- Clonidine
- Methyldopa: - Yohimbine
Prazosin
Prazosin: a1 antagonist
MoA: Binds and antagonizes a1 receptor; causes relaxation of smooth muscles (blood, uterus, GI)
Indications:
- Benign Prostatic Hyperplasia; relaxes smooth muscle around prostate
- Hypertension as an add-on (due to several adverse effects in high doses for systemic effect) -> Take before bed to prevent orthostatic hypotension + syncope
Adverse Effects:
- CV: Orthostatic hypotension, rebound tachycardia, palpitations, chest pain
- CNS: Dizziness, drowsiness, depression
Clonidine
Clonidine: Centrally acting a2 agonist
MoA: Activates A2 receptors in the CNS to prevent NE release
Indications:
- Hypertension; but is not a preferred treatment; use secondary
Methyldopa
Methyldopa: Adrenergic neuron blocker; centrally acting a2 agonist
MoA: Same as clonidine + inhibits Dopamine production and therefore NE/Epi
Indications:
- Pregnancy-Induced HTN: Preferred with combined a/B antagonist labetalol
Examples of “-olol”s: Beta antagonists/Beta blockers/Selective B1 Blockers or nonselective
Propranolol, Timolol (nonselective), Atenolol, Metoprolol (selective)
MoA: Antagonizes B1 receptors for negative ino/chronotropic, or B2 to contract smooth muscle
- B2 is generally less wanted; makes breathing harder
- Cardioprotective; Decreases cardiac workload, O2 demand, output, renin secretion
Indications:
- Exertional Angina/CAD: Chest pain from lack of cardiac O2; B1 blocker reduces workload
- Hypertension: Reducing cardiac force/rate/output = less pressure with each stroke
- Mild to Moderate Heart Failure (will make severe failure worse)
- Cardiac Arrhythmias (Supraventricular tachycardia)
—-
- Glaucoma: Timolol; nonselective B2 used is an eyedrop
- Migraines/Parkinson’s: Propranolol can be used to reduce tremors, migraines
Reduces heart rate, blood pressure (performance anxiety, sharpshooting PED)
- Pheochromocytoma: Adrenal medulla tumour; must be surgically removed
Inhibit entire SympNS pathway
Adverse Effects:
- CV: Bradycardia, heart failure, erectile dysfunction
- CNS: Dizziness, lethargy, depression (blood doesn’t reach the brain)
- Resp: Bronchospasm, mucus production in COPD, asthma
Special Considerations/ Contraindications:
- Elderly: Give them thiazides/loop diuretics instead for HTN
- Asthmatics/COPD: Don’t give as it might exacerbate condition (lung secretions)
Diabetics: Masks symptoms of hypoglycemia; tachycardia, shivering, sweating (or sepsis)
Severe Heart Failure: Don’t give
Ex: Labetalol
Labetalol
Labetalol: Combined a/B antagonist
MoA: Antagonizes both a and B receptors- relaxes vascular resistance, heart rate/force
Indications:
Pregnancy-Induced HTN: Preferred with adrenergic neuron blocker methyldopa
Neuromuscular Blocking Agents/Paralysis-Inducing Drugs. Adverse effects, special considerations and examples.
General Adverse Effects:
- Hyperkalemia: With depolarizing blockers; lots of K+ is released into blood without repolarize
- Muscle Pain: With depolarizing blockers, esp. In muscular patients; lots of twitching/soreness
- Malignant Hyperthermia: With succinylcholine; Genetic reaction; mutated Ca2+ channels -> more K+ dumped in blood, rise in body temp, tachycardia, muscle rigidity
- Increased Intragastric Pressure: Risk of regurgitation, aspiration -> fasted before surgery
- Increased Intraocular Pressure: 1-5 minutes after IV injection; nobody knows why
Ex: Tubocurarine and Succinylcholine
Special Considerations:
- Elderly, Myasthenia Gravis -> Reduced dose
- Burns and Upper Motor Neuron Diseases -> Increased dose
Tubocurarine
Tubocurarine: Non-depolarizing blocking agent; NM receptor antagonist -> Pancuronium, Atracurium
MoA: Binds to NM receptors as a competitive inhibitor of ACh; inability to bind = paralysis
Reversibility: Uses AChE inhibitors (Neostigmine, Edrophonium)
- AChE inhibitors allow ACh to stay in the NMJ; outcompetes tubocurarine
Indications:
- Surgical Relaxation: People’s bodies still twitch during surgery; requires paralysis
- Endotracheal Intubation: People don’t like having tubes shoved down their throats
- Assisting Ventilation: Critically ill respiratory failure; decreases chest-wall resistance
- Convulsions: For muscular spasms of epilepsy; doesn’t treat epilepsy itself
