Pharmacology basics Flashcards
Volume of distribution
Vd= (amount of drug in body)/(plasma drug concentration)
- Vd high when drug goes everywhere OR if plasma proteins low (cirrhosis, kidney disease)
Half-life of drug
First-order elimination (rate of elimination proportional to drug concentration in blood= constant fraction eliminated per unit time)
- Exponential elimination
Takes 4-5 half-lives to reach steady state with a drug infused at steady rate
- 97% of a drug is excreted in 4x t1/2
- To calculate clearance of drug, need to know t1/2= (0.7 x Vd)/CL or
(0. 7 xVd) / (rate of elimination of drug/plasma drug concentration)
- To calculate clearance of drug, need to know t1/2= (0.7 x Vd)/CL or
Clearance (CL)
CL= rate of elimination of drug/plasma drug concentration= Vd x elimination constant (Ke)
Loading dose= Cp x Vd/F
- Cp= target plasma concentration
Maintenance dose= Cp x CL/F
- F= bioavailability
Zero order elmination
Drug elimination constant
- Cp decreases linearly (vs first-order exponential)
Ex: Phenytoin, Ethanol, Aspirin
Urine pH/Drug elimination
Weak acid (phenobarbital, methotrexate, aspirin): eliminate with bicarb
Weak base (amphetamines): eliminate with ammonium chloride
Nicotinic receptors
Stimulated by Ach
- Ligand-gated Na+/K+ channels
Nn= autonomic ganglia
+ Adrenal medulla
Nm= Neuromuscular junction
Muscarinic receptors
Stimulated by Ach
- G-protein coupled receptors of parasympathetic system
+ Sympathetic sweat glands
Gq receptor types
H1, alpha-1, V1, M1, M3
- HAVe 1 M&M
Activate Phospholipase C–> cleave PIP2 (lipid-derived)–>
- DAG==> PKC
- IP3–> Ca+2 increase in cell–> smooth muscle contraction
Gs receptor types
Beta1, Beta2, D1, H2, V2
Activates adenylyl cyclase
- -> cAMP–> PKA–>
1. increase Ca+2 concentration in heart muscle–> contractility
2. block myosin light chain kinase (prevent smooth muscle contraction)
Gi receptor types
M2, alpha-2, D2
- MAD 2s
Blocks adenylyl cyclase
- Decreased Ca+2 in heart (decreased contractility)= M2
- Increases myosin light chain kinase activity (MLCK)–> smooth muscle contraction= alpha-2
Vesamicol
Blocks VAchT (packaging of Ach in presynaptic terminals)
Hemicholinium
Blocks ChT (influx of choline)–> can’t use with choline acetyl transferase to make Ach
Metyrosine
Blocks tyrosine hydroxylase
- Can’t convert Tyrosine to DOPA
Reserpine
Blocks VMAT: can’t packages DA, NE, epi
Guanethidine, bretylium
Blocks release of Noradrenergic vesicles from presynaptic terminal (NE, DA, Epi can’t get out)
Bethanchol
Direct cholinomimetic agonist
- Activates bowel, bladder smooth muscle
- Resistant to AchE
Use:
- Post-operative ileus, neurogenic ileus, urinary retention (nonobstructive)
Carbachol
Direct cholinomimetic agonist (Ach)
- Identical to Ach (not AchE resistant)
Use:
- Glaucoma, pupillary contraction, relief of IOP
“Carbon copy of Ach”
Pilocarpine
Direct Cholinomimetic agonist
- Contracts ciliary muscle of eye
- Pupillary sphincter contraction
- Resistant to AchE
Use:
- Stimulates sweat, tears, saliva
- Open/closed angle glaucoma
“Cry onto your pillow”
Neostigmine
Indirect cholinomimetic (anti-AchE) - No CNS penetration (Neo= No-CNS penetration)
Use:
- Post-op ileus
- Neurogenic ileus, urinary retention
- MG
- Reverse NM junction blockade (post-op)
Pyridostigmine
Indirect cholinomimetic (anti-AchE) - no CNS penetration
Use:
- MG (long-acting)
Edrophonium
Indirect cholinomimetic (anti-AchE)
Use:
- MG (short-acting)- test
Physostigmine
Indirect cholinomimetic (anti-AchE) - Crosses BBB (thus can reverse CNS effects of anticholinergic toxicity)
Use:
- Atropine/anticholinergic overdose
Donepexil
Indirect cholinomimetic (anti-AchE) - Increases Ach
Use:
- Alzheimer’s disease
Cholinesterase inhibitor poisoning (organophosphate poisoning)
Organophosphates (parathion) inhibit AchE
- Pupils small, decreased breathing/HR
- Lots of fluid excretion
- Muscle twitching
(Diarrhea, diaphoresis, urination, miosis, bronchospasm, bradycardia, emesis, lacrimation, salivation)
Antidote= Atropine (anticholinergic) + Pralidoxime (regenerates active AchE- otherwise muscle spasm–> paralysis)
Atropine, homatropine, tropicamide
Muscarinic antagonists (M3)
Use: mydriasis, cycloplegia
“Belladonna/Nightshade”
- Atropine also decreases airway secretions, acid secretion, gut motility, bladder urgency
Toxicity of Atropine:
- Hot as a hare, Dry as a bone, Red as a beet, Blind as a bat, Mad as a hatter
- Jimson weed–> Gardner’s pupil (mydriasis d/t plant alkaloids)
Benztropine
Muscarinic antagonist (M1)
CNS depression
Use:
- Parkinson’s disease dystonia, tremor
Scopolamine
Muscarinic antagonist (M1)
Use: motion sickness (prevents vestibular transmission)
Ipratropium, Tiotropium
Muscarinic antagonist (M3) (parasympathetic control of asthma vs noradrengergic)
Use: COPD, asthma
- Blocks respiratory secretions
Oxybutynin
Muscarinic antagonist (M3)
Use:
- Reduce urgency in mild cystitis, reduce bladder spasms
Glycopyrrolate
Muscarinic antagonist (M3)
Use:
- Parenteral: pre-op to reduce airway secretions
- Oral: stop drooling, peptic ulcer
Terbutaline, Ritodrine
Beta agonists
Use: prevent premature contractions (tocolytics)
Clonidine, alpha-methyldopa
Centrally acting alpha-2 agonist
- Decreases sympathetic outflow
Use:
- Hypertension, esp. with renal disease (no decrease in blood flow to kidney)
Phenoxybenzamine
Nonselective irreversible alpha blocker
Use:
- Pre-op pheochromocytoma excision
Tox: orthostatic hypotension, reflex tacchycardia
Phentolamine
Nonselective reversible alpha blocker
Use:
- Give to patients who have eaten tyramine-containing food while on MAO-I
-zosins
Alpha-1 blockers
Use:
- HTN
- BPH–> urinary retention
Tox: 1st dose orthostatic hypotension, dizziness, H/A
Mirtazapine
Alpha-2 blocker
Use: depression
Tox: sedation, increased serum cholesterol, increased appetite
Beta-1-selective antagonists
Acebutolol (partial) Betaxolol Esmolol Atenoolol Metoprolol
Nonselective antagonists
Propanolol
Timolol
Nadolol
Pindolol (partial)
Nonselective alpha and beta antagonists
Carvedilol
Labetolol
Antidote for beta-blocker
Glucagon
Antidote for digitalis
Normalize K+, Lidocaine, Anti-dig Fab fragments, Mg+2
Iron antidote
Deferoxamine, Deferasirox
Lead antidote
CaEDTA, dimercaprol, succimer, pencillamine
Mercury, arsenic, Gold antidote
Dimercaprol (BAL), succimer
Copper, arsenic, Gold antidote
pencillamine
Overdoses to treat with NaHCO3 (alkalinize urine):
Salicylates
TCAs
Barbituates
Benzo overdose tx
Flumazenil
tPA, streptokinase, urokinase overdose tx
Aminocaproic acid
Epinephrine
Stimulates: all sympathetics
Use: anaphylaxis, glaucoma, asthma, hypotension
Norepinephrine
Alpha-1, Alpha-2, some Beta-1 stimulation
Use: Hypotension (but decreases renal perfusion)
Isoproterenol
Beta-1 and beta-2 stimulation
Use: Torsades de Pointes (tachycardia decreases shortened QT interval)
- Bradyarrhythmias (can worsen ischemia)
Dopamine
High dose: Alpha-1, 2 stimulation
Medium dose: beta-1, 2 stimulation
Low dose: D1 receptors
Use: shock (renal perfusion), heart failure, inotrope and chronotrope
Dobutamine
beta1 stimulation
Use: heart failure, cardiac stress-test
- Inotrope, chronotrope
Phenylephrine
Alpha1, alpha2 stimulation
Use: hypotension (vasoconstrictor) while allowing compensatory decrease in HR (vagal stimulation)
- Ocular procedures (mydriasis)
- Rhinitis (decongestant)
Albuterol, Salmeterol, terbutaline
B1, B2 stimulation
Metaproterenol and albuterol for acute asthma
Salmeterol for long-term asthma or COPD control
Terbutaline to decrease premature contractions
Ritodrine
B2
Use: reduces premature uterine contractions
Amphetamine
Indirect general agonist
- Releases stored catecholamines
Ephedrine
indirect general agonist
- Releases stored catecholamines
Cocaine
Inirect general agonist
- Reuptake inhibitor
