HIV Fusion Inhibitor;

Binds gp41 of viral envelope preventing conformational change req for viral entry into host cell;

Admin SQ, 2X a day;

No CYP;

Resistance with gp41 mutations but No cross resistance with OTHER drugs;

Only for tx-experienced pts who are failing HAART;

SE: Hypersensitivity and 8x increased risk of bacterial pneumonia*

HIV Fusion Inhibitor;

CCR5 antagonist - binds CCR5 on Macrophages and prevents fusion of viral and host cell membranes;

Requires CYP3A4 for activity (interactions here);

Resistance at P-glycoprotein pump;

Tx R5 HIV serotype ONLY (50% of pt eligible);

SE: cough, rash, dizziness, bladder irritation, HEPATOTOX and cardiac toxicity possible.

AZT;

Nucleoside Reverse Transcriptase Inhibitor (NRTI);  Nucleoside analog (pyr-T) and competitive inhibitor of viral DNA synthesis - blocks elongation in previously uninfected cells (little effect on cells already infected);

Req (+P) X3 for action;

Reduces perinatal HIV transmission;

Metabolized by glucaronidation;

Avoid fatty meals, which ↓ AUC;

SE: MYELOSUPPRESSION, and rarely lactic acidosis and/or lipodystrophy

NRTI;

Nucleoside analog (pur- A,G) forms active ddATP - competitive inhibitor of viral DNA synthesis - blocks elongation in previously uninfected cells (little effect on cells already infected);

Req (+P) X3 for action;

Don't take w/ acidic foods (↓ AUC);

SE - PERIPHERAL NEUROPATHY, PANCREATITIS, lactic acidosis, lipodystrophy, many drug interaxns (Ganciclovir ↑ [plasma] and methadone ↓ [plasma])

NRTI;

Anti-retroviral and Anti-HBV;

 Nucleoside analog (pyr-C) and competitive inhibitor of viral DNA synthesis - blocks elongation in previously uninfected cells (little effect on cells already infected);

Req (+P) X3 for action;

 Longest NRTI t1/2;

SE - lactic acidosis, lipodystrophy

NRTI;

Nucleoside analog (pyr-T) and competitive inhibitor of viral DNA synthesis - blocks elongation in previously uninfected cells (little effect on cells already infected);

Req (+P) X3 for action;

SE: [worst SE of all NTRIs] PERIPHERAL NEUROPATHY, PANCREATITIS, lactic acidosis, lipodystrophy, hepatic steatosis, many drug interaxns (competes with AZT for activation enzymes)

NRTI;

Nucleoside Reverse Transcriptase Inhibitor (NRTI);  Nucleoside analog (pur-G) and competitive inhibitor of viral DNA synthesis - blocks elongation in previously uninfected cells (little effect on cells already infected);

Req (+P) X3 for action;

  Metabolized by EtOH Dehydrogenase;

SE: HYPERSENSITIVITY (genetic predisposition), lactic acidosis, lipodystrophy

Non-Nucleoside Reverse Transcriptase Inh (NNRTI);

Allosteric binding causes altered active site - inhibiting the enzymatic axn of RT;

No HIV-2 axn (HIV-1 only);

No activation req;

Hepatic CYP450 - INDUCER - ↓ plasma levels of PI's;

SE: HEPATOTOXIC, somnolence, fever, nausea, maculopapular rash on the trunk and extremities;

NNRTI;

Allosteric binding causes altered active site - inhibiting the enzymatic axn of RT;

No HIV-2 axn (HIV-1 only);

No activation req;

Hepatic CYP450 - INHIBITOR - ↑ plasma levels of PI's;

SE: maculopapular rash on the trunk and extremities;

Non-Nucleoside Reverse Transcriptase Inh (NNRTI);

Allosteric binding causes altered active site - inhibiting the enzymatic axn of RT;

No HIV-2 axn (HIV-1 only);

No activation req;

Hepatic CYP450 - INDUCER - ↓ plasma levels of PI's;

 SE - NEUROPSYCHIATRIC (HA, dizziness, strange dreams), TERATOGENIC, maculopapular rash;

Nucleotide (already has one Pi) Inhibitor; Inhibits reverse transcriptase; 

Requires ONLY 2 phosphorylation events for activation;

No CYP actions;

Once daily dosing;

SE: GI, ↑ liver enzymes, proximal renal tubulopathy (loss of P and Ca - bone tox possible);

Resistance via thymidine analog mutations + Cross resistance with Zidovudine (NRTI)-associated mutations.

Integrase inhibitor;

Blocks integration of viral (HIV-1 only) genome into host genome;

Oral admin, bid;

UGT metabolism (not CYP) by glucaronidation - drug interactions with rifampin (which induces its metab and ↓ drug levels) and atazanavir (PI, blocks its met and ↑ drug levels);

SE: N/V, fever, HA

Protease inhibitor;

Competitive, reversible, protease inhib, esp in monocytes, macrophages - blocks viral MATURATION;

CYP3A4 Inhibition;

UGT INHIBITION - hyyperbilirubinemia, jaundice + heart block*;

SE - hyperlipidemia, DM, lipodystrophy, ↑ liver enzymes, bleeding risk;

Protease inhibitor;

Competitive, reversible, protease inhib, esp in monocytes, macrophages - blocks viral MATURATION;

CYP3A4 Inhibition (but least amognst PIs);

Significant increase in AUC when taken with meals*;

SE - hyperlipidemia, DM, lipodystrophy, ↑ liver enzymes, bleeding risk;

Protease inhibitor;

Competitive, reversible, protease inhib, esp in monocytes, macrophages - blocks viral MATURATION;

CYP3A4 Inhibition - most potent amognst PIs;

SE: Hepatotox*, hyperlipidemia, DM, lipodystrophy, ↑ liver enzymes, bleeding risk;

Protease inhibitor;

Competitive, reversible, protease inhib, esp in monocytes, macrophages - blocks viral MATURATION;

CYP3A4 Inhibition;

SE:hyperlipidemia, DM, lipodystrophy, ↑ liver enzymes, bleeding risk;

Protease inhibitor;

Competitive, reversible, protease inhib, esp in monocytes, macrophages - blocks viral MATURATION;

CYP3A4 Inhibition;

SE - ALOPECIA, KIDNEY STONES, LIPODYSTROPHY, hyperlidemia, DM, inc liver enzymes, bleeding risk;

Protease inhibitor;

Competitive, reversible, protease inhib, esp in monocytes, macrophages - blocks viral MATURATION;

CYP3A4 Inhibition;

Decent increase in AUC if taken w/ meals;

SE:hyperlipidemia, DM, lipodystrophy, ↑ liver enzymes, bleeding risk;

Anti-Herpes - Nucleoside (purine) analog;

Inhibits vDNA pol causing chain termination;

Requires phosphorylation by viral thymidine kinase;

Tx - HSV (herpes keratitis, latent HSV, fever blisters, genital, HSV encephalitis), VZV, CMV (bone marrow transplant pts);

SE - HA, nausea, diarrhea;

At high doses: renal and CNS tox (crystalline nephropathy / tremors, delirium, seizures);

Anti-Herpes - Nucleoside (purine) analog;

Acyclovir Prodrug (all else same as ACV):

Inhibits vDNA pol causing chain termination;

Requires phosphorylation by viral thymidine kinase;

Tx - HSV (herpes keratitis, latent HSV, fever blisters, genital, HSV encephalitis), VZV, CMV (bone marrow transplant pts);

SE - HA, nausea, diarrhea;

At high doses: renal and CNS tox (crystalline nephropathy / tremors, delirium, seizures);

Anti-Herpes - Nucleoside (guanine) analog;

Prodrug of penciclovir;

Competitive inhibitor of viral DNA pol - does not cause chain termination. Still requires activation by vTK;

High bioavailibility;

Tx: HSV, VZV, EBV, HBV (post-liver transplant),

[oral alternative to ACV];

SE: Well tolorated (some HA, N/V)

Anti-Herpes - Nucleoside (guanine) analog;

Competitive inhibitor of viral DNA pol - does not cause chain termination. Still req activation by vTK;

High bioavailibility;

Tx: HSV, VZV, EBV, HBV (post-liver transplant),

[oral alternative to ACV];

SE: Well tolorated (some HA, N/V)

Anti-Herpes - Nucleoside (purine) analog;

Inhibits vDNA pol - chain termination;

Req activation by viral TK;

PO admin;

Tx: DoC to tx CMV retinitis in AIDS pt;

Given with Valganciclovir - 100X more potent than Acyclovir;

SE - MYELOSUPPRESSION, TERATOGENIC,

HA, N/D;

Anti-Herpes - Nucleoside (purine) analog;

Prodrug - requires activation by esterases following PO admin of ganciclovir***

Inhibits vDNA pol - chain termination;

Req activation by viral TK;

PO admin;

Tx: DoC to tx CMV retinitis in AIDS pt;

Given with Ganciclovir - 100X more potent than Acyclovir;

SE - MYELOSUPPRESSION, TERATOGENIC,

HA, N/D;

Anti-Herpes - cytidine NucleoTIDE analog;

Does not req activation by viral TK (used to tx ACV-resistant pts);

Tx: HSV, VZV, CMV RETINITIS (IV admin delays progression of CMV retinitis in HIV+ pts);

SE: NEPHROTOXIC, neutropenia, carcinogenic, ocular hypotony

Anti-Herpes - Pyrophosphate analog;

"Non-nucleoside";

Inhibits viral DNA pol by blocking its cleavage from dNTP (blocks viral DNA synthesis), ALSO Inhibts HIV 1-Reverse Transcriptase;

No activation required;

Tx: nucleoside resistant cases (HSV, VZV, CMV), CMV retinitis (ACV and GCV-resistant strains), HIV (RT inhibition);

SE - NEPHROTOX, N/V, anemia, fatigue

Anti-hepatitis - Nucleotide (A) analog;

Inhibits HBV DNA polylmerase;

Req 2x phosphorylation by cellular kinases to activate;

Tx: HBV;

No cross resisitance but additive effects w/ Lamivudine, ↑ AUC when co-admin with Ibuprofen;

SE: rebound hepatitis, nephrotoxicity, lactic acidosis and hepatomegaly with steatosis

Anti-viral, anti-immune, anti-proliferative;

Activates the Jak-Stat pathway and Inhibits viral entry into host cells, viral transciption, uncoating, and viral protein synthesis;

Tx: HBV, HCV, HPV, HHV-8 (kaposi);

SE: myelosuppression, N/V, neurotoxicity, creatinine elevation, and proteinuria (according to micro can also cause alopecia, depression and suicidal ideation)

Anti-hepatits drug - nucleoside analog (G);

Competitive inhibitor of GTP 5' capping of viral mRNAs; Ribavirin triphosphate concentrates in RBCs;

Tx: HCV, RSV;

SE: hemolytic anemia, myelosuppression, teratogenic. Adjust dose for pt with ClCr < 30 ml/min

Anti-Parkinsonism, Anti-flu (influenza) drug;

Uncoating inhibitor;

Blocks HA glycoprotein binding + blocks binding to M2 ion channel in viral envelope. Prohibits internal acidification (uncoating);

Works on Flu-A ONLY + Enhances DA release (PD tx);

"Good alternative to flu vaccine" (in IC and elderly pt);

Resistance is the result of a single aa sub in the TM region of the M2 channel;

SE: anorexia, nausia, CNS in elderly (restlessness, depression, psychosis, hallucinations, confusion);

CI: Caution in pt with preexisting seizure or psychiatric conditions

Anti-Parkinsonism, Anti-flu (influenza) drug;

Uncoating inhibitor;

Blocks HA glycoprotein binding + blocks binding to M2 ion channel in viral envelope. Prohibits internal acidification (uncoating);

Works on Flu-A ONLY + Enhances DA release (PD tx);

"Good alternative to flu vaccine" (in IC and elderly pt);

Resistance is the result of a single aa sub in the TM region of the M2 channel;

SE: less CNS SE than Amantidine

CI: Caution in pt with preexisting seizure or psychiatric conditions

(Relenza);

Anti-flu - Viral Release Inhibitor;

Inhibits viral neuraminidase which prevents cleavage of sialic acid and prevents detachment from the host = viral aggregation and ↓ viral spread;

Resistance via NA or HA mutations;

Admin via inhalation (low PO bioavail);

Tx: flu-A (2nd line, Aman/Rimantadine resistant strains) and B

(Tamiflu);

Anti-flu - Viral Release Inhibitor;

Inhibits viral neuraminidase which prevents cleavage of sialic acid and prevents detachment from the host = viral aggregation and ↓ viral spread;

Resistance via NA or HA mutations;

PO admin;

Tx: flu-A (2nd line, Aman/Rimantadine resistant strains) and B;

SE: N/V

[Thorazine]

Typical Anti-Psychotic - low potency;

Inhbits D2 receptor - effective for positive symptoms; Aliphatic side chain - low potency (↓ risk of EPS, ↑ risk of anti-muscarinic effects);

Tx: Huntington's chorea (DA antag);

SE: Corneal deposits, ↑ PRL (severe), ↓ INSULIN (impairs glc tolorance), Jaundice, ANTI-DIURETIC, ORTHOSTATIC hypoT, skin rxns (urticaria and dermatitis), EPS;

CI: In dementia-related psychosis (↑ mortality in the elderly)

Typical Anti-Psychotic - high potency;

Inhibits D2 receptor - effective for positive symptoms; Piperazine group - ↑ potency (↑ risk of EPS, ↓ anti-muscarinic effects);

SE: EPS, ↑ PRL, skin rxns (urticaria and dermatitis)

Typical Anti-Psychotic;

Inhibits D2 receptor - effective for positive symptoms; Piperdine ring - ↓ incidence of EPS;

SE - ↑ PRL, highly anti-muscarinic

[Haldol]

Typical Anti-Psychotic - very high potency;

Inhibits D2 receptor - effective for positive symptoms;

Tx: Huntington's chorea (DA antagonism);

SE - EPS, ↑ PRL, less orthostatic hypoT than with other typical antipsychotics.

Atypical Anti-Psychotic;

D2 (low affinity) and 5-HT2A (high affinity) antagonism;

↑ efficacy for Negative Sx (in addition to tx + sx);

5HT2A antg limits EPS SE;

SE - BLOOD DYSCRASIAS (w/ leukopenia prodrome), ↑ risk of DM typeII, weight gain (esp in kids and adolescents);

Atypical Anti-Psychotic;

D2 (low affinity) and 5-HT2A (high affinity) antagonism;

↑ efficacy for Negative Sx (in addition to tx + sx);

5HT2A antg limits EPS SE;

Tx: only approved agent for CHILDREN and TEENS;

SE - ↑ risk of DM typeII, moderate risk metabolic syndrome, ↑ PRL secretion and less/minor orthostatic hypoT;

Atypical Anti-Psychotic;

D2 (low affinity) and 5-HT2A (high affinity) antagonism;

↑ efficacy for Negative Sx (in addition to tx + sx);

5HT2A antg limits EPS SE;

SE - WEIGHT GAIN, ↑ risk of DM typeII, high risk of Metabolic Syndrome*

Atypical Anti-Psychotic;

D2 (low affinity) and 5-HT2A (high affinity) antagonism;

↑ efficacy for Negative Sx (in addition to tx + sx);

5HT2A antg limits EPS SE;

SE - ↑ risk of DM typeII, moderate incidence of metabolic syndrome.

No ↑ PRL*

Atypical Anti-Psychotic;

D2 (low affinity), 5-HT2A, 5-H1A, 5HT2C (high affinity) antagonism* (note different than many atypicals);

↑ efficacy for Negative Sx (in addition to tx + sx);

5HT2A antg limits EPS SE;

SE - ↑ risk of DM typeII, low incidence of metabolic syndrome

[Abilify];

Atypical Anti-Psychotic;

3MoA: D2 partial agonist, 5-HT2 antagonist, and 5-HT1A partial agonist;

↑ efficacy for Negative symptoms (as well as positives);

No effect/possible↓ of PRL levels;

SE - ↑ risk of DM typeII, low incidence of metabolic syndrome;

Cortex - ↓ seizure threshold;

Basal ganglia - ↑ DA metabolism + DA blockade (EPS - dystonia, akinesia, parkinsonian syndrome, perioral tremor, neuroleptic malig syndrome,tardive dyskinesia), ↑ Ach turnover;

Limbic - main site of anti-psychotic efx;

Hypothalamus - ↑ PRL;

Brainstem - dec reflexes;

CTZ - protect AGAINST N/V

Atypicals ↑ risk of Type II DM;

↑ PRL secretion (due to inhibition of D2) - Avoid in patients with breast carcinomas. Sustained hyperPRL can cause sexual dysfxn, amenorrhea, gynecomastia, galactorrhea, hypoestrogenism (poss osteopenia);

Direct and indirect effects;

Orthostatic hypotension - esp with chlorpromazine

Acute dystonia;

Akathesia;

Parkinsonian syndrome;

Neuroleptic Malignant Syndrome;

Perioral tremor;

Tardive dyskinesia

(Dilantin)

Anti-Epilepsy - Hydantoin;

Stabilizes inactive Na channels;

Met by CYP2C4, induces 2C and 3A;

Highly protein bound - competes w/ other drugs (warfarin, OCT, carbamazepine);

Tx: Never the DoC. 2nd choice to tx Partial or Tonic-Clonic seizures, also 2nd line to tx status epilepticus;

SE - [narrow TI*] nystagmus, ataxia, arrhythmias, megaloblastic anemia, coarsened face, hirsutism, gingival hyperplasia, peripheral neuropathy, bone disruption, teratogenic*

Rarely: Drug-induced lupus, SJS, TEN

AED - Barbiturate;

Prolongs the opening of the GABA receptor - ↑ Cl- influx. At high doses blocks Na/Ca and AMPA;

Induce CYP2b6 and UGT (enhances the metabolism of many other AEDs and ↓ effectiveness of OCs);

Tx: partial and generalized tonic-clonic seizures but not DoC due to sedation;

SE - Sedation*, lethargy, nystagmus, rash, megaloblastic anemia (due to ↓ folate)*, ↓ vitD

AED, Mood-stabilizer;

Inhibits Na+ channel recovery from inactive state;

Met by CYP2C9,3A4 to active 10,11-epoxide;

Induces CYP1A2, 2B6, 2C19, UGT - worst regarding drug interactions;

Tx: DOC for partial seizures (simple or complex) and tonic-clonic seizures. Mood stabilizer (bipolar), tx trigeminal neuralgia;

Tx depression (esp assoc w/ Huntington's);

SE - blood dyscrasias, diplopia, N/V, ataxia

AED;

Inhibits T-type Ca channels - prevents 3Hz spike/waves;

↑  AUC when given w/ valproic acid;

Met by hydroxylation;

Tx: DOC for absence seizures;

SE - [tolerance], euphoria, hiccups, fatigue, dizziness

AED;

3 MoA: Stabalizes inactive Na channels, ↓ Ca current, stimulates GABA synth/inhibits degradation;

Met by UGT via beta-ox - also inhibits it;

Inh CYP2C9;

Tx: absence + T/C. DOC for myoclonic, atonic and atypical absence;

↑ [plasma] phenobarb, phenytoin, carbamazepine;

SE: heartburn, hepatotoxicity, teratogenic;

Anti-epilepsy - BNZ;

↑ opening of GABA Cl- channel - potentiate GABA actions;

Can be given rectally;

Tx: refractory generalized (myoclonic, atonic, absence) but not first or second line;

SE - sedation, lethargy, rapid tolorance

(Valium)

Anti-epilepsy - BNZ;

↑ opening of GABA Cl- channel - potentiate GABA actions;

Can be given rectally;

Tx: IV or rectal admin as DoC for Status Epilepticus;

SE - sedation, lethargy, rapid tolorance

(Ativan)

Anti-epilepsy - BNZ;

↑ opening of GABA Cl- channel - potentiate GABA axns;

Long Acting;

Can be given rectally;

Tx: IV admin for status epilepticus (not DoC);

SE - sedation, lethargy, rapid tolorance

Anti-epilepsy;

Structural analog of GABA, and may ↑ GABA release;

Tx: [adjunct] partial, neuropathic pain, trigeminal neuralgia;

SE: somnolence, ataxia;

No major drug interactions*

Anti-epilepsy;

Delays recovery of inactivated Na channels, may inhibit glu release;

Tx: [adjunct] partial, T/C, absence, atypical/atonic/myoclonic;

SE: Nausia, dizziness, visual disturbance, rash, Stephen Johnson Syndrome* (1%)

Anti-epilepsy;

MOA not understood;

Tx: adjunct for partial sizure tx and monotherapy for T/C and myoclonic;

SE - dizzy, somnolence

Anti-epileptic;

Inhibits voltage Na channels, ↓Ca2+ current, ↑/enhances GABA axn, inhibits AMPA receptors;

Tx: refractory partial with or without T/C seizures;

SE: Kidney stones

Anti-epileptic;

Inhibits NMDA-evoked responses, prevents uptake and↑ actions of GABA;

Tx: [adjunct] partial and secondary generalizes seizures;

SE - aplastic anemia;

FAANG: Felbamate, Anaplastic Anemia, NMDA blocker, increases GABA

Anti-epileptic;

Inhibits Na channels and T-type Ca channels (↓ Ca current);

Tx: Broad Specturm - parital seizures (adjunct in adults), infantile spasm, myoclonic, generalized and absence;

Met by CYP3A4;

Regenerates glutathione.

Tx: Acetaminophen OD if blood concentrations are > 150 ug/mL at 4 h or 75 ug/mL at 8 hrs.

SE: Bad taste, N/V, anaphylaxis (give slowly);

Anticholinergis and opiates interfere with PO absorption of NAC.

BNZ antagonist;

Used to tx OD of BNZ and BRA - reverses respiratory depression but also precipitates withdrawl;

Not routinely used;

SE: N/V, panic attacks, seizures;

[Digibind]

Sheep Ig that sequesters the drug, preventing its actions on target tissues;

Tx: Digoxin OD;

Corrects hyperkalemia but elevates serum levels of digoxin by freeing it from the tissues.

Opoid receptor antagonist;

Short half life, must dose accordingly;

Tx: Opoid OD,

Beware that it will trigger withdrawl symptoms* (chills, pain, tremor, cramps, sweating, tachycardia, N/V/D, panic attacks, paranoia)

Opoid receptor antagonist;

Longer Half life*;

Tx: Opoid OD,

Beware that it will trigger withdrawl symptoms* (chills, pain, tremor, cramps, sweating, tachycardia, N/V/D, panic attacks, paranoia)

Achase Inhibitor in small doses IV;

Tx: Anti-cholinergic OD;

SE: Bradycardia, seizures;

Achase Inhibitor in small doses IV;

Tx: Anti-cholinergic OD;

SE: Bradycardia, seizures;

CI: with TCAs due to the possibility of causing heart block.

Treatment of choice for toxic inhalation, particularily with irritants (chlorine, ammonia, sulfur dioxide);

Note that humidivied oxygen is prefered to treat corrosive inhalant toxicity and that 100% oxygen alone is used to tx Carbon Monoxide poisoning

Cyanide Kit;

Tx: Cyanide poisoning (CN blocks Oxygen binding causing HA, N/V, syncope, seizures and coma);

A small dose of amyl nitrite is inhaled and is followed by IV Na-Nitrite (converts some Hgb to metHgb. Cyanide preferentially bonds to metHb rather than the cytochrome oxidase it was bound to. This converts metHb → cyanmethemoglobin).

In the last step, the IV Na Thiosulfate converts the cyanmethemoglobin to thiocyanate, sulfite and Hb. Thiocyanate is excreted in the urine.

Competitive Antagonist at the Muscarinic Ach receptors;

Given in cases of insecticide, nerve gas, organophosphate or carbamate poisioning to reverse bradycardia.

2PAM;

Binds to organophosphate-inhibited Achase molecules and frees the Achases;

Used to tx organophosphate poisioning;

Give slowly to prevent NM block, muscle spasms, laryngospasm, HTN and tachycardia.

Chelating Agent;

Used in cases of mild/asymptomatic lead poisioning in children, arsenic, and mercury poisioning;

Renally excreted so hydration is important.

Chelating Agent;

Tx: Severe/encephalophatic cases of lead poisoning and is the DoC in Arsenic posioning;

Nephrotoxic, may cause HTN, fever, tachy, HA, N/V, burning in the mouth, urticaria, and sweating;

Hemolysis risk in G6PD deficient patients*

Chelating Agent;

Inactive metabolite of penicillin;

For copper, Iron, lead and merucury posioning;

Minimal toxicity compared to other chelating agents.

Iron-only chelating agent;

IV admin is primary tx for iron overload;

Causes red urine, elevation of HR, hypoT, fever, and flushing. Shock is possible.

Chelator;

Tx: Iron overload in transfusion patients;

Causes diarrhea, HA, cough, fever, elevation of Cr and LFTs, and audio/visual disturbance.

Tx: Ratlesnake bites;

Uses small Ab fragments that are less likely to induce Ab response than whole IgG products.

When to Use Antivenom:

If there is rapid progression of swelling, significant coagulation defects, NM paralysis, or CV collapse.

There are several factors to consider when deciding when to begin treatment of an AIDS pt.

If the pt is symptomatic = Treat

Asymptomatic Situations

• CD4+ < 200 cells/uL = Treat
• CD4+ is between 200 and 350 cells/uL = Offer treatment with pros and cons.
• If CD4+ > 350 cells/uL and Plasma HIV RNA > 100,000 copies/mL = most will defer therapy (though some docs may choose to tx).
• If CD4+ > 350 cells/uL and Plasma HIV RNA <100,000 copies/mL = Defer Therapy

Protease Inhibitors

General MoA, uses, excretion and side effects

PI's are the most effective ART availible. Work in acutely and chronically infected cells;

Names end in -navir;

MoA: Competitive inhbitiors of protease binding on monocytes and macrophages which prevents cleavage of viral proteins and viral maturation. The result is the production of non-infectious viruses;

Bind reversibly to the protease active sight with greateer affinity for the HIV asp protease than for the human protease;

Each different drug in this class selects for different protease mutations;

Poor systemic bioaviailibilty;

Minimal renal excretion (no dose adjustment needed in renal failure pts);

General SE: Hyperlipidemia, GI distress, Diabetes, Lipodystrophy, elevation of LFTs (bleeding risk);

Many drug interactions due to inhibition of CYP3A4: Ketoconazole ↑ [PI].

Rifampin ↓ PI AUC.

The AUC for Methadone is reduced by PIs.

Silenafil augments PI AUC.

↓ [Oral Contraceptive].

These are the herpesvirus drugs, suffix = "-cyclovir"

Acyclic nucleoside analogs that inhibit viral DNApol, require activation by viral thymidine kinase;

Mutations in viral DNA polymerases or absence of viral TKs lead to resistance against these drugs.

Prolixin Decanoate, Haldol Decanoate, Risperidal Consta;

These formulations are the antipsychotic with a fatty acid complexed to them making them more lipophilic.

Are injected IM where tissue esterases hydrolyze the drug and allow slow release of the active compound;

Consider for patients who are non-compliant, have had several relapses, default on oral meds or have poor oral absorption/ideosyncratic pharm rxns.

Weight Gain/Metabolic syndrome (esp with clozapine > olanzapine), 

Urticaria/dermatitis (esp with phenothiazines),

Blood dyscrasias (esp with clozpine)

To treat N/V (act on CTZ to ↑ DA and reduce Nausea);

To treat alcoholic hallucinations during detox;

Neuropsychiatric dz marked by movement disorders (Tourette's, HD, intractable hiccups).

Adults: Analgesics > sedative hypnotics/antipsychotics > cleaning supplies > antidepressants

Children: Cosmetics/Personal care items > Cleaning supplies > Analgesics

Ingestion >>> Dermal > Inhalation

* Note that the MCC of fatal poisonings are as follows: Ingestion (75%) >> Inhalation > Unknown route > parental

T/F

At least 25% of cases of intoxication require crtical care and management

FALSE

Only 3.3% of all cases are considered critical and the majority (73%) are managed outside of the hospital*

FALSE

SDAC should not be routinely admininstered in the management of poisioned patients due to the high incidence of aspiration-related deaths.

Only effective with very protected airway, when given within 1 hr post ingestion and even then is not the DoC (still occasionally used for Asprin OD)

Ipecac is an emetic agent that is currently OTC and is often abused.

There is no evidence for improved outcomes in cases of overdose.

Gastric decontamination methods are only used for patients with life-threatening exposures.

Gastric Lavage involves placement of an NG tube and irrigation of the stomach and bowel with pulses of small amounts of liquids.

SE: perforation, aspiration, hypoxia.

No evidence for sig improvement of outcomes but still used with AC in tx TCA OD and OD of immediate release beta blockers or CCBs.

Whole Bowel Irrigation involves triggering rapid elimination of the gut contents using PGE isotonic water. Can cause bowel obstruction, or perforation, hemorrage, cramps, N/V.

Used in cases of sustained release beta blocker or CCB OD and with Theophylline OD.

Hemodialysis: ultrafiltration of the blood. Rquires that the toxin is water-soluble, relatively small, and mostly unbound in plasma.

Used in cases of severe Asprin or severe Theophylline OD (note that hemodialysis is used to tx theo OD but that hemoperfusion is prefered).

Hemoperfusion involves passing blood through a charcoal cartridge filter to remove drugs bound to plasma proteins.

Used in cases of Carbamazepine, Phenobarbital, Phenytoin, and Theophylline OD*

Present with RUQ pain (though often this does not set in until it is too late for tx);

Tx: NAC in the first 8 hours if levels are high enough (150 ug/ml at 4 hr or 75 at 8 hrs);

Death is from hepatic failure or secondary complications at 4-7 days.

Pt comes into the ED vomiting and sweating. He is breathing deeply and sweating profusely. When you question him you must repeat yourself several times as he appears to be unable to hear you properly.

What is the likely cause of these sx and what is the tx?

Acetylslaicylic acid OD;

Sx: N/V, sweating, tinnitus, lethargy, hyperpnea. Causes metabolic alk followed by acidosis (wind up effect due to crossing BBB). Can cause delerium and edema;

Tx: Charcoal is debated but occasionally used.

Fluids + dextrose, raising blood pH with NaHCO3 to ionize the drug is prefered for mild-moderate cases.

Hemodialysis if serum levels > 100 mg/dL or there is acute respiratory; or renal failure.

Pts are drowsy, confused, lack coordination, repiratory depression (reps acidosis), antegrade amnesia (think roofies)*

Death is more common when BNZ OD is combined with large amounts of alcohol;

Primary tx of choice = Supportive care (resp support),

Flumazenil is not routinely used due to SE.

Pt was found by her roommate who reported she was not breathing. When EMS arrived they had to intubate the pt due to severe hypoventilation and reported early signs of shock as well as dark lesions on the patients hands.

What is the most likely agent that caused these sympotms? Further complications? Treatment?

Barbituate OD;

Note the severe respiratory depression (without a celing and leading to shock, distinguishing it from BNZ OD), pt also had barbituate blisters on her hands (black lesions also often seen on the knees and buttocks);

Alternate sx include delerium, combative behavior, paranoia, tachy/bradycardias, hypoT, diphoresis, and decreased bowel sounds;

Complications include ARDS, shock and death (MC than with BNZ);

Tx Pheno and Aprobarbital OD: urniary alkalinization.

Tx All: ABCs, pressors to raise BP, dextrose and sodium bicarbonate, GI decontamination and/or hemoperfusion if severe.

What are the Sx and Tx of OD with Beta blockers?

Are there differences in tx based on the formulation of the drug?

Sx of BB OD: hypoT, low pulse, widening of QRS, ventricular arrhythmias (d/t memb stabilizing fx of bbs), sizures, ↓ respiration, hypoglycemia, and hyperkalemia;

Treatment depends on whether the drug is Immediate Release (gastric lavage and AC) or sustained release (whole bowel irrigation);

General tx: Atropine to correct bradicardia (coadmin with calcium), Glucagon (reverses decreased contractility of th eheart and raises blood glucose), and NE (pressor)

Sx: HypoT, AV block, vasodilation, hyperglycemia, metabolic acidosis, MI, bowel infarct;

Treatment depends on whether the drug is Immediate Release (gastric lavage and AC) or sustained release (whole bowel irrigation);

General tx: Atropine to correct bradicardia (coadmin with calcium), Glucagon (reverses decreased contractility of th eheart and raises blood glucose, give with Insulin), and (pressor)

A patient in the ICU becomes delirious and tells you that there are large spiders all over his room.

Labs report a plasma potassium level of 5.2 mEq/L.

What is the most likely etiology of these symptoms?

What other findings would be likely on more extensive physical exam?

Digoxin toxicity!

Sx: Malaise, vomiting, abdominal pain, delerium, hallucinations, arrhythmias;

Hyperkalemia is the mark of poisoning*

Further examination would likely reveal arrhythmias;

Tx: AC (debated) and/or Digibind

What are the key symptoms of Opioid OD?

How would you tx a pt with opoid OD?

Unconsciousness, Respiratory depression, Pinpoint pupils;

Hypotension, bradycardia, vomiting, and GI stasis are also often present;

Tx: Supportive Ventilation (primary*),

Naloxone (be prepared for withdrawl sx)

You have a pt in the ED whose roommate tells you that he "OD'ed" but he cannot tell you what the pt took.

As you are securing the pt's airway, he begins to seize.

What drugs are you now considering as the source of his OD?

Theophylline - ↑ cAMP, causes seizure,s hypoT, hypoK, hypergly, arrhythmias;

TCA's - primarily cardiotoxic, VA's, QRS widening, arrhythmias, hypoT.

Beta Blockers - hyperK, hypoT, VAs, reduced resp rate;

Note that Carbon Monoxide, Cyanide, hydrogen sufide, and Nitrogen oxides can all also cause seizures but the suggestion of the friend was that he "took something" not that he inhaled something or was found in a closed garage.

TCAs are cardiotoxic wihtin hours of OD causing conduction delays arrhythmias, and altering QRS,

also cause hypoT, changes in mental status, seizures and coma;

Tx: AC + Gastric lavage,

Bicarbonate (raising pH displaces drug from Na+ channels), vasopressor (NE) + IV fluids

Theophylline increases cAMP;

Causes sinus tachy, tremors, vomiting, hypoT, hypoK, hypergly (beta 2 effect), aTach/vTach, PVC, seizures;

Tx: Supportive care,

or gut decontamination + beta blockers (for tachy);

Hemodialysis if levels are> 100 mg/L OR seizures are present.

An 3 year old girl is brought into the ED. She is writhing in her fathers arms and is disorientated, her face is flushed and her pupils are dilated. Her father tells you that she got into the medicine cabinet but that there were several bottles open and he does not know what she took.

What is the cause of her symptoms and how would you treat them?

Anticholinergic OD: "Red as a beat, Hot as a hare, Dry as a bone, Blind as a bat, and Mad as a hatter"

This includes antihistaminesm antidepressants, antipsychotics, and antiemetics***

Pts are flushed, dehydrated, agitated, delerius, tachycardic, have dilated pupils and urinary retention;

Tx: Supportive care, sedation with a benzo may be req as is a urinary catheter (esp in older men),

Physostigmine

Nitrogen oxides (which cause methmoglobinemia, dysmpnea, cyanosis, syncope and seizures).

MB converts methmoglobinemia back to Hb.

Mneumonic for the sympotms of organophosphate/carbmate poisoning;

Salivation

Lacrimation

Urination

Defecation

GI Symptoms

Emesis

Bronchorrhea, Bronchospasm, Bradycardia

Caustic Acids cause injury by coagulative necorsis which is replaced by granulation tissue.

The stomach is the MC organ effected. Can cause GI perf/hemorrage, metabolic acidosis, hemolysis, renal failure, death.

Caustic Bases cause liquefactive necrosis and primarily effect the esophagus causing edema (poss airway obstruction), and also forms granulation tissue during healing. Strictures form as the tissues scar.

T/F

Gastric lavage or NG suction should accompany anti-emetics in the treatment of ingested caustic acids/bases.

False.

Treatment of choice is Intubation with gastric lavage or NG suction, however, antiemetics and neutrilzation of the acid or base should never be used

(anti-emetics because it will burn on the way up too and neutralization because the process is exothermic and will burn the pt).

T/F

Monotherapy is the most effective way to treat epilepsy

True!

Monotherapy is recommended (as is beginning treatment at low doses) due to the extensive drug interactions of anti-epilepsy drugs.

Anti-Epileptic drug - Hydantoin;

Water-soluble form of phenytoin = parenteral admin;

Stabilizes Na+ channels in inactive state and blocks Ca2+ channels;

Tx: acute status epilepticus, partial, or tonic clonic seizures (never DoC);

SE: Narrow TI,

Arrhythmias, esp in the elderly

AED - Hydantoin;

Prodrug that is demathylated to nirvanol(active);

Similar MoA (Na+ block) but worse SE than Phenytoin;

Phase I and II metabolism

AED - Hydantoin;

Tx: partial or generalized Tonic-clonic seizures in pt who are hypersensitive to phenytoin*

No gingival hyperplasia and no hirsuism but less effective as an AED and requires more frequent dosing.

AED - Barbiturate;

Prodrug (N-methyl phenobarbital) - demethylated in the liver to active form (MoA and SE same as pheno)

AED - Barbituate;

Rapidly converted to Phenobarbital + PEMA (Active Metabolite);

Acts like phenobarbital.

Carbamazepine is a CYP Inducer!

↓ levels of valproate, lamotrigine, tigabine, topiramate and haloperidol;

Carbamazepine ↓ the effectiveness of oral contraceptives;

Metabolism of carbamazepine is reduced by propoxyphene, erythromycin, cimetidine, fluoxetine, and isonazid;

AED;

Prodrug;

Inhbitis Na+ channel revovery form inactive state;

Less potent (and less toxic) than carbamazepine;

Tx: Partial seizures in a dults, generalized tonic-clonic seizures and trigeminal neuralgia*

AED;

Inhibits T-type Ca channels - prevents 3Hz spike/waves;

SE - [tolerance], euphoria, hiccups, fatigue, dizziness

Carbamazepine

2nd choices are phenytoin, valproate, lamotrigine, gabapentin, zonisamide, levateracetam

Carbamazepine

2nd choices are phenytoin or valproate.

Ethosuximide

2nd choice - valproate or lamotrigine

Valproate

2nd choice - lamotrigine or clonazepam

Diazepam

2nd choice - lorazepam or phenytoin

1) Stop the antipsychotic drug that induced the syndrome,

2) Get hyperthermia under control (cooling blankets etc...),

3) Circulatory and vent support,

4) Drugs such as bromocriptine (DA Agonist) and Dantrolene (muscle relaxant) may be used,

5) Aggressive hydration (to preserve the kidneys which can be damaged by elevated CPK).