H1, alpha-1, V1, M1, M3 - HAVe 1 M&M Activate Phospholipase C--> cleave PIP2 (lipid-derived)--> 1. DAG==> PKC 2. IP3--> Ca+2 increase in cell--> smooth muscle contraction

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)

M2, alpha-2, D2 - MAD 2s Blocks adenylyl cyclase 1. Decreased Ca+2 in heart (decreased contractility)= M2 2. Increases myosin light chain kinase activity (MLCK)--> smooth muscle contraction= alpha-2

Direct cholinomimetic agonist - Activates bowel, bladder smooth muscle - Resistant to AchE Use: - Post-operative ileus, neurogenic ileus, urinary retention (nonobstructive)

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"

``` 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)

Pharmacology basics Flashcards by Emily Cheston

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)

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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)

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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

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Zero order elmination

Drug elimination constant
- Cp decreases linearly (vs first-order exponential)

Ex: Phenytoin, Ethanol, Aspirin

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Urine pH/Drug elimination

Weak acid (phenobarbital, methotrexate, aspirin): eliminate with bicarb

Weak base (amphetamines): eliminate with ammonium chloride

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Nicotinic receptors

Stimulated by Ach
- Ligand-gated Na+/K+ channels

Nn= autonomic ganglia
+ Adrenal medulla
Nm= Neuromuscular junction

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Muscarinic receptors

Stimulated by Ach
- G-protein coupled receptors of parasympathetic system
+ Sympathetic sweat glands

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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

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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)

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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

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Vesamicol

Blocks VAchT (packaging of Ach in presynaptic terminals)

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Hemicholinium

Blocks ChT (influx of choline)–> can’t use with choline acetyl transferase to make Ach

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Metyrosine

Blocks tyrosine hydroxylase

- Can’t convert Tyrosine to DOPA

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Reserpine

Blocks VMAT: can’t packages DA, NE, epi

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Guanethidine, bretylium

Blocks release of Noradrenergic vesicles from presynaptic terminal (NE, DA, Epi can’t get out)

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Bethanchol

Direct cholinomimetic agonist

Activates bowel, bladder smooth muscle
Resistant to AchE

Use:
- Post-operative ileus, neurogenic ileus, urinary retention (nonobstructive)

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Carbachol

Direct cholinomimetic agonist (Ach)
- Identical to Ach (not AchE resistant)

Use:
- Glaucoma, pupillary contraction, relief of IOP
“Carbon copy of Ach”

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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”

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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)

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Pyridostigmine

Indirect cholinomimetic (anti-AchE)
- no CNS penetration

Use:
- MG (long-acting)

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Edrophonium

Indirect cholinomimetic (anti-AchE)

Use:
- MG (short-acting)- test

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Physostigmine

Indirect cholinomimetic (anti-AchE)
- Crosses BBB (thus can reverse CNS effects of anticholinergic toxicity)

Use:
- Atropine/anticholinergic overdose

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Donepexil

Indirect cholinomimetic (anti-AchE)
- Increases Ach

Use:
- Alzheimer’s disease

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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